Thyroid hormones play an important physiological role in maintaining adult bone structure and strength. Consequently, thyroid dysfunction is related to skeletal outcomes. Overt hyperthyroidism is an established cause of high bone turnover with accelerated bone loss, leading to osteoporosis and increased fracture risk. Hyperthyroidism induced by thyroid-stimulating hormone-suppressive therapy in patients with differentiated thyroid cancer is a cause of secondary osteoporosis. In contrast, there is a lack of evidence on the negative impact of hypothyroidism on bone health. Considering the clinical updates on the importance of bone health in thyroid dysfunction, the Task Force from the Clinical Practice Guidelines Development Committee of the Korean Thyroid Association recently developed a position statement on the evaluation and management of bone health of patients with thyroid diseases, particularly focused on endogenous hyperthyroidism and thyroid-stimulating hormone-suppressive therapy-associated hyperthyroidism in patients with differentiated thyroid cancer. Herein, we review the Korean Thyroid Association’s position statement on the evaluation and management of bone health associated with thyroid diseases.
Type II deiodinase (DIO2) is thought to provide triiodothyronine (T3) to the nucleus to meet intracellular needs by deiodinating the prohormone thyroxine. DIO2 is expressed widely in many tissues and plays an important role in a variety of physiological processes, such as controlling T3 content in developing tissues (e.g., bone, muscles, and skin) and the adult brain, and regulating adaptive thermogenesis in brown adipose tissue (BAT). However, the identification and cloning of DIO2 have been challenging. In recent years, several clinical investigations have focused on the Thr92Ala polymorphism, which is closely correlated with clinical syndromes such as type 2 diabetes, obesity, hypertension, and osteoarthritis. Thr92Ala-DIO2 was also found to be related to bone and neurodegenerative diseases and tumors. However, relatively few reviews have synthesized research on individual deiodinases, especially DIO2, in the past 5 years. This review summarizes current knowledge regarding the physiological functions of DIO2 in thyroid hormone signaling and adaptive thermogenesis in BAT and the brain, as well as the associations between Thr92Ala-DIO2 and bone and neurodegenerative diseases and tumors. This discussion is expected to provide insights into the physiological functions of DIO2 and the clinical syndromes associated with Thr92Ala-DIO2.
Caloric restriction (CR) is now a popular lifestyle choice due to its ability in experimental animals to improve lifespan, reduce body weight, and lessen oxidative stress. However, more and more emerging evidence suggests this treatment requires careful consideration because of its detrimental effects on the skeletal system. Experimental and clinical studies show that CR can suppress bone growth and raise the risk of fracture, but the specific mechanisms are poorly understood. Reduced mechanical loading has long been thought to be the primary cause of weight loss-induced bone loss from calorie restriction. Despite fat loss in peripheral depots with calorie restriction, bone marrow adipose tissue (BMAT) increases, and this may play a significant role in this pathological process. Here, we update recent advances in our understanding of the effects of CR on the skeleton, the possible pathogenic role of BMAT in CR-induced bone loss, and some strategies to mitigate any potential side effects on the skeletal system.
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.
Background Ferroptosis, which is caused by an iron-dependent accumulation of lipid hydroperoxides, is a type of cell death linked to diabetic kidney disease (DKD). Previous research has shown that fatty acid binding protein 4 (FABP4) is involved in the regulation of ferroptosis in diabetic retinopathy. The present study was constructed to explore the role of FABP4 in the regulation of ferroptosis in DKD.
Methods We first detected the expression of FABP4 and proteins related to ferroptosis in renal biopsies of patients with DKD. Then, we used a FABP4 inhibitor and small interfering RNA to investigate the role of FABP4 in ferroptosis induced by high glucose in human renal proximal tubular epithelial (HG-HK2) cells.
Results In kidney biopsies of DKD patients, the expression of FABP4 was elevated, whereas carnitine palmitoyltransferase-1A (CP-T1A), glutathione peroxidase 4, ferritin heavy chain, and ferritin light chain showed reduced expression. In HG-HK2 cells, the induction of ferroptosis was accompanied by an increase in FABP4. Inhibition of FABP4 in HG-HK2 cells changed the redox state, sup-pressing the production of reactive oxygen species, ferrous iron (Fe2+), and malondialdehyde, increasing superoxide dismutase, and reversing ferroptosis-associated mitochondrial damage. The inhibition of FABP4 also increased the expression of CPT1A, reversed lipid deposition, and restored impaired fatty acid β-oxidation. In addition, the inhibition of CPT1A could induce ferroptosis in HK2 cells.
Conclusion Our results suggest that FABP4 mediates ferroptosis in HG-HK2 cells by inhibiting fatty acid β-oxidation.
Diabetes, obesity and metabolism Big Data Articles (National Health Insurance Service Database)
Background Coronavirus disease 2019 (COVID-19) can cause various extrapulmonary sequelae, including diabetes. However, it is unclear whether these effects persist 30 days after diagnosis. Hence, we investigated the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) in the post-acute phase of COVID-19.
Methods This cohort study used data from the Health Insurance Review and Assessment Service, a representative national healthcare database in Korea. We established a cohort of 348,180 individuals diagnosed with COVID-19 without a history of diabetes between January 2020 and September 2021. The control group consisted of sex- and age-matched individuals with neither a history of diabetes nor COVID-19. We assessed the hazard ratios (HR) of newly diagnosed T2DM patients with COVID-19 compared to controls, adjusted for age, sex, and the presence of hypertension and dyslipidemia.
Results In the post-acute phase, patients with COVID-19 had an increased risk of newly diagnosed T2DM compared to those without COVID-19 (adjusted HR, 1.30; 95% confidence interval [CI], 1.27 to 1.33). The adjusted HRs of non-hospitalized, hospitalized, and intensive care unit-admitted patients were 1.14 (95% CI, 1.08 to 1.19), 1.34 (95% CI, 1.30 to 1.38), and 1.78 (95% CI, 1.59 to 1.99), respectively. The risk of T2DM in patients who were not administered glucocorticoids also increased (adjusted HR, 1.29; 95% CI, 1.25 to 1.32).
Conclusion COVID-19 may increase the risk of developing T2DM beyond the acute period. The higher the severity of COVID-19 in the acute phase, the higher the risk of newly diagnosed T2DM. Therefore, T2DM should be included as a component of managing long-term COVID-19.
Adrenal gland Big Data Articles (National Health Insurance Service Database)
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
Chaiho Jeong, Jeongmin Lee, Jinyoung Kim, Jeonghoon Ha, Kwanhoon Jo, Yejee Lim, Mee Kyoung Kim, Hyuk-Sang Kwon, Tae-Seo Sohn, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek
Endocrinol Metab. 2023;38(2):260-268. Published online April 27, 2023
Background Persistence with denosumab in male patients has not been adequately investigated, although poor denosumab persistence is associated with a significant risk of rebound vertebral fractures.
Methods We retrospectively evaluated 294 Korean male osteoporosis patients treated with denosumab at three medical centers and examined their persistence with four doses of denosumab injection over 24 months of treatment. Persistence was defined as the extent to which a patient adhered to denosumab treatment in terms of the prescribed interval and dose, with a permissible gap of 8 weeks. For patients who missed their scheduled treatment appointment(s) during the follow-up period (i.e., no-shows), Cox proportional regression analysis was conducted to explore the factors associated with poor adherence. Several factors were considered, such as age, prior anti-osteoporotic drug use, the treatment provider’s medical specialty, the proximity to the medical center, and financial burdens of treatment.
Results Out of 294 male patients, 77 (26.2%) completed all four sequential rounds of the denosumab treatment. Out of 217 patients who did not complete the denosumab treatment, 138 (63.6%) missed the scheduled treatment(s). Missing treatment was significantly associated with age (odds ratio [OR], 1.03), prior bisphosphonate use (OR, 0.76), and prescription by non-endocrinologists (OR, 2.24). Denosumab was stopped in 44 (20.3%) patients due to medical errors, in 24 (11.1%) patients due to a T-score improvement over –2.5, and in five (2.3%) patients due to expected dental procedures.
Conclusion Our study showed that only one-fourth of Korean male osteoporosis patients were fully adherent to 24 months of denosumab treatment.
Background Although an inverse association between the N-terminal prohormone brain natriuretic peptide (NT-proBNP) and obesity exists, only few major studies have assessed the association between NT-proBNP levels and skeletal muscle mass in asymptomatic healthy adults. Therefore, this cross-sectional study was conducted.
Methods We assessed participants who underwent health examinations at Kangbuk Samsung Hospital in South Korea from January 2012 to December 2019. Appendicular skeletal muscle mass was measured using a bioelectrical impedance analyzer, and the skeletal muscle mass index (SMI) was calculated. Participants were divided into the control, mildly low skeletal muscle mass (LMM) (−2 standard deviation [SD] < SMI ≤−1 [SD]), and severely LMM groups (SD ≤−2) based on their SMI. The association between elevated NT-proBNP level (≥125 pg/mL) and skeletal muscle mass was assessed using multivariable logistic regression analysis with adjustment for confounding factors.
Results This study enrolled 15,013 participants (mean age, 37.52±9.52; men, 54.24%; control, n=12,827; mildly LMM, n=1,998; severely LMM, n=188). Prevalence of elevated NT-proBNP was higher in mildly and severely LMM groups than in the control group (control, 1.19%; mildly LMM, 1.4%; severely LMM, 4.26%; P=0.001). The adjusted odds ratio (OR) of elevated NT-proBNP was significantly higher in severely LMM (OR, 2.87; 95% confidence interval [CI], 1.3 to 6.37) than in control (OR, 1.00; reference) or mildly LMM groups (OR, 1.24; 95% CI, 0.81 to 1.89).
Conclusion Our results showed that NT-proBNP elevation were more prevalent in participants with LMM. In addition, our study showed an association between skeletal muscle mass and NT-proBNP level in a relatively young and healthy adult population.
This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.