Endocrinology and Metabolism

Original Article

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; Received May 11, 2024 Accepted July 19, 2024 Published online December 4, 2024; DOI: https://doi.org/10.3803/EnM.2024.2040 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: 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.

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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Abstract PDF PubReader ePub: 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.

Calcium & bone metabolism
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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Abstract PDF PubReader ePub: 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.

Calcium & bone metabolism
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.

Citations

Citations to this article as recorded by

Hypoparathyroidism update
Cherie Chiang
Current Opinion in Endocrinology, Diabetes & Obesity.2024;[Epub] CrossRef
Potential of Calcilytics as a Novel Treatment for Post-Surgical Hypoparathyroidism
Han Seok Choi
Endocrinology and Metabolism.2024; 39(3): 534. CrossRef

Original Articles

Calcium & bone metabolism
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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Abstract PDF Supplementary Material PubReader ePub: 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.

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.

Citations

Citations to this article as recorded by

The Levothyroxine Odyssey: Navigating the Path of Survivorship in Thyroid Cancer
Jin Hwa Kim
Endocrinology and Metabolism.2024; 39(2): 283. CrossRef
Levothyroxine Dosage and the Increased Risk of Second Primary Malignancy in Thyroid Cancer Survivors
Young Joo Park
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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Burden of non-alcoholic fatty liver disease in subclinical hypothyroidism
Mahmood Dhahir Al-Mendalawi
Journal of Clinical and Scientific Research.2024; 13(1): 68. CrossRef

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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Diagnosis and therapeutic approach to bone health in patients with hypopituitarism
Justyna Kuliczkowska-Płaksej, Aleksandra Zdrojowy-Wełna, Aleksandra Jawiarczyk-Przybyłowska, Łukasz Gojny, Marek Bolanowski
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Shunichi Yokota, Hotaka Ishizu, Takuji Miyazaki, Daisuke Takahashi, Norimasa Iwasaki, Tomohiro Shimizu
Biomedicines.2024; 12(4): 843. CrossRef
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Annales d'Endocrinologie.2024; 85(6): 604. CrossRef
Review on the protective activity of osthole against the pathogenesis of osteoporosis
Jincai Chen, Xiaofei Liao, Juwen Gan
Frontiers in Pharmacology.2023;[Epub] CrossRef
Estudio comparativo tras la cirugía tiroidea y otras variables asociadas al desarrollo de osteoporosis en una cohorte latinoamericana
María Paula Ciliberti Artavia, Juan Sebastián Theran León, Jaime Alberto Gómez Ayala, Valentina Cabrera Peña, Rafael Guillermo Parales Strauch, Edgar Camilo Blanco Pimiento, Luis Andres Dulcey Sarmiento, Juan Camilo Martínez, Juan Camilo Mayorca, María Al
Revista Salud y Desarrollo.2023; 7(2): e605. CrossRef

Calcium & bone metabolism
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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Calorie restriction induces mandible bone loss by regulating mitochondrial function
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Bone.2025; 190: 117326. CrossRef
Obesity, diabetes and risk of bone fragility: How BMAT behavior is affected by metabolic disturbances and its influence on bone health
Gregório Corrêa Guimarães, João Bosco Costa Coelho, João Gabriel Oliveira Silva, Ana Carolina Chalfun de Sant’Ana, Cássia Alves Carrilho de Sá, Júlia Marques Moreno, Lívia Marçal Reis, Camila Souza de Oliveira Guimarães
Osteoporosis International.2024; 35(4): 575. CrossRef
Bone Marrow Adipose Tissue Is Not Required for Reconstitution of the Immune System Following Irradiation in Male Mice
Jessica A. Keune, Carmen P. Wong, Adam J. Branscum, Scott A. Menn, Urszula T. Iwaniec, Russell T. Turner
International Journal of Molecular Sciences.2024; 25(4): 1980. CrossRef
Dietary restriction plus exercise change gene expression of Cxcl12 abundant reticular cells in female mice
Aoi Ikedo, Yuuki Imai
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Journal of Bone and Mineral Research.2024;[Epub] CrossRef
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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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The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1167. CrossRef
Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications
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Nature Communications.2024;[Epub] CrossRef
Evaluation of multiple organophosphate insecticide exposure in relation to altered thyroid hormones in NHANES 2007‐2008 adult population
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Thyroid-function reference ranges in the diagnosis of thyroid dysfunction in adults
Salman Razvi
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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.

Citations

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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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Bone Metabolism
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

Citations to this article as recorded by

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
Endocrinology and Metabolism.2024; 39(2): 375. CrossRef
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
Diagnostics.2023; 13(20): 3182. CrossRef

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