Endocrinology and Metabolism

Review Articles

Miscellaneous
Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer: Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park; Endocrinol Metab. 2023;38(6):619-630. Published online November 21, 2023; DOI: https://doi.org/10.3803/EnM.2023.1814

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Metabolism is a dynamic network of biochemical reactions that support systemic homeostasis amidst changing nutritional, environmental, and physical activity factors. The circulatory system facilitates metabolite exchange among organs, while the endocrine system finely tunes metabolism through hormone release. Endocrine disorders like obesity, diabetes, and Cushing’s syndrome disrupt this balance, contributing to systemic inflammation and global health burdens. They accompany metabolic changes on multiple levels from molecular interactions to individual organs to the whole body. Understanding how metabolic fluxes relate to endocrine disorders illuminates the underlying dysregulation. Cancer is increasingly considered a systemic disorder because it not only affects cells in localized tumors but also the whole body, especially in metastasis. In tumorigenesis, cancer-specific mutations and nutrient availability in the tumor microenvironment reprogram cellular metabolism to meet increased energy and biosynthesis needs. Cancer cachexia results in metabolic changes to other organs like muscle, adipose tissue, and liver. This review explores the interplay between the endocrine system and systems-level metabolism in health and disease. We highlight metabolic fluxes in conditions like obesity, diabetes, Cushing’s syndrome, and cancers. Recent advances in metabolomics, fluxomics, and systems biology promise new insights into dynamic metabolism, offering potential biomarkers, therapeutic targets, and personalized medicine.

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Editorial: Tumor metabolism and programmed cell death
Dan-Lan Pu, Qi-Nan Wu
Frontiers in Endocrinology.2024;[Epub] CrossRef

Calcium & bone metabolism
Nuclear Factor-Kappa B Regulation of Osteoclastogenesis and Osteoblastogenesis: Brendan F. Boyce, Jinbo Li, Zhenqiang Yao, Lianping Xing; Endocrinol Metab. 2023;38(5):504-521. Published online September 26, 2023; DOI: https://doi.org/10.3803/EnM.2023.501

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Maintenance of skeletal integrity requires the coordinated activity of multinucleated bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoclasts form resorption lacunae on bone surfaces in response to cytokines by fusion of precursor cells. Osteoblasts are derived from mesenchymal precursors and lay down new bone in resorption lacunae during bone remodeling. Nuclear factorkappa B (NF-κB) signaling regulates osteoclast and osteoblast formation and is activated in osteoclast precursors in response to the essential osteoclastogenic cytokine, receptor activator of NF-κB ligand (RANKL), which can also control osteoblast formation through RANK-RANKL reverse signaling in osteoblast precursors. RANKL and some pro-inflammatory cytokines, including tumor necrosis factor (TNF), activate NF-κB signaling to positively regulate osteoclast formation and functions. However, these cytokines also limit osteoclast and osteoblast formation through NF-κB signaling molecules, including TNF receptor-associated factors (TRAFs). TRAF6 mediates RANKL-induced osteoclast formation through canonical NF-κB signaling. In contrast, TRAF3 limits RANKL- and TNF-induced osteoclast formation, and it restricts transforming growth factor β (TGFβ)-induced inhibition of osteoblast formation in young and adult mice. During aging, neutrophils expressing TGFβ and C-C chemokine receptor type 5 (CCR5) increase in bone marrow of mice in response to increased NF-κB-induced CC motif chemokine ligand 5 (CCL5) expression by mesenchymal progenitor cells and injection of these neutrophils into young mice decreased bone mass. TGFβ causes degradation of TRAF3, resulting in decreased glycogen synthase kinase-3β/β-catenin-mediated osteoblast formation and age-related osteoporosis in mice. The CCR5 inhibitor, maraviroc, prevented accumulation of TGFβ+/CCR5+ neutrophils in bone marrow and increased bone mass by inhibiting bone resorption and increasing bone formation in aged mice. This paper updates current understanding of how NF-κB signaling is involved in the positive and negative regulation of cytokine-mediated osteoclast and osteoblast formation and activation with a focus on the role of TRAF3 signaling, which can be targeted therapeutically to enhance bone mass.

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The Role of Rosavin in the Pathophysiology of Bone Metabolism
Piotr Wojdasiewicz, Paweł Turczyn, Anna Lach-Gruba, Łukasz A. Poniatowski, Daryush Purrahman, Mohammad-Reza Mahmoudian-Sani, Dariusz Szukiewicz
International Journal of Molecular Sciences.2024; 25(4): 2117. CrossRef
The role of monocyte/macrophage chemokines in pathogenesis of osteoarthritis: A review
Hao Luo, Linfeng Li, Song Han, Tao Liu
International Journal of Immunogenetics.2024;[Epub] CrossRef
The effect of low-level laser therapy on osteoclast differentiation: Clinical implications for tooth movement and bone density
Chun-Yi Huang, Huynh Hoai Thuong Le, Hsiao-Chi Tsai, Chih-Hsin Tang, Jian-Hong Yu
Journal of Dental Sciences.2024;[Epub] CrossRef
Genetic Deficiency of the Long Pentraxin 3 Affects Osteogenesis and Osteoclastogenesis in Homeostatic and Inflammatory Conditions
Valentina Granata, Dario Strina, Maria Lucia Schiavone, Barbara Bottazzi, Alberto Mantovani, Antonio Inforzato, Cristina Sobacchi
International Journal of Molecular Sciences.2023; 24(23): 16648. CrossRef

Calcium & bone metabolism
Skeletal Senescence with Aging and Type 2 Diabetes: Joshua Nicholas Farr; Endocrinol Metab. 2023;38(3):295-301. Published online June 14, 2023; DOI: https://doi.org/10.3803/EnM.2023.1727

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Osteoporosis and type 2 diabetes (T2D) are common diseases that often coexist. While both of these diseases are associated with poor bone quality and increased fracture risk, their pathogenesis of increased fracture risk differs and is multifactorial. Mounting evidence now indicates that key fundamental mechanisms that are central to both aging and energy metabolism exist. Importantly, these mechanisms represent potentially modifiable therapeutic targets for interventions that could prevent or alleviate multiple complications of osteoporosis and T2D, including poor bone quality. One such mechanism that has gained increasing momentum is senescence, which is a cell fate that contributes to multiple chronic diseases. Accumulating evidence has established that numerous boneresident cell types become susceptible to cellular senescence with old age. Recent work also demonstrates that T2D causes the premature accumulation of senescent osteocytes during young adulthood, at least in mice, although it remains to be seen which other bone-resident cell types become senescent with T2D. Given that therapeutically removing senescent cells can alleviate age-related bone loss and T2D-induced metabolic dysfunction, it will be important in future studies to rigorously test whether interventions that eliminate senescent cells can also alleviate skeletal dysfunction in context of T2D, as it does with aging.

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Single-cell sequencing reveals an important role of SPP1 and microglial activation in age-related macular degeneration
Shizhen Lei, Mang Hu, Zhongtao Wei
Frontiers in Cellular Neuroscience.2024;[Epub] CrossRef
The synergistic effect of diabetes mellitus and osteoporosis on the all-cause mortality: a cohort study of an American population
Weihua Li, Siyu Xie, Shengdong Zhong, Liting Lan
Frontiers in Endocrinology.2024;[Epub] CrossRef
Identification of systemic biomarkers and potential drug targets for age-related macular degeneration
Shizhen Lei, Mang Hu, Zhongtao Wei
Frontiers in Aging Neuroscience.2024;[Epub] CrossRef

Miscellaneous
Brown Adipose Tissue: Activation and Metabolism in Humans: Imane Hachemi, Mueez U-Din; Endocrinol Metab. 2023;38(2):214-222. Published online March 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1659

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Brown adipose tissue (BAT) is a thermogenic organ contributing to non-shivering thermogenesis. BAT becomes active under cold stress via sympathetic nervous system activation. However, recent evidence has suggested that BAT may also be active at thermoneutrality and in a postprandial state. BAT has superior energy dissipation capacity compared to white adipose tissue (WAT) and muscles. Thus, it has been proposed that the recruitment and activation of additional BAT may increase the overall energy-expending capacity in humans, potentially improving current whole-body weight management strategies. Nutrition plays a central role in obesity and weight management. Thus, this review discusses human studies describing BAT hyper-metabolism after dietary interventions. Nutritional agents that can potentially recruit brown adipocytes via the process of BAT-WAT transdifferentiation are also discussed.

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Spermidine activates adipose tissue thermogenesis through autophagy and fibroblast growth factor 21
Yinhua Ni, Liujie Zheng, Liqian Zhang, Jiamin Li, Yuxiang Pan, Haimei Du, Zhaorong Wang, Zhengwei Fu
The Journal of Nutritional Biochemistry.2024; 125: 109569. CrossRef
A natural sustained-intestinal release formulation of red chili pepper extracted capsaicinoids (Capsifen®) safely modulates energy balance and endurance performance: a randomized, double-blind, placebo-controlled study
N. Roopashree, Das S. Syam, I. M. Krishnakumar, K. N. Mala, Bradley S. Fleenor, Jestin Thomas
Frontiers in Nutrition.2024;[Epub] CrossRef
MRI Methods to Visualize and Quantify Adipose Tissue in Health and Disease
Katerina Nikiforaki, Kostas Marias
Biomedicines.2023; 11(12): 3179. CrossRef

Calcium & Bone Metabolism
Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism: Hye-Sun Park, Namki Hong, Jong Ju Jeong, Mijin Yun, Yumie Rhee; Endocrinol Metab. 2022;37(5):744-755. Published online October 25, 2022; DOI: https://doi.org/10.3803/EnM.2022.1589

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Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi–single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient’s clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.

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Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue
Anne L. Worth, Mesrop Ayrapetyan, Susan J. Maygarden, Zibo Li, Zhanhong Wu, Chris B. Agala, Lawrence T. Kim
Journal of Surgical Research.2024; 293: 618. CrossRef
Use of [18F]fluorocholine PET/CT in the detection of primary hyperparathyroidism in paediatrics: a case report
Helena Martínez Sánchez, Francisca Moreno Macián, Sara León Cariñena, Carmen de Mingo Alemany, Lidia Blasco González, Raquel Sánchez Vañó
Journal of Pediatric Endocrinology and Metabolism.2024;[Epub] CrossRef
A Rare Case of Hyperfunctioning Lipoadenoma Presenting as a Cystic Pararthyroid Lesion
Jinyoung Kim, Ohjoon Kwon, Tae-Jung Kim, So Lyung Jung, Eun Ji Han, Ki-Ho Song
Journal of Bone Metabolism.2023; 30(2): 201. CrossRef
Role of 18F-Fluorocholine Positron Emission Tomography (PET)/Computed Tomography (CT) in Diagnosis of Elusive Parathyroid Adenoma
Janan R Badier, Pokhraj P Suthar, Jagadeesh S Singh, Miral D Jhaveri
Cureus.2023;[Epub] CrossRef
Pitfalls of DualTracer 99m-Technetium (Tc) Pertechnetate and Sestamibi Scintigraphy before Parathyroidectomy: Between Primary-Hyperparathyroidism-Associated Parathyroid Tumour and Ectopic Thyroid Tissue
Mara Carsote, Mihaela Stanciu, Florina Ligia Popa, Oana-Claudia Sima, Eugenia Petrova, Anca-Pati Cucu, Claudiu Nistor
Medicina.2023; 60(1): 15. CrossRef
Diagnostic Performance of Magnetic Resonance Imaging for Parathyroid Localization of Primary Hyperparathyroidism: A Systematic Review
Max H. M. C. Scheepers, Zaid Al-Difaie, Lloyd Brandts, Andrea Peeters, Bjorn Winkens, Mahdi Al-Taher, Sanne M. E. Engelen, Tim Lubbers, Bas Havekes, Nicole D. Bouvy, Alida A. Postma
Diagnostics.2023; 14(1): 25. CrossRef

Original Articles

Diabetes, Obesity and Metabolism
High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging: Patcharapong Pantiya, Chanisa Thonusin, Natticha Sumneang, Benjamin Ongnok, Titikorn Chunchai, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Busarin Arunsak, Natthaphat Siri-Angkul, Sirawit Sriwichaiin, Nipon Chattipakorn, Siriporn C. Chattipakorn; Endocrinol Metab. 2022;37(4):630-640. Published online August 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1430

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Background
High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.
Methods
Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.
Results
The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.
Conclusion
The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

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Associations that Cardiorespiratory Fitness and Body Mass Index Loss Have with Deficit Accumulation Frailty
KAYLONI OLSON, DENISE K. HOUSTON, JOHNATHAN ROSS, RENA R. WING, FELICIA R. SIMPSON, AMBARISH PANDEY, MICHAEL P. WALKUP, MIA YANG, MARK A. ESPELAND
Medicine & Science in Sports & Exercise.2024; 56(4): 717. CrossRef
Interplay between obesity and aging on myocardial geometry and function: Role of leptin-STAT3-stress signaling
Wei Jin, Fei Tu, Feng Dong, Qinqin Deng, Miyesaier Abudureyimu, Wei Yu, Guo-jun Cai, Jian-ming Pei, Zhaohui Pei, Jun Ren
Biochimica et Biophysica Acta (BBA) - General Subjects.2023; 1867(2): 130281. CrossRef
Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings
Jaime A. Gallo-Villegas, Juan C. Calderón
European Journal of Applied Physiology.2023; 123(5): 945. CrossRef

Diabetes, Obesity and Metabolism
The Impact of Insulin Resistance on Hepatic Fibrosis among United States Adults with Non-Alcoholic Fatty Liver Disease: NHANES 2017 to 2018: Ji Cheol Bae, Lauren A. Beste, Kristina M. Utzschneider; Endocrinol Metab. 2022;37(3):455-465. Published online June 21, 2022; DOI: https://doi.org/10.3803/EnM.2022.1434

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Background
We aimed to investigate the association of hepatic steatosis with liver fibrosis and to assess the interactive effects of hepatic steatosis and insulin resistance on liver fibrosis in a nationally representative sample of United States adults.
Methods
We conducted a cross-sectional analysis using data from National Health and Nutrition Examination Survey 2017 to 2018, which for the first time included transient elastography to assess liver stiffness and hepatic steatosis. We evaluated the association between hepatic steatosis (using controlled attenuation parameter [CAP]) and clinically significant liver fibrosis (defined as liver stiffness ≥7.5 kPa) using logistic regression with an interaction term for hepatic steatosis and insulin resistance (defined as homeostatic model assessment of insulin resistance ≥3.0).
Results
Among adults undergoing transient elastography (n=2,023), 45.9% had moderate or greater hepatic steatosis and 11.3% had clinically significant liver fibrosis. After adjustment for demographic and metabolic factors, the odds of significant liver fibrosis increased as CAP score rose (odds ratio, 1.35 per standard deviation increment; 95% confidence interval, 1.11 to 1.64). We detected a significant interaction effect between CAP score and insulin resistance on the probability of significant liver fibrosis (P=0.016 for interaction). The probability of significant liver fibrosis increased in the presence of insulin resistance with increasing CAP score, while those without insulin resistance had low probability of significant liver fibrosis, even with high CAP scores.
Conclusion
Individuals with hepatic steatosis had higher odds of fibrosis when insulin resistance was present. Our findings emphasize the importance of the metabolic aspects of the disease on fibrosis risk and suggest a need to better identify patients with metabolic associated fatty liver disease.

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Association of insulin resistance indicators with hepatic steatosis and fibrosis in patients with metabolic syndrome
Tzu-chia Kuo, Yang-bor Lu, Chieh-lun Yang, Bin Wang, Lin-xin Chen, Ching-ping Su
BMC Gastroenterology.2024;[Epub] CrossRef
No More NAFLD: The Term Is Now MASLD
Ji Cheol Bae
Endocrinology and Metabolism.2024; 39(1): 92. CrossRef
Insulin Resistance/Sensitivity Measures as Screening Indicators of Metabolic-Associated Fatty Liver Disease and Liver Fibrosis
Mohammad E. Khamseh, Mojtaba Malek, Soodeh Jahangiri, Sohrab Nobarani, Azita Hekmatdoost, Marieh Salavatizadeh, Samira Soltanieh, Haleh Chehrehgosha, Hoda Taheri, Zeinab Montazeri, Fereshteh Attaran, Faramarz Ismail-Beigi, Fariba Alaei-Shahmiri
Digestive Diseases and Sciences.2024;[Epub] CrossRef
The association of Neuromedin U levels and non-alcoholic fatty liver disease: A comparative analysis
Murat Keskin, Sercan Avul, Aylin Beyaz, Nizameddin Koca
Heliyon.2024; 10(5): e27291. CrossRef
Oral Insulin Alleviates Liver Fibrosis and Reduces Liver Steatosis in Patients With Metabolic Dysfunction-associated Steatohepatitis and Type 2 Diabetes: Results of Phase II Randomized, Placebo-controlled Feasibility Clinical Trial
Yuval Ishay, Joel Neutel, Yotam Kolben, Ram Gelman, Orly Sneh Arbib, Oliver Lopez, Helena Katchman, Rizwana Mohseni, Miriam Kidron, Yaron Ilan
Gastro Hep Advances.2024; 3(3): 417. CrossRef
Comparative and Predictive Significance of Serum Leptin Levels in Non-alcoholic Fatty Liver Disease
Mehwish Qamar, Abeer Fatima, Ambreen Tauseef, Muhammad I Yousufzai, Ibrahim Liaqat, Qanbar Naqvi
Cureus.2024;[Epub] CrossRef
Greater Severity of Steatosis Is Associated with a Higher Risk of Incident Diabetes: A Retrospective Longitudinal Study
Ji Min Han, Jung Hwan Cho, Hye In Kim, Sunghwan Suh, Yu-Ji Lee, Jung Won Lee, Kwang Min Kim, Ji Cheol Bae
Endocrinology and Metabolism.2023; 38(4): 418. CrossRef
Hepatic T-cell senescence and exhaustion are implicated in the progression of fatty liver disease in patients with type 2 diabetes and mouse model with nonalcoholic steatohepatitis
Byeong Chang Sim, Yea Eun Kang, Sun Kyoung You, Seong Eun Lee, Ha Thi Nga, Ho Yeop Lee, Thi Linh Nguyen, Ji Sun Moon, Jingwen Tian, Hyo Ju Jang, Jeong Eun Lee, Hyon-Seung Yi
Cell Death & Disease.2023;[Epub] CrossRef
Familial clustering of nonalcoholic fatty liver disease in first‐degree relatives of adults with lean nonalcoholic fatty liver disease
Sorachat Niltwat, Chanin Limwongse, Natthinee Charatcharoenwitthaya, Duangkamon Bunditvorapoom, Wimolrak Bandidniyamanon, Phunchai Charatcharoenwitthaya
Liver International.2023; 43(12): 2713. CrossRef
Metabolic Score for Insulin Resistance Is Inversely Related to Incident Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease
Jun-Hyuk Lee, Yu-Jin Kwon, Kyongmin Park, Hye Sun Lee, Hoon-Ki Park, Jee Hye Han, Sang Bong Ahn
Nutrients.2022; 14(15): 3039. CrossRef
DPP-4 Inhibitor in Type 2 Diabetes Mellitus Patient with Non-Alcoholic Fatty Liver Disease: Achieving Two Goals at Once?
Ji Cheol Bae
Endocrinology and Metabolism.2022; 37(6): 858. CrossRef

Review Article

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.

Citations

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The ageing thyroid: implications for longevity and patient care
Diana van Heemst
Nature Reviews Endocrinology.2024; 20(1): 5. CrossRef
Incidence and Determinants of Spontaneous Normalization of Subclinical Hypothyroidism in Older Adults
Evie van der Spoel, Nicolien A van Vliet, Rosalinde K E Poortvliet, Robert S Du Puy, Wendy P J den Elzen, Terence J Quinn, David J Stott, Naveed Sattar, Patricia M Kearney, Manuel R Blum, Heba Alwan, Nicolas Rodondi, Tinh-Hai Collet, Rudi G J Westendorp,
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
Rosalie B. T. M. Sterenborg, Inga Steinbrenner, Yong Li, Melissa N. Bujnis, Tatsuhiko Naito, Eirini Marouli, Tessel E. Galesloot, Oladapo Babajide, Laura Andreasen, Arne Astrup, Bjørn Olav Åsvold, Stefania Bandinelli, Marian Beekman, John P. Beilby, Jette
Nature Communications.2024;[Epub] CrossRef
Evaluation of multiple organophosphate insecticide exposure in relation to altered thyroid hormones in NHANES 2007‐2008 adult population
Massira Ousseni Diawara, Songtao Li, Mingzhi Zhang, Francis Manyori Bigambo, Xu Yang, Xu Wang, Tianyu Dong, Di Wu, Chenghao Yan, Yankai Xia
Ecotoxicology and Environmental Safety.2024; 273: 116139. CrossRef
Thyroid-function reference ranges in the diagnosis of thyroid dysfunction in adults
Salman Razvi
Nature Reviews Endocrinology.2024; 20(5): 253. CrossRef
Association between exposure to chemical mixtures and epigenetic ageing biomarkers: Modifying effects of thyroid hormones and physical activity
Wanying Shi, Jianlong Fang, Huimin Ren, Peijie Sun, Juan Liu, Fuchang Deng, Shuyi Zhang, Qiong Wang, Jiaonan Wang, Shilu Tong, Song Tang, Xiaoming Shi
Journal of Hazardous Materials.2024; 469: 134009. CrossRef
DNA Methylation in Autoimmune Thyroid Disease
Nicole Lafontaine, Scott G Wilson, John P Walsh
The Journal of Clinical Endocrinology & Metabolism.2023; 108(3): 604. CrossRef
A Causality between Thyroid Function and Bone Mineral Density in Childhood: Abnormal Thyrotropin May Be Another Pediatric Predictor of Bone Fragility
Dongjin Lee, Moon Ahn
Metabolites.2023; 13(3): 372. CrossRef
Serum Lipidomic Analysis Reveals Biomarkers and Metabolic Pathways of Thyroid Dysfunction
Hua Dong, Wenjie Zhou, Xingxu Yan, Huan Zhao, Honggang Zhao, Yan Jiao, Guijiang Sun, Yubo Li, Zuncheng Zhang
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Developmental and environmental modulation of fecal thyroid hormone levels in wild Assamese macaques (Macaca assamensis)
Verena Behringer, Michael Heistermann, Suchinda Malaivijitnond, Oliver Schülke, Julia Ostner
American Journal of Primatology.2023;[Epub] CrossRef
Prevalence of Functional Alterations and the Effects of Thyroid Autoimmunity on the Levels of TSH in an Urban Population of Colombia: A Population-Based Study
Hernando Vargas-Uricoechea, Valentina Agredo-Delgado, Hernando David Vargas-Sierra, María V. Pinzón-Fernández
Endocrine, Metabolic & Immune Disorders - Drug Targets.2023; 23(6): 857. CrossRef
Genetic determinants of thyroid function in children
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
European Journal of Endocrinology.2023; 189(2): 164. CrossRef
Relationship between Thyroid CT Density, Volume, and Future TSH Elevation: A 5-Year Follow-Up Study
Tomohiro Kikuchi, Shouhei Hanaoka, Takahiro Nakao, Yukihiro Nomura, Takeharu Yoshikawa, Md Ashraful Alam, Harushi Mori, Naoto Hayashi
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Thyroid Stimulating Hormone and Thyroid Hormones (Triiodothyronine and Thyroxine): An American Thyroid Association-Commissioned Review of Current Clinical and Laboratory Status
Katleen Van Uytfanghe, Joel Ehrenkranz, David Halsall, Kelly Hoff, Tze Ping Loh, Carole A. Spencer, Josef Köhrle
Thyroid®.2023; 33(9): 1013. CrossRef
Blood hormones and suicidal behaviour: A systematic review and meta-analysis
Xue-Lei Fu, Xia Li, Jia-Mei Ji, Hua Wu, Hong-Lin Chen
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Original Articles

Calcium & Bone Metabolism
Computed Tomography-Derived Skeletal Muscle Radiodensity Is an Early, Sensitive Marker of Age-Related Musculoskeletal Changes in Healthy Adults: Yeon Woo Jung, Namki Hong, Joon Chae Na, Woong Kyu Han, Yumie Rhee; Endocrinol Metab. 2021;36(6):1201-1210. Published online December 13, 2021; DOI: https://doi.org/10.3803/EnM.2021.1206

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Background
A decrease in computed tomography (CT)-derived skeletal muscle radiodensity (SMD) reflects age-related ectopic fat infiltration of muscle, compromising muscle function and metabolism. We investigated the age-related trajectory of SMD and its association with vertebral trabecular bone density in healthy adults.
Methods
In a cohort of healthy adult kidney donors aged 19 to 69 years (n=583), skeletal muscle index (SMI, skeletal muscle area/height2), SMD, and visceral-to-subcutaneous fat (V/S) ratio were analyzed at the level of L3 from preoperative CT scans. Low bone mass was defined as an L1 trabecular Hounsfield unit (HU) <160 HU.
Results
L3SMD showed constant decline from the second decade (annual change –0.38% and –0.43% in men and women), whereas the decline of L3SMI became evident only after the fourth decade of life (–0.37% and –0.18% in men and women). One HU decline in L3SMD was associated with elevated odds of low bone mass (adjusted odds ratio, 1.07; 95% confidence interval, 1.02 to 1.13; P=0.003), independent of L3SMI, age, sex, and V/S ratio, with better discriminatory ability compared to L3SMI (area under the receiver-operating characteristics curve 0.68 vs. 0.53, P<0.001). L3SMD improved the identification of low bone mass when added to age, sex, V/S ratio, and L3SMI (category-free net reclassification improvement 0.349, P<0.001; integrated discrimination improvement 0.015, P=0.0165).
Conclusion
L3SMD can be an early marker for age-related musculoskeletal changes showing linear decline throughout life from the second decade in healthy adults, with potential diagnostic value for individuals with low bone mass.

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A review of radiological definitions of sarcopenia in cancer
James W. Wang, Jiarong Chen, Alison H. McGregor, Matthew Williams
JCSM Clinical Reports.2023; 8(2): 36. CrossRef
Weight‐adjusted waist as an integrated index for fat, muscle and bone health in adults
Kyoung Jin Kim, Serhim Son, Kyeong Jin Kim, Sin Gon Kim, Nam Hoon Kim
Journal of Cachexia, Sarcopenia and Muscle.2023; 14(5): 2196. CrossRef

Thyroid
Comparison of Korean vs. American Thyroid Imaging Reporting and Data System in Malignancy Risk Assessment of Indeterminate Thyroid Nodules: Sunyoung Kang, Seul Ki Kwon, Hoon Sung Choi, Min Joo Kim, Young Joo Park, Do Joon Park, Sun Wook Cho; Endocrinol Metab. 2021;36(5):1111-1120. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1208

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Background
The management of cytologically indeterminate thyroid nodules is challenging for clinicians. This study aimed to compare the diagnostic performance of the Korean Thyroid Imaging Reporting and Data Systems (K-TIRADS) with that of the American College of Radiology (ACR)-TIRADS for predicting the malignancy risk of indeterminate thyroid nodules.
Methods
Thyroid nodules diagnosed by fine-needle aspiration (FNA) followed by surgery or core needle biopsy at a single referral hospital were enrolled.
Results
Among 200 thyroid nodules, 78 (39.0%) nodules were classified as indeterminate by FNA (Bethesda category III, IV, and V), and 114 (57.0%) nodules were finally diagnosed as malignancy by surgery or core needle biopsy. The area under the curve (AUC) was higher for FNA than for either TIRADS system in all nodules, while all three methods showed similar AUCs for indeterminate nodules. However, for Bethesda category III nodules, applying K-TIRADS 5 significantly increased the risk of malignancy compared to a cytological examination alone (50.0% vs. 26.5%, P=0.028), whereas applying ACR-TIRADS did not lead to a change.
Conclusion
K-TIRADS and ACR-TIRADS showed similar diagnostic performance in assessing indeterminate thyroid nodules, and K-TIRADS had beneficial effects for malignancy prediction in Bethesda category III nodules.

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The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules
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Comparison of diagnostic performance of two ultrasound risk stratification systems for thyroid nodules: a systematic review and meta-analysis
Yun Jin Kang, Hee Sun Ahn, Gulnaz Stybayeva, Ju Eun Lee, Se Hwan Hwang
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Diagnostic Performance of ACR and Kwak TI-RADS for Benign and Malignant Thyroid Nodules: An Update Systematic Review and Meta-Analysis
Yun Jin Kang, Gulnaz Stybayeya, Ju Eun Lee, Se Hwan Hwang
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Review Article

Diabetes, Obesity and Metabolism
Receptor-Mediated Muscle Homeostasis as a Target for Sarcopenia Therapeutics: Jong Hyeon Yoon, Ki-Sun Kwon; Endocrinol Metab. 2021;36(3):478-490. Published online June 28, 2021; DOI: https://doi.org/10.3803/EnM.2021.1081

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Sarcopenia is a disease characterized by age-related decline of skeletal muscle mass and function. The molecular mechanisms of the pathophysiology of sarcopenia form a complex network due to the involvement of multiple interconnected signaling pathways. Therefore, signaling receptors are major targets in pharmacological strategies in general. To provide a rationale for pharmacological interventions for sarcopenia, we herein describe several druggable signaling receptors based on their role in skeletal muscle homeostasis and changes in their activity with aging. A brief overview is presented of the efficacy of corresponding drug candidates under clinical trials. Strategies targeting the androgen receptor, vitamin D receptor, Insulin-like growth factor-1 receptor, and ghrelin receptor primarily focus on promoting anabolic action using natural ligands or mimetics. Strategies involving activin receptors and angiotensin receptors focus on inhibiting catabolic action. This review may help to select specific targets or combinations of targets in the future.

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The Current Landscape of Pharmacotherapies for Sarcopenia
Gulistan Bahat, Serdar Ozkok
Drugs & Aging.2024; 41(2): 83. CrossRef
Associations of micronutrient dietary patterns with sarcopenia among US adults: a population-based study
Yining Liu, Xiangliang Liu, Linnan Duan, Yixin Zhao, Yuwei He, Wei Li, Jiuwei Cui
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Impact of Vitamin D Level on Sarcopenia in Elderly People: A Critical Review
Saniya Khan, Sunil Kumar, Sourya Acharya, Anil Wanjari
Journal of Health and Allied Sciences NU.2023; 13(04): 453. CrossRef
Novel Potential Targets for Function-Promoting Therapies: Orphan Nuclear Receptors, Anti-inflammatory Drugs, Troponin Activators, Mas Receptor Agonists, and Urolithin A
Waly Dioh, Vihang Narkar, Anurag Singh, Fady Malik, Luigi Ferrucci, Cendrine Tourette, Jean Mariani, Rob van Maanen, Roger A Fielding, Lewis A Lipsitz
The Journals of Gerontology: Series A.2023; 78(Supplement): 44. CrossRef
Alverine citrate promotes myogenic differentiation and ameliorates muscle atrophy
Jong Hyeon Yoon, Seung-Min Lee, Younglang Lee, Min Ju Kim, Jae Won Yang, Jeong Yi Choi, Ju Yeon Kwak, Kwang-Pyo Lee, Yong Ryoul Yang, Ki-Sun Kwon
Biochemical and Biophysical Research Communications.2022; 586: 157. CrossRef
Adeno-associated virus-mediated expression of an inactive CaMKIIβ mutant enhances muscle mass and strength in mice
Takahiro Eguchi, Yuji Yamanashi
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Gastric Mobility and Gastrointestinal Hormones in Older Patients with Sarcopenia
Hsien-Hao Huang, Tse-Yao Wang, Shan-Fan Yao, Pei-Ying Lin, Julia Chia-Yu Chang, Li-Ning Peng, Liang-Kung Chen, David Hung-Tsang Yen
Nutrients.2022; 14(9): 1897. CrossRef
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Marcela Kanova, Pavel Kohout
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Original Articles

Endocrine Research
Effect of CCL11 on In Vitro Myogenesis and Its Clinical Relevance for Sarcopenia in Older Adults: Da Ae Kim, So Jeong Park, Jin Young Lee, Jeoung Hee Kim, Seungjoo Lee, Eunju Lee, Il-Young Jang, Hee-Won Jung, Jin Hoon Park, Beom-Jun Kim; Endocrinol Metab. 2021;36(2):455-465. Published online April 14, 2021; DOI: https://doi.org/10.3803/EnM.2020.942

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Background
The C-C motif chemokine ligand 11 (CCL11) has been receiving attention as a potential pro-aging factor. Accordingly, it may be involved in muscle metabolism and sarcopenia, a key component of aging phenotypes. To clarify this potential, we investigated the effects of CCL11 on in vitro muscle biology and its clinical relevance for sarcopenia parameters in older adults.
Methods
Myogenesis was induced in mouse C2C12 myoblasts with 2% horse serum. Human blood samples were collected from 79 participants who underwent a functional assessment. Thereafter, CCL11 level was measured using a quantikine ELISA kit. Sarcopenia was defined using the Asian-specific guideline.
Results
Recombinant CCL11 treatment significantly stimulated myogenesis in a dose-dependent manner, and consistently increased the expression of myogenic differentiation markers. Among the C-C chemokine receptors (CCRs), CCR5, not CCR2 and CCR3, was predominantly expressed in muscle cells. Further, the CCR5 inhibitor blocked recombinant CCL11-stimulated myogenesis. In a clinical study, serum CCL11 level was not significantly different according to the status of sarcopenia, low muscle mass, weak muscle strength, and poor physical performance, and was not associated with skeletal muscle index, grip strength, short physical performance battery score, gait speed, and time to complete 5 chair stands, after adjusting for sex, age, and body mass index.
Conclusion
Contrary to expectations, CCL11 exerted beneficial effects on muscle metabolism at least in vitro system. However, its impact on human muscle health was not evident, suggesting that circulating CCL11 may not be a useful biomarker for sarcopenia risk assessment in older adults.

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Mapping the causal associations of cytokines with sarcopenia and aging traits: Evidence from bidirectional Mendelian randomization
Mingchong Liu, Xiao Fu, Daqian Yu, Meng Li, Yutao Pan, Chensong Yang, Guixin Sun
Journal of Cachexia, Sarcopenia and Muscle.2024;[Epub] CrossRef
C-C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease
Zhiwen Fan, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Yong Xu, Jie Li, Xiaoping Zou, Zilong Li
JHEP Reports.2023; : 100754. CrossRef
C–C motif chemokine CCL11 is a novel regulator and a potential therapeutic target in non-alcoholic fatty liver disease
Zhiwen Fan, Xinyue Sun, Xuelian Chen, Huimin Liu, Xiulian Miao, Yan Guo, Yong Xu, Jie Li, Xiaoping Zou, Zilong Li
JHEP Reports.2023; 5(9): 100805. CrossRef
Lumican Inhibits Osteoclastogenesis and Bone Resorption by Suppressing Akt Activity
Jin-Young Lee, Da-Ae Kim, Eun-Young Kim, Eun-Ju Chang, So-Jeong Park, Beom-Jun Kim
International Journal of Molecular Sciences.2021; 22(9): 4717. CrossRef
Aldosterone Inhibits In Vitro Myogenesis by Increasing Intracellular Oxidative Stress via Mineralocorticoid Receptor
Jin Young Lee, Da Ae Kim, Eunah Choi, Yun Sun Lee, So Jeong Park, Beom-Jun Kim
Endocrinology and Metabolism.2021; 36(4): 865. CrossRef

Clinical Study
Development of a Non-Invasive Liver Fibrosis Score Based on Transient Elastography for Risk Stratification in Patients with Type 2 Diabetes: Chi-Ho Lee, Wai-Kay Seto, Kelly Ieong, David T.W. Lui, Carol H.Y. Fong, Helen Y. Wan, Wing-Sun Chow, Yu-Cho Woo, Man-Fung Yuen, Karen S.L. Lam; Endocrinol Metab. 2021;36(1):134-145. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.887

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Background
In non-alcoholic fatty liver disease (NAFLD), transient elastography (TE) is an accurate non-invasive method to identify patients at risk of advanced fibrosis (AF). We developed a diabetes-specific, non-invasive liver fibrosis score based on TE to facilitate AF risk stratification, especially for use in diabetes clinics where TE is not readily available.
Methods
Seven hundred sixty-six adults with type 2 diabetes and NAFLD were recruited and randomly divided into a training set (n=534) for the development of diabetes fibrosis score (DFS), and a testing set (n=232) for internal validation. DFS identified patients with AF on TE, defined as liver stiffness (LS) ≥9.6 kPa, based on a clinical model comprising significant determinants of LS with the lowest Akaike information criteria. The performance of DFS was compared with conventional liver fibrosis scores (NFS, FIB-4, and APRI), using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values (NPV).
Results
DFS comprised body mass index, platelet, aspartate aminotransferase, high-density lipoprotein cholesterol, and albuminuria, five routine measurements in standard diabetes care. Derived low and high DFS cut-offs were 0.1 and 0.3, with 90% sensitivity and 90% specificity, respectively. Both cut-offs provided better NPVs of >90% than conventional fibrosis scores. The AUROC of DFS for AF on TE was also higher (P<0.01) than the conventional fibrosis scores, being 0.85 and 0.81 in the training and testing sets, respectively.
Conclusion
Compared to conventional fibrosis scores, DFS, with a high NPV, more accurately identified diabetes patients at-risk of AF, who need further evaluation by hepatologists.

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Implementation of a liver health check in people with type 2 diabetes
Kushala W M Abeysekera, Luca Valenti, Zobair Younossi, John F Dillon, Alina M Allen, Mazen Noureddin, Mary E Rinella, Frank Tacke, Sven Francque, Pere Ginès, Maja Thiele, Philip N Newsome, Indra Neil Guha, Mohammed Eslam, Jörn M Schattenberg, Saleh A Alqa
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Non-Invasive Measurement of Hepatic Fibrosis by Transient Elastography: A Narrative Review
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Review Articles

Miscellaneous
Sarcopenia and Muscle Aging: A Brief Overview: Tam Dao, Alexander E. Green, Yun A Kim, Sung-Jin Bae, Ki-Tae Ha, Karim Gariani, Mi-ra Lee, Keir J. Menzies, Dongryeol Ryu; Endocrinol Metab. 2020;35(4):716-732. Published online December 23, 2020; DOI: https://doi.org/10.3803/EnM.2020.405

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The world is facing the new challenges of an aging population, and understanding the process of aging has therefore become one of the most important global concerns. Sarcopenia is a condition which is defined by the gradual loss of skeletal muscle mass and function with age. In research and clinical practice, sarcopenia is recognized as a component of geriatric disease and is a current target for drug development. In this review we define this condition and provide an overview of current therapeutic approaches. We further highlight recent findings that describe key pathophysiological phenotypes of this condition, including alterations in muscle fiber types, mitochondrial function, nicotinamide adenine dinucleotide (NAD⁺) metabolism, myokines, and gut microbiota, in aged muscle compared to young muscle or healthy aged muscle. The last part of this review examines new therapeutic avenues for promising treatment targets. There is still no accepted therapy for sarcopenia in humans. Here we provide a brief review of the current state of research derived from various mouse models or human samples that provide novel routes for the development of effective therapeutics to maintain muscle health during aging.

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Hypothalamus and Pituitary gland
Current National and International Guidelines for the Management of Male Hypogonadism: Helping Clinicians to Navigate Variation in Diagnostic Criteria and Treatment Recommendations: Ahmed Al-Sharefi, Richard Quinton; Endocrinol Metab. 2020;35(3):526-540. Published online September 22, 2020; DOI: https://doi.org/10.3803/EnM.2020.760

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Male hypogonadism—rebadged by some as testosterone deficiency syndrome—is a clinical and biochemical diagnosis of increasing worldwide interest. Organic male hypogonadism—usually permanent—is well-established, but aging men may also exhibit lower serum testosterone levels; principally due to burden of extra-gonadal comorbidities such as obesity, diabetes and metabolic syndrome, but with an underlying intact hypothalamo-pituitary-testicular (HPT) axis capable of springing back into operation once comorbidities are addressed. Despite encouraging observational data and plausible theoretical underpinning, evidence for efficacy and safety of testosterone in this “aging” group of men is lacking; addressing comorbid illnesses remains the key priority instead. Nevertheless, in recent years, accumulation of misleading information online has triggered a global tsunami of testosterone prescriptions. Despite this, many men with organic hypogonadism remain undiagnosed or untreated; many more face a diagnostic odyssey before achieving care by the appropriate specialist. As testosterone therapy is not without risk several clinical practice guidelines have been published specialist societies to guide physicians on best practice. However, these are heterogeneous in key areas, reflecting divergent approaches to the same evidence basis. Herein, we navigate the major clinical practice guidelines on male hypogonadism and test their respective recommendations against current best evidence.

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