Endocrinology and Metabolism

Original Articles

Thyroid
Unexpected Cancellation of Radioactive Iodine Treatment after Thyroid Hormone Withdrawal: Lessons from a Case Series: Hye-Seon Oh, Won Gu Kim, Won Bae Kim, Jin-Sook Ryu, Min Ji Jeon, Tae Yong Kim; Endocrinol Metab. 2026;41(2):300-307. Published online April 8, 2026; DOI: https://doi.org/10.3803/EnM.2025.2798

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Abstract PDF Supplementary Material PubReader ePub: Background
Radioactive iodine treatment (RAIT) is an essential therapy for differentiated thyroid cancer. However, unforeseen complications arising during thyroid hormone withdrawal (THW) can lead to Cancellation of the scheduled treatment. This study aimed to identify cases in which THW-RAIT was discontinued due to THW-related complications and to explore potentially preventable causes to improve patient management.
Methods
Among 4,174 patients who underwent THW-RAIT between 2012 and 2024, 39 did not complete the planned treatment. After excluding Cancellations unrelated to THW, 11 (0.26%) patients with unexpected THW-related medical issues were analyzed.
Results
The median age of the included patients was 61 years (range, 23 to 70), and 10 were male. The reasons for THW-RAIT Cancellation were hyponatremia (n=1), abnormal liver function (n=1), renal dysfunction (n=3), and combined liver and renal dysfunction (n=6). The patient with hyponatremia was taking a thiazide diuretic. Most cases of liver dysfunction were associated with prior use of herbal medications, whereas renal dysfunction was linked to diuretic or nonsteroidal anti-inflammatory drug use, pre-existing conditions such as single kidney or diabetic nephropathy, or inadequate oral intake during low-iodine preparation. Two cases of concurrent liver and renal dysfunction were attributed to rhabdomyolysis following intense exercise or heavy physical labor.
Conclusion
Enhanced patient education, comprehensive pre-treatment assessment, and careful avoidance of high-risk medications are essential to prevent THW-related complications and minimize disruptions in RAIT.

Thyroid
Triiodothyronine Is Associated with Incidence/Resolution of Steatotic Liver Disease: Longitudinal Study in Euthyroid Korean: Hye In Kim, Jun Young Kim, Jung Hwan Cho, Ji Min Han, Sunghwan Suh, Ji Cheol Bae, Tae Hyuk Kim, Sun Wook Kim, Jong Ryeal Hahm, Jae Hoon Chung; Endocrinol Metab. 2025;40(1):135-145. Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2040

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Background
The positive relationship between triiodothyronine (T3) and steatotic liver disease (SLD) demonstrated only in crosssectional study. We aimed to evaluated whether total T3 (TT3) is associated with the development/resolution of SLD in longitudinal design.
Methods
This retrospective, longitudinal, population-based cohort study included 1,665 South Korean euthyroid adults with ≥4 thyroid function test. We explored the impact of mean TT3 during follow-up on development/resolution of either SLD (diagnosed by ultrasound) or modified metabolic dysfunction-associated steatotic liver disease (MASLD) using Cox proportional hazards regression models.
Results
During about median 5 years follow-up, 807/1,216 (66.3%) participants among participants without SLD at baseline developed SLD, and 253/318 (79.5%) participants among participants with SLD at baseline SLD resolved fatty liver. Mean TT3 rather than thyroid stimulating hormone or mean free thyroxine was significantly related with development (adjusted hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.00 to 1.02; P=0.002) and resolution (adjusted HR, 0.97; 95% CI, 0.96 to 0.99; P=0.005) of SLD. Compared with low mean TT3 group, high mean TT3 group was positively associated with development of SLD (adjusted HR, 1.20; 95% CI, 1.05 to 1.38; P=0.008) and inversely associated with resolution of SLD (adjusted HR, 0.66; 95% CI, 0.51 to 0.85; P=0.001). The statistical significance remained for development (adjusted HR, 1.29; 95% CI, 1.10 to 1.51; P=0.001) and resolution (adjusted HR, 0.71; 95% CI, 0.54 to 0.94; P=0.018) of modified MASLD.
Conclusion
In Korean euthyroid adults, TT3 level was associated with development and resolution of either SLD or modified MASLD.

Citations

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Association Between Thyroid Dysfunction and Non-Alcoholic Fatty Liver Disease: A Systematic Review
Tanya ., Aryan Kler, Sunil Singh Bains
International Journal of Health Sciences and Research.2025; : 171. CrossRef

Review Articles

Thyroid
Thyroid Hormone-Mediated Selective Autophagy and Its Implications in Countering Metabolic Dysfunction-Associated Steatotic Liver Disease: Rohit A. Sinha; Endocrinol Metab. 2024;39(5):686-692. Published online October 14, 2024; DOI: https://doi.org/10.3803/EnM.2024.2068

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The influence of thyroid hormone (TH) on liver metabolism has attracted the attention of pharmacologists seeking new treatments for metabolic dysfunction-associated steatotic liver disease (MASLD), an increasingly common metabolic disorder. In this context, the selective induction of autophagy by TH in preclinical models has been identified as a promising mechanism. In this process, TH clears intrahepatic fat through lipophagy while protecting against inflammation and mitochondrial damage in hepatocytes via mitophagy. Furthermore, TH-induced aggrephagy may represent a protective mechanism to mitigate the development of MASLD-associated hepatocellular carcinoma. Considering the defects in autophagy observed during the progression of human MASLD, the induction of autophagy by TH, its metabolites, and its analogs represent a novel strategy to combat hepatic damage across the MASLD spectrum.

Citations

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The many pathways driving liver inflammation in MASH
Herbert Tilg, Timon E. Adolph, Stefano Romeo, Rohit Loomba
Cell Metabolism.2026; 38(6): 1054. CrossRef
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Sameeah Mejbel Hamad Algenabi, Anwar Nather Seiwan, Maha Hussein Hashem Sabra, Doaa I. Mohamed, Lobna Fouad Abd ElAziz Bassyouni, Dalia Alaa El-Din Aly El-Waseef, Samar F. Ezzat, Omnyah A. El-Kharashi, Hanaa F. Abd El-Kareem, Hyfa A. Alzahrani, Fawzyah Ob
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Rosellina M. Mancina, Luca Valenti, Stefano Romeo
Nature Metabolism.2025; 7(11): 2199. CrossRef
Repurposing levothyroxine for managing metabolic dysfunction-associated steatotic liver disease
Leonidas H. Duntas, Stergios A. Polyzos, Ulrike Gottwald-Hostalek, Bogumila Urgatz, Paul M. Yen
Endocrine.2025; 90(3): 1043. CrossRef

Mineral, Bone & Muscle
Roles of Parathyroid Hormone and Fibroblast Growth Factor 23 in Advanced Chronic Kidney Disease: Yosuke Nakagawa, Hirotaka Komaba; Endocrinol Metab. 2024;39(3):407-415. Published online May 16, 2024; DOI: https://doi.org/10.3803/EnM.2024.1978

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Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) each play a central role in the pathogenesis of chronic kidney disease (CKD)-mineral and bone disorder. Levels of both hormones increase progressively in advanced CKD and can lead to damage in multiple organs. Secondary hyperparathyroidism (SHPT), characterized by parathyroid hyperplasia with increased PTH secretion, is associated with fractures and mortality. Emerging evidence suggests that these associations may be partially explained by PTH-induced browning of adipose tissue and increased energy expenditure. Observational studies suggest a survival benefit of PTHlowering therapy, and a recent study comparing parathyroidectomy and calcimimetics further suggests the importance of intensive PTH control. The mechanisms underlying the regulation of FGF23 secretion by osteocytes in response to phosphate load have been unclear, but recent experimental studies have identified glycerol-3-phosphate, a byproduct of glycolysis released by the kidney, as a key regulator of FGF23 production. Elevated FGF23 levels have been shown to be associated with mortality, and experimental data suggest off-target adverse effects of FGF23. However, the causal role of FGF23 in adverse outcomes in CKD patients remains to be established. Further studies are needed to determine whether intensive SHPT control improves clinical outcomes and whether treatment targeting FGF23 can improve patient outcomes.

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World Journal of Nephrology.2026;[Epub] CrossRef
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Bongsung Kim, Kyu-Na Lee, Kyungdo Han, Mee Kyoung Kim
Osteoporosis International.2026;[Epub] CrossRef
Pre-Parathyroidectomy PTH as an Integrated Biomarker of Glandular Remodeling and Skeletal Turnover in Secondary Hyperparathyroidism
Min-Tser Liao, Chia-Chao Wu, Yi-Chou Hou, Kuo-Wang Tsai, Li-Jane Shih, Kuo-Cheng Lu, Chien-Lin Lu
International Journal of Molecular Sciences.2026; 27(11): 5094. CrossRef
Allopurinol has no effect on calcitriol or other CKD-MBD biomarkers: a randomized double-blind study
Tiago E Costa, Julia C Lauar, Mariana L R Innecchi, Luiza Karla R P Araujo, Venceslau A Coelho, Luciene M dos Reis, Rosa M A Moysés, Rosilene M Elias
Journal of the Endocrine Society.2026;[Epub] CrossRef
Gene expression and hormonal signaling in osteoporosis: from molecular mechanisms to clinical breakthroughs
Gurinderdeep Singh, Ronald Darwin, Krishna Chandra Panda, Shaikh Amir Afzal, Shashwat Katiyar, Ram C. Dhakar, Sangeetha Mani
Journal of Biomaterials Science, Polymer Edition.2025; 36(10): 1466. CrossRef
Correlation linking fibroblast growth factor 23 in circulation (FGF-23) and serum aldosterone levels in different stages of chronic kidney disease
Amira Hassan Elsaid Dohuim, Medhat Abd El Megeid Ghazy, Nahla Abdel Aziz Nosair, Amr Khalifa Hussien
The Egyptian Journal of Internal Medicine.2025;[Epub] CrossRef
Effects of Blood Flow Restriction Training and Possible Applications in Chronic Kidney Disease: A Narrative Review
Shen Liu, Zhuo Wang, Jia-fu Tang, Yong-long Yang, Wei-xiu Ji, Da-qi Xu
Current Physical Medicine and Rehabilitation Reports.2025;[Epub] CrossRef
Correlation Between Fibroblast Growth Factor 23 and Biochemical Parameters in Hemodialysis Patients With End-Stage Renal Disease
Barat Yusubov, Mirkhalig Javadov, Khanbaba Huseynov, Muradali Bakhshiyev
Cureus.2025;[Epub] CrossRef
Serum FGF-23 and Vitamin D Deficiency as Predictors of Metabolic Syndrome in Chronic Kidney Disease

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Efficacy of Different Doses of Sodium in the Dialysis Fluid on the Levels of Calcium, Phosphorus and Parathyroid Hormone in Patients Undergoing Chronic Hemodialysis
Asieh Aref, Ladan Mirzaei, Ali Ghorbani, Samaneh Tirom, Elham Farhadi
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Hanine AlArab, Anna Zenno, Melinda Pierce
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Xiaotong Yuan
American Journal of Translational Research.2025; 17(11): 8612. CrossRef

Mineral, Bone & Muscle
Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone: Lars Rejnmark; Endocrinol Metab. 2024;39(2):262-266. Published online April 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.1916

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The conventional treatment of hypoparathyroidism (HypoPT) includes active vitamin D and calcium. Despite normalization of calcium levels, the conventional treatment is associated with fluctuations in calcium levels, hypercalciuria, renal impairment, and decreased quality of life (QoL). Replacement therapy with parathyroid hormone (PTH)(1-84) is an option in some countries. However, convincing beneficial effects have not been demonstrated, which may be due to the short duration of action of this treatment. Recently, palopegteriparatide (also known as TransCon PTH) has been marketed in Europe and is expected also to be approved in other countries. Palopegteriparatide is a prodrug with sustained release of PTH(1-34) designed to provide stable physiological PTH levels for 24 hours/day. A phase 3 study demonstrated maintenance of normocalcemia in patients with chronic HypoPT, with no need for conventional therapy. Furthermore, this treatment lowers urinary calcium and improves QoL. Another long-acting PTH analog with effects on the parathyroid hormone receptor (eneboparatide) is currently being tested in a phase 3 trial. Furthermore, the treatment of autosomal dominant hypocalcemia type 1 with a calcilytic (encaleret) is also being tested. All in all, improved treatment options are on the way that will likely take the treatment of HypoPT to the next level.

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Construction of a predictive model for postoperative hypoparathyroidism in papillary thyroid cancer based on the Inflammatory Load Index
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Long-Term Morbidity after Postoperative Hypoparathyroidism in Thyroid Cancer Patients: A Nationwide Population-Based Cohort Study
Seong Hee Ahn, Sung-Hyo Seo, Chai Young Jung, Dong Han Yu, Ki-Pyo Kim, Youngjoon Kim, Yongin Cho, Da Hea Seo, So Hun Kim, Jun-Il Yoo, Seongbin Hong
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First Reported Use of Recombinant Parathyroid Hormone in Kenny–Caffey Syndrome Type 2: A Case Report and Literature Review
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Clinical characteristics of chinese patients with autosomal dominant hypocalcemia type 1: a single-center study
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Gender differences in long-term complications of chronic hypoparathyroidism: a systematic review
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Original Articles

Mineral, Bone & Muscle
Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality: Sung Hye Kong, Jeong Mo Bae, Jung Hee Kim, Sang Wan Kim, Dohyun Han, Chan Soo Shin; Endocrinol Metab. 2024;39(2):375-386. Published online March 21, 2024; DOI: https://doi.org/10.3803/EnM.2023.1827

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Background
Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses.
Methods
We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis.
Results
The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations.
Conclusion
Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

Citations

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Aberrant Histone Methylation Profile in Patients with Sporadic Primary Hyperparathyroidism
Poonam Kumari, Sanjay Kumar Bhadada, Ashutosh Kumar Arya, Jyotdeep Kaur, Naresh Sachdeva, Uma Nahar Saikia, Divya Dahiya, Anoop Kumar, Chirag Kharbanda, Sudhaker D Rao
The Journal of Clinical Endocrinology & Metabolism.2026; 111(6): 1680. CrossRef
Stearoyl-CoA Desaturase 5 (SCD5) in Lipid Remodeling: From Molecular Control to Pathophysiology
Veronika Zámbó, Gabriella Orosz, Miklós Csala, Éva Kereszturi
Journal of Lipid Research.2026; : 101078. CrossRef

Thyroid Big Data Articles (National Health Insurance Service Database)
Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study: Min-Su Kim, Jang Won Lee, Min Kyung Hyun, Young Shin Song; Endocrinol Metab. 2024;39(2):288-299. Published online March 4, 2024; DOI: https://doi.org/10.3803/EnM.2023.1815

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Background
Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients.
Methods
We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy.
Results
A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05–1.24 and 1.17– 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence.
Conclusion
High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

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Risk of atrial fibrillation in patients with differentiated thyroid cancer: a nationwide population-based analysis
Jung Heo, Seo Young Sohn, Yun Jin Kim, Sung Woo Cho
The Korean Journal of Internal Medicine.2026; 41(2): 286. CrossRef
Tailoring TSH suppression in differentiated thyroid carcinoma: evidence, controversies, and future directions
Xinxin Song, Xin Zhi, Linxue Qian
Endocrine.2025; 89(1): 1. CrossRef
The Levothyroxine Odyssey: Navigating the Path of Survivorship in Thyroid Cancer
Jin Hwa Kim
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Levothyroxine Dosage and the Increased Risk of Second Primary Malignancy in Thyroid Cancer Survivors
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Clinical Thyroidology®.2024; 36(7): 258. CrossRef

Thyroid
Thyroid Hormone Reference Intervals among Healthy Individuals In Lanzhou, China: Yan Lu, Wen-Xia Zhang, De-Hong Li, Lian-Hua Wei, Yu-Jun Zhang, Fu-Na Shi, Shen Zhou; Endocrinol Metab. 2023;38(3):347-356. Published online June 14, 2023; DOI: https://doi.org/10.3803/EnM.2023.1638

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Background
The common reference intervals (RIs) for thyroid hormones currently used in China are provided by equipment manufacturers. This study aimed to establish thyroid hormone RIs in the population of Lanzhou, a city in the subplateau region of northwest China, and compare them with previous reports and manufacturer-provided values.
Methods
In total, 3,123 individuals (1,680 men, 1,443 women) from Lanzhou, an iodine-adequate area of China, perceived as healthy were selected. The Abbott Architect analyzer was used to determine the serum concentration of thyroid hormones. The 95% RI was estimated using the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively.
Results
The serum levels of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), antithyroglobulin (ATG) antibody, and antithyroid peroxidase (ATPO) antibody levels were significantly correlated with sex (P<0.05). TSH, total thyroxine (TT4), and ATPO levels were significantly correlated with age (P<0.05). The serum levels of TSH, ATG, and ATPO in men were significantly lower than in women; in contrast, the serum TT3 level was significantly higher in men than in women (P<0.05). Serum TSH, TT3, TT4, and ATG levels differed across age groups (P<0.05), but no such variation was observed for ATG levels (P>0.05). The established RIs of TSH, ATG, and ATPO in this study differed between sexes (P<0.05). The thyroid hormone RIs established herein were inconsistent with the manufacturer-provided values.
Conclusion
The RIs of thyroid hormones in the healthy population of Lanzhou were inconsistent with those in the manufacturer’s manual. Validated sex-specific values are required for diagnosing thyroid diseases.

Citations

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Comparison of thyroid hormones reference intervals based on thyroid antibody levels: A multicenter study
Havva Beyter, Osman Acar, Oytun Portakal, Özlem Gülbahar, Gülsüm F. Türkeş, Neslihan Yıldırım Saral, Muhittin Abdülkadir Serdar, Aysel Ozpinar, Rajeevan Selvaratnam
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BMC Endocrine Disorders.2026;[Epub] CrossRef
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Review Articles

Thyroid
Evaluation and Management of Bone Health in Patients with Thyroid Diseases: A Position Statement of the Korean Thyroid Association: A Ram Hong, Ho-Cheol Kang; Endocrinol Metab. 2023;38(2):175-189. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1701

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Thyroid hormones play an important physiological role in maintaining adult bone structure and strength. Consequently, thyroid dysfunction is related to skeletal outcomes. Overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, leading to osteoporosis and increased fracture risk. Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with differentiated thyroid cancer is a cause of secondary osteoporosis. In contrast, there is a lack of evidence on the negative impact of hypothyroidism on bone health. Considering the clinical updates on the importance of bone health in thyroid dysfunction, the Task Force from the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association recently developed a position statement on the evaluation and management of bone health of patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid-stimulating hormone-suppressive therapy-associated hyperthyroidism in patients with differentiated thyroid cancer. Herein, we review the Korean Thyroid Association’s position statement on the evaluation and management of bone health associated with thyroid diseases.

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Mineral, Bone & Muscle
New Insights into Calorie Restriction Induced Bone Loss: Linyi Liu, Clifford J. Rosen; Endocrinol Metab. 2023;38(2):203-213. Published online April 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1673

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Caloric restriction (CR) is now a popular lifestyle choice due to its ability in experimental animals to improve lifespan, reduce body weight, and lessen oxidative stress. However, more and more emerging evidence suggests this treatment requires careful consideration because of its detrimental effects on the skeletal system. Experimental and clinical studies show that CR can suppress bone growth and raise the risk of fracture, but the specific mechanisms are poorly understood. Reduced mechanical loading has long been thought to be the primary cause of weight loss-induced bone loss from calorie restriction. Despite fat loss in peripheral depots with calorie restriction, bone marrow adipose tissue (BMAT) increases, and this may play a significant role in this pathological process. Here, we update recent advances in our understanding of the effects of CR on the skeleton, the possible pathogenic role of BMAT in CR-induced bone loss, and some strategies to mitigate any potential side effects on the skeletal system.

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Thyroid
Thyroid Function across the Lifespan: Do Age-Related Changes Matter?: John P. Walsh; Endocrinol Metab. 2022;37(2):208-219. Published online April 14, 2022; DOI: https://doi.org/10.3803/EnM.2022.1463

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Circulating concentrations of thyrotropin (TSH) and thyroxine (T4) are tightly regulated. Each individual has setpoints for TSH and free T4 which are genetically determined, and subject to environmental and epigenetic influence. Pituitary-thyroid axis setpoints are probably established in utero, with maturation of thyroid function continuing until late gestation. From neonatal life (characterized by a surge of TSH and T4 secretion) through childhood and adolescence (when free triiodothyronine levels are higher than in adults), thyroid function tests display complex, dynamic patterns which are sexually dimorphic. In later life, TSH increases with age in healthy older adults without an accompanying fall in free T4, indicating alteration in TSH setpoint. In view of this, and evidence that mild subclinical hypothyroidism in older people has no health impact, a strong case can be made for implementation of age-related TSH reference ranges in adults, as is routine in children.

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Diabetes, Obesity and Metabolism
Effects of Intermittent Fasting on the Circulating Levels and Circadian Rhythms of Hormones: Bo Hye Kim, Yena Joo, Min-Seon Kim, Han Kyoung Choe, Qingchun Tong, Obin Kwon; Endocrinol Metab. 2021;36(4):745-756. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.405

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Intermittent fasting has become an increasingly popular strategy in losing weight and associated reduction in obesity-related medical complications. Overwhelming studies support metabolic improvements from intermittent fasting in blood glucose levels, cardiac and brain function, and other health benefits, in addition to weight loss. However, concerns have also been raised on side effects including muscle loss, ketosis, and electrolyte imbalance. Of particular concern, the effect of intermittent fasting on hormonal circadian rhythms has received little attention. Given the known importance of circadian hormonal changes to normal physiology, potential detrimental effects by dysregulation of hormonal changes deserve careful discussions. In this review, we describe the changes in circadian rhythms of hormones caused by intermittent fasting. We covered major hormones commonly pathophysiologically involved in clinical endocrinology, including insulin, thyroid hormones, and glucocorticoids. Given that intermittent fasting could alter both the level and frequency of hormone secretion, decisions on practicing intermittent fasting should take more considerations on potential detrimental consequences versus beneficial effects pertaining to individual health conditions.

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Original Article

Thyroid
Thyroid Hormone Profile and Its Prognostic Impact on the Coronavirus Disease 2019 in Korean Patients: Jiyeon Ahn, Min Kyung Lee, Jae Hyuk Lee, Seo Young Sohn; Endocrinol Metab. 2021;36(4):769-777. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1109

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Background
Data on the association between coronavirus disease 2019 (COVID-19) and thyroid have been reported, including overt thyrotoxicosis and suppression of thyroid function. We aimed to evaluate the thyroid hormone profile and its association with the prognosis of COVID-19 in Korean patients.
Methods
The clinical data of 119 patients with COVID-19, admitted in the Myongji Hospital, Goyang, South Korea, were retrospectively evaluated. The thyroid hormone profiles were analyzed and compared based on disease severity (non-severe disease vs. severe to critical disease). Clinical outcomes were analyzed according to the tertiles of thyroid hormones.
Results
Of the 119 patients, 76 (63.9%) were euthyroid, and none presented with overt thyroid dysfunction. Non-thyroidal illness syndrome was the most common manifestation (18.5%), followed by subclinical thyrotoxicosis (14.3%) among patients with thyroid dysfunction. Thyroid stimulating hormone (TSH) and triiodothyronine (T3) levels were significantly lower in patients with severe to critical disease than in those with non-severe disease (P<0.05). Patients in the lowest T3 tertile (<0.77 ng/mL) had higher rates of mechanical ventilation, intensive care unit admission, and death than those in the middle and highest (>1.00 ng/mL) T3 tertiles (P<0.05). COVID-19 patients in the lowest T3 tertile were independently associated with mortality (hazard ratio, 5.27; 95% confidence interval, 1.09 to 25.32; P=0.038) compared with those in the highest T3 tertile.
Conclusion
Thyroid dysfunction is common in COVID-19 patients. Changes in serum TSH and T3 levels may be important markers of disease severity in COVID-19. Decreased T3 levels may have a prognostic significance in COVID-19 related outcome.

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COVID-19 and thyroid function: What do we know so far?
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Review Articles

Thyroid
The Role of Thyroid Hormone in the Regulation of Cerebellar Development: Sumiyasu Ishii, Izuki Amano, Noriyuki Koibuchi; Endocrinol Metab. 2021;36(4):703-716. Published online August 9, 2021; DOI: https://doi.org/10.3803/EnM.2021.1150

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The proper organized expression of specific genes in time and space is responsible for the organogenesis of the central nervous system including the cerebellum. The epigenetic regulation of gene expression is tightly regulated by an intrinsic intracellular genetic program, local stimuli such as synaptic inputs and trophic factors, and peripheral stimuli from outside of the brain including hormones. Some hormone receptors are expressed in the cerebellum. Thyroid hormones (THs), among numerous circulating hormones, are well-known major regulators of cerebellar development. In both rodents and human, hypothyroidism during the postnatal developmental period results in abnormal morphogenesis or altered function. THs bind to the thyroid hormone receptors (TRs) in the nuclei and with the help of transcriptional cofactors regulate the transcription of target genes. Gene regulation by TR induces cell proliferation, migration, and differentiation, which are necessary for brain development and plasticity. Thus, the lack of TH action mediators may directly cause aberrant cerebellar development. Various kinds of animal models have been established in a bid to study the mechanism of TH action in the cerebellum. Interestingly, the phenotypes differ greatly depending on the models. Herein we summarize the actions of TH and TR particularly in the developing cerebellum.

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Histone Deacetylase 3 Inhibitor Alleviates Cerebellar Defects in Perinatal Hypothyroid Mice by Stimulating Histone Acetylation and Transcription at Thyroid Hormone-Responsive Gene Loci
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Mineral, Bone & Muscle
Normocalcemic Primary Hyperparathyroidism: Need for a Standardized Clinical Approach: Guido Zavatta, Bart L. Clarke; Endocrinol Metab. 2021;36(3):525-535. Published online June 1, 2021; DOI: https://doi.org/10.3803/EnM.2021.1061

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Since normocalcemic primary hyperparathyroidism (NHPT) was first defined at the Third International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism in 2008, many papers have been published describing its prevalence and possible complications. Guidelines for the management of this condition are still lacking, and making the diagnosis requires fulfillment of strict criteria. Recent studies have shown that intermittent oscillations of serum calcium just below and slightly above the normal limits are very frequent, therefore challenging the assumption that serum calcium must be consistently normal to make the diagnosis. There is debate if these variations in serum calcium outside the normal range should be included under the rubric of NHPT or, rather, a milder form of classical primary hyperparathyroidism. Innovative approaches to define NHPT have been proposed that still need to be validated in prospective studies. Non-classical complications, especially cardiovascular complications, have been associated with NHPT, indicating that hyperparathyroidism may be a cardiovascular risk factor. New associations between parathyroid hormone (PTH) and several other comorbidities have also been reported from observational studies, suggesting that excessive PTH secretion might cause tissue dysfunction independent of serum calcium. Heterogeneous studies using different definitions of NHPT, however, make it difficult to draw definitive conclusions regarding the role of PTH excess when complications other than osteoporosis or kidney stones are described. This review will focus on clinical aspects and suggest an approach to NHPT.

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Original Article

Clinical Study
Radioactive Parathyroid Adenomas on Sestamibi Scans: Low Parathyroid Hormone Secretory Potential and Large Volume: Sung Hye Kong, Jung Hee Kim, Sang Wan Kim, Chan Soo Shin; Endocrinol Metab. 2021;36(2):351-358. Published online April 6, 2021; DOI: https://doi.org/10.3803/EnM.2020.823

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Background
We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.
Methods
The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent ^99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.
Results
Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [–] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m². Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (–) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (–) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm³ [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm³ [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.
Conclusion
Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.

Citations

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Association Between Biochemical Parameters, Parathyroid Gland Morphometry, and Dual-Phase MIBI SPECT/CT Findings in Primary Hyperparathyroidism
Anna Krzentowska, Aleksander Józef Konturek, Filip Gołkowski, Anna Merklinger-Gruchała, Marcin Barczyński
Journal of Clinical Medicine.2026; 15(5): 1973. CrossRef
Study on Uptake Ratio of ^99mTc-MIBI Parathyroid Scan
Jung-Soo Kim, Jin-Eui Kim
Journal of Radiological Science and Technology.2025; 48(5): 513. CrossRef
Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality
Sung Hye Kong, Jeong Mo Bae, Jung Hee Kim, Sang Wan Kim, Dohyun Han, Chan Soo Shin
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Incidentally detected follicular thyroid carcinoma mimicking parathyroid adenoma on Tc-99m MIBI scan: A case report
Yeon-Hee Han, Hwan-Jeong Jeong, Sun Young Lee, Seok Tae Lim
Medicine.2024; 103(18): e38107. CrossRef
Atypical parathyroid tumor: clinical and parathyroid hormone response to surgical treatment
Antonio Giulio Napolitano, Massimo Monacelli, Valeria Liparulo, Eleonora Coviello, Domenico Pourmolkara, Stefano Avenia, Andrea Polistena
Annals of Surgical Treatment and Research.2023; 105(2): 76. CrossRef
The Relationship between Planar and SPECT/CT Parameters and Functional Markers in Primary Hyperparathyroidism
Guler Silov, Serpil Erdogan Ozbodur
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Review Articles

Thyroid
Best Achievements in Translational and Basic Thyroidology in 2020: Sun Wook Cho, Young Joo Park; Endocrinol Metab. 2021;36(1):36-40. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.104

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Abstract PDF PubReader ePub: This review discusses articles published in 2020 that presented noteworthy achievements in translational and basic thyroidology. Previously unresolved questions about thyroid hormone receptor actions and signaling mechanisms were answered using various novel in vitro and in vivo models. Using high resolution cryo-electron microscopy, the fine functional structure of thyroglobulin was demonstrated, and new insights into the pathogenesis of thyroid disease were achieved, with a focus on research into thyroid-disrupting chemicals and the gut microbiome. Novel therapeutic approaches were tried in the field of advanced thyroid cancer treatments.

Thyroid
Best Achievements in Clinical Thyroidology in 2020: Eun Kyung Lee, Young Joo Park; Endocrinol Metab. 2021;36(1):30-35. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2021.103

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This review highlights the most interesting research in thyroidology conducted in 2020. The publications of interest discussed below dealt with the following topics: thyroid dysfunction, risk of thyroid cancer, molecular diagnostics and new therapeutics for thyroid cancer, and thyroid disease in the coronavirus disease 2019 pandemic era.

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EpCAM activates the ERK-EGR1 signaling axis and promotes TNF-α-induced the progression of anaplastic thyroid cancer
Chi-Chiu Lee, Yi-Jen Su, Sushree Shankar Panda, Chiung-Yi Chiu, Chung-Hsuan Wu, Tsai-Ming Lu, Pi-Chun Li, Yen-Lin Huang, Ruey-Long Hong, Shao-Hsi Hung, Cassian Yee, Stephen Y. Lai, Han-Chung Wu
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Use of long non-coding RNAs for the molecular diagnosis of papillary thyroid cancer
Daham Kim, Juyeon Yu, Jiwon Kim, Yoon-a Hwang, Jin Kyong Kim, Cheol Ryong Ku, Jung Hyun Yoon, Jin Young Kwak, Kee-Hyun Nam, Eun Jig Lee
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Miscellaneous
Rare PTH Gene Mutations Causing Parathyroid Disorders: A Review: Joon-Hyop Lee, Munkhtugs Davaatseren, Sihoon Lee; Endocrinol Metab. 2020;35(1):64-70. Published online March 19, 2020; DOI: https://doi.org/10.3803/EnM.2020.35.1.64

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Since parathyroid hormone (PTH) was first isolated and its gene (PTH) was sequenced, only eight PTH mutations have been discovered. The C18R mutation in PTH, discovered in 1990, was the first to be reported. This autosomal dominant mutation induces endoplasmic reticulum stress and subsequent apoptosis in parathyroid cells. The next mutation, which was reported in 1992, is associated with exon skipping. The substitution of G with C in the first nucleotide of the second intron results in the exclusion of the second exon; since this exon includes the initiation codon, translation initiation is prevented. An S23P mutation and an S23X mutation at the same residue were reported in 1999 and 2012, respectively. Both mutations resulted in hypoparathyroidism. In 2008, a somatic R83X mutation was detected in a parathyroid adenoma tissue sample collected from a patient with hyperparathyroidism. In 2013, a heterozygous p.Met1_Asp6del mutation was incidentally discovered in a case-control study. Two years later, the R56C mutation was reported; this is the only reported hypoparathyroidism-causing mutation in the mature bioactive part of PTH. In 2017, another heterozygous mutation, M14K, was detected. The discovery of these eight mutations in the PTH gene has provided insights into its function and broadened our understanding of the molecular mechanisms underlying mutation progression. Further attempts to detect other such mutations will help elucidate the functions of PTH in a more sophisticated manner.

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Thyroid
Bisphenols and Thyroid Hormone: Min Joo Kim, Young Joo Park; Endocrinol Metab. 2019;34(4):340-348. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.340

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In recent decades, attention has been directed toward the effects of bisphenol A (BPA) on human health. BPA has estrogenic activity and is regarded as a representative endocrine disruptor. In addition, mounting evidence indicates that BPA can disrupt thyroid hormone and its action. This review examined human epidemiological studies to investigate the association between BPA exposure and thyroid hormone levels, and analyzed in vivo and in vitro experiments to identify the causal relationship and its mechanism of action. BPA is involved in thyroid hormone action not only as a thyroid hormone receptor antagonist, but also through several other mechanisms. Since the use of bisphenols other than BPA has recently increased, we also reviewed the effects of other bisphenols on thyroid hormone action.

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Miscellaneous
Intraoperative Parathyroid Hormone Monitoring in the Surgical Management of Sporadic Primary Hyperparathyroidism: Zahra F. Khan, John I. Lew; Endocrinol Metab. 2019;34(4):327-339. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.327

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Abstract PDF PubReader ePub

Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized medical centers worldwide. Using the Miami or “>50% intraoperative PTH drop” criterion, IPM confirms the complete excision of all hyperfunctioning parathyroid tissue before the operation is finished, and helps guide the surgeon to identify additional hyperfunctioning parathyroid glands that may necessitate further extensive neck exploration when intraoperative parathyroid hormone (PTH) levels do not drop sufficiently. The intraoperative PTH assay is also used to differentiate parathyroid from non-parathyroid tissues during operations using fine needle aspiration samples and to lateralize the side of the neck harboring the hypersecreting parathyroid through differential jugular venous sampling when preoperative localization studies are negative or equivocal. The use of IPM underscores the recognition and understanding of sporadic primary hyperparathyroidism (SPHPT) as a disease of function rather than form, where the surgeon is better equipped to treat such patients with quantitative instead of qualitative information for durable long-term operative success. There has been a significant paradigm shift over the last 2 decades from conventional to focused parathyroidectomy guided by IPM. This approach has proven to be a safe and rapid operation requiring minimal dissection performed in an ambulatory setting for the treatment of SPHPT.

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Original Articles

Adrenal gland
Effects of Altered Calcium Metabolism on Cardiac Parameters in Primary Aldosteronism: Jung Soo Lim, Namki Hong, Sungha Park, Sung Il Park, Young Taik Oh, Min Heui Yu, Pil Yong Lim, Yumie Rhee; Endocrinol Metab. 2018;33(4):485-492. Published online November 30, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.4.485

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Background

Increasing evidence supports interplay between aldosterone and parathyroid hormone (PTH), which may aggravate cardiovascular complications in various heart diseases. Negative structural cardiovascular remodeling by primary aldosteronism (PA) is also suspected to be associated with changes in calcium levels. However, to date, few clinical studies have examined how changes in calcium and PTH levels influence cardiovascular outcomes in PA patients. Therefore, we investigated the impact of altered calcium homeostasis caused by excessive aldosterone on cardiovascular parameters in patients with PA.

Methods

Forty-two patients (mean age 48.8±10.9 years; 1:1, male:female) whose plasma aldosterone concentration/plasma renin activity ratio was more than 30 were selected among those who had visited Severance Hospital from 2010 to 2014. All patients underwent adrenal venous sampling with complete access to both adrenal veins.

Results

The prevalence of unilateral adrenal adenoma (54.8%) was similar to that of bilateral adrenal hyperplasia. Mean serum corrected calcium level was 8.9±0.3 mg/dL (range, 8.3 to 9.9). The corrected calcium level had a negative linear correlation with left ventricular end-diastolic diameter (LVEDD, ρ=−0.424, P=0.031). Moreover, multivariable regression analysis showed that the corrected calcium level was marginally associated with the LVEDD and corrected QT (QTc) interval (β=−0.366, P=0.068 and β=−0.252, P=0.070, respectively).

Conclusion

Aldosterone-mediated hypercalciuria and subsequent hypocalcemia may be partly involved in the development of cardiac remodeling as well as a prolonged QTc interval, in subjects with PA, thereby triggering deleterious effects on target organs additively.

Citations

Citations to this article as recorded by

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis
Anning Wang, Yuhan Wang, Hongzhou Liu, Xiaodong Hu, Jiefei Li, Huaijin Xu, Zhimei Nie, Lingjing Zhang, Zhaohui Lyu
Frontiers in Endocrinology.2022;[Epub] CrossRef

Miscellaneous
Novel Mutation in PTHLH Related to Brachydactyly Type E2 Initially Confused with Unclassical Pseudopseudohypoparathyroidism: Jihong Bae, Hong Seok Choi, So Young Park, Do-Eun Lee, Sihoon Lee; Endocrinol Metab. 2018;33(2):252-259. Published online June 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.252

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Background

Autosomal-dominant brachydactyly type E is a congenital abnormality characterized by small hands and feet, which is a consequence of shortened metacarpals and metatarsals. We recently encountered a young gentleman exhibiting shortening of 4th and 5th fingers and toes. Initially, we suspected him having pseudopseudohypoparathyroidism (PPHP) because of normal biochemical parameters, including electrolyte, Ca, P, and parathyroid hormone (PTH) levels; however, his mother and maternal grandmother had the same conditions in their hands and feet. Furthermore, his mother showed normal biochemical parameters. To the best of our knowledge, PPHP is inherited via a mutated paternal allele, owing to the paternal imprinting of GNAS (guanine nucleotide binding protein, alpha stimulating) in the renal proximal tubule. Therefore, we decided to further analyze the genetic background in this family.

Methods

Whole exome sequencing was performed using genomic DNA from the affected mother, son, and the unaffected father as a negative control.

Results

We selected the intersection between 45,490 variants from the mother and 45,646 variants from the son and excluded 27,512 overlapping variants identified from the father. By excluding homogenous and compound heterozygous variants and removing all previously reported variants, 147 variants were identified to be shared by the mother and son. Variants that had least proximities among species were excluded and finally 23 variants remained.

Conclusion

Among them, we identified a defect in parathyroid hormone like hormone (PTHLH), encoding the PTH-related protein, to be disease-causative. Herein, we report a family affected with brachydactyly type E2 caused by a novel PTHLH mutation, which was confused with PPHP with unclassical genetic penetrance.

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A Heterozygous Splice-Site Mutation in PTHLH Causes Autosomal Dominant Shortening of Metacarpals and Metatarsals
Monica Reyes, Bert Bravenboer, Harald Jüppner
Journal of Bone and Mineral Research.2019; 34(3): 482. CrossRef
A 3.06-Mb interstitial deletion on 12p11.22-12.1 caused brachydactyly type E combined with pectus carinatum
Jia Huang, Hong-Yan Liu, Rong-Rong Wang, Hai Xiao, Dong Wu, Tao Li, Ying-Hai Jiang, Xue Zhang
Chinese Medical Journal.2019; 132(14): 1681. CrossRef
Parathyroid Hormone-Related Protein in the Hand or Out of Hand?
Sang Wan Kim
Endocrinology and Metabolism.2018; 33(2): 202. CrossRef

Review Article

Thyroid
Evaluation of Thyroid Hormone Levels and Urinary Iodine Concentrations in Koreans Based on the Data from Korea National Health and Nutrition Examination Survey VI (2013 to 2015): Jae Hoon Chung; Endocrinol Metab. 2018;33(2):160-163. Published online May 4, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.2.160

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No nationwide data have been published about thyroid hormone levels and urinary iodine concentrations (UICs) in Korea. The Korea Centers for Disease Control and Prevention and the Korean Thyroid Association established a project to evaluate the nationwide thyroid hormone profile and UICs in healthy Koreans as part of the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2013 to 2015), a nationwide, cross-sectional survey of the Korean population that enrolled 7,061 individuals who were weighted to represent the entire Korean population. Based on the KNHANES VI, the geometric mean value of serum thyroid stimulating hormone was 2.16 mIU/L, and its reference interval was 0.59 to 7.03 mIU/L. The mean value of serum free thyroxine was 1.25 ng/dL, and its reference interval was 0.92 to 1.60 ng/dL. The median UIC in the Korean population was reported to be 294 μg/L, corresponding to ‘above requirements’ iodine intake according to the World Health Organization recommendations. A U-shaped relationship of UIC with age was found. The prevalence of overt hyperthyroidism and overt hypothyroidism in the Korean population based on the KNHANES VI was 0.54% and 0.73%, respectively.

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Correlation between shift work and non-alcoholic fatty liver disease among male workers in the steel manufacturing company of Korea: a cross-sectional study
Kiseok Kim, Yong-Jin Lee, Soon-Chan Kwon, Young-Sun Min, Hyun Kyo Lee, Gwangin Baek, Sang Hyeon Kim, Eun-Chul Jang
Annals of Occupational and Environmental Medicine.2022;[Epub] CrossRef
Subclinical Hypothyroidism: Prevalence, Health Impact, and Treatment Landscape
Won Sang Yoo, Hyun Kyung Chung
Endocrinology and Metabolism.2021; 36(3): 500. CrossRef
T4+T3 Combination Therapy: An Unsolved Problem of Increasing Magnitude and Complexity
Wilmar M. Wiersinga
Endocrinology and Metabolism.2021; 36(5): 938. CrossRef
Update on Thyroid Hormone Levels and Thyroid Dysfunction in the Korean Population Based on Data from the Korea National Health and Nutrition Examination Survey VI (2013 to 2015)
Jae Hoon Chung
Endocrinology and Metabolism.2020; 35(1): 7. CrossRef
Different Relationships Between Thyrotropin and Muscle Strength According to Sex and Age in Euthyroid Koreans (The 6th Korea National Health and Nutritional Examination Survey 2014–2015)
Seong Hee Ahn, Da Hea Seo, Yongin Cho, Mihye Jung, So Hun Kim, Seongbin Hong
Thyroid®.2020; 30(12): 1710. CrossRef

Original Articles

Miscellaneous
Effects of Serum Albumin, Calcium Levels, Cancer Stage and Performance Status on Weight Loss in Parathyroid Hormone-Related Peptide Positive or Negative Patients with Cancer: Ji-Yeon Lee, Namki Hong, Hye Ryun Kim, Byung Wan Lee, Eun Seok Kang, Bong-Soo Cha, Yong-ho Lee; Endocrinol Metab. 2018;33(1):97-104. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.97

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Background

A recent animal study showed that parathyroid hormone-related peptide (PTHrP) is associated with cancer cachexia by promoting adipose tissue browning, and we previously demonstrated that PTHrP predicts weight loss (WL) in patients with cancer. In this study, we investigated whether prediction of WL by PTHrP is influenced by clinical factors such as serum albumin, corrected calcium levels, cancer stage, and performance status (PS).

Methods

A cohort of 219 patients with cancer whose PTHrP level was measured was enrolled and followed for body weight (BW) changes. Subjects were divided into two groups by serum albumin (cutoff value, 3.7 g/dL), corrected calcium (cutoff value, 10.5 mg/dL), cancer stage (stage 1 to 3 or 4), or PS (Eastern Cooperative Oncology Group 0 to 1 or 2 to 4), respectively. Clinically significant WL was defined as either percent of BW change (% BW) <−5% or % BW <−2% plus body mass index (BMI) <20 kg/m².

Results

After a median follow-up of 327 days, 74 patients (33.8%) experienced clinically significant WL. A positive PTHrP level was associated with a 2-fold increased risk of WL after adjusting for age, baseline BMI, serum albumin, corrected calcium level, cancer stage, and PS. The effect of PTHrP on WL remained significant in patients with low serum albumin, stage 4 cancer, and good PS. Regardless of calcium level, the effect of PTHrP on WL was maintained, although there was an additive effect of higher calcium and PTHrP levels.

Conclusion

Early recognition of patients with advanced cancer who are PTHrP positive with hypercalcemia or hypoalbuminemia is needed for their clinical management.

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Targeting of HIF2-driven cachexia in kidney cancer
Muhannad Abu-Remaileh, Laura A. Stransky, Nikita Bhalerao, Nitin H. Shirole, Qinqin Jiang, Eddy Saad, Marc Machaalani, Sean M. Vigeant, Hilina Woldemichael, Charles Xu, Jing Lu, Hairong Wei, Zhihong Liu, William Sun, Kei Enomoto, Toni K. Choueiri, Jason R
Nature Medicine.2026; 32(1): 245. CrossRef
Cancer knocks you out by fasting: Cachexia as a consequence of metabolic alterations in cancer
Salvatore Cortellino, Margherita D'Angelo, Massimiliano Quintiliani, Antonio Giordano
Journal of Cellular Physiology.2025;[Epub] CrossRef
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Cohn May, Gueron Or, Segal Gad, Zubli Daniel, Hakim Hila, Fizdel Boris, Liber Pninit, Amir Hadar, Barkai Galia
Journal of Clinical Medicine.2024; 13(5): 1409. CrossRef
Parathyroid hormone related protein (PTHrP) in patients with pancreatic carcinoma and overt signs of disease progression and host tissue wasting
Britt-Marie Iresjö, Serkan Kir, Kent Lundholm
Translational Oncology.2023; 36: 101752. CrossRef
Development and Characterization of a Cancer Cachexia Rat Model Transplanted with Cells of the Rat Lung Adenocarcinoma Cell Line Sato Lung Cancer (SLC)
Eiji Kasumi, Miku Chiba, Yoshie Kuzumaki, Hiroyuki Kuzuoka, Norifumi Sato, Banyu Takahashi
Biomedicines.2023; 11(10): 2824. CrossRef
Role of Parathyroid Hormone and Parathyroid Hormone-Related Protein in Protein-Energy Malnutrition
Praopilad Srisuwarn, Sinee Disthabanchong
Frontiers in Bioscience-Landmark.2023;[Epub] CrossRef
Inhibition of epidermal growth factor receptor suppresses parathyroid hormone‐related protein expression in tumours and ameliorates cancer‐associated cachexia
Bahar Zehra Camurdanoglu Weber, Samet Agca, Aylin Domaniku, Sevval Nur Bilgic, Dilsad H. Arabaci, Serkan Kir
Journal of Cachexia, Sarcopenia and Muscle.2022; 13(3): 1582. CrossRef
Metabolic Reprogramming in Adipose Tissue During Cancer Cachexia
Bahar Zehra Camurdanoglu Weber, Dilsad H. Arabaci, Serkan Kir
Frontiers in Oncology.2022;[Epub] CrossRef

Site-Specific Difference of Bone Geometry Indices in Hypoparathyroid Patients: Hye-Sun Park, Da Hea Seo, Yumie Rhee, Sung-Kil Lim; Endocrinol Metab. 2017;32(1):68-76. Published online February 6, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.68

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Background

Hypoparathyroid patients often have a higher bone mineral density (BMD) than the general population. However, an increase in BMD does not necessarily correlate with a solid bone microstructure. This study aimed to evaluate the bone microstructure of hypoparathyroid patients by using hip structure analysis (HSA).

Methods

Ninety-five hypoparathyroid patients >20 years old were enrolled and 31 of them had eligible data for analyzing bone geometry parameters using HSA. And among the control data, we extracted sex-, age-, and body mass index-matched three control subjects to each patient. The BMD data were reviewed retrospectively and the bone geometry parameters of the patients were analyzed by HSA.

Results

The mean Z-scores of hypoparathyroid patients at the lumbar spine, femoral neck, and total hip were above zero (0.63±1.17, 0.48±1.13, and 0.62±1.10, respectively). The differences in bone geometric parameters were site specific. At the femoral neck and intertrochanter, the cross-sectional area (CSA) and cortical thickness (C.th) were higher, whereas the buckling ratio (BR) was lower than in controls. However, those trends were opposite at the femoral shaft; that is, the CSA and C.th were low and the BR was high.

Conclusion

Our study shows the site-specific effects of hypoparathyroidism on the bone. Differences in bone components, marrow composition, or modeling based bone formation may explain these findings. However, further studies are warranted to investigate the mechanism, and its relation to fracture risk.

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Vertebral fractures, trabecular bone score and their determinants in chronic hypoparathyroidism
S. Saha, V. Mannar, D. Kandasamy, V. Sreenivas, R. Goswami
Journal of Endocrinological Investigation.2022; 45(9): 1777. CrossRef
Epidemiology and Financial Burden of Adult Chronic Hypoparathyroidism
Sigridur Bjornsdottir, Steven Ing, Deborah M Mitchell, Tanja Sikjaer, Line Underbjerg, Zaki Hassan-Smith, Jad Sfeir, Neil J Gittoes, Bart L Clarke L
Journal of Bone and Mineral Research.2020; 37(12): 2602. CrossRef
Effect of Endogenous Parathyroid Hormone on Bone Geometry and Skeletal Microarchitecture
A Ram Hong, Ji Hyun Lee, Jung Hee Kim, Sang Wan Kim, Chan Soo Shin
Calcified Tissue International.2019; 104(4): 382. CrossRef
Bone responses to chronic treatment of adult hypoparathyroid patients with PTH peptides
Sofie Malmstroem, Lars Rejnmark, Dolores M. Shoback
Current Opinion in Endocrine and Metabolic Research.2018; 3: 51. CrossRef

Clinical Study
Triiodothyronine Levels Are Independently Associated with Metabolic Syndrome in Euthyroid Middle-Aged Subjects: Hye Jeong Kim, Ji Cheol Bae, Hyeong Kyu Park, Dong Won Byun, Kyoil Suh, Myung Hi Yoo, Jae Hyeon Kim, Yong-Ki Min, Sun Wook Kim, Jae Hoon Chung; Endocrinol Metab. 2016;31(2):311-319. Published online May 13, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.311

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Background

Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort.

Methods

A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders.

Results

Of the study patients, 12% (n=1,664) had MetS. A higher T3 level and T3-to-T4 ratio were associated with unfavourable metabolic profiles, such as higher body mass index, systolic and diastolic blood pressure, triglycerides, fasting glucose and glycated hemoglobin, and lower high density lipoprotein cholesterol levels. The proportion of participants with MetS increased across the T3 quartile categories (P for trend <0.001) and the T3-to-T4 ratio quartile categories (P for trend <0.001). The multi-variate-adjusted OR (95% confidence interval) for MetS in the highest T3 quartile group was 1.249 (1.020 to 1.529) compared to the lowest T3 quartile group, and that in the highest T3-to-T4 ratio quartile group was 1.458 (1.141 to 1.863) compared to the lowest T3-to-T4 ratio quartile group, even after adjustment for potential confounders.

Conclusion

Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications.

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Jinyan Chen, Kexin Zhang, Yuqun Wang, Xiaofei Zhang, Guoji Xiong, Xiaodong Sun, Ningning Hou, Yang Zhang, Chengxia Kan
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Fengjuan Hu, Hu Liu, Linlin Gu, Shuli Jia, Lixing Zhou, Wanyu Zhao, Xiaolei Liu, Birong Dong
Journal of Diabetes.2026;[Epub] CrossRef
Associations of free triiodothyronine and thyroxine with blood pressure in Chinese coronary artery disease adults
Hongli Dong, Ping Hu, Jie Wang, Nan Lu
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Victoria Persky, Chibuzor Abasilim, Konstantina Tsintsifas, Tessa Day, Robert M Sargis, Martha Daviglus, Jianwen Cai, Sally Freels, Robert Kaplan, Carmen R Isasi, Amber Pirzada, Michelle L Meyer, Gregory A Talavera, Bharat Thyagarajan, Shivani Agarwal, No
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Myxedema in Both Hyperthyroidism and Hypothyroidism: A Hormetic Response?
Salvatore Sciacchitano, Angela Napoli, Monica Rocco, Claudia De Vitis, Rita Mancini
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Maša Kenda, Urša Pečar Fonović, Janko Kos, Marija Sollner Dolenc
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Stella Iacovides, Shane K. Maloney, Sindeep Bhana, Zareena Angamia, Rebecca M. Meiring, Carla Pegoraro
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Han-Bin Huang, Po-Keng Cheng, Chi-Ying Siao, Yuan-Ting C. Lo, Wei-Chun Chou, Po-Chin Huang
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Clinical Parameters Are More Likely to Be Associated with Thyroid Hormone Levels than with Thyrotropin Levels: A Systematic Review and Meta-Analysis
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The role of thyroid hormone in metabolism and metabolic syndrome
Patrícia de Fátima dos Santos Teixeira, Patrícia Borges dos Santos, Carmen Cabanelas Pazos-Moura
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Association between Abdominal Fat Distribution and Free Triiodothyronine in a Euthyroid Population
Xiaomin Nie, Yiting Xu, Xiaojing Ma, Yunfeng Xiao, Yufei Wang, Yuqian Bao
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Peng Cai, Yan Peng, YuXi Chen, Li Li, Wei Chu, Yan Wang, Xukai Wang
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Şenay DURMAZ CEYLAN, Şuuri Ahsen CEYLAN, Fatih EKER, Aşkın GÜNGÜNEŞ
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Yi-Cheng Chang, Shih-Che Hua, Chia-Hsuin Chang, Wei-Yi Kao, Hsiao-Lin Lee, Lee-Ming Chuang, Yen-Tsung Huang, Mei-Shu Lai
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Luís Raposo, Sandra Martins, Daniela Ferreira, João Tiago Guimarães, Ana Cristina Santos
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Diego Urrunaga-Pastor, Mirella Guarnizo-Poma, Enrique Moncada-Mapelli, Luis G. Aguirre, Herbert Lazaro-Alcantara, Socorro Paico-Palacios, Betzi Pantoja-Torres, Vicente A. Benites-Zapata
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Articles inEndocrinology and Metabolismin 2016
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Endocrine Research
Thyroid Hormone Regulates the mRNA Expression of Small Heterodimer Partner through Liver Receptor Homolog-1: Hwa Young Ahn, Hwan Hee Kim, Ye An Kim, Min Kim, Jung Hun Ohn, Sung Soo Chung, Yoon-Kwang Lee, Do Joon Park, Kyong Soo Park, David D. Moore, Young Joo Park; Endocrinol Metab. 2015;30(4):584-592. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.584

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Background

Expression of hepatic cholesterol 7α-hydroxylase (CYP7A1) is negatively regulated by orphan nuclear receptor small heterodimer partner (SHP). In this study, we aimed to find whether thyroid hormone regulates SHP expression by modulating the transcriptional activities of liver receptor homolog-1 (LRH-1).

Methods

We injected thyroid hormone (triiodothyronine, T3) to C57BL/6J wild type. RNA was isolated from mouse liver and used for microarray analysis and quantitative real-time polymerase chain reaction (PCR). Human hepatoma cell and primary hepatocytes from mouse liver were used to confirm the effect of T3 in vitro. Promoter assay and electrophoretic mobility-shift assay (EMSA) were also performed using human hepatoma cell line

Results

Initial microarray results indicated that SHP expression is markedly decreased in livers of T3 treated mice. We confirmed that T3 repressed SHP expression in the liver of mice as well as in mouse primary hepatocytes and human hepatoma cells by real-time PCR analysis. LRH-1 increased the promoter activity of SHP; however, this increased activity was markedly decreased after thyroid hormone receptor β/retinoid X receptor α/T3 administration. EMSA revealed that T3 inhibits specific LRH-1 DNA binding.

Conclusion

We found that thyroid hormone regulates the expression of SHP mRNA through interference with the transcription factor, LRH-1.

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Giuseppe Ferrandino, Rachel R. Kaspari, Olga Spadaro, Andrea Reyna-Neyra, Rachel J. Perry, Rebecca Cardone, Richard G. Kibbey, Gerald I. Shulman, Vishwa Deep Dixit, Nancy Carrasco
Proceedings of the National Academy of Sciences.2017;[Epub] CrossRef

Review Articles

Adrenal gland
Hypoparathyroidism: Replacement Therapy with Parathyroid Hormone: Lars Rejnmark, Line Underbjerg, Tanja Sikjaer; Endocrinol Metab. 2015;30(4):436-442. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.436

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Hypoparathyroidism (HypoPT) is characterized by low serum calcium levels caused by an insufficient secretion of parathyroid hormone (PTH). Despite normalization of serum calcium levels by treatment with activated vitamin D analogues and calcium supplementation, patients are suffering from impaired quality of life (QoL) and are at increased risk of a number of comorbidities. Thus, despite normalization of calcium levels in response to conventional therapy, this should only be considered as an apparent normalization, as patients are suffering from a number of complications and calcium-phosphate homeostasis is not normalized in a physiological manner. In a number of recent studies, replacement therapy with recombinant human PTH (rhPTH(1-84)) as well as therapy with the N-terminal PTH fragment (rhPTH(1-34)) have been investigated. Both drugs have been shown to normalize serum calcium while reducing needs for activated vitamin D and calcium supplements. However, once a day injections cause large fluctuations in serum calcium. Twice a day injections diminish fluctuations, but don't restore the normal physiology of calcium homeostasis. Recent studies using pump-delivery have shown promising results on maintaining normocalcemia with minimal fluctuations in calcium levels. Further studies are needed to determine whether this may improve QoL and lower risk of complications. Such data are needed before replacement with the missing hormone can be recommended as standard therapy.

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Maja Djordjevic Milosevic, Anita Skakic, Marina Andjelkovic, Angelica Maria Delgado-Vega, Håkan Thonberg, Kristel Klaassen, Jovana Komazec, Bozica Kecman, Nikola Jocic, Erik Björck, Anna Lindstrand, Maja Stojiljkovic
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Static Magnetic Field-Mediated Parathyroid Xenotransplantation Modulates Lymphocyte Migration: A Potential Immunosuppression-Free Long-Term Treatment for Hypoparathyroidism
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Die HypAus-Studie
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Mineral, Bone & Muscle
Emerging Therapies for Osteoporosis: Michael R. McClung; Endocrinol Metab. 2015;30(4):429-435. Published online December 31, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.4.429

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Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients.

Citations

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Original Articles

Thyroid
Weight Changes in Patients with Differentiated Thyroid Carcinoma during Postoperative Long-Term Follow-up under Thyroid Stimulating Hormone Suppression: Seo Young Sohn, Ji Young Joung, Yoon Young Cho, Sun Mi Park, Sang Man Jin, Jae Hoon Chung, Sun Wook Kim; Endocrinol Metab. 2015;30(3):343-351. Published online August 4, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.343

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Background

There are limited data about whether patients who receive initial treatment for differentiated thyroid cancer (DTC) gain or lose weight during long-term follow-up under thyroid stimulating hormone (TSH) suppression. This study was aimed to evaluate whether DTC patients under TSH suppression experience long-term weight gain after initial treatment. We also examined the impact of the radioactive iodine ablation therapy (RAIT) preparation method on changes of weight, comparing thyroid hormone withdrawal (THW) and recombinant human TSH (rhTSH).

Methods

We retrospectively reviewed 700 DTC patients who underwent a total thyroidectomy followed by either RAIT and levothyroxine (T4) replacement or T4 replacement alone. The control group included 350 age-matched patients with benign thyroid nodules followed during same period. Anthropometric data were measured at baseline, 1 to 2 years, and 3 to 4 years after thyroidectomy. Comparisons were made between weight and body mass index (BMI) at baseline and follow-up.

Results

Significant gains in weight and BMI were observed 3 to 4 years after initial treatment for female DTC but not in male patients. These gains among female DTC patients were also significant compared to age-matched control. Women in the THW group gained a significant amount of weight and BMI compared to baseline, while there was no increase in weight or BMI in the rhTSH group. There were no changes in weight and BMI in men according to RAIT preparation methods.

Conclusion

Female DTC patients showed significant gains in weight and BMI during long-term follow-up after initial treatment. These changes were seen only in patients who underwent THW for RAIT.

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The complexity of the relationship between thyroid disease and body weight
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Effectiveness of a Low-Iodine Diet in Post-Thyroidectomy Thyroid Cancer Patients Receiving I-131 Therapy at the Vietnam National Cancer Hospital
Bach Viet HOANG, Thuy Thi TRAN, Anh Tran Mai LE, Tien Thi Hong NGUYEN, Dung Thi NGUYEN, Huong Thi LE
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Effects of a low-iodine diet in post-thyroidectomy thyroid cancer patients undergoing I 131 therapy at the Vietnam National Cancer Hospital
Bach Viet Hoang, Tien Thi Hong Nguyen, Yen Thi Duong, Hoa Thi Thanh Nguyen, Thu Ha Nguyen, Thanh Thi Nguyen, Lieu Thi Thu Nguyen, Huong Thi Le
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Factors influencing the quality of life in survivors of differentiated thyroid cancer based on patient-reported outcomes: a single-center cross-sectional study
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The Changes of Weight, Body Composition and Metabolic Parameters According to Treatment Modality in Patients with Thyroid Cancer
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International Journal of Thyroidology.2025; 18(2): 171. CrossRef
Impact of a mobile health intervention based on multi-theory model of health behavior change on self-management in patients with differentiated thyroid cancer: protocol for a randomized controlled trial
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Thyroidectomy Effects on the Body Mass Index and Thyroid-Stimulating Hormone: A Systematic Review and Meta-Analysis
Hyder Mirghani, Ahmad M Fnjan, Abdullah F Almalki, Ali F Almadan, Omar Abdullah M Alammar, Abdulaziz S Alhwiati, Amer A Laradhi, Ahmed M Bakour, Mohamad A Aljahed, Abdulmajeed M Alzahrani
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Pre-surgery dietician counseling can prevent post-thyroidectomy body weight gain: results of an intervention trial
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Postthyroidectomy obesity in a Korean population: does the extent of surgery matter?
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Weight Changes After Thyroid Surgery for Patients with Benign Thyroid Nodules and Thyroid Cancer: Population-Based Study and Systematic Review and Meta-Analysis
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Does the Risk of Metabolic Syndrome Increase in Thyroid Cancer Survivors?
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Thyroid hormone and its metabolites in relation to quality of life in patients treated for differentiated thyroid cancer
E.T. Massolt, M. van der Windt, T.I.M. Korevaar, B.L.R. Kam, J.W. Burger, G.J.H. Franssen, I. Lehmphul, J. Köhrle, W.E. Visser, R.P. Peeters
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High Serum Levels of Thyroid-Stimulating Hormone and Sustained Weight Gain in Patients with Thyroid Cancer Undergoing Radioiodine Therapy
Hyo Jung Seo, June-Key Chung, Keon Wook Kang, E. Edmund Kim, Gi Jeong Cheon, Jin Chul Paeng, Dong Soo Lee, Young Joo Park, Do Joon Park, Jae Gol Choe
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Obesity and Metabolism
Serum Concentrations of Ghrelin and Leptin according to Thyroid Hormone Condition, and Their Correlations with Insulin Resistance: Kyu-Jin Kim, Bo-Yeon Kim, Ji-Oh Mok, Chul-Hee Kim, Sung-Koo Kang, Chan-Hee Jung; Endocrinol Metab. 2015;30(3):318-325. Published online May 18, 2015; DOI: https://doi.org/10.3803/EnM.2015.30.3.318

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Background

Thyroid hormones can influence energy metabolism and insulin sensitivity via their interaction with adipocytokines and gut hormones. The aims of this study were to evaluate differences in serum ghrelin and leptin concentrations according to thyroid hormone levels, and to investigate the correlation of insulin resistance.

Methods

A total of 154 patients (57 hyperthyroid patients, 61 euthyroid patients, and 36 hypothyroid patients; mean age, 47.9 years) were enrolled. Serum leptin, ghrelin, and insulin levels were measured and insulin resistance was calculated using the formula of the homeostasis model assessment of insulin resistance (HOMA-IR).

Results

There were no differences in mean concentrations of ghrelin or leptin among the three groups. There were no significant differences in insulin levels between the groups (P=0.06), although hyperthyroid patients had borderline statistically significantly higher levels of insulin than did euthyroid subjects by post hoc test (26.4 µIU/mL vs. 16.1 µIU/mL, P=0.057). Regarding HOMA-IR index, the mean levels were highest in the hyperthyroid group among those of the three groups (hyperthyroid vs. euthyroid vs. hypothyroid, 6.7 vs. 3.8 vs. 4.4, P=0.068). Plasma levels of ghrelin were significantly negatively correlated with age, insulin, glucose, body mass index (BMI), and HOMA-IR. Plasma levels of leptin showed significant positive correlation with BMI and triglyceride. There were no significant correlations among thyroid hormone, thyrotropin, ghrelin, leptin, or insulin.

Conclusion

The present study found that serum ghrelin, leptin, and insulin levels didn't differ according to thyroid function conditions. Further studies with larger numbers of patients are required to establish a direct relationship between plasma ghrelin, leptin, and thyroid hormone.

Citations

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Thyroid Hormone Replacement Dose Is Not Associated with Anti-TPO and Anti-TG Antibody Titers in Hashimoto’s Disease
Małgorzata Szczuko, Olimpia Szmigiel, Urszula Szczuko, Leon Rudak, Karolina Wrońska, Lidia Kwiatkowska, Małgorzata Tomasik, Anhelli Syrenicz, Jakub Pobłocki
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Relationship between ghrelin and thyroid disease: a meta-analysis
Caihong Xin, Jiayi Yao, Huijuan Li, Xin Sun, Huijuan Wang
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Thyroid disorders and gastrointestinal dysmotility: an old association
Guang-Meng Xu, Ming-Xin Hu, Si-Yu Li, Xuan Ran, Hao Zhang, Xiang-Fu Ding
Frontiers in Physiology.2024;[Epub] CrossRef
Insulin resistance, leptin and adiponectin in lean and hypothyroid children and adolescents with obesity
Doaa El Amrousy, Dalia El-Afify, Shaimaa Salah
BMC Pediatrics.2022;[Epub] CrossRef
Mediators of energy homeostasis in hyperthyroidism
Avinash Patil, Suresh Vaikkakara, Mani Deepthi Dasari, Sandeep Ganta, Alok Sachan, Kiranmayi S. Vinapamula
Archives of Endocrinology and Metabolism.2022;[Epub] CrossRef
STUDY OF GHRELIN LEVELS IN HYPOTHYROID PATIENTS BEFORE AND AFTER TREATMENT
Peeyush Yadav, G. G. Kaushik
INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH.2021; : 52. CrossRef
Acylated Ghrelin Attenuates l-Thyroxin–induced Cardiac Damage in Rats by Antioxidant and Anti-inflammatory Effects and Downregulating Components of the Cardiac Renin–angiotensin System
Rehab Badi
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Experimental hypothyroidism in adult male rats: the effects of Artemisia dracunculus aqueous extract on serum thyroid hormones, lipid profile, leptin, adiponectin, and antioxidant factors
Mohammad Mohsen Mohammadi, Mahdi Saeb, Saeed Nazifi
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Leptin, neuropeptide Y (NPY), melatonin and zinc levels in experimental hypothyroidism and hyperthyroidism: relation with melatonin and the pineal gland
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Leptin, NPY, Melatonin and Zinc Levels in Experimental Hypothyroidism and Hyperthyroidism: The Relation to Zinc
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Bridget Martinez, Rudy M. Ortiz
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Role of the Orexin System on the Hypothalamus-Pituitary-Thyroid Axis
Antonietta Messina, Carolina De Fusco, Vincenzo Monda, Maria Esposito, Fiorenzo Moscatelli, Anna Valenzano, Marco Carotenuto, Emanuela Viggiano, Sergio Chieffi, Vincenzo De Luca, Giuseppe Cibelli, Marcellino Monda, Giovanni Messina
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Serum Concentrations of Ghrelin and Leptin according to Thyroid Hormone Condition, and Their Correlations with Insulin Resistance (Endocrinol Metab2015;30:318-25, Kyu-Jin Kim et al.)
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Serum Concentrations of Ghrelin and Leptin according to Thyroid Hormone Condition, and Their Correlations with Insulin Resistance (Endocrinol Metab2015;30:318-25, Kyu-Jin Kim et al.)
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Preoperative Localization and Intraoperative Parathyroid Hormone Assay in Korean Patients with Primary Hyperparathyroidism: Eirie Cho, Jung Mi Chang, Seok Young Yoon, Gil Tae Lee, Yun Hyi Ku, Hong Il Kim, Myung-Chul Lee, Guk Haeng Lee, Min Joo Kim; Endocrinol Metab. 2014;29(4):464-469. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.464

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Background

The intraoperative parathyroid hormone (IOPTH) assay is widely used in patients with primary hyperparathyroidism (PHPT). We investigated the usefulness of the IOPTH assay in Korean patients with PHPT.

Methods

We retrospectively reviewed the data of 33 patients with PHPT who underwent parathyroidectomy. Neck ultrasonography (US) and ^99mTc-sestamibi scintigraphy (MIBI scan) were performed preoperatively and IOPTH assays were conducted.

Results

The sensitivity of neck US and MIBI scans were 91% and 94%, respectively. A 50% decrease in parathyroid hormone (PTH) levels 10 minutes after excision of the parathyroid gland was obtained in 91% (30/33) of patients and operative success was achieved in 97% (32/33) of patients. The IOPTH assay was 91% true-positive, 3% true-negative, 0% false-positive, and 6% false-negative. The overall accuracy of the IOPTH assay was 94%. In five cases with discordant neck US and MIBI scan results, a sufficient decrease in IOPTH levels helped the surgeon confirm the complete excision of the parathyroid gland with no additional neck exploration.

Conclusion

The IOPTH assay is an accurate tool for localizing hyperfunctioning parathyroid glands and is helpful for evaluating cases with discordant neck US and MIBI scan results.

Citations

Citations to this article as recorded by

Intraoperative Parathyroid Hormone Monitoring Criteria in Primary Hyperparathyroidism
Phillip Staibano, Michael Au, Han Zhang, Sheila Yu, Winnie Liu, Jesse D. Pasternak, Xing Xing, Carolyn D. Seib, Lisa Orloff, Nhu-Tram Nguyen, Michael K. Gupta, Eric Monteiro, Sameer Parpia, Tyler McKechnie, Alex Thabane, J. E. M. (Ted) Young, Mohit Bhanda
JAMA Otolaryngology–Head & Neck Surgery.2025; 151(3): 190. CrossRef
Single-Center Experience of Parathyroidectomy Using Intraoperative Parathyroid Hormone Monitoring
Seong Hoon Kim, Si Yeon Lee, Eun Ah Min, Young Mi Hwang, Yun Suk Choi, Jin Wook Yi
Medicina.2022; 58(10): 1464. CrossRef
The natural history and hip geometric changes of primary hyperparathyroidism without parathyroid surgery
Kyong Yeun Jung, A. Ram Hong, Dong Hwa Lee, Jung Hee Kim, Kyoung Min Kim, Chan Soo Shin, Seong Yeon Kim, Sang Wan Kim
Journal of Bone and Mineral Metabolism.2017; 35(3): 278. CrossRef
The utility of the radionuclide probe in parathyroidectomy for primary hyperparathyroidism
MS Lim, M Jinih, CH Ngai, NM Foley, HP Redmond
The Annals of The Royal College of Surgeons of England.2017; 99(5): 369. CrossRef
Articles in 'Endocrinology and Metabolism' in 2014
Won-Young Lee
Endocrinology and Metabolism.2015; 30(1): 47. CrossRef

Case Reports

1-34 PTH Could Reverse Impaired Bone Mineralization Induced By the Overdose of Bisphosphonate.: Kyeong Hye Park, Kwang Joon Kim, Han Seok Choi, Kyoung Min Kim, Eun Young Lee, Seonhui Han, Hyun Sil Kim, Daham Kim, Hannah Seok, Eun Yeong Choe, Yumie Rhee, Sung Kil Lim; Endocrinol Metab. 2012;27(3):247-250. Published online September 19, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.3.247

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Abstract PDF: Bisphosphonates are the mainstay of osteoporosis treatment. Despite the fact that bisphosphonates have a relatively good safety record and are tolerated well by the majority of patients, serious adverse events have been associated with their use. A 41-year-old man had been diagnosed with osteoporosis and had taken etidronate 200 mg/day daily for 2 years due to the judgmental error. He was referred for the management of refractory bone pain and generalized muscle ache. Serum calcium, phosphate, 25-hydroxy-vitamin D (25(OH)D), and immunoreactive parathyroid hormone (iPTH) were within normal range. Plain X-ray showed multiple fractures. Whole body bone scan confirmed multiple sites of increased bone uptakes. Tetracycline-labeled bone biopsy showed typical findings of osteomalacia. He was diagnosed with iatrogenic, etidronate-induced osteomalacia. The patient received daily parathyroid hormone (PTH) injection for 18 months. PTH effectively reverses impaired bone mineralization caused by etidronate misuse. Currently, he is doing well without bone pain. Bone mineral density significantly increased, and the increased bone uptake was almost normalized after 18 months. This case seems to suggest that human PTH (1-34) therapy, possibly in association with calcium and vitamin D, is associated with important clinical improvements in patients with impaired bone mineralization due to the side effect of bisphosphonate.

A Case of CATCH22 Syndrome with Normal Parathyroid Function.: Min Jeong Lee, So Yeon An, Chang Bum Bae, Young Bae Sohn, Yoon Sok Chung; Endocrinol Metab. 2012;27(2):151-154. Published online June 20, 2012; DOI: https://doi.org/10.3803/EnM.2012.27.2.151

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Abstract PDF

CATCH 22 is a medical acronym for cardiac defects, abnormal faces, thymic hypoplasia, cleft palate, and hypocalcemia, and a variable deletion on chromosome 22. It includes DiGeorge syndrome, conotruncal anomaly face syndrome, and velo-cardio-facial syndrome. It has a prevalence estimated at 1:3,000-1:6,000. Most deletions occur at de novo, but autosomal dominant inheritance is observed in 6-10% of cases. Hormonal disorders are common in patients with CATCH22 syndrome. While hypoparathyroidism was the predominant endocrine disturbance that has been documented in the DiGeorge syndrome, other hormonal defects, such as growth hormone deficiency, hypothyroidism, and hyperthyroidism have been occurred in patients with CATCH22 syndrome. The spectrum of parathyroid gland dysfunction in this syndrome ranges from severe neonatal hypocalcemia to normal parathyroid function. Most patients are usually diagnosed in young age, but a few patients with mild abnormality are presented later in life. We report a case of CATCH22 syndrome with normal parathyroid hormone and calcium level in an adult. The diagnosis of CATCH22 syndrome was confirmed by fluorescence in situ hybridization analysis.

Citations

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A Case of CATCH22 Syndrome Diagnosed in Postmenopausal Woman
Seung Kyung Lee, Min Jeong Lee, Hyo Jin Lee, Bu Kyung Kim, Young Bae Sohn, Yoon-Sok Chung
Journal of Bone Metabolism.2013; 20(1): 57. CrossRef

Original Articles

The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change in Bone Mineral Density in an Animal Model of Osteoporosis.: Seung Hun Lee, Jung Min Koh, Young Sun Lee, Beom Jun Kim, Je Yong Choi, Ghi Su Kim; Endocrinol Metab. 2011;26(4):303-309. Published online December 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.4.303

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BACKGROUND
We hypothesized that combination therapy of cathepsin K inhibitor (CTKi) and human parathyroid hormone (1-34) (teriparatide, PTH) would overcome the coupling phenomenon of bone resorption and formation and thus may rapidly increase bone mass. METHODS: We selected a dose of zoledronic acid (ZA) that had shown similar effects with CTKi on body bone mineral density (BMD) change during the preliminary experiment. Female mice were subjected to ovariectomized (OVX control) or a sham operation (SHAM group). The mice were treated with CTKi (CTKi group), ZA (ZA group), PTH (PTH group) or with a combination of PTH with ZA (ZA + PTH group) or CTKi (CTKi + PTH group) for 8 weeks. Total BMD was measured before the operation and at 4 and 8 weeks. RESULTS: In the preliminary results, 10 microg/kg of ZA showed similar BMD changes with CTKi. Compared with the OVX control, BMD in the SHAM, ZA, CTKi, PTH, ZA + PTH, and CTKi + PTH groups was significantly increased after treatment. BMD in the CTKi + PTH group, but not in the ZA + PTH group increased more significantly than in the PTH group at the end of treatment. Compared with the OVX control, changes in BMD in the SHAM, ZA, CTKi, PTH, ZA + PTH, and CTKi + PTH groups increased significantly after 8 weeks of treatment. The change in BMD in the CTKi + PTH group, but not in the ZA + PTH group was more significantly increased than the change in BMD in the PTH group. CONCLUSION: When combined with PTH, CTKi augmented the anabolic action of PTH. Therefore, combination therapy with CTKi and PTH might be a new therapeutic modality capable of overcoming the coupling phenomenon, thereby markedly and rapidly increasing bone mass.

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The Effects of Combination Therapy of Cathepsin K Inhibitor and PTH on Change of Bone Mineral Density in Animal Model of Osteoporosis
Yumie Rhee
Endocrinology and Metabolism.2011; 26(4): 295. CrossRef

Effect of Thyroid Hormone to the Expression of Bile Salt Export Pump.: Hwa Young Ahn, Kwan Jae Lee, Soon Hui Kim, Eun Ky Kim, Ah Reum Kang, Jung Ah Lim, Ji Won Yoon, Kyung Won Kim, Do Joon Park, Bo Youn Cho, Young Joo Park; Endocrinol Metab. 2011;26(3):232-238. Published online September 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.3.232

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Abstract PDF

BACKGROUND
Bile acids were important for the regulation of cholesterol homeostasis. Thyroid hormone increased the expression of CYP7A1 (cholesterol 7alpha-hydroxylase), catalyzing the first step in the biosynthesis of bile acids. However, the effect of thyroid hormone on bile acid export has not been previously assessed. The principal objective of this study is to evaluate the effects of thyroid hormone on the bile salt export pump (BSEP). METHODS: Thyroid hormone, T3 (1 mg/g) was administered to male mice via intraperitoneal injection. After 6 hours and 5 days of T3 treatment, we measured serum total and LDL cholesterol and hepatobiliary bile acid concentrations. We assessed the changes associated with bile acid synthesis and transport. In order to evaluate the direct effect of thyroid hormone, we assessed the changes in the levels of BSEP protein after T3 administration in human hepatoma cells. RESULTS: Serum total and LDL cholesterol were reduced and hepatobiliary bile acid concentrations were increased following T3 treatment. Expressions of Cyp7a1 and BSEP mRNA were increased following T3 treatment. The levels of the BSEP protein in the mouse liver as well as in the human hepatoma cells were increased after T3 treatment. CONCLUSION: Thyroid hormone can regulate LDL cholesterol metabolism. It increases bile acid synthesis and the excretion of bile acids via increased BSEP expression.

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Hypothyroidism Increases Cholesterol Gallstone Prevalence in Mice by Elevated Hydrophobicity of Primary Bile Acids
Irina Kube, Luca Bartolomeo Tardio, Ute Hofmann, Ahmed Ghallab, Jan G. Hengstler, Dagmar Führer, Denise Zwanziger
Thyroid®.2021; 31(6): 973. CrossRef
Thyroid Dysfunction and Cholesterol Gallstone Disease
Irina Kube, Denise Zwanziger
Experimental and Clinical Endocrinology & Diabetes.2020; 128(06/07): 455. CrossRef
Thyroid hormone receptor β1 stimulates ABCB4 to increase biliary phosphatidylcholine excretion in mice
Julien Gautherot, Thierry Claudel, Frans Cuperus, Claudia Daniela Fuchs, Thomas Falguières, Michael Trauner
Journal of Lipid Research.2018; 59(9): 1610. CrossRef

Case Report

Successful Localization of Distant Metastasis in Parathyroid Carcinoma Using Intraoperative Parathyroid Hormone Assay.: Ho Cheol Hong, Sun Won Kim, Tae Hyung Kim, In Hye Cha, Jae Hee Ahn, Hye Jin Yoo, Hee Young Kim, Ji A Seo, Hyun Koo Kim, Sin Gon Kim, Nan Hee Kim, Kyung Mook Choi, Jae Bok Lee, Sei Hyun Baik, Dong Seop Choi; Endocrinol Metab. 2011;26(1):92-96. Published online March 1, 2011; DOI: https://doi.org/10.3803/EnM.2011.26.1.92

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Abstract PDF

Intra-operative parathyroid hormone (IOPTH) assay is a useful tool to confirm complete excision of all hyper-functioning parathyroid gland tissue. In this report, we describe a case with successful localization of distant metastasis in a patient with parathyroid carcinoma using the IOPTH assay. A 53-year-old man presented to our clinic with a serum calcium level of 11.8 mg/dL and an intact PTH level of 233.3 pg/mL. He had been treated for parathyroid carcinoma eleven years ago. Two suspected metastatic lesions were detected on the chest computed tomography. Due to the vastly different surgical field necessary to excise each lesion, we preferentially removed only one lesion and we monitored the other remaining suspected lesion without resection via IOPTH assay. Six months later, the patient's serum calcium and intact PTH levels remained within their normal ranges. To the best of our knowledge, this is the first case to effectively utilize IOPTH assay for the management of metastatic parathyroid carcinoma.

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The association of abdominal obesity, obesity and parathyroid hormone in Korean adults (aged≥50 years): The Korea National Health and Nutrition Survey, 2011
Kyu Su Lee, Yo Sang Yoon, Hyun Yoon
Journal of the Korea Academia-Industrial cooperation Society.2015; 16(6): 3882. CrossRef

Original Article

Identification and Validation of the Relationship of the Anabolic Effect of Parathyroid Hormone with the Wnt/beta-catenin Canonical Pathway.: Se Hwa Kim, Juan Ji An, Yumie Rhee, Sung Kil Lim; J Korean Endocr Soc. 2007;22(6):411-418. Published online December 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.6.411

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Abstract PDF

BACKGROUND
It has been well established that daily injections of low dose parathyroid hormone (PTH) increase bone mass in animals and humans. However, the precise mechanisms by which PTH exerts its anabolic action on bone are incompletely understood. The canonical Wnt-b-catenin signaling pathway has recently been demonstrated to have an important role in bone cell function. In the present study, we have examined the interaction between the PTH and Wnt signaling pathways in mouse osteoblastic MC3T3-E1 cells. METHODS & RESULTS: MC3T3-E1 cells were treated with 0.01-0.84 micrometer recombinant PTH. beta-catenin expression was significantly increased after 30 minutes of exposure to PTH and reached a maximum 2.7 fold increase at 1 hr and expression then faded at 6 hrs. In addition, treatment with PTH increased nuclear accumulation of activated beta-catenin; the ratio between the nuclear to cytoplasmic protein was more than three fold at 30 minutes and beyond. Moreover, PTH stimulated T-cell factor/lymphoid enhancer factor (TCF/LEF) reporter gene activity in MC3T3-E1 cells. Confocal microscopy revealed nuclear translocation of beta-catenin by PTH as compared with a glycogen synthase kinase-3beta (GSK-3beta) inhibitor. CONCLUSION: These results suggest that the anabolic mechanism of PTH might be partially associated with the Wnt-canonical pathway. The appropriate target of another anabolic agent should be determined through further studies of this pathway.

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Effects of N-acetyl-l-cysteine on fish hepatoma cells treated with mercury chloride and ionizing radiation
Jin Kyu Kim, Min Han, Mohammad Nili
Chemosphere.2011; 85(10): 1635. CrossRef
Bone Forming Effect of PTH through Wnt/β-catenin Signaling System
Dong Jin Chung, Min Young Chung
Journal of Korean Endocrine Society.2007; 22(6): 407. CrossRef

Case Reports

A Case of Resistance Syndrome to Thyroid Hormone Associated with Mutation (G345D) in the Thyroid Hormone Receptor Beta Gene.: Tae Jin Park, Joon Koo Kang, Kyoung Woo Seo, Hae Jin Kim, Yoon Sok Chung, Kwan Woo Lee, Seon Yong Jeong, Hyon Ju Kim, Dae Jung Kim; J Korean Endocr Soc. 2007;22(4):277-281. Published online August 1, 2007; DOI: https://doi.org/10.3803/jkes.2007.22.4.277

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Abstract PDF

Resistance syndrome to thyroid hormone (RTH) is a rare autosomal dominant disease that is characterized by decreased tissue responsiveness to thyroid hormone, and it is mainly due to mutations of the thyroid hormone receptor beta (THRB) gene. We report here on a 36-years old male who had mild thyroid goiter and general weakness. The thyroid function test showed elevated levels of total T3 and free T4. The levels of TSH and the free alpha subunit were in normal ranges. Mutation analysis of the THRB gene revealed the missense mutation G345D. We report here on the clinical features and THRB gene mutation analysis of a case of RTH.

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A Case of Resistance to Thyroid Hormone with Thyroid Cancer
Hee Kyung Kim, Doi Kim, Eun Hyung Yoo, Ji In Lee, Hye Won Jang, Alice Hyun Kyung Tan, Kyu Yeon Hur, Jae Hyeon Kim, Kwang-Won Kim, Jae Hoon Chung, Sun Wook Kim
Journal of Korean Medical Science.2010; 25(9): 1368. CrossRef

A Case of Primary Hyperparathyroidism Caused by Cystic Parathyroid Adenoma, Diagnosed during Intra-Operative PTH Monitoring.: Hye Jin Yoo, Nan Hee Kim, Soo Yeon Park, Dong Jin Kim, Sae Jeung Yang, Ju Ri Park, Hee Young Kim, Ji A Seo, Kye Won Lee, Sin Gon Kim, Kyung Mook Choi, Jae Bok Lee, Young Seok Lee, Sei Hyun Baik, Dong Seop Choi; J Korean Endocr Soc. 2005;20(3):278-282. Published online June 1, 2005; DOI: https://doi.org/10.3803/jkes.2005.20.3.278

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Abstract PDF: Primary hyperparathyroidism is the most frequent cause of hypercalcemia, and its prevalence is increasing due to the routine examination of serum calcium levels. Primary hyperparathyroidims is most commonly caused by an adenoma or hyperplasia of the parathyroid gland. A cystic parathyroid adenoma is an extremely rare cause of primary hyperparathyroidism. In our case, a-79-year old female presented with lower back pain and constipation. Her serum calcium, phosphate and immunoreactive parathyroid homone levels were 15.6, 1.8mg/dL and 371.8pg/mL, respectively. Neck CT revealed a cystic mass and a contour bulging heterogeneous mass in the left inferior right thyroid gland, respectively. These mass lesions were removed, and the intra-operative parathyroid hormone levels monitored, to confirm the complete resection. After removing the left cystic mass to the inferior thyroid, the serum calcium and immunoreactive parathyroid hormone levels quickly returned to normal. We report a case of primary hyperparathyroidism, caused by a cystic parathyroid adenoma, with a brief review of the literature

Original Articles

The Effect of T3 on Thyroid Hormone Receptor Dynamics in Thyroid Hormone Response Element of Chicken Lysozyme Silencer.: Seong Jin Lee, Cheol Young Park, In Kyung Jeong, Eun Gyung Hong, Cheol Soo Choi, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park, P Reed Larsen; J Korean Endocr Soc. 2003;18(4):379-391. Published online August 1, 2003

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Abstract PDF: BACKGROUND
The regulation of gene transcription can be controlled by both positive (enhancer) and negative (silencer) regulatory sequences. Several enhancer and silencer elements have been described in the 5' region of the chicken lysozyme gene. The silencer located at -2.4 kb upstream of the chicken lysozyme gene is composed of two separate modules (F1 and F2) that can function as silencers by themselves, but also show synergistic repression after multimerization. The F1 module is bound by a protein termed NeP1 and F2 module, a F2 thyroid hormone response element (F2-TRE), and can be bound by the thyroid hormone receptor (TR). F2-TRE has an inverted palindromic structure, with high affinity to TR. Although many current reported results have tried to explain the regulatory mechanism of chicken lysozyme gene expression due to the thyroid hormone, there have been few studies that clarify the TR dynamics in the F2-TRE of the chicken lysozyme gene, either with or without exposure of the thyroid hormone. Here, the changes in the TR binding patterns in the F2-TRE of the chicken lysozyme gene are described, both before and after T3 stimulation over time. METHODS: Using the stably transfected rat pituitary somatotroph tumor cell line, GC8 cells, with the F2-TRE inserted 5' to the thymidine kinase (TK) promoter, together with a mouse TRalpha- expressing plasmid, a chromatin immunoprecipitation (ChIP) technique was employed to reveal the TR-TRE interaction before and after T3 stimulation. Following the cross-linking and sonication of the cells, the immunoprecipitation was performed overnight, at 4 degrees C, with TRalpha1, TRbeta1 and TRbeta2 antibodies, respectively. The binding patterns and amounts of TRalpha1, TRbeta1 and TRbeta2 to the F2-TRE, before and after 12 hours of 100 nM T3 stimulation, were analyzed using conventional and quantitative real-time polymerase chain reactions (RQ-PCR). The ChIP technique was used to give a basal value for 20 minutes and 1, 2, 4, 6, 8 and 12 hours after the 100 nM T3 stimulation, and RQ-PCR was then performed. Western blot with TRalpha1, TRbeta1 and TRbeta2 antibodies were also performed. RESULTS: After 12 hours of 100 nM T3 stimulation of the GC8 cells, the TRalpha1 and TRbeta2 binding to the F2-TRE increased, but the TR 1 binding to the F2-TRE decreased, by conventional PCR. Although all the TR isoforms were bound to the F2-TRE by RQ-PCR, the TR 1 binding to the F2-TRE, after 12 hours of 100 nM T3 stimulation, was significantly increased (1.01-->2.73, delta=+170.3%, p<0.05), but the change in the amount of TRbeta2 binding was not significant (2.53-->2.98, delta=+17.8%). The TRbeta1 binding was significantly decreased compared with that of the basal level (4.59-->2.06, delta=-55.1%, p<0.05). The total TR bindings to the F2-TRE had a tendency to decrease after 12 hours of 100 nM T3 stimulation (8.13-->7.77, delta=-4.4%). The binding patterns and amounts of TRalpha1, TRbeta1 and TRbeta2, both before and after the 100 nM T3 stimulation, were also identified over time. While the TRbeta1 bindings to the F2-TRE after 1 hour of 100 nM T3 stimulation were acutely reduced, those of the TRalpha1 at 20 minutes and 6 hours were increased. The TRbeta2 bindings showed a maximal increase at 20 minutes. The directions of the TR binding patterns, between the before and after 2 hours of 100 nM T3 stimulation, were identical to those for between 4 and 6 hours of T3 stimulation. There was no significant difference in the TR bindings to the F2-TRE in relation to the amounts (1.5 vs. 4.5 microliter) of TR antibodies used during the ChIP assays. The Western blots showed no significant change of the levels of each TR isoform proteins, either before or after 12 hours of exposure to 100 nM T3. CONCLUSION: These results show the dynamic binding patterns of the TR isoforms to the F2-TRE of the chicken lysozyme gene, both before and after T3 stimulation, over time. Further investigation, however, will be needed to clarify the mechanisms of our observations. The ChIP technique may then be used to reveal the dynamic models of the cofactors, as well as TR isoforms, in the TR-regulated transcription machinery.

Thyroid Hormone Receptor Dynamics in Thyroid Hormone Response Elements of the Human Type 1 Iodothyronine Deiodinase Gene.: Seong Jin Lee, Cheol young Park, In Kyung Jeong, Eun Gyung Hong, Cheol Soo Choi, Hyeon Kyu Kim, Doo Man Kim, Jae Myung Yoo, Sung Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, Sung Woo Park, P Reed Larsen; J Korean Endocr Soc. 2003;18(3):283-295. Published online June 1, 2003

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Abstract PDF: BACKGROUND
Type 1 iodothyronine deiodinase (D1), the product of the hdio1 gene, is involved in thyroid hormone activation by the deiodination of thyroxine (T4) to form 3, 5, 3'-triiodothyronine (T3). Recent studies have identified two thyroid hormone response elements (TREs) in the 5 flanking region of the hdio1 gene. TRE1, proximal to TRE in the hdio1 gene, consists of a direct repeat of thyroid hormone receptor (TR) binding octamers with 10 bp separating the two TR binding sites. The upstream TRE, TRE2, is a classical direct repeat of retinoid X receptor (RXR)/TR binding half-sites with a 4-bp separation. There are few studies clarifying the TR dynamics in the TRE of a specific gene with or without the exposure of activated thyroid hormone. We evaluated TR binding patterns in the proximal and distal TREs of the hdio1 gene before and after T3 stimulation. METHODS: We employed chromatin immunoprecipitation (ChIP) technique to investigate the TR-TRE interaction before and after T3 stimulation in human hepatocellular carcinoma HepG2 cell line.Following cross-linking and sonication of the cells, immunoprecipitation was performed overnight at 4degrees C with TR 1, TR 1 and TR 2 antibodies. We analyzed the binding patterns and amounts of TR 1, TR 1 and TR 2 to TRE1 and TRE2 before and after 12 hours stimulation with 100 nM T3 by using conventional and quantitative real-time polymerase chain reactions (RQ-PCR). Reverse transcriptional PCR (RT-PCR) and Western blot with TR 1, TR 1 and TR 2 antibodies were performed to measure the levels of hdio1 mRNA and TR 1, TR 1 and TR 2 proteins before and after 12 hours exposure to 100 nM T3. RESULTS: In TRE1, TR 1 binding was significantly decreased after 12 hours stimulation with 100nM T3 (3.74-->1.97, delta=-47.3%, p<0.05), but TR 1 and TR 2 bindings were not detected by conventional PCR and RQ-PCR. Although all TR isoforms were bound to TRE2, the binding patterns were quite different. While TRalpha1 and TR 1 bindings to TRE2 after 12 hours stimulation with 100 nM T3 were significantly decreased (10.41-->3.01, delta=-71.1%, p<0.05; 12.56 --> 2.93, delta=-76.7%, p<0.05, respectively), TR 2 binding was increased but not significantly (9.17 --> 9.84, delta=+7.3%). Total TR bindings in TRE2 were significantly decreased after 12 hours stimulation with 100 nM T3 (32.14 --> 15.78, delta=-50.9%, p<0.05). The TR bindings to TRE1 and TRE2 were not significantly different by the amounts of TR antibodies used during ChIP assays. The levels of hdio1 mRNA were significantly increased, 2.03 times, after 12 hours exposure to 100nM T3 (p<0.001). Western blot showed no significant change of the level of each TR isoform protein before and after 12 hours exposure to 100 nM T3. CONCLUSION: Our results demonstrate the dynamics of TR 1 at proximal TRE (TRE1) and the switching phenomenon of TR isoforms at distal TRE (TRE2) of the hdio1 gene after T3 stimulation. Further investigation, however, is needed to clarify the mechanisms of these observations.

Case Report

A Case of Syndrome of Resistance to Thyroid Hormone Associated with Mutation(M313T) in Thyroid Hormone Receptor Beta Gene.: Jae Kyung Hwang, Kyung Won Kim, Tae Yong Kim, Sang Wan Kim, Young Joo Park, Do Joon Park, Seong Yeon Kim, Hong Kyu Lee, Bo Youn Cho; J Korean Endocr Soc. 2003;18(2):206-213. Published online April 1, 2003

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Abstract PDF: Syndrome of resistance to thyroid hormone(RTH) is inherited by an autosomal dominant trait, and characterized by elevated thyroid hormone levels with reduced responsiveness of the pituitary and peripheral tissues to thyroid hormone action. All of the reported RTH patients have various mutations in the ligand-binding domain coding region of the thyroid hormone receptor beta gene. A 21-year-old man visited our hospital complaining of fatigue. He had mild thyroid goiter and intermittent palpitation. Thyroid function test showed elevated total T3, free T4, and TSH levels. Levels of TSH free a-subunit and basal pituitary hormones, except prolactin, were normal. MRI of the sellar region showed no abnormal finding. TSH response to TRH stimulation was normal, and TSH values to TRH stimulation after T3 suppression revealed partial response. Sequeuce analysis of the thyroid hormone receptor beta gene confirmed a heterozygous missense mutation in exon 9; and the amino acid alteration was a substitution of a threonine(ACG) for a methionine(ATG) at codon313. Sequeuce analysis of the parents showed no mutation.We report the first case of a man with RTH caused by a de novo mutation(M313T) in TRbeta gene, confirmed by sequeuce analysis.

Original Articles

Changes in Plasma Leptin Levels Relating to Short-Term Thyroid Manipulation in Rats.: Min Seon Kim, Cho Ya Yoon, Young Min Cho, Hye Seung Jung, Chan Soo Shin, Kyong Soo Park, Seong Yeon Kim, Bo Youn Cho, Hong Kyu Lee, Stephen R Bloom; J Korean Endocr Soc. 2002;17(2):197-205. Published online April 1, 2002

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Abstract PDF: BACKGROUND
Leptin, an adipocyte derived hormone, and thyroid hormone have similar effects on energy homeostasis, such that a shortage of both hormones is associated with decreased energy expenditure and increased body weight. Therefore, for the maintenance of energy homeostasis may require a close interaction between leptin and thyroid hormone. This study was performed to investigate the change in plasma leptin levels relating to short-term thyroid manipulation causing no significant change in body weight. METHODS: Hypothyroidism was induced by surgical thyroidectomy and hyperthyroidism by subcutaneous injection of 50 g of L-T3/100 g body weight/day, for 5 days, in 6~8 weeks old male Wistar rats. Body weights and food intakes were monitored daily until sacrifice. Plasma samples were collected, and the thyroid stimulating hormone (TSH), free triiodothyronine (T3) and leptin levels measured. The plasma leptin levels in rats with hypothyroidism and hyperthyroidism were compared with those of body weights at death and food intakes during the study, atched controls. RESULTS: The rats treated with L-T3 consumed equal amount of food as freely fed, rats but their final body weights were significantly lower (L-T3 treated 220.0 +/- 1.8 vs. freely fed 226.0 +/- 2.0 g, p<0.05). There was no difference in food intake during study, and final body weight, between the thyroidectomised rats and their paired controls (thyroidectomised 220.4 +/- 1.7 vs. paired 223.9 +/- 4.7 g, P=NS). Plasma leptin levels in the L-T3 treated rats were significantly lower than those in freely fed rats (L-T3 treated 1.7 +/- 0.1 vs. freely fed 4.8 +/- 0.2 ng/ml, p<0.005). Conversely, the thyroidectomised rats had higher plasma leptin levels, compared to those of their paired controls (thyroidectomised 4.8 +/- 0.3 vs. paired 1.7 +/- 0.1 ng/ml, p<0.005). CONCLUSION: The Plasma leptin levels in the rats were decreased by short term hyperthyroidism, while they were increased by short term hypothyroidism. These findings suggest that thyroid hormones may affect the production or secretion of leptin

Effects of Thyroid Hormone on Preduction of Interleukin-6 and Interleukin-11 in Human Bone Marrow Stromal Cells.: Chul Hee Kim, Dong Kwan Kim, Hong Kyu Kim, Young Ki Song, Ki Soo Kim; J Korean Endocr Soc. 1997;12(4):557-564. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is well known that excessive thyroid hormone in the body is associated with bone loss. However, the mechanism by which thyroid hormone affects bone cell metabolism remains unclear. It has been shown that thyroid hormones stimulate osteoclastic bone resorption indirectly via some unknown mediators secreted by osteoblasts, This study was undertaken to determine if interleukin-6 (IL-6) or interleukin-11 (IL-l1) could be the mediator (s) of thyroid hormone-induced bone loss. METHODS: We treated primary cultured human bone rnarrow stromal cells with 3,5,3-triiodo-thyronine (T) and measured basal and interleukin-l (IL-1)-stimulated IL-6/IL-ll production. We also investigated the possible modulating effect of 17B-estradiol (17B-E2.) on thyroid hormone action. RESULTS: T3 at 10 (-12) ~ 10 (-8) M concentration, significantly increased the basal IL-6 production in a dose-dependent manner, and also potentiated the stimulatory effect of IL-1 on IL-6 production. However, T failed to elicit a detectable effect on basal or IL-1-stimulated IL-11 production. Treat#ment with l7B-E2. inhibited IL-1-stimulated IL-6 production, but the effects of T3 on IL-6 production were not affected by 17/B-E. CONCLUSION: These results suggest that thyroid hormone may increase bone resorption by increasing basal IL-6 production and potentiating IL-1-induced IL-6 production from osteoblast-lineage cells, and these effects were independent of estrogen status.

Mutations in Thyroid Hormone Receptor-beta Associated with Patients with Generalized Resistance and Pituitary Resistance to Thyroid Hormone.: Yong Seok Yun, Sung Kkwan Hong, Chul Woo Ahn, Jae Hyun Nam, Seok Won Park, Bong Su Cha, Young Duk Song, Eun Jig Lee, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh; J Korean Endocr Soc. 2000;15(1):113-120. Published online January 1, 2001

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Abstract PDF: We report a point mutation in the TRbeta gene in korean patients with generalized resistance and pituitary resistance to thyroid hormone. One mutation at TRbeta (P453S) were detected in patient with pituitary resistance to thyroid, which showed different phenotype, generalized resistance to thyroid hormone, in her mothers. But, the other (C31Y), did not show clear relations with the disease. Therefore, further study of molecular and cellular basis will be warranted to explain the clear mechanism of the resistance to thyroid hormone.

Anabolic Effects of Recombinant Human Parathyroid Hormone (1-84) on Bone Histomorphometry in Overiectomized Rats.: Young Jun Won, Du Hong Park, Jae Hyun Nam, Jong In Yook, Jin Kim, Kyung Rae Kim, Hyun Chul Lee, Kap Bum Huh, Sung Kil Lim; J Korean Endocr Soc. 1999;14(1):81-90. Published online January 1, 2001

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Abstract PDF: To evaluate the anabolic effects of human recombinant parathyroid hormone [hrPTH(1-84)], we examined effect of low-dose and high-dose of [hrPTH(1-84)] and estradiol on bone histomorphometry in ovariectomized rats. Sixty Sprague-Dawley female rats aged 8~10 weeks were used. Eight weeks after ovariectomy, or sham operation, rats were given daily sc injection of hrPTH (1-84), 30 pg/kg (OVX+L group), 150 pg/kg (OVX+H group), 17-estradiol (30 pg/kg, OVX+E group) or vehicle (OVX+V group) for 4 weeks. After double tetracycline labeling, all rats were killed at day 84. We completed the histomorphometric analysis of distal femoral metaphyseal cancellous bone for trabecular bone volume (TBV), mean trabecular plate thickness (MTPT), mean trabecular plate density (MTPD), mean trabecular plate separation (MTPS), mean osteoid seam width (OSW) and appositional rate (AR). The histomorphometric parameters (TBV, MTPT, OSW and AR) of trabecular bone mass in (OVX+E) group were higher than those in (OVX+V) group. The TBV of trabecular bone in PTH treated groups were higher than that in sham operated, (OVX+V) and (OVX+E) group. The histomorphometric parameters (TBV, MTPD, OSW and AR) of trabecular bone mass in (OVX+H) group showed a tendency to be higher than those in (OVX+L) group, but statistically not significant. In conclusion, Low dose (30 mg/kg) hrPTH (1-84) also shows a sufficient anabolic effect on trabecular bone.

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