Endocrinology and Metabolism

Review Article

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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Abstract PDF PubReader ePub: 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.

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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Abstract PDF Supplementary Material PubReader ePub: 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.

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
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Reviews in Endocrine and Metabolic Disorders.2024;[Epub] CrossRef
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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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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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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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Wanying Shi, Jianlong Fang, Huimin Ren, Peijie Sun, Juan Liu, Fuchang Deng, Shuyi Zhang, Qiong Wang, Jiaonan Wang, Shilu Tong, Song Tang, Xiaoming Shi
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Tessa A Mulder, Purdey J Campbell, Peter N Taylor, Robin P Peeters, Scott G Wilson, Marco Medici, Colin Dayan, Vincent V W Jaddoe, John P Walsh, Nicholas G Martin, Henning Tiemeier, Tim I M Korevaar
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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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The prevalence of thyroid disorders in COVID-19 patients: a systematic review and meta-analysis
Sadra Ashrafi, Hossein Hatami, Razieh Bidhendi-Yarandi, Mohammad Hossein Panahi
BMC Endocrine Disorders.2024;[Epub] CrossRef
Thyroid Stimulating Hormone as a Possible Additional COVID-19 Outcome Marker
Anamarija Zrilic Vrkljan, Ana Majic Tengg, Tanja Palaversa, Srecko Marusic, Lana Ruzic, Ines Bilic-Curcic, Maja Cigrovski Berkovic
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Effect of Hypothalamic Adrenal Axis and Thyroid Function Alterations on Prognosis of Critically Ill COVID-19 Patients
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Aleksandra Piekarska, Marta Góral, Marta Kozula, Aleksandra Jawiarczyk-Przybyłowska, Katarzyna Zawadzka, Marek Bolanowski
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The Spectrum of Thyroid Function Tests and Autoantibodies During Hospitalization and After Six Months of Discharge in COVID-19 Patients: Does COVID-19 Trigger Autoimmunity?
Ziynet Alphan Uc, Pinar Yagcı, Zelal Adibelli, Cevdet Duran
Endocrine Research.2023; 48(2-3): 44. CrossRef
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Mingyao Zhong, Yue Gao, Hongling Hu, Xuan Zhu, Lulu Gan, Ling Li, Cheng Xiang, Yimin Yan, Zhe Dai
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The Association Between COVID-19 and Thyroxine Levels: A Meta-Analysis
Yiru Chen, Xiuneng Li, Yu Dai, Jingjing Zhang
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The New Entity of Subacute Thyroiditis amid the COVID-19 Pandemic: From Infection to Vaccine
Mihaela Popescu, Adina Ghemigian, Corina Maria Vasile, Andrei Costache, Mara Carsote, Alice Elena Ghenea
Diagnostics.2022; 12(4): 960. CrossRef
Potential of Endogenous Oxytocin in Endocrine Treatment and Prevention of COVID-19
Stephani C. Wang, Fengmin Zhang, Hui Zhu, Haipeng Yang, Yang Liu, Ping Wang, Vladimir Parpura, Yu-Feng Wang
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The Association Between FT3 With the Outcome and Inflammation/Coagulopathy/Fibrinolysis of COVID-19
Jiayi Deng, Siye Zhang, Fei Peng, Quan Zhang, Yi Li, Yanjun Zhong
Frontiers in Endocrinology.2022;[Epub] CrossRef
Primary hypothyroidism with an episode of ventricular tachycardia in a patient with COVID-19
Pin-Hsu Liao, Yu-Cheng Cheng, Po-Yu Liu, I-Te Lee
Medicine.2022; 101(25): e29243. CrossRef
Low triiodothyronine syndrome is associated with stroke‐associated pneumonia
Huijun Chen, Minjie Xu, Yezhi Huang, Jincai He, Wenwei Ren
European Journal of Clinical Investigation.2022;[Epub] CrossRef
Association of thyroid dysfunction and COVID-19: A systematic review and meta-analysis
Mohammad Darvishi, Mohammad Reza Nazer, Hamze Shahali, Majid Nouri
Frontiers in Endocrinology.2022;[Epub] CrossRef
The prognostic utility of serum thyrotropin in hospitalized Covid-19 patients: statistical and machine learning approaches
E. Pappa, P. Gourna, G. Galatas, M. Manti, A. Romiou, L. Panagiotou, R. Chatzikyriakou, N. Trakas, G. Feretzakis, C. Christopoulos
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Thyrotropin Levels in Patients with Coronavirus Disease 2019: Assessment during Hospitalization and in the Medium Term after Discharge
Abdallah Al-Salameh, Noémie Scherman, Imane Adda, Juliette André, Yoann Zerbib, Julien Maizel, Jean-Daniel Lalau, Etienne Brochot, Claire Andrejak, Rachel Desailloud
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COVID-19 and thyroid function: What do we know so far?
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Frontiers in Endocrinology.2022;[Epub] CrossRef

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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Neuropeptides and Their Roles in the Cerebellum
Zi-Hao Li, Bin Li, Xiao-Yang Zhang, Jing-Ning Zhu
International Journal of Molecular Sciences.2024; 25(4): 2332. CrossRef
Exploring the underlying molecular mechanism of tri(1,3-dichloropropyl) phosphate-induced neurodevelopmental toxicity via thyroid hormone disruption in zebrafish by multi-omics analysis
Ying Xu, Lei Yang, Yanguo Teng, Jian Li, Na Li
Aquatic Toxicology.2023; 258: 106510. CrossRef
Association of Maternal TSH, FT4 With Children's BMI Trajectories, and Obesity: A Birth Cohort Study
Mengting Yang, Shanshan Zhang, Yuzhu Teng, Xue Ru, Linlin Zhu, Yan Han, Xingyong Tao, Hui Cao, Shuangqin Yan, Fangbiao Tao, Kun Huang
The Journal of Clinical Endocrinology & Metabolism.2023; 109(1): e190. CrossRef
Thyroid hormone receptor beta: Relevance in human health and diseases
Ghausiya Rehman, Neha Kumari, Farhad Bano, Rakesh K. Tyagi
Endocrine and Metabolic Science.2023; 13: 100144. CrossRef
Targeting Thyroid Hormone/Thyroid Hormone Receptor Axis: An Attractive Therapy Strategy in Liver Diseases
Qianyu Tang, Min Zeng, Linxi Chen, Nian Fu
Frontiers in Pharmacology.2022;[Epub] CrossRef
Histone Deacetylase 3 Inhibitor Alleviates Cerebellar Defects in Perinatal Hypothyroid Mice by Stimulating Histone Acetylation and Transcription at Thyroid Hormone-Responsive Gene Loci
Alvin Susetyo, Sumiyasu Ishii, Yuki Fujiwara, Izuki Amano, Noriyuki Koibuchi
International Journal of Molecular Sciences.2022; 23(14): 7869. CrossRef
Selection-driven adaptation to the extreme Antarctic environment in the Emperor penguin
Federica Pirri, Lino Ometto, Silvia Fuselli, Flávia A. N. Fernandes, Lorena Ancona, Nunzio Perta, Daniele Di Marino, Céline Le Bohec, Lorenzo Zane, Emiliano Trucchi
Heredity.2022; 129(6): 317. CrossRef
Long-term depression–inductive stimulation causes long-term potentiation in mouse Purkinje cells with a mutant thyroid hormone receptor
Ayane Ninomiya, Izuki Amano, Michifumi Kokubo, Yusuke Takatsuru, Sumiyasu Ishii, Hirokazu Hirai, Nobutake Hosoi, Noriyuki Koibuchi
Proceedings of the National Academy of Sciences.2022;[Epub] CrossRef

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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Surgery for Normocalcemic Hyperparathyroidism
Pallavi Kulkarni, David Goldenberg
Otolaryngologic Clinics of North America.2024; 57(1): 111. CrossRef
Linea guida sulla gestione terapeutica dell’iperparatiroidismo primario sporadico nell’adulto
Fabio Vescini, Marco Boniardi, Marina Carotti, Elena Castellano, Cristiana Cipriani, Cristina Eller-Vainicher, Sandro Giannini, Maurizio Iacobone, Francesca Pace, Antonio Stefano Salcuni, Federica Saponaro, Stefano Spiezia, Annibale Versari, Guido Zavatta
L'Endocrinologo.2024; 25(2): 222. CrossRef
Evaluation of the Thiazide Challenge Test to Differentiate Primary From Hypercalciuria-Related Hyperparathyroidism
Ewout Verly, Bruno Lapauw, Charlotte Verroken
The Journal of Clinical Endocrinology & Metabolism.2024;[Epub] CrossRef
DXA-based bone strain index in normocalcemic primary hyperparathyroidism
Gaia Tabacco, Anda Mihaela Naciu, Carmelo Messina, Gianfranco Sanson, Luca Rinaudo, Roberto Cesareo, Stefania Falcone, Nicola Napoli, Fabio Massimo Ulivieri, Andrea Palermo
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Iperparatiroidismo primario normocalcemico
Silvia Egiddi, Luigi Bonifazi Meffe, Anda Mihaela Naciu, Gaia Tabacco, Nicola Napoli, Andrea Palermo
L'Endocrinologo.2023; 24(3): 249. CrossRef
The Russian registry of primary hyperparathyroidism, latest update
Natalia G. Mokrysheva, Anna K. Eremkina, Alina R. Elfimova, Elena V. Kovaleva, Anastasiia P. Miliutina, Ekaterina E. Bibik, Anna M. Gorbacheva, Ekaterina A. Dobreva, Irina S. Maganeva, Julia A. Krupinova, Rustam H. Salimkhanov, Lizaveta A. Aboishava, Elen
Frontiers in Endocrinology.2023;[Epub] CrossRef
Incidental Normocalcemic Primary Hyperparathyroidism Presenting With Symptomatic Hypophosphatemia: A Case Report
Omar Tabbikha, Joanne Chamy, Michael El Khoury
Cureus.2023;[Epub] CrossRef
Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism
Juan Carlos Ramirez-Sandoval, Lluvia Marino, Gabriel Cojuc-Konigsberg, Estefania Reul-Linares, Nathalie Desire Pichardo-Cabrera, Cristino Cruz, Elisa Naomi Hernández-Paredes, Nathan Berman-Parks, Vanessa Vidal-Ruíz, Jonathan Mauricio Estrada-Linares, Alfr
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Preoperative Thoracic Muscle Mass Predicts Bone Density Change After Parathyroidectomy in Primary Hyperparathyroidism
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The Journal of Clinical Endocrinology & Metabolism.2022; 107(6): e2474. CrossRef
Applications of Metabolomics in Calcium Metabolism Disorders in Humans
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International Journal of Molecular Sciences.2022; 23(18): 10407. CrossRef
Serum Calcium/Phosphorus Ratio in Biochemical Screening of Primary Hyperparathyroidism
Nagihan Bestepe, Fatma Neslihan Cuhaci, Burcak Polat, Berna Evranos Ogmen, Didem Ozdemir, Reyhan Ersoy, Bekir Cakir
Revista da Associação Médica Brasileira.2022; 68(12): 1668. CrossRef

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.

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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
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

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.

Citations

Citations to this article as recorded by

Compensation for iodine deficiency conditions with drugs based on duckweed substrate
M. Kh. Sadulaev, M. I. Usmanova, T. T. Tataev, A. M. Inderbiev, A. S.-A. Zhamalullayla, A. Salamova
BIO Web of Conferences.2023; 76: 03002. CrossRef
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
Frontiers in Oncology.2022;[Epub] CrossRef
Ultrasound-Guided Fine-Needle Aspiration with or without Negative Pressure for Different Types of Thyroid Nodules
Qi Zhou, Wenjun Wu, Fang Wang, Xiaohua Gong, Xiaojun Chen
International Journal of General Medicine.2021; Volume 14: 5475. CrossRef

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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Valerie Walker
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Molecular and Clinical Spectrum of Primary Hyperparathyroidism
Smita Jha, William F Simonds
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Rare cause of persistent hypocalcaemia in infancy due to PTH gene mutation
Savita Khadse, Vrushali Satish Takalikar, Radha Ghildiyal, Nikhil Shah
BMJ Case Reports.2023; 16(9): e256358. CrossRef
Homozygous Ser-1 to Pro-1 mutation in parathyroid hormone identified in hypocalcemic patients results in secretion of a biologically inactive pro-hormone
Patrick Hanna, Ashok Khatri, Shawn Choi, Severine Brabant, Matti L. Gild, Marie L. Piketty, Bruno Francou, Dominique Prié, John T. Potts, Roderick J. Clifton-Bligh, Agnès Linglart, Thomas J. Gardella, Harald Jüppner
Proceedings of the National Academy of Sciences.2023;[Epub] CrossRef
Genetics of monogenic disorders of calcium and bone metabolism
Paul J. Newey, Fadil M. Hannan, Abbie Wilson, Rajesh V. Thakker
Clinical Endocrinology.2022; 97(4): 483. CrossRef
Homozygous missense variant of PTH (c.166C>T, p.(Arg56Cys)) as the cause of familial isolated hypoparathyroidism in a three-year-old child
Stine Linding Andersen, Anja Lisbeth Frederiksen, Astrid Bruun Rasmussen, Mette Madsen, Ann-Margrethe Rønholt Christensen
Journal of Pediatric Endocrinology and Metabolism.2022; 35(5): 691. CrossRef
Novel PTH Gene Mutations Causing Isolated Hypoparathyroidism
Colin P Hawkes, Jamal M Al Jubeh, Dong Li, Susan E Tucker, Tara Rajiyah, Michael A Levine
The Journal of Clinical Endocrinology & Metabolism.2022; 107(6): e2449. CrossRef

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