Endocrinology and Metabolism

Original Articles

Thyroid
Long-Term Changes in the Mortality Rates of Thyroid Cancer in Korea: Analysis of Korean National Data from 1985 to 2020: Yun Mi Choi, Min-Ju Kim, Jiwoo Lee, Mi Kyung Kwak, Min Ji Jeon, Tae Yong Kim, Eun-Gyoung Hong, Won Bae Kim, Won Gu Kim; Endocrinol Metab. 2023;38(5):588-595. Published online September 8, 2023; DOI: https://doi.org/10.3803/EnM.2023.1723

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Abstract PDF Supplementary Material PubReader ePub: Background
Thyroid cancer mortality has been largely overlooked as relatively stable given the large gap between thyroid cancer incidence and mortality. This study evaluated long-term trends in age-standardized mortality rates (ASMRs) throughout Korea and compared them with mortality data reported by the Surveillance, Epidemiology, and End Results (SEER).
Methods
Cancer-specific mortality data from 1985 to 2020 were obtained from Statistics Korea. ASMRs from thyroid cancer were calculated based on the Korean mid-year resident registration population of 2005. We assessed SEER*Explorer and downloaded the mortality data.
Results
The ASMR increased from 0.19 to 0.77/100,000 between 1985 and 2002 but decreased continuously to 0.36/100,000 in 2020. The annual percent change (APC) in the ASMR between 1985 and 2003 and between 2003 and 2020 was 6.204 and −4.218, respectively, with similar patterns observed in both men and women. The ASMR of the SEER showed a modest increase from 1988 to 2016 and then stabilized. In subgroup analysis, the ASMR of the old age group (≥55 years) increased significantly from 0.82 in 1985 to 3.92/100,000 in 2002 (APC 6.917) but then decreased again to 1.86/100,000 in 2020 (APC −4.136). ASMRs according to the age group in the SEER showed a relatively stable trend even in the elderly group.
Conclusion
The ASMR of thyroid cancer in Korea had increased from 1985 to 2002 but has since been steadily decreasing. This trend was mainly attributed to elderly people aged 55 or over. The absolute APC value of Korea was much higher than that of the SEER.

Diabetes, obesity and metabolism
Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study: Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee, Committee of Big Data, Korean Endocrine Society; Endocrinol Metab. 2023;38(5):525-537. Published online September 7, 2023; DOI: https://doi.org/10.3803/EnM.2023.1765

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Background
This study investigated the risk of cause-specific mortality according to glucose tolerance status in elderly South Koreans.
Methods
A total of 1,292,264 individuals aged ≥65 years who received health examinations in 2009 were identified from the National Health Information Database. Participants were classified as normal glucose tolerance, impaired fasting glucose, newly-diagnosed diabetes, early diabetes (oral hypoglycemic agents ≤2), or advanced diabetes (oral hypoglycemic agents ≥3 or insulin). The risk of system-specific and disease-specific deaths was estimated using multivariate Cox proportional hazards analysis.
Results
During a median follow-up of 8.41 years, 257,356 deaths were recorded. Diabetes was associated with significantly higher risk of all-cause mortality (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.57 to 1.60); death due to circulatory (HR, 1.49; 95% CI, 1.46 to 1.52), respiratory (HR, 1.51; 95% CI, 1.47 to 1.55), and genitourinary systems (HR, 2.22; 95% CI, 2.10 to 2.35); and neoplasms (HR, 1.30; 95% CI, 1.28 to 1.32). Diabetes was also associated with a significantly higher risk of death due to ischemic heart disease (HR, 1.70; 95% CI, 1.63 to 1.76), cerebrovascular disease (HR, 1.46; 95% CI, 1.41 to 1.50), pneumonia (HR, 1.69; 95% CI, 1.63 to 1.76), and acute or chronic kidney disease (HR, 2.23; 95% CI, 2.09 to 2.38). There was a stepwise increase in the risk of death across the glucose spectrum (P for trend <0.0001). Stroke, heart failure, or chronic kidney disease increased the risk of all-cause mortality at every stage of glucose intolerance.
Conclusion
A dose-dependent association between the risk of mortality from various causes and severity of glucose tolerance was noted in the elderly population.

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The Characteristics and Risk of Mortality in the Elderly Korean Population
Sunghwan Suh
Endocrinology and Metabolism.2023; 38(5): 522. CrossRef

Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study: Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho; Endocrinol Metab. 2023;38(4):406-417. Published online August 3, 2023; DOI: https://doi.org/10.3803/EnM.2023.1703

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Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

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Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)
Alireza Jafari, Hamid Najafipour, Mitra Shadkam, Sina Aminizadeh
Lipids in Health and Disease.2023;[Epub] CrossRef
Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus
Kaisheng Yuan, Bing Wu, Ruiqi Zeng, Fuqing Zhou, Ruixiang Hu, Cunchuan Wang
Diabetes, Obesity and Metabolism.2023;[Epub] CrossRef

Adrenal gland Big Data Articles (National Health Insurance Service Database)
Mortality and Severity of Coronavirus Disease 2019 in Patients with Long-Term Glucocorticoid Therapy: A Korean Nationwide Cohort Study: Eu Jeong Ku, Keeho Song, Kyoung Min Kim, Gi Hyeon Seo, Soon Jib Yoo; Endocrinol Metab. 2023;38(2):253-259. Published online March 21, 2023; DOI: https://doi.org/10.3803/EnM.2022.1607

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Background
The severity of coronavirus disease 2019 (COVID-19) among patients with long-term glucocorticoid treatment (LTGT) has not been established. We aimed to evaluate the association between LTGT and COVID-19 prognosis.
Methods
A Korean nationwide cohort database of COVID-19 patients between January 2019 and September 2021 was used. LTGT was defined as exposure to at least 150 mg of prednisolone (≥5 mg/day and ≥30 days) or equivalent glucocorticoids 180 days before COVID-19 infection. The outcome measurements were mortality, hospitalization, intensive care unit (ICU) admission, length of stay, and mechanical ventilation.
Results
Among confirmed patients with COVID-19, the LTGT group (n=12,794) was older and had a higher proportion of comorbidities than the control (n=359,013). The LTGT group showed higher in-hospital, 30-day, and 90-day mortality rates than the control (14.0% vs. 2.3%, 5.9% vs. 1.1%, and 9.9% vs. 1.8%, respectively; all P<0.001). Except for the hospitalization rate, the length of stay, ICU admission, and mechanical ventilation proportions were significantly higher in the LTGT group than in the control (all P<0.001). Overall mortality was higher in the LTGT group than in the control group, and the significance remained in the fully adjusted model (odds ratio [OR], 5.75; 95% confidence interval [CI], 5.31 to 6.23) (adjusted OR, 1.82; 95% CI, 1.67 to 2.00). The LTGT group showed a higher mortality rate than the control within the same comorbidity score category.
Conclusion
Long-term exposure to glucocorticoids increased the mortality and severity of COVID-19. Prevention and early proactive measures are inevitable in the high-risk LTGT group with many comorbidities.

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Glucocorticoids as a Double-Edged Sword in the Treatment of COVID-19: Mortality and Severity of COVID-19 in Patients Receiving Long-Term Glucocorticoid Therapy
Eun-Hee Cho
Endocrinology and Metabolism.2023; 38(2): 223. CrossRef
Pituitary Diseases and COVID-19 Outcomes in South Korea: A Nationwide Cohort Study
Jeonghoon Ha, Kyoung Min Kim, Dong-Jun Lim, Keeho Song, Gi Hyeon Seo
Journal of Clinical Medicine.2023; 12(14): 4799. CrossRef

Diabetes, Obesity and Metabolism
Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients: Ja Young Jeon, Shin Han-Bit, Bum Hee Park, Nami Lee, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee, Seung Jin Han; Endocrinol Metab. 2023;38(1):139-145. Published online February 6, 2023; DOI: https://doi.org/10.3803/EnM.2022.1594

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Abstract PDF Supplementary Material PubReader ePub: Background
Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients.
Methods
We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model.
Results
Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE.
Conclusion
Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis: Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, Ji Sung Yoon; Endocrinol Metab. 2022;37(5):759-769. Published online October 5, 2022; DOI: https://doi.org/10.3803/EnM.2022.1515

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Background
This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death.
Methods
This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]–4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed.
Results
A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321).
Conclusion
Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

Citations

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Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study
Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Cardiovascular Diabetology.2023;[Epub] CrossRef

Review Article

Adrenal Gland
Long-Term Outcomes of Congenital Adrenal Hyperplasia: Anna Nordenström, Svetlana Lajic, Henrik Falhammar; Endocrinol Metab. 2022;37(4):587-598. Published online July 8, 2022; DOI: https://doi.org/10.3803/EnM.2022.1528

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A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.

Citations

Citations to this article as recorded by

Congenital adrenal hyperplasia: New biomarkers and adult treatments
Bleuenn Dreves, Yves Reznik, Antoine Tabarin
Annales d'Endocrinologie.2023; 84(4): 472. CrossRef
Interpretation of Steroid Biomarkers in 21-Hydroxylase Deficiency and Their Use in Disease Management
Kyriakie Sarafoglou, Deborah P Merke, Nicole Reisch, Hedi Claahsen-van der Grinten, Henrik Falhammar, Richard J Auchus
The Journal of Clinical Endocrinology & Metabolism.2023; 108(9): 2154. CrossRef
Impact of Newborn Screening on Adult Height in Patients With Congenital Adrenal Hyperplasia (CAH)
Heike Hoyer-Kuhn, Alexander J Eckert, Gerhard Binder, Walter Bonfig, Angelika Dübbers, Stefan Riedl, Joachim Woelfle, Helmuth G Dörr, Reinhard W Holl
The Journal of Clinical Endocrinology & Metabolism.2023; 108(11): e1199. CrossRef
Specialty grand challenge in adrenal endocrinology
Henrik Falhammar
Frontiers in Endocrinology.2023;[Epub] CrossRef
Contexts of care for people with differences of sex development
Alexandra E. Kulle, Martina Jürgensen, Ulla Döhnert, Lisa Malich, Louise Marshall, Olaf Hiort
Medizinische Genetik.2023; 35(3): 181. CrossRef
Cardiovascular risk in Cuban adolescents and young adults with congenital adrenal hyperplasia
Tania M. Espinosa Reyes, Alba Katherine Pesántez Velepucha, Julio Oscar Cabrera Rego, Wendy Valdés Gómez, Emma Domínguez Alonso, Henrik Falhammar
BMC Endocrine Disorders.2023;[Epub] CrossRef
Increased Prevalence of Accidents and Injuries in Congenital Adrenal Hyperplasia: A Population-based Cohort Study
Henrik Falhammar, Angelica Lindén Hirschberg, Agneta Nordenskjöld, Henrik Larsson, Anna Nordenström
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef
Landscape of Adrenal Tumours in Patients with Congenital Adrenal Hyperplasia
Mara Carsote, Ana-Maria Gheorghe, Claudiu Nistor, Alexandra-Ioana Trandafir, Oana-Claudia Sima, Anca-Pati Cucu, Adrian Ciuche, Eugenia Petrova, Adina Ghemigian
Biomedicines.2023; 11(11): 3081. CrossRef
Editorial: Recent advances in diagnosis and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Semra Çaglar Çetinkaya
Frontiers in Endocrinology.2023;[Epub] CrossRef
Approach of Heterogeneous Spectrum Involving 3beta-Hydroxysteroid Dehydrogenase 2 Deficiency
Andreea Gabriela Nicola, Mara Carsote, Ana-Maria Gheorghe, Eugenia Petrova, Alexandru Dan Popescu, Adela Nicoleta Staicu, Mihaela Jana Țuculină, Cristian Petcu, Ionela Teodora Dascălu, Tiberiu Tircă
Diagnostics.2022; 12(9): 2168. CrossRef
Effetti di Crinecerfont sulla secrezione di ACTH nell’iperplasia surrenalica congenita: uno studio di fase 2
Marianna Rita Stancampiano, Silvia Laura Carla Meroni, Giovanna Weber, Gianni Russo
L'Endocrinologo.2022; 23(6): 662. CrossRef

Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018: Eugene Han, Sun Ok Song, Hye Soon Kim, Kang Ju Son, Sun Ha Jee, Bong-Soo Cha, Byung-Wan Lee; Endocrinol Metab. 2022;37(3):466-474. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.1440

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Background
Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate.
Methods
The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed.
Results
In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (p<0.001). In a subgroup analysis according to the presence of comorbid diseases, the number and proportion of deaths remained steady in the group with diabetes only, but steadily increased in the groups with diabetes combined with dyslipidemia and/or hypertension. Compared to the control population, the increase in the mean death age was higher in the population with diabetes. This trend was more prominent in the groups with dyslipidemia and/or hypertension than in the diabetes only group. Deaths from vascular disease and diabetes decreased, whereas deaths from cancer and pneumonia increased. The decline in the proportion of deaths from vascular disease was greater in the diabetes groups with hypertension and/or dyslipidemia than in the control population.
Conclusion
The age at death in the population with diabetes increased more steeply and reached a comparable level to those without diabetes.

Citations

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Analysis of Cause-of-Death Mortality in Children and Young Adults with Diabetes: A Nationwide 10-Year Follow-Up Cohort Study
Iee-Ho Choi, Sang-Woo Yeom, Sun-Young Kim, Jihye You, Jong-Seung Kim, Minsun Kim
Children.2023; 10(2): 358. CrossRef
Age at Mortality in Patients with Type 2 Diabetes Who Underwent Kidney Transplantation: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Sun Ok Song, Eugene Han, Kang Ju Son, Bong-Soo Cha, Byung-Wan Lee
Journal of Clinical Medicine.2023; 12(9): 3160. CrossRef
Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study
Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee
Endocrinology and Metabolism.2023; 38(5): 525. CrossRef

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Association of High-Density Lipoprotein Cholesterol Phenotypes with the Risk of Cardiovascular Diseases and Mortality: A Cohort Study in Korea: Ga Eun Nam, Youn Huh, Jin-Hyung Jung, Kyungdo Han, Seon Mee Kim, on Behalf of the Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity; Endocrinol Metab. 2022;37(2):261-271. Published online April 25, 2022; DOI: https://doi.org/10.3803/EnM.2021.1259

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Background
We investigated whether low high-density lipoprotein cholesterol (HDL-C) and isolated and non-isolated low HDL-C levels are associated with the risk of cardiovascular diseases and all-cause mortality among Korean adults.
Methods
We included 8,665,841 individuals aged ≥20 years who had undergone a health examination provided by the Korean National Health Insurance Service (NHIS) in 2009 and were followed up until the end of 2018. The hazard ratios (HRs) and 95% confidence intervals (CIs) for study outcomes were calculated using multivariable Cox proportional hazard regression analysis.
Results
During the 8.2 years of mean follow-up, myocardial infarction (MI), stroke, and all-cause mortality occurred in 81,431, 110,996, and 244,309 individuals, respectively. After adjusting for confounding variables (model 3), individuals with low HDL-C and lower HDL quartiles were associated with significantly increased risks of all three outcomes, compared to those with normal HDL-C and highest HDL-C quartile (all P<0.001), respectively. HRs for incident MI (1.28; 95% CI, 1.26 to 1.30), stroke (1.13; 95% CI, 1.11 to 1.15), and all-cause mortality (1.07; 95% CI, 1.05 to 1.08) increased in the non-isolated low HDL-C group compared to the normal HDL-C group. Isolated low HDL-C also showed an increase in the HRs of incident stroke (1.06; 95% CI, 1.04 to 1.08) and all-cause mortality (1.30; 95% CI, 1.28 to 1.32).
Conclusion
Low HDL-C and non-isolated low HDL-C were associated with increased risk of MI, stroke, and all-cause mortality, and isolated low HDL-C was associated with incident stroke and all-cause mortality risk.

Citations

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Association between cholesterol levels and dementia risk according to the presence of diabetes and statin use: a nationwide cohort study
You-Bin Lee, Min Young Kim, Kyungdo Han, Bongsung Kim, Jiyun Park, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Sang-Man Jin
Scientific Reports.2022;[Epub] CrossRef

Adrenal Gland Big Data Articles (National Health Insurance Service Database)
Epidemiology and Long-Term Adverse Outcomes in Korean Patients with Congenital Adrenal Hyperplasia: A Nationwide Study: Jung Hee Kim, Sunkyu Choi, Young Ah Lee, Juneyoung Lee, Sin Gon Kim; Endocrinol Metab. 2022;37(1):138-147. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1328

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Background
Previous studies on the epidemiology and complications of congenital adrenal hyperplasia (CAH) were conducted in Western countries and in children/adolescents. We aimed to explore the epidemiology of CAH, as well as the risk of comorbidities and mortality, in a Korean nationwide case-control study.
Methods
CAH patients (n=2,840) were included between 2002 and 2017 from the National Health Insurance Service database and the Rare Intractable Disease program. CAH patients were compared, at a 1:10 ratio, with age-, sex-, and index year-matched controls (n=28,400).
Results
The point prevalence of CAH patients in Korea was 1 in 18,745 persons in 2017. The annual incidence rate declined between 2003 and 2017 from 3.25 to 0.41 per 100,000 persons. CAH patients were at elevated risk for cardiovascular disease (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.4 to 1.9), stroke (OR, 1.7; 95% CI, 1.3 to 2.0), diabetes mellitus (OR, 2.8; 95% CI, 2.6 to 3.1), dyslipidemia (OR, 2.4; 95% CI, 2.2 to 2.6), and psychiatric disorders (OR, 1.5; 95% CI, 1.3 to 1.6). Fracture risk increased in CAH patients aged over 40 years (OR, 1.4; 95% CI, 1.1 to 1.7). CAH patients were at higher risk of mortality than controls (hazard ratio, 1.6; 95% CI, 1.3 to 2.0).
Conclusion
Our nationwide study showed a recent decline in the incidence of CAH and an elevated risk for cardiovascular, metabolic, skeletal, and psychiatric disorders in CAH patients. Lifelong management for comorbidity risk is a crucial component of treating CAH patients.

Citations

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Анализ распространенности и заболеваемости надпочечниковой недостаточностью в мире
М. Ю. Юкина, Н. Ф. Нуралиева, Е. А. Трошина
Ateroscleroz.2023; 18(4): 426. CrossRef
Big Data Research in the Field of Endocrine Diseases Using the Korean National Health Information Database
Sun Wook Cho, Jung Hee Kim, Han Seok Choi, Hwa Young Ahn, Mee Kyoung Kim, Eun Jung Rhee
Endocrinology and Metabolism.2023; 38(1): 10. CrossRef
Long-term cardiometabolic morbidity in young adults with classic 21-hydroxylase deficiency congenital adrenal hyperplasia
Beatrice Righi, Salma R. Ali, Jillian Bryce, Jeremy W. Tomlinson, Walter Bonfig, Federico Baronio, Eduardo C. Costa, Guilherme Guaragna-Filho, Guy T’Sjoen, Martine Cools, Renata Markosyan, Tania A. S. S. Bachega, Mirela C. Miranda, Violeta Iotova, Henrik
Endocrine.2023; 80(3): 630. CrossRef
Serum steroid profile captures metabolic phenotypes in adults with classic congenital adrenal hyperplasia
Chang Ho Ahn, Jaeyoon Shim, Han Na Jang, Young Ah Lee, Sang-Won Lee, Man Ho Choi, Jung Hee Kim
The Journal of Steroid Biochemistry and Molecular Biology.2023; 234: 106374. CrossRef
Long‐term health consequences of congenital adrenal hyperplasia
Riccardo Pofi, Xiaochen Ji, Nils P. Krone, Jeremy W. Tomlinson
Clinical Endocrinology.2023;[Epub] CrossRef
Hyperandrogenism and Cardiometabolic Risk in Pre- and Postmenopausal Women—What Is the Evidence?
Angelica Lindén Hirschberg
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef
Predictors of Cardiovascular Morbidities in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia
Suranut Charoensri, Richard J Auchus
The Journal of Clinical Endocrinology & Metabolism.2023;[Epub] CrossRef
Long-Term Outcomes of Congenital Adrenal Hyperplasia
Anna Nordenström, Svetlana Lajic, Henrik Falhammar
Endocrinology and Metabolism.2022; 37(4): 587. CrossRef

Brief Report

Thyroid
Outcomes and Predictors of 30-Day Readmissions for Hyperthyroidism: A Nationwide Study: Michael Salim, Zain El-amir, Asim Kichloo, Farah Wani, Ehizogie Edigin, Hafeez Shaka; Endocrinol Metab. 2021;36(6):1307-1311. Published online December 1, 2021; DOI: https://doi.org/10.3803/EnM.2021.1190

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Abstract PDF Supplementary Material PubReader ePub: Hyperthyroidism is associated with an elevated risk of cardiovascular events and worse hospital outcomes. The Nationwide Readmissions Database (NRD) 2018 was used to determine the characteristics of 30-day readmission in patients with hyperthyroidism. The 30-day all-cause readmission rate for hyperthyroidism was 10.3%. About 21.7% had hyperthyroidism as the principal diagnosis on readmission. Readmissions were associated with an increased odds of inpatient mortality (odds ratio, 7.04; 95% confidence interval [CI], 3.97 to 12.49), length of stay (5.2 days vs. 4.0 days; 95% CI, 0.7 to 1.8), total hospital charges, and cost of hospitalizations. Independent predictors of 30-day all-cause readmissions included Charlson Comorbidity Index ≥3 (adjusted hazard ratio [aHR], 1.76; 95% CI, 1.15 to 2.71), discharge against medical advice (aHR, 2.30; 95% CI, 1.50 to 3.53), protein-energy malnutrition (aHR, 1.54; 95% CI, 1.15 to 2.07), and atrial fibrillation (aHR, 1.41; 95% CI, 1.11 to 1.79). Aggressive but appropriate monitoring is warranted in patients with hyperthyroidism to prevent readmissions.

Original Articles

Diabetes, Obesity and Metabolism Big Data Articles (National Health Insurance Service Database)
Cardiovascular Outcomes of Obesity According to Menopausal Status: A Nationwide Population-Based Study: Bo Kyung Koo, Sang-Hyun Park, Kyungdo Han, Min Kyong Moon; Endocrinol Metab. 2021;36(5):1029-1041. Published online October 21, 2021; DOI: https://doi.org/10.3803/EnM.2021.1197

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Background
We estimated the effect of obesity on the incidence of cardiovascular disease (CVD) and mortality in women according to menopausal status.
Methods
Women aged 40 to 69 years under routine health check-ups provided by the National Health Insurance Service in 2009 were followed up till 2018 (n=2,208,559).
Results
In premenopausal women, a significant increment of mortality rate was found in underweight and obesity class II (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.31 to 1.67; and HR, 1.25; 95% CI, 1.12 to 1.39) compared to normal body mass index (BMI); overweight and obesity class I did not affect mortality rate. In postmenopausal women, obesity as well as overweight status reduced the risk of mortality compared to normal BMI (HR, 0.86; 95% CI, 0.83 to 0.88; and HR, 0.84; 95% CI, 0.82 to 0.86). By contrast, there was a linear association between CVD and BMI above the normal range irrespective of menopausal status, which was attenuated in diabetic women.
Conclusion
The current study replicated the J-shaped relationship between BMI and mortality, being more prominent in the postmenopausal group. The risk of CVD was linearly increased as BMI was increased above the normal range irrespective of menopausal status.

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A nationwide cohort study on diabetes severity and risk of Parkinson disease
Kyungdo Han, Bongsung Kim, Seung Hwan Lee, Mee Kyoung Kim
npj Parkinson's Disease.2023;[Epub] CrossRef
Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus
Min Kyong Moon, Junghyun Noh, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong
Diabetes & Metabolism Journal.2023; 47(1): 45. CrossRef
The effect of menopause on cardiovascular risk factors according to body mass index in middle-aged Korean women
Do Kyeong Song, Young Sun Hong, Yeon-Ah Sung, Hyejin Lee, Aysha Almas
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Low‐quality muscle mass rather than normal‐quality muscle mass determines fibrosis progression in biopsy‐proven NAFLD
Yun Kyu Lee, Bo Kyung Koo, Sae Kyung Joo, Dong Hyeon Lee, Heejoon Jang, Jee Won Chai, Myoung Seok Lee, Si Won Jang, Young Ho So, Jeong Hwan Park, Mee Soo Chang, Won Kim
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Diabetes severity is strongly associated with the risk of active tuberculosis in people with type 2 diabetes: a nationwide cohort study with a 6-year follow-up
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Mee Kyoung Kim, Kyungdo Han, Bongsung Kim, Jinyoung Kim, Hyuk-Sang Kwon
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Bo Kyung Koo
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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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Thyroxine changes in COVID-19 pandemic: A systematic review and meta-analysis
Ziqi Li, Pengwei Hou, Shuwen Mu, Renzhi Wang, Hui Miao, Ming Feng, He Wang, Wentai Zhang, Yihao Chen, Tianshun Feng, Shousen Wang, Yi Fang
Frontiers in Endocrinology.2023;[Epub] CrossRef
The Influence of SARS-CoV-2 Infection on the Thyroid Gland
Aleksandra Piekarska, Marta Góral, Marta Kozula, Aleksandra Jawiarczyk-Przybyłowska, Katarzyna Zawadzka, Marek Bolanowski
Biomedicines.2023; 11(2): 614. CrossRef
Thyroid Function Abnormalities and Outcomes in Hospitalized Patients with COVID-19 Infection: A Cross-Sectional Study
Deepika Patel, Dukhabandhu Naik, Sadishkumar Kamalanathan, Kadhiravan Tamilarasu, Jayaprakash Sahoo, Ayan Roy, Chandhana Merugu, Varun Suryadevara
Hormone and Metabolic Research.2023; 55(03): 169. CrossRef
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
Transient low T3 syndrome in patients with COVID-19: a new window for prediction of disease severity
Mingyao Zhong, Yue Gao, Hongling Hu, Xuan Zhu, Lulu Gan, Ling Li, Cheng Xiang, Yimin Yan, Zhe Dai
Frontiers in Endocrinology.2023;[Epub] CrossRef
The Association Between COVID-19 and Thyroxine Levels: A Meta-Analysis
Yiru Chen, Xiuneng Li, Yu Dai, Jingjing Zhang
Frontiers in Endocrinology.2022;[Epub] CrossRef
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
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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
Frontiers in Endocrinology.2022;[Epub] CrossRef
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
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Low triiodothyronine syndrome is associated with stroke‐associated pneumonia
Huijun Chen, Minjie Xu, Yezhi Huang, Jincai He, Wenwei Ren
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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
Endocrine.2022; 80(1): 86. CrossRef
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
Life.2022; 12(12): 2014. CrossRef
COVID-19 and thyroid function: What do we know so far?
Camila Lüdke Rossetti, Juliana Cazarin, Fabio Hecht, Fabyan Esberard de Lima Beltrão, Andrea Cláudia Freitas Ferreira, Rodrigo Soares Fortunato, Helton Estrela Ramos, Denise Pires de Carvalho
Frontiers in Endocrinology.2022;[Epub] CrossRef

Diabetes, Obesity and Metabolism
High Fibrosis-4 Index Is Related with Worse Clinical Outcome in Patients with Coronavirus Disease 2019 and Diabetes Mellitus: A Multicenter Observational Study: Sung-Woo Kim, Jae-Han Jeon, Jun Sung Moon, Mi Kyung Kim; Endocrinol Metab. 2021;36(4):800-809. Published online August 20, 2021; DOI: https://doi.org/10.3803/EnM.2021.1040

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Background
Based on recent evidence on the importance of the presence of diabetes mellitus (DM) and fibrosis-4 (FIB-4) index in coronavirus disease 2019 (COVID-19) mortality, we analyzed whether these factors could additively predict such mortality.
Methods
This multicenter observational study included 1,019 adult inpatients admitted to university hospitals in Daegu. The demographic and laboratory findings, mortality, prevalence of severe disease, and duration of quarantine were compared between patients with and without DM and/or a high FIB-4 index. The mortality risk and corresponding hazard ratio (HR) were analyzed using the Kaplan-Meier method and Cox proportional hazard models.
Results
The patients with DM (n=217) exhibited significantly higher FIB-4 index and mortality compared to those without DM. Although DM (HR, 2.66; 95% confidence interval [CI], 1.63 to 4.33) and a high FIB-4 index (HR, 4.20; 95% CI, 2.21 to 7.99) were separately identified as risk factors for COVID-19 mortality, the patients with both DM and high FIB-4 index had a significantly higher mortality (HR, 9.54; 95% CI, 4.11 to 22.15). Higher FIB-4 indices were associated with higher mortality regardless of DM. A high FIB-4 index with DM was more significantly associated with a severe clinical course with mortality (odds ratio, 11.24; 95% CI, 5.90 to 21.41) than a low FIB-4 index without DM, followed by a high FIB-4 index alone and DM alone. The duration of quarantine and hospital stay also tended to be longer in those with both DM and high FIB-4 index.
Conclusion
Both DM and high FIB-4 index are independent and additive risk factors for COVID-19 mortality.

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COVID-19 and hepatic injury: Diversity and risk assessment
Fares E M Ali, Mostafa K Abd El-Aziz, Mahmoud M Ali, Osama M Ghogar, Adel G Bakr
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Differential Effects of COVID-19 Hospitalization on the Trajectory of Liver Disease Progression
Dilara Hatipoğlu, Connor Mulligan, Jeffrey Wang, Juan Peticco, Reid Grinspoon, Sanjay Gadi, Camilla Mills, Jay Luther, Raymond T. Chung
Gastro Hep Advances.2023; 2(4): 480. CrossRef
Association of non-alcoholic fatty liver and metabolic-associated fatty liver with COVID-19 outcomes: A systematic review and meta-analysis
Gowthami Sai Kogilathota Jagirdhar, Rakhtan K Qasba, Harsha Pattnaik, Kaanthi Rama, Akshat Banga, Shiva Teja Reddy, Anna Carolina Flumignan Bucharles, Rahul Kashyap, Praveen Reddy Elmati, Vikas Bansal, Yatinder Bains, Theodore DaCosta, Salim Surani
World Journal of Gastroenterology.2023; 29(21): 3362. CrossRef
COVID-19 and Fatty Liver Disorders
Maria Guarino, Valentina Cossiga, Francesco Cutolo, Maria Attanasio, Raffaele Lieto, Filomena Morisco
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Tiangui Li, Peng Wang, Xiao Gong, Weelic Chong, Yang Hai, Chao You, Juan Kang, Fang Fang, Yu Zhang
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Brief Report

Diabetes, Obesity and Metabolism
Dipeptidyl Peptidase-4 Inhibitors and COVID-19-Related Deaths among Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Observational Studies: Dimitrios Patoulias, Michael Doumas; Endocrinol Metab. 2021;36(4):904-908. Published online July 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.1048

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The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.

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