Clinical Endocrinology最新文献

Background: Congenital hyperinsulinism (CHI) is a rare but significant cause of persistent hypoglycemia in neonates and infants. Mutations in several genes, including ABCC8 and KCNJ11, are known to cause CHI. However, data on CHI from our region remain limited.

Purpose: To assess the genetic spectrum, clinical characteristics, and outcomes of patients with CHI.

Methods: This was a single-centre observational study conducted in the Department of Endocrinology and the Multidisciplinary Research Unit at Sher-i-Kashmir Institute of Medical Sciences, Srinagar, involving six unrelated patients with clinically suspected CHI who underwent detailed clinical evaluation and targeted genetic testing using a 19-gene panel associated with CHI, including hyperinsulinism-hyperammonaemia syndrome. Genetic analysis was performed using Sanger sequencing, followed by parental segregation analysis to determine the inheritance patterns.

Results: The mean age at presentation was 24.2 days. Parental consanguinity was present in 3/6 cases. Three patients (50%) presented with hypoglycemic seizures, while the remaining presented with feeding refusal and lethargy. Likely pathogenic variants were identified in three patients (50%). The most commonly affected gene was ABCC8 (n = 2), followed by KCNJ11 (n = 1). Detected ABCC8 variants included a likely novel pathogenic splice variant (c.1009_1011 + 11del) and a frameshift variant (c.453del), whereas the KCNJ11 missense variant identified was c.107 T > A. The likely pathogenic homozygous novel variant, c.1009_1011 + 11del, resulted in a 14 base pair deletion in the intron six and exon six junction of the gene. The mutation affected the invariant GT donor splice site downstream of exon 6 (5 splice). Clinically, two patients responded to diazoxide therapy, while four were classified as diazoxide-unresponsive. Partial pancreatectomy was performed in two of the diazoxide-unresponsive cases. The mean duration of follow-up was 22 months (range: 2-42 months).

Conclusion: This study documents a likely novel ABCC8 pathogenic variant from a region with limited prior data on CHI, enhancing global understanding of its genetic diversity. Our findings emphasize the importance of integrating genetic testing into standard diagnostic protocols for timely and tailored interventions. The main limitations of this study include the use of Sanger sequencing as the sole genetic testing approach and the absence of functional validation of the identified variants.

Background: Differentiated thyroid carcinoma (DTC) is typically managed surgically with favourable outcomes. However, surgery may have dire consequences when the tumour invades critical structures. Neoadjuvant therapy with tyrosine kinase inhibitors (TKIs) has emerged as a potential strategy to improve resectability and reduce morbidity in advanced DTC. We evaluated the efficacy and safety of neoadjuvant TKI therapy in patients with advanced or unresectable DTC.

Methods: A retrospective study was conducted on patients with advanced DTC treated with neoadjuvant TKIs (lenvatinib or dabrafenib/trametinib) followed by curative intent surgery between 2023 and 2025. Data on disease extent, genetic alterations, treatment regimens, and adverse effects were collected. Radiologic response was assessed by CT or PET-CT according to the RECIST 1.1 criteria. Surgical outcomes were evaluated by the degree of morbidity and by tumour involvement in the surgical margins.

Results: Nine patients were included, seven treated with lenvatinib, two treated with dabrafenib/trametinib on the basis of molecular alterations. The median duration of TKI therapy was 5 months, and no disease progression was observed throughout. Radiological assessment revealed a median reduction in tumour burden of 23.53%, contributing to improved tumour resectability. All patients underwent surgical resection with preservation of critical structures. Elevated TSH levels during neoadjuvant therapy was correlated with a positive treatment response (p = 0.028).

Conclusions: Neoadjuvant TKIs may improve the surgical outcomes of patients with advanced DTC. Decision-guided radiological and blood-based surrogate biomarkers, such as TSH, can assist in evaluating treatment response and guide decisions regarding treatment duration and extent of surgical resection.

Introduction: Acromegaly is a rare chronic disease caused by excessive secretion of growth hormone. Even with biochemical control, hormonal imbalance may lead to cerebral changes. This study aimed to evaluate the presence of white matter hyperintensities (WMHs) in patients with acromegaly.

Materials and methods: We retrospectively enrolled 37 acromegaly patients who underwent gadolinium-enhanced brain MRI to detect WMHs and their distribution. We analysed potential contributing factors such as cardiovascular comorbidities, migraine, inflammatory markers (plasma interleukin-33), and hand skin perfusion using laser speckle contrast analysis.

Results: WMHs were found in 24 patients (64.9%), with nine showing a higher lesion burden. Patients with WMHs were older [63 years (IQR 47.5-67.5) versus 48 years (IQR 44-53), p = 0.023] and had a longer disease duration [19 years (IQR 11.5-26.5) versus 13 years (IQR 12-15), p = 0.028] than those without WMHs. Hypertension (22/37) and migraine (18/37) were the most common comorbidities. A higher WMH burden was significantly associated with hypertension (p = 0.05), while no significant link was found between WMHs and migraine (p > 0.05).

Conclusion: Several factors in acromegaly may affect brain structure, promoting WMH development, such as aging, disease duration, and hypertension. Therefore, in patients with acromegaly, we suggested the early management of cardiovascular comorbidities and regular radiological follow-up, not limited to the study of the pituitary gland. Future prospective studies are necessary to confirm our preliminary observations and to clarify the potential role of disease activity and treatment in WMH development.

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: Despite an increased cerebrovascular disease risk, the impact of Polycystic Ovary Syndrome (PCOS) on cerebrovascular haemodynamics and function is unknown. This study characterised cerebrovascular haemodynamics and function in women with PCOS versus healthy controls.

Design: Case-control study.

Patients: Fifteen women with PCOS (age: 31 ± 6 years; body mass index (BMI): 31.8 ± 5.7 kg/m²) and 16 controls (age: 30 ± 7 years; BMI: 29.9 ± 5.5 kg/m²).

Measurements: Resting global cerebral blood (CBF) was assessed by 3T MRI. Middle- and posterior cerebral artery blood velocities (MCAv, PCAv) were measured by Doppler ultrasound and pulsatility index (MCA_PI, PCA_PI) calculated. Neurovascular coupling (NVC), internal carotid artery cerebrovascular reactivity (CVR_CO2) and dynamic cerebral autoregulation (dCA) directional sensitivity were assessed using a visual stimulus, 6% fixed-inspired CO₂ and repeated squat-stand manoeuvres, respectively.

Results: Resting CBF (PCOS: 57.2 ± 7.5 ml/100 g/min; controls: 61.6 ± 11.6 ml/100 g/min, p = 0.25) and MCAv, PCAv, MCA_PI and PCA_PI (all p > 0.05) were similar between groups. NVC (14 ± 4.9% vs. 13 ± 3.4%, p = 0.45), CVR_CO2 (5.1 ± 1.9% vs. 6.5 ± 2.9%, p = 0.20) and dCA directional sensitivity were similar between groups. However, women with PCOS had elevated relative PCA_PI during NVC (PCOS: 12.0 ± 5.6% vs. controls: 7.0 ± 3.8%, p = 0.04), and impaired vasodilation of the internal carotid artery during CVR_CO2 (PCOS: -0.10 ± 0.22 mm vs. controls: 0.18 ± 0.24 mm, p < 0.01).

Conclusions: Cerebrovascular function is largely preserved in women with PCOS, although elevated arterial pulsatility and impaired vasodilatory response to carbon dioxide may indicate early endothelial dysfunction in the cerebral vasculature. Larger studies are needed to confirm this in view of our limited study power.

Background: Patients with medium and high-risk papillary thyroid carcinoma (PTC) demonstrate significantly poorer clinical outcomes compared to their low-risk counterparts. However, current prognostic stratification for this patient population remains suboptimal due to the absence of reliable biomarkers. This investigation aims to evaluate the clinical utility and prognostic potential of three hematological inflammatory indices: the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) in medium and high-risk PTC cases.

Methods: This study analyzed 1070 PTC patients from the "DTCC study" (2014-2016), a multicenter prospective cohort investigating the initial management of differentiated thyroid cancer (DTC) in China. Preoperative hematological parameters (including PLR, NLR, and SII) and baseline clinical characteristics were evaluated to assess their prognostic significance.

Results: In medium and high-risk PTC patients, PLR ≤ 115.6 predicted increased recurrence risk (OR = 4.579, 95% CI: 1.863-11.255, p = 0.001) and worse disease-free survival (DFS; p = 0.001). Multivariate Cox regression confirmed PLR ≤ 115.6 as an independent prognostic factor for reduced DFS (HR = 3.080, 95% CI: 1.115-8.507, p = 0.030). Notably, this association persisted in intermediate-risk patients. Among high-risk PTC patients, however, SII ≤ 360.9 (rather than PLR) demonstrated stronger predictive value for recurrence (OR = 15.154, 95% CI: 1.873-122.640, p = 0.011). Consistently, multivariate analysis identified SII ≤ 360.9 as an independent risk factor for shorter DFS (HR = 14.399, 95% CI: 1.823-113.730, p = 0.011).

Conclusion: Our findings demonstrate that PLR and SII emerged as risk stratification-specific prognostic biomarkers: PLR independently predicted prognosis in intermediate-risk cases, while SII showed superior predictive value for prognosis in high-risk patients. The differential utility of these indices-PLR for intermediate-risk stratification patients and SII for high-risk stratification patients-highlights their complementary roles in clinical decision-making. As routinely available, cost-effective inflammatory markers, PLR and SII may enhance risk-adapted surveillance strategies, though further validation is warranted to standardize cutoff values and integrate them into existing clinical management systems.

Trial registration: The trial was registered at ClinicalTrials. gov under the identifier NCT02638077.

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.

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.