Clinical Endocrinology最新文献

Background and aims: Prediabetes-a reversible metabolic condition characterized by impaired fasting glucose, elevated HbA1c, or reduced glucose tolerance-is a major precursor to type 2 diabetes mellitus (T2DM), especially in high-risk populations like India. This review evaluates the impact of culturally tailored lifestyle interventions in preventing type 2 diabetes in adults with prediabetes.

Methods: This PRISMA-compliant systematic review (PROSPERO: CRD420251085667) included RCTs from 2020 to 2025 on adults (≥18 years) with prediabetes. It assessed lifestyle interventions-diet, exercise, yoga, and behavioral support-using the Jadad scale and Downs & Black checklist.

Results: Six high-quality RCTs demonstrated significant improvements in glycemic parameters, cardiometabolic profiles, and reductions in diabetes incidence. Yoga-based protocols yielded notable declines in HbA1c and stress biomarkers. Dietary counseling and formula diets achieved normoglycemia and metabolic benefits independent of weight loss. Long-duration interventions also reduced frailty and disability risks, enhancing overall health outcomes.

Conclusions: Culturally adapted lifestyle interventions show strong efficacy and scalability in reversing prediabetes and reducing progression to T2DM. Integration of such strategies into national diabetes prevention programs may enhance sustainable metabolic health and address the unique needs of high-risk populations.

Objective: Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease that requires long-term glycemic control. The long-term real-world evidence for glucagon-like peptide-1 receptor agonists remains limited. This study aimed to evaluate the sustained glycemic and weight-lowering effects of dulaglutide in patients with T2DM who had maintained therapy for at least 3 years.

Methods: This retrospective cohort study analyzed 403 patients with T2DM who were treated continuously with weekly doses of dulaglutide for ≥ 3 years between 2016 and 2023 at a single tertiary hospital. Baseline and follow-up data on glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), and body weight were also assessed.

Results: The participants had a mean age of 60.0 years, with a mean diabetes duration of 17.4 years. Over a mean follow-up of 4.3 years, HbA1c decreased from 8.7% (72 mmol/mol) to 7.6% (60 mmol/mol), reflecting a mean reduction of 1.1% (12 mmol/mol) (p < 0.001), and body weight decreased by 2.9 kg (p < 0.001). Baseline HbA1c level was the strongest predictor of glycemic improvement.

Conclusions: Dulaglutide provided durable improvements in glycemic control and weight reduction for more than 3 years, even in patients with long-standing T2DM and comorbidities. These results support its role as a long-term treatment option in real-world clinical practice.

Context: Sheehan's syndrome (SS) is a rare cause of hypopituitarism. Data on skeletal health in patients with this condition is limited and predictors of low bone mineral density (BMD) are not well elucidated. We aimed to explore hormonal profile and BMD in a large multicentric cohort of treated SS patients.

Design and patients: The study recruited patients with SS on stable hormone replacement (n = 110) and healthy female controls (n = 102). The hormonal profile (cortisol, DHEAS, T4, TSH, prolactin, IGF1) was analyzed. Bone turnover markers (P1NP, β-CTX) were estimated by electrochemiluminescence assay. BMD was evaluated using DXA. Prevalence and predictors of low BMD were assessed.

Results: The cohort comprised 110 patients with SS with a mean age of 45.3 ± 10.5 years and a delay of 7.9 ± 6.3 years from disease onset to diagnosis. Patients were on glucocorticoid (94.6%) and levothyroxine (90.5%) replacement, with prior exposure to estrogen-progestin (66.7%). Bone turnover markers were not significantly different between the two groups. Low BMD (osteopenia/osteoporosis) was prevalent in a significantly greater proportion of the cases as compared to controls at the lumbar spine (94% vs 47%) and femoral neck (80% vs 36%). The most important predictor of low BMD at the lumbar spine was the length of delay prior to diagnosis (OR 1.48 (95% CI 1.002-2.206), p = 0.04).

Conclusion: SS is characterized by a high prevalence of multiple pituitary hormone deficiencies, including hypoprolactinaemia. Low BMD is highly prevalent in SS compared to age, and BMI-matched controls. Despite adequate relevant hormone replacement therapy, a longer delay in diagnosing is the major determinant of low BMD in patients with SS.

Objective: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is a severe and increasingly common form of pancreatitis requiring prompt triglyceride-lowering therapy. This study aimed to evaluate the safety and effectiveness of a standardized fixed-dose insulin drip protocol option implemented across a healthcare system.

Design: Multicenter retrospective cohort study.

Patients: A total of 466 adult patients admitted with HTG-AP between 15 July 2017, and 10 October 2024. Patients were divided into pre-protocol (n = 242) and post-protocol (n = 224) groups based on implementation of the fixed-dose insulin protocol on 10 June 2021.

Measurements: The primary outcome was intensive care unit (ICU) length of stay. Secondary outcomes included hospital length of stay and time to achieve triglyceride levels < 1000 mg/dL (11.3 mmol/L). Safety outcomes included incidence of hypoglycemia and hypokalemia.

Results: Baseline demographics were generally similar between groups, with higher rates of a history of diabetes and hyperlipidemia in the post-protocol group. No statistically significant differences were observed in ICU length of stay, hospital length of stay, or time to triglyceride reduction. Mild hypoglycemia was more common post-protocol (36.6% vs. 25.2%, p = 0.008), while rates of severe hypoglycemia and hypokalemia were low and comparable between groups.

Conclusions: The fixed-dose insulin protocol demonstrated similar clinical outcomes to historical care with an acceptable safety profile. This protocol offers a reproducible and standardized approach to managing HTG-AP in diverse inpatient settings.

Objective: Virilizing ovarian tumors (VOT) are rare in the paediatric population. The literature regarding their clinical spectrum, hormonal profile, imaging characteristics, histology, and outcomes is limited. Here, we perform a systematic review on the characteristics of paediatric VOT.

Design and methods: A systematic review was conducted in accordance with PRISMA guidelines. Databases including PubMed and Google Scholar were searched to identify English-language reports of paediatric (< 20 years) VOT with biochemical evidence of hyperandrogenemia and histological confirmation of an ovarian neoplasm. Data on demographics, clinical features, hormone profiles, imaging, tumor histology, management and outcomes were extracted and analysed.

Results: A total of 117 paediatric patients (median age: 15 years) with VOT were included. The most common symptoms were hirsutism (73.5%), clitoromegaly (68.4%), menstrual irregularity (n = 79), and voice change (60.7%). Children < 8 years had shorter diagnostic latency with less frequent hyperandrogenic manifestations. Baseline 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosteroe sulfate (DHEAS) were elevated in 70% and 18.3% of patients, respectively. Median tumor size was 6.6 cm, whereas tumors were bilateral in eight patients. Juvenile granulosa cell tumors and Sertoli-Leydig cell tumors were most common in the < 8 years and > 13 years groups, respectively. Recurrence was rare over a median follow-up of 1 year.

Conclusion: Hyperandrogenic manifestations are less frequent in children < 8 years with VOT. Elevated 17-OHP and/or DHEAS should not exclude the possibility of VOT. Etiological spectrum of paediatric VOT is relatively age-specific. Larger multicenter studies with longer follow-up are warranted to better delineate prognosis and management strategies.

Background: Prolactin (PRL) is a pleiotropic hormone, traditionally associated with lactation, but now recognised for its role in reproduction, metabolism, and neuroendocrine and immune regulation. While the clinical features and consequences of hyperprolactinemia are well known, hypoprolactinemia is poorly understood.

Results: The causes of PRL deficiency range from genetic mutation to acquired pituitary diseases and rare isolated disorders. Its diagnostic evaluation is often challenging, due to the lack of standardised lower reference limits. Nonetheless, growing evidence links hypoprolactinemia not only to postpartum agalactia, but also to reproductive and sexual dysfunction, and to metabolic alterations and increased cardiometabolic risk. Data from animal models and rare human cases further suggest that PRL exerts unique biological functions that are not fully compensated by other pituitary hormones. PRL measurement, when interpreted alongside gonadotropin levels and clinical context, may help in the differential diagnosis of secondary amenorrhoea. Markedly low PRL levels-especially in association with hypogonadotropic profiles-may support a diagnosis of functional hypothalamic amenorrhoea.

Conclusions: PRL should be recognised as a hormone whose deficiency may cause broader systemic disturbances. A comprehensive understanding of hypoprolactinemia is essential to better define its diagnostic criteria and clinical significance.

Objective: Polycystic ovary syndrome (PCOS) is associated with an increased risk of cerebrovascular disease, but the effects on cerebrovascular function are unknown. In this pilot study, we sought to compare cerebrovascular perfusion, pulsatility, reactivity and metabolism between women with PCOS and healthy volunteers using MRI, and investigated the influence of testosterone and insulin resistance on these parameters.

Design: Case-control pilot study.

Patients: Fifteen patients with PCOS (age: 32.0 ± 7.4 years; body mass index [BMI]: 31.8 ± 5.7 kg/m²) and 12 healthy controls (HC) (age: 30.7 ± 6.4 years; BMI: 30.2 ± 5.8 kg/m²).

Measurements: We used 3T magnetic resonance imaging (MRI) to assess several aspects of cerebrovascular function: (1) perfusion (cerebral blood flow [CBF] and arterial arrival time [AAT]; PCOS N = 15; HC N = 12), (2) pulsatility index (PCOS N = 15; HC N = 12), (3) breath-hold induced cerebrovascular reactivity (CVR; PCOS N = 15; HC N = 10), and (4) global oxygen metabolism (oxygen extraction fraction [OEF] and cerebral metabolic rate of oxygen [CMRO₂]; PCOS N = 9; HC N = 8). Linear regression models investigated the contribution of PCOS status, serum testosterone and Homeostatic Model Assessment for Insulin Resistance (HOMA2-IR). Regional analysis underwent false discovery rate (FDR) correction for multiple comparisons.

Results: Overall baseline CBF was not statistically different in PCOS patients compared to controls after adjustment for other variables (χ²(1) = 3.29; p = 0.07) but did show evidence for regional reduction with PCOS status in the transverse temporal gyrus (χ²(84) = 110.31; p = 0.03; -29.05 mL/100 g/min ± 7.26 [standard error; SE]). Similarly, while PCOS status was not associated with overall CVR (χ²(1) = 0.78; p = 0.38), there was evidence of a regional interaction (χ²(84) = 154.25; p < 0.001) in the parahippocampus (1.37% signal change ± 0.27 [SE]) and pericalcarine cortex (1.04% signal change ± 0.26 [SE]). Neither testosterone nor HOMA2-IR was associated with any outcome measure.

Conclusions: We observed regional reduction in cerebral blood flow and regional increase in cerebrovascular reactivity in women with PCOS compared to healthy controls. However, due to the limited statistical power and unclear menstrual timing in this pilot study, these results require further replication.

Background: Inactivating pathogenic variants (PVs) in CYP24A1 (MIM*126065), which encodes the enzyme vitamin D-24-hydroxylase, were initially identified in patients with infantile hypercalcemia (IH). Although CYP24A1 PVs were originally associated with a recessive inheritance pattern, it is now understood that heterozygous (monoallelic) variants may also lead to milder phenotypes.

Subjects and methods: Eight patients from six families, who presented with hypercalcemia, normal or elevated 25-hydroxyvitamin D (25(OH)D₃), suppressed or low-normal parathyroid hormone (PTH), and hypercalciuria and/or nephrocalcinosis were included in the study.

Results: Eight patients (five females) were diagnosed with IH based on clinical and laboratory assessment. The median age at presentation was 9.1 months (range: 5.0-44.4 months). The most common reason for referral was vomiting, reported in 50% of patients. Four patients (50%) were born to consanguineous parents. The mean serum calcium 3.6 ± 0.7 mmol/L (median 3.5; range 2.8-4.6) and 25(OH)D₃ 970.7 ± 880.5 nmol/L (median 845.4; range 89.9-2069) levels were elevated. Data on 1,25(OH)₂D₃ levels were available for three patients; two patients with biallelic PVs exhibited elevated concentrations, whereas the monoallelic patient showed a normal level. Hypercalciuria and/or nephrocalcinosis were present in 87.5% of the patients. Eight distinct CYP24A1 PVs were identified in eight patients. Of these, two patients were homozygous, four were compound heterozygous and two were heterozygous for the respective variants. We detected mild hypercalcemia and/or nephrocalcinosis/nephrolithiasis in 40% of monoallelic parents.

Conclusions: Monoallelic or biallelic PVs in the CYP24A1 gene play a significant role in the aetiology of hypercalcemia and/or nephrocalcinosis/nephrolithiasis. Early genetic diagnosis is essential for guiding clinical management, particularly to avoid inappropriate vitamin D supplementation and to minimize the risk of long-term renal complications.