Endocrinology and Metabolism

Hypothalamus and pituitary gland Big Data Articles (National Health Insurance Service Database)
Long-Term Prognosis and Systemic Impact of Acromegaly: Analyses Utilizing Korean National Health Insurance Data: Sangmo Hong, Kyungdo Han, Cheol-Young Park; Endocrinol Metab. 2025;40(1):1-9. Published online February 4, 2025; DOI: https://doi.org/10.3803/EnM.2024.2285

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Abstract PDF PubReader ePub: Acromegaly is a rare endocrine disorder caused by excessive growth hormone secretion. Its low prevalence poses challenges in studying its long-term prognosis and systemic effects. To address this research gap, we conducted five studies using nationwide cohort data from the Korean National Health Insurance Database (NHID). This review consolidates the findings of these studies, which examined various long-term effects of acromegaly. The results demonstrated significant associations between acromegaly and increased mortality, a higher prevalence of mortality, cardiovascular outcomes, neurodegenerative diseases, depression, end-stage kidney disease, respiratory complications, specifically bronchiectasis, spine & hip fracture, and malignancy. These findings highlight the critical need for early diagnosis, comprehensive care, and long-term monitoring, and underscore the importance of a multidisciplinary approach in managing acromegaly.

Diabetes, obesity and metabolism
Gestational Diabetes Mellitus: Mechanisms Underlying Maternal and Fetal Complications: Jooyeop Lee, Na Keum Lee, Joon Ho Moon; Endocrinol Metab. 2025;40(1):10-25. Published online January 23, 2025; DOI: https://doi.org/10.3803/EnM.2024.2264

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Gestational diabetes mellitus (GDM) affects over 10% of all pregnancies, both in Korea and worldwide. GDM not only increases the risk of adverse pregnancy outcomes such as preeclampsia, preterm birth, macrosomia, neonatal hypoglycemia, and shoulder dystocia, but it also significantly increases the risk of developing postpartum type 2 diabetes mellitus and cardiovascular disease in the mother. Additionally, GDM is linked to a higher risk of childhood obesity and diabetes in offspring, as well as neurodevelopmental disorders, including autistic spectrum disorder. This review offers a comprehensive summary of clinical epidemiological studies concerning maternal and fetal complications and explores mechanistic investigations that reveal the underlying pathophysiology.

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Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management
Rahul Mittal, Karan Prasad, Joana R. N. Lemos, Giuliana Arevalo, Khemraj Hirani
International Journal of Molecular Sciences.2025; 26(5): 2320. CrossRef

Hypothalamus and pituitary gland
Medical Treatment of Cushing’s Syndrome: Laurence Guignat, Jerome Bertherat; Endocrinol Metab. 2025;40(1):26-38. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.501

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Abstract PDF PubReader ePub: Endogenous Cushing’s syndrome (CS) refers to the manifestations of chronic cortisol excess. This rare disease is associated with multiple comorbidities, impaired quality of life, and increased mortality. The management of CS remains challenging. Regardless of the underlying cause, surgical resection of the tumor is typically the first-line and preferred treatment. However, when surgery is not feasible or has been unsuccessful, medical therapies may be employed to control CS. The therapeutic strategy should be individualized based on the recommendations of a multidisciplinary team of experts and the patient’s preferences, informed by detailed information on the available options. All medications require careful monitoring, along with adequate instructions for patients and caregivers. The aim of this mini-review is to provide an overview of the main medical therapies currently used to treat CS, including their efficacy, safety, and management. Despite the availability of new drugs in recent years, the need remains for more effective specific targeted pharmacological therapies.

Hypothalamus and pituitary gland
Pituitary Neuroendocrine Tumors in Multiple Endocrine Neoplasia: Sang Ouk Chin, Constance Chik, Toru Tateno; Endocrinol Metab. 2025;40(1):39-46. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.2074

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Abstract PDF PubReader ePub: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant disorder characterized by tumors of the pituitary, parathyroid, and endocrine-gastrointestinal tract. Pituitary neuroendocrine tumors (PitNETs) occur in about 40% of MEN1 cases, with 10% being the first manifestation. Recent studies show a slight female predominance, with microPitNETs (<1 cm) being more common than macroPitNETs (>1 cm). Functional PitNETs (FPitNETs) are more frequent than non-functional ones (36% to 48%), with prolactinomas being the most common FPitNETs. MEN1-associated PitNETs are often plurihormonal, larger, and more invasive compared to sporadic types, though patient age and FPitNET proportions are similar. MEN1 mutation-negative patients tend to have larger, symptomatic PitNETs at diagnosis. Six patients with MEN1 have been reported to have pituitary carcinomas, including a mutation- negative patient. Treatment approach between PitNETs in MEN1 and sporadic types appears to be similar. PitNETs also occur in MEN4, but their epidemiology is less understood. In patients with a MEN1-like phenotype and negative genetic testing, MEN4 should be considered.

Calcium & bone metabolism
Long-Term Efficacy and Safety of Denosumab: Insights beyond 10 Years of Use: Jeonghoon Ha, Youn-Ju Lee, Jinyoung Kim, Chaiho Jeong, Yejee Lim, Jeongmin Lee, Ki-Hyun Baek, on Behalf of the Catholic Medical Center Bone Research Group; Endocrinol Metab. 2025;40(1):47-56. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2125

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Abstract PDF PubReader ePub: Osteoporosis management in post-menopausal women focuses on fracture prevention, with denosumab as a key therapeutic option. Despite its proven efficacy in reducing fracture risk and increasing bone mineral density (BMD) over 10 years, its long-term impact remains uncertain. We evaluated the literature on its efficacy and safety beyond the initial decade. Clinical trials and real-world studies confirm denosumab’s sustained efficacy, especially in lumbar spine BMD, with hip BMD stabilizing. Concerns about adverse events (AEs) like hypocalcemia and osteonecrosis of the jaw necessitate vigilant monitoring. Risks of atypical femoral fractures and malignancies also require attention, despite unclear links to treatment duration. Clinical guidelines for denosumab beyond 10 years are limited, emphasizing the need for careful monitoring. In certain scenarios, such as advanced chronic kidney disease, prolonged denosumab may be required to balance AE risks with fracture prevention benefits. Denosumab shows potential for long-term efficacy in augmenting BMD; however, monitoring for AEs is crucial to guide clinical decision-making effectively.

Diabetes, obesity and metabolism
Evolving Characteristics of Type 2 Diabetes Mellitus in East Asia: Joonyub Lee, Kun-Ho Yoon; Endocrinol Metab. 2025;40(1):57-63. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2193

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Abstract PDF PubReader ePub: In East Asians, type 2 diabetes mellitus (T2DM) is primarily characterized by significant defects in insulin secretion and comparatively low insulin resistance. Recently, the prevalence of T2DM has rapidly increased in East Asian countries, including Korea, occurring concurrently with rising obesity rates. This trend has led to an increase in the average body mass index among East Asian T2DM patients, highlighting the influence of insulin resistance in the development of T2DM within this group. Currently, the incidence of T2DM in Korea is declining, which may indicate potential adaptive changes in insulin secretory capacity. This review focuses on the changing epidemiology of T2DM in East Asia, with a particular emphasis on the characteristics of peak functional β-cell mass.

Miscellaneous
Redefining Polycystic Ovary Syndrome: Transformative Diagnostic and Management Changes in the 2023 Guidelines: A Ram Hong; Endocrinol Metab. 2025;40(1):64-66. Published online February 11, 2025; DOI: https://doi.org/10.3803/EnM.2024.2263

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Diabetes, obesity and metabolism
Highlights of the Most Recent American Diabetes Association Guidelines: From Evidence to Practice: Mee Kyoung Kim; Endocrinol Metab. 2025;40(1):67-69. Published online February 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2329

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Thyroid
Treatment of Graves’ Disease: Faster Remission or Longer but Safe, That Is the Question: Chan-Hee Jung; Endocrinol Metab. 2025;40(1):70-72. Published online February 24, 2025; DOI: https://doi.org/10.3803/EnM.2025.2333

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Calcium & bone metabolism
Elevated Circulating Sclerostin Levels in Frail Older Adults: Implications beyond Bone Health: Ji Yeon Baek, Seong Hee Ahn, Il-Young Jang, Hee-Won Jung, Eunhye Ji, So Jeong Park, Yunju Jo, Eunju Lee, Dongryeol Ryu, Seongbin Hong, Beom-Jun Kim; Endocrinol Metab. 2025;40(1):73-81. Published online October 24, 2024; DOI: https://doi.org/10.3803/EnM.2024.2100

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Abstract PDF Supplementary Material PubReader ePub: Background
Sclerostin, initially recognized for its pivotal role in bone metabolism, has gained attention for its multifaceted impact on overall human health. However, its influence on frailty—a condition that best reflects biological age—has not been thoroughly investigated.
Methods
We collected blood samples from 244 older adults who underwent comprehensive geriatric assessments. Sclerostin levels were quantified using an enzyme-linked immunosorbent assay. Frailty was assessed using two validated approaches: the phenotypic model by Fried and the deficit accumulation frailty index (FI) by Rockwood.
Results
After controlling for sex, age, and body mass index, we found that serum sclerostin levels were significantly elevated in frail individuals compared to their robust counterparts (P<0.001). There was a positive correlation between serum sclerostin concentrations and the FI (P<0.001). Each standard deviation increase in serum sclerostin was associated with an odds ratio of 1.87 for frailty (P=0.003). Moreover, participants in the highest quartile of sclerostin levels had a significantly higher FI and a 9.91-fold increased odds of frailty compared to those in the lowest quartile (P=0.003 and P=0.039, respectively).
Conclusion
These findings, which for the first time explore the association between circulating sclerostin levels and frailty, have significant clinical implications, positioning sclerostin as one of potential blood-based biomarkers for frailty that captures the comprehensive physical, mental, and social aspects of the elderly, extending beyond its traditional role in bone metabolism.

Calcium & bone metabolism Big Data Articles (National Health Insurance Service Database)
Elevated Fracture Risks in Patients Using Inhaled Corticosteroids: A Korean Nationwide Study: Sung Hye Kong, Ae Jeong Jo, Chan Mi Park, Kyun Ik Park, Ji Eun Yun, Jung Hee Kim; Endocrinol Metab. 2025;40(1):82-92. Published online August 30, 2024; DOI: https://doi.org/10.3803/EnM.2024.1990

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Abstract PDF Supplementary Material PubReader ePub: Background
In this comprehensive retrospective nationwide cohort study, we examined the relationships between various asthma medications and bone health, utilizing data from the National Health Insurance Service database of South Korea.
Methods
From 2015 to 2019, the relevant dataset included 168,611 individuals aged 66 years, among whom 8,747 were diagnosed with asthma. We focused on a subset of 6,173 patients, all 66-year-old women. Participants were categorized into four groups: nonusers of asthma medication (n=2,868), leukotriene antagonist users (n=2,281), inhaled corticosteroid (ICS) users (n=517), and those using a combination of ICS and long-acting beta-agonist (ICS+LABA) medication (n=507). The primary outcomes measured were the incidences of major osteoporotic fractures and hip fractures during the follow-up period.
Results
Over 2.7 years of follow-up, 615 cases of major osteoporotic fractures and 96 cases of hip fractures were recorded. ICS users exhibited a heightened risk of both injuries, with hazard ratios of 1.38 (95% confidence interval [CI], 1.18 to 1.63; P<0.001) for major osteoporotic fractures and 1.56 (95% CI, 1.33 to 1.83; P<0.001) for hip fractures. Similarly elevated risks were observed in the ICS+LABA group. Notably, the risk associated with ICS was particularly pronounced among patients with osteopenia for both fracture types. Overall, the use of ICS, alone or in combination with LABA, in patients with asthma is associated with significantly increased risks of osteoporotic fractures, especially among those with osteopenia.
Conclusion
These findings underscore the importance of considering bone health when managing asthma, especially in older patients and those with existing bone density issues.

Calcium & bone metabolism
Carnitine Metabolite as a Potential Circulating Biomarker for Sarcopenia in Men: Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young‑Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee; Endocrinol Metab. 2025;40(1):93-102. Published online November 28, 2024; DOI: https://doi.org/10.3803/EnM.2024.2117

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Abstract PDF Supplementary Material PubReader ePub: Background
Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia.
Methods
Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort.
Results
An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027).
Conclusion
C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Risk of Diabetes Mellitus in Adults with Intellectual Disabilities: A Nationwide Cohort Study: Hye Yeon Koo, In Young Cho, Yoo Jin Um, Yong-Moon Mark Park, Kyung Mee Kim, Chung Eun Lee, Kyungdo Han; Endocrinol Metab. 2025;40(1):103-111. Published online November 20, 2024; DOI: https://doi.org/10.3803/EnM.2024.2126

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Abstract PDF Supplementary Material PubReader ePub: Background
Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations.
Methods
This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID.
Results
Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001).
Conclusion
Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

Diabetes, obesity and metabolism
Tirzepatide and Cancer Risk in Individuals with and without Diabetes: A Systematic Review and Meta-Analysis: A.B.M. Kamrul-Hasan, Muhammad Shah Alam, Deep Dutta, Thanikai Sasikanth, Fatema Tuz Zahura Aalpona, Lakshmi Nagendra; Endocrinol Metab. 2025;40(1):112-124. Published online January 15, 2025; DOI: https://doi.org/10.3803/EnM.2024.2164

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Abstract PDF Supplementary Material PubReader ePub: Background
Data on the carcinogenic potential of tirzepatide from randomized controlled trials (RCTs) are limited. Furthermore, no meta-analysis has included all relevant RCTs to assess the cancer risk associated with tirzepatide.
Methods
RCTs involving patients receiving tirzepatide in the intervention arm and either a placebo or any active comparator in the control arm were searched through electronic databases. The primary outcome was the overall risk of any cancer, and secondary outcomes were the risks of specific types of cancer in the tirzepatide versus the control groups.
Results
Thirteen RCTs with 13,761 participants were analyzed. Over 26 to 72 weeks, the tirzepatide and pooled control groups had identical risks of any cancer (risk ratio, 0.78; 95% confidence interval, 0.53 to 1.16; P=0.22). The two groups had comparable cancer risks in patients with and without diabetes. In subgroup analyses, the risks were also similar in the tirzepatide versus placebo, insulin, and glucagon-like peptide-1 receptor agonist groups. The overall cancer risk was also comparable for different doses of tirzepatide compared to the control groups; only a 10-mg tirzepatide dose had a lower risk of any cancer than placebo. Furthermore, compared to the control groups (pooled or separately), tirzepatide did not increase the risk of any specific cancer types. Despite greater increments in serum calcitonin with 10- and 15-mg tirzepatide doses than with placebo, the included RCTs reported no cases of papillary thyroid carcinoma.
Conclusion
Tirzepatide use in RCTs over 26 to 72 weeks did not increase overall or specific cancer risk.

Thyroid Big Data Articles (National Health Insurance Service Database)
Unveiling Risk Factors for Treatment Failure in Patients with Graves’ Disease: A Nationwide Cohort Study in Korea: Jung A Kim, Kyeong Jin Kim, Jimi Choi, Kyoung Jin Kim, Eyun Song, Ji Hee Yu, Nam Hoon Kim, Hye Jin Yoo, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Sin Gon Kim; Endocrinol Metab. 2025;40(1):125-134. Published online January 13, 2025; DOI: https://doi.org/10.3803/EnM.2024.2093

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Abstract PDF Supplementary Material PubReader ePub

Background
Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice.
Methods
We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years.
Results
Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi.
Conclusion
ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Citations

Citations to this article as recorded by

Treatment of Graves’ Disease: Faster Remission or Longer but Safe, That Is the Question
Chan-Hee Jung
Endocrinology and Metabolism.2025; 40(1): 70. CrossRef

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