Endocrine journal最新文献

Gestational diabetes mellitus (GDM) is closely associated with adverse fetal outcomes. Maternal underweight is associated with low birth weight (LBW) and small for gestational age (SGA). Despite the high proportion of underweight women with GDM in Asian populations, evidence on the association between underweight and the risk of LBW or SGA in GDM is limited and inconsistent. The aim of this study is to investigate this issue in Japanese women with GDM. We enrolled 641 women with GDM at the Hamamatsu University Hospital. Data on maternal body mass index (BMI), and fetal birth weight (including LBW and SGA) were collected from medical records. Logistic regression analysis was used to estimate crude odds ratios (ORs) and 95% confidence intervals (CIs) for the association between underweight and fetal birth weight. At pre-pregnancy, the prevalences of underweight (BMI <18.5 kg/m²), obesity (BMI ≥25 kg/m²), SGA, and LBW were 13.5%, 26.4%, 7.2%, and 13.3%, respectively. Pre-pregnancy underweight was independently and positively associated with SGA (adjusted OR: 2.56, 95% CI: 1.15-5.46) and LBW (adjusted OR: 3.07, 95% CI: 1.31-7.13). Obesity at age 20 but not at pre-pregnancy was independently and inversely associated with SGA (adjusted OR: 0.11, 95% CI: 0.01-0.88). In conclusion, among Japanese women with GDM, pre-pregnancy underweight, but not underweight at age 20, was significantly associated with SGA and LBW. On the other hand, obesity at age 20 was independently and inversely associated with SGA.

Liddle syndrome is a rare monogenic form of hypertension that can be misdiagnosed as essential hypertension or, in the context of obesity, be mistaken for metabolic syndrome. This case report describes a 19-year-old Chinese male with obesity, hypertension, insulin resistance, impaired glucose tolerance, dyslipidemia, and hyperuricemia-a classic presentation of metabolic syndrome. However, the early onset of severe hypertension and a strong family history prompted further investigation. Laboratory evaluation revealed mild hypokalemia, suppressed plasma renin activity and normal aldosterone levels, raising suspicion for Liddle syndrome. Whole exome sequencing was performed to explore monogenic causes of hypertension, which identified a novel heterozygous frameshift variant in the SCNN1B gene (NM_000336.3:c.1711_1713delinsAA). This variant leads to the loss of the PY motif-a functionally critical and indispensable structural element of the epithelial sodium channel (ENaC) β-subunit-and was classified as likely pathogenic in accordance with the ACMG/AMP guidelines. The patient was initiated on targeted therapy with amiloride, which rapidly normalized his blood pressure and hypokalemia, thereby confirming the diagnosis. This case highlights the diagnostic challenge of distinguishing monogenic hypertension from metabolic syndrome in young, obese individuals. It emphasizes the necessity of systematically investigating for secondary causes in this population. Key steps include obtaining a family history, screening for hypokalemia, evaluating renin and aldosterone levels, and assessing the response to standard therapy. Identifying a rare disorder like Liddle syndrome allows for a paradigm shift in management from empiric to targeted treatment, which is essential for preventing the debilitating long-term sequelae of chronic hypertension.

Trans-sellar encephalocele (TSE) is a rare congenital anomaly of the cranial base characterized by herniation of intracranial contents through the sellar floor. Although clinical presentations are diverse, the prevalence and characteristics of endocrine dysfunction due to hypothalamic-pituitary involvement are unclear. This study aimed to clarify endocrine function in patients with TSE and emphasized the importance of multidisciplinary management. Here, we present two adult cases of TSE with progressive visual impairment and evident pituitary hormone deficiencies, and conducted a comprehensive literature review to investigate endocrine function and its postoperative outcomes in patients with TSE. Both cases presented with growth hormone (GH) deficiency and diabetes insipidus and showed deterioration in GH secretion, which was postoperatively assessed using dynamic testing, despite minimal or no direct manipulation of the pituitary gland. In a literature review, 87 cases from 41 case reports and 3 review articles were identified. Among the 87 cases, pituitary dysfunction was identified in 41 (47.1%); however, detailed hormonal assessments were performed in only 25 (28.7%) of the cases. In 33 cases with documented preoperative and postoperative endocrine status, pituitary function worsened in 16 (48.5%), improved in 6 (18.2%), and remained unchanged in 11 (33.3%) postoperatively. Pituitary dysfunction occurred in nearly half of patients with TSE, but was frequently underdiagnosed due to inadequate endocrine assessment. Comprehensive endocrine evaluation, including dynamic GH testing, performed at diagnosis and perioperatively, may be essential in optimizing patient outcomes.

Osilodrostat is an oral steroidogenesis inhibitor used in the treatment of hypercortisolism. It works by inhibiting 11-beta-hydroxylase, a key enzyme in cortisol synthesis. As a consequence of drug action, adrenal insufficiency can be observed in about 40% of patients. Although this effect has been accepted as a consequence of therapy, recent reports suggest adrenal insufficiency can persist even after discontinuation of osilodrostat. We present the case of a 74-year-old female patient who developed prolonged adrenal insufficiency after withdrawal of osilodrostat. The patient was diagnosed with ectopic ACTH-dependent Cushing's syndrome and underwent radiotherapy for a primary lesion located in the anterior mediastinum. During treatment, osilodrostat was introduced (2 to 4 mg/d), and adrenal insufficiency developed within four weeks. Hydrocortisone (intermittently dexamethasone) replacement therapy was initiated, and over time, undetectable morning cortisol levels continued. After de-escalating the osilodrostat dose, the drug was withdrawn 15 months after initiation. Despite being off the drug for 11 months, the patient with adrenal insufficiency (morning serum cortisol: 37.2 nmol/L), still requires hydrocortisone substitution. The underlying mechanism of prolonged adrenal insufficiency after osilodrostat discontinuation remains unclear. It is unknown whether this is due to permanent inhibition of 11-beta-hydroxylase or interference at another step in steroidogenesis. Factors such as treatment duration, dose, or individual sensitivity may play a role, but other mechanisms, such as an adrenolytic effect, should also be considered. We expect an increase of similar cases, which we believe will lead to further research to better understand the mechanisms behind prolonged adrenocortical blockade after osilodrostat discontinuation.

Few studies have investigated the distribution of blood pressure (BP) and associated factors in pediatric patients with X-linked hypophosphatemic rickets (XLH). We analyzed snapshot baseline data from the SUNFLOWER study, a longitudinal observational cohort study of patients with XLH in Japan and South Korea (NCT03745521/UMIN000031605). We used data from pediatric participants aged 5-17 years who were 120-189.9 cm (males) and 120-179.9 cm (females) in height and had a history of conventional treatment. Systolic and diastolic BP (SBP and DBP, respectively) were categorized into percentile ranks based on age, sex, and height. Ordinal logistic regression analyses were performed to investigate the association between BP and exposure factors, including estimated glomerular filtration rate, serum intact parathyroid hormone levels, serum intact fibroblast growth factor 23 levels, urinary calcium/creatinine ratio, and body mass index standard deviation score (BMI-SDS). Forty-five participants were eligible for the subgroup analysis. Of these, 44 were evaluated after one patient with missing BP data was excluded. After height adjustment, three patients (6.8%) were at or above the 95th percentile for SBP, and five (11.4%) were at or above the 95th percentile for DBP. Regarding age adjustment, one patient (2.3%) was at or above the 95th percentile for SBP and three (6.8%) were at or above the 95th percentile for DBP. In the association analysis, age- and height-adjusted BP was positively correlated with BMI-SDS. These results suggest that some pediatric patients with XLH exhibit high BP and that a high BMI-SDS may be a risk factor.

The impact of changes in obesity-related parameters on kidney functions is unclear. To evaluate the association of body weight (BW) and waist circumference (WC) changes with estimated glomerular filtration rate (eGFR) and proteinuria in obese individuals, we conducted retrospective analysis of the Japan Specific Health Checkup cohort of 664,926 participants (Japanese residents aged 40-74 years) from 2008 to 2011. Participants were classified into nine groups based on BW and WC changes from baseline. Sex differences were stratified. Generalized estimating equations were used to evaluate eGFR changes within each group and the effect of BW or WC changes on eGFR. In a similar manner, the impact of BW and WC changes on the incidence of proteinuria was measured. As a result, total of 20,326 participants with a body mass index of ≥25 kg/m² and available baseline data, 1-year BW and WC, and 4-year eGFR measurements were included in the analysis. The eGFR slope was -0.59 (95% confidence interval [CI], -0.66 to -0.51). At a threshold change of approximately 5%, compared to the group with unchanged BW and WC, males with decreased BW and WC had improved eGFR at 3 years (1.75; 95% CI, 0.49 to 3.02). Contrastingly, females with increased BW and WC had worsened eGFR at 3 years (-3.44; 95% CI, -6.40 to -0.47). These trends were similar when the thresholds were changed or when the outcome was proteinuria. In conclusion, males with decreasing WC and BW had improved kidney function. Future studies should evaluate specific lifestyle factors.

This review summarizes recent basic and clinical advances in cortisol-producing adrenal tumors, including Cushing's syndrome (CS) and mild autonomous cortisol secretion (MACS). Recent clinical reports on the epidemiology and diagnostic challenges of CS and MACS are presented. The review highlights recent progress in understanding the molecular pathogenesis of adrenal cortisol-producing tumors. A major recent finding is the discovery of loss-of-function mutation in KDM1A as the underlying cause of the long-standing mystery of diet-dependent CS in primary bilateral macronodular adrenal hyperplasia (PBMAH). Furthermore, the recent clarification of the molecular basis of cortisol-producing adenomas (CPAs) has deepened our understanding of the functional differences in the autonomicity of CPAs between overt CS and MACS. These findings made us reconsider the categorization of adrenal tumors, including non-functioning adrenal tumors (NFATs). Finally, we reviewed the rarely discussed but critical condition of immune reconstitution inflammatory syndrome (IRIS) following CS treatment, including a case from our own experience. IRIS should be kept in mind when initiating treatment for CS patients with extremely high serum cortisol levels.

Pheochromocytomas and paragangliomas are characterized by two key features: endocrine disorders with excessive catecholamine secretion and a hereditary or metastatic nature, making early diagnosis and treatment crucial. This clinical practice guideline is a revision of the 2018 edition, which considers recent advances in clinical practice and changes to the health insurance coverage in Japan. Patients presenting with symptoms such as palpitations, headaches, hypertension, or abdominal tumors should undergo screening and confirmation with measurement of fractionated catecholamines and their metabolites in the blood and urine. When the tumor is located in the adrenal glands, it is diagnosed as a pheochromocytoma; when it is located outside the adrenal gland and confirmed by ¹²³I-MIBG scintigraphy or ¹⁸F-FDG PET, it is diagnosed as a paraganglioma. Treatment begins with inhibiting catecholamine action using α-blockers, and if that is insufficient, metyrosine is used in combination, followed by laparoscopic tumor removal. Given the metastatic potential, long-term postoperative follow-up is essential. Even in cases of metastasis, tumor debulking should be considered. Treatment options are selected based on the amount of remaining tumor, symptom severity, and lesion progression, including CVD chemotherapy or radionuclide therapies such as ¹³¹I-MIBG or ¹⁷⁷Lu-DOTATATE. Genetic testing guides the management of different variants, and significant progress has been made in molecularly targeted drug trials. Therefore, further advances in individualized and long-term management are required.

In the liver, hepatocyte death occurs during the regeneration process following injury. While hepatocyte death triggers regeneration through hepatocyte proliferation in the non-steatotic liver, it impairs this process in the steatotic liver. Both the number and mode of hepatocyte death during regeneration change in the steatotic liver, affecting regeneration and thereby contributing to the progression of acute liver injury and metabolic dysfunction-associated steatotic liver disease (MASLD). Apoptosis, a non-inflammatory mode of cell death, predominantly occurs during liver regeneration. As hepatic steatosis progresses, sporadic and scattered apoptotic cell death increases, leading to delayed regeneration. In severe steatotic livers undergoing regeneration, the mode of cell death shifts to pro-inflammatory necroptosis. This transition leads to inflammation around the dead hepatocytes, resulting in zonal hepatocyte death and further impairing regeneration, thus exacerbating acute liver injury and MASLD. The integrated stress response (ISR), mediated by phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2α), plays a crucial role in regulating hepatocyte death during steatotic liver regeneration. The ISR-induced transcription factor C/EBP homologous protein (CHOP) promotes apoptosis, thereby delaying regeneration. When ISR is further enhanced, activating transcription factor 3 (ATF3) is upregulated, inducing the expression of receptor-interacting protein kinase 3 (RIPK3), which shifts cell death mode from apoptosis to necroptosis. While treatments for MASLD targeting apoptosis have shown limited success, future therapies targeting necroptosis and its regulatory molecules may provide novel therapeutic strategies.

This study aimed to investigate the association between body composition and lung function. Metabolic body composition can independently predict the risk of poor lung function. Accordingly, this cross-sectional observational study included adults aged ≥18 years who attended annual health examinations at Xiamen Chang-Gung Hospital from 2013 to 2016. The study evaluated the association between lung function and metabolic body composition, after correcting for possible influencing factors. Males had a higher body mass index and waist-to-hip ratio and a higher prevalence of smoking and drinking histories. Additionally, men showed significantly higher mean arterial pressure, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, insulin, and homeostasis model assessment for insulin resistance values than those of women (all p < 0.001). The proportion of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) was also higher in men than in women (17.91% vs. 25.20% and 11.28% vs. 13.67%, respectively). However, female participants demonstrated better pulmonary function. The prevalence of restrictive lung disease (RLD) was substantially higher in men than in women. The study findings suggest that MUO, and to a lesser extent, metabolic obesity with normal weight (MONW), are independent risk factors for RLD. These results imply that MUO, and to a lesser extent, MONW, may serve as potential screening markers for preclinical RLD in annual health checkups.