搜索结果：European journal of endocrinology

MODY (Maturity-Onset Diabetes of the Young) is characterized by autosomal dominant mode of inheritance, early onset of diabetes in the absence of autoimmunity directed to pancreatic β-cells, impaired insulin secretory capacity, however, maintained over time, and extra-pancreatic manifestations in some patients. Its prevalence has been estimated 0.6% to 6.5% of all diabetes in Europe and the USA. Pathogenic variants in the genes encoding glucokinase or transcription factors HNF1A or HNF4A are responsible for the majority of cases of monogenic forms of diabetes referred to as MODY. The objective of the French National Diagnosis and Care Protocol (PNDS, Protocole National de Diagnostic et de Soins) dedicated to GCK-MODY (formerly MODY2), HNF1A-MODY (MODY3), and HNF4A-MODY (MODY1) is to provide to health professionals a guide for optimal management and care of patients, based on a critical literature review and multidisciplinary expert consensus. The PNDS, written by members of the French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), is available on the French Health Authority website (in French). Thorough analysis of personal and family history, clinical examination and biochemical testing are key to raise the diagnosis, which has to be confirmed by molecular analysis. The attending physician, in conjunction with the national care network, will ensure that the patient receives optimal care through regular follow-up and screening. Overall, the management of patients with MODY requires the collaboration of several health care providers.

Limited availability of corticotropin-releasing hormone (CRH) currently complicates the differentiation of adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS). The diagnostic value of common screening tests in distinguishing Cushing's disease (CD) from ectopic CS (ECS) remains unclear. To assess the diagnostic performance of screening tests, alone and in combination, in differentiating CD from ECS. Retrospective multicenter study enrolling patients with confirmed ACTH-dependent CS and available screening tests at diagnosis. Data are expressed as multiples of upper limit of normal (×ULN). Optimal cut-offs were determined using Youden's Index. Combination with composite score models and machine learning (ML) algorithm were performed. A total of 566 patients were included (509 [90%] with CD). The optimal morning ACTH cut-off was 1.8×ULN (sensitivity 74%, specificity 77%, AUC=0.776 [CI-95% 0.688-0.853]). 24h-urinary free cortisol (24h-UFC) showed the best performance (cut-off 5.9×ULN, sensitivity 72%, specificity 83%, AUC=0.854 [0.816-0.923]), followed by the 1 mg dexamethasone suppression test (12.8×ULN, sensitivity 70%, specificity 86%, AUC=0.828 [0.740-0.906]). Using a composite score, a cut-off of 1.5 yielded 78% sensitivity and 92% specificity (AUC=0.865 [0.798-0.933]). Combining this score with pituitary MRI-findings, sensitivity and specificity were 88% and 85% (AUC=0.931 [0.887-0.974]). ML algorithm (balanced random forest) including screening tests-results yielded a sensitivity of 71% and specificity of 84% (AUC=0.853 [0.741-0.966]), while including the MRI-findings variant achieved a sensitivity and specificity of 76% and 91% (AUC=0.902 [0.805-0.999]). Combining screening tests in composite scoring and ML differentiates ACTH-dependent CS and offers a potential diagnostic alternative to CRH-stimulation test.

An adrenal crisis is a potentially life-threatening medical emergency, which requires rapid treatment with glucocorticoids. Guidelines advise immediate self-administration of hydrocortisone by intramuscular injection using an emergency management kit in case an adrenal crisis is suspected. However, self-injection is often not performed due to administration complexity or patient anxiety. Pulmonary administration of glucocorticoids may be a more patient-friendly and suitable alternative, especially when administered using a dry powder inhaler. Before advancing to the development of a dry powder inhaler, we aimed to evaluate whether the pharmacokinetics of inhaled prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis. Twelve healthy participants (aged 23-31 years, 50% females) received two separate doses of prednisolone sodium succinate, equivalent to 56.1 and 112.2 mg prednisolone on separate occasions, administered via a nebulizer. The primary outcome was the time to reach a target plasma concentration of 200 nmol/L. The median times to achieve this plasma concentration (excluding the nebulization time of approximately 10 minutes) were 17 (13 - 23) minutes and 9 (5-11) minutes for the 56.1 and 112.2 mg doses, respectively. Furthermore, pulmonary administered prednisolone sodium succinate was well tolerated. The results of this study, particularly the short time to the target plasma concentration, indicate that prednisolone sodium succinate is rapidly absorbed via the lungs and that the pharmacokinetics of inhaled nebulized prednisolone sodium succinate are suitable for the outpatient treatment of adrenal crisis.

X-linked hypophosphataemia (XLH) is a rare genetic disorder characterised by defective bone and tooth mineralisation. Burosumab is a recombinant, human, anti-fibroblast growth factor 23 monoclonal antibody approved for treating XLH. Due to the rarity of the disease, additional safety data for the treatment of XLH with burosumab are required. A post-authorisation safety study analysis of data for paediatric participants from the International X-linked Hypophosphataemia Registry. This study included standard diagnostic and monitoring clinical data at participating centres, regardless of treatment. This was a second interim analysis performed 5 years after study initiation in the paediatric population. Primary objectives assessed safety outcomes in children and adolescents with XLH. The secondary objective compared safety outcomes with burosumab vs phosphate and/or active vitamin D. In total, 340 participants were treated with ≥1 dose of burosumab, and 91 were treated with phosphate and/or active vitamin D. Overall, 37.4% and 22.0% of participants in the burosumab or phosphate and/or active vitamin D cohorts, respectively, experienced ≥1 adverse event. The proportions of participants with events were similar among children and adolescents. Forty-nine (14.4%) participants reported events possibly/probably related to burosumab. No events led to the withdrawal of burosumab. In both cohorts, no serious adverse events were considered related to treatment, and there were no deaths. Hospitalisations occurred in ∼71% of participants. Hyperphosphataemia, elevated parathyroid hormone, and ectopic mineralisation events were rare. The safety profile of burosumab was consistent with previous studies, and no new safety concerns were reported for children or adolescents.

The scarcity of robust long-term safety data has contributed to increasing restrictions on the use of gonadotropin-releasing hormone analog (GnRHa) treatment in transgender and gender diverse adolescents (TGDAs) in several countries. Methodological limitations of earlier studies have led to controversy and debate, underscoring the urgent need for high-quality evidence in this field. To present a study design using target trial emulation (TTE) to evaluate long-term safety of GnRHa treatment in TGDAs using observational data from national healthcare registries, and highlight methodological challenges. We applied a stepwise TTE approach, to emulate a randomized trial using real-world data. The main methodological challenges were identified as the selection of the control group and the definition of time zero. To address these, we engaged independent experts in causal inference to review the concept design and provide feedback on potential solutions. Expert feedback was systematically summarized and discussed. The resulting study design will select late-presenting TGDA individuals as the control group and defines time zero as the initiation of GnRHa treatment for the intervention group, with the equivalent age assigned as time zero in controls. Sensitivity analyses using alternative control groups and time zero definitions will be included to assess robustness. This approach allows for adjustment of confounders and aims to emulate the conditions of a randomized trial as closely as possible within the constraints of observational data. This discussion paper serves as a methodological example of target trial emulation with observational data to study long-term safety of GnRHa in TGDA. By transparently addressing methodological challenges and incorporating expert input, this approach offers a feasible and ethically sound alternative to RCTs, and contributes to the evidence base needed for informed clinical and policy decisions in transgender healthcare.

Breast cancer (BC) remains a leading cause of cancer-related deaths among women. Administration of anthracyclines and/or anti-human epidermal growth factor receptor-2 (HER2) antibodies has been associated with chemotherapy-induced cardiotoxicity. Cardio-oncology rehabilitation programs aim to mitigate these outcomes. However, their preventive role in cancer therapy-related cardiac dysfunction (CTRCD) remains uncertain. To evaluate the effectiveness of a structured exercise program compared with only exercise recommendation in preventing CTRCD, defined by the 2022 European Society of Cardiology criteria, as a left ventricular ejection fraction above 50%, with a relative decrease in global longitudinal strain exceeding 15% from baseline and/or a newly detected elevation in cardiac troponin I or T or natriuretic peptides. Secondary outcomes include the impact on systolic and diastolic echocardiographic parameters, cardiometabolic biomarkers, quality of life, and exploring the role of traditional cardiovascular risk factors in CTRCD onset. CARPTOX-BC is a randomized, open-label clinical trial with an active control group. Women aged 18-70 years with stage I-III BC scheduled for neoadjuvant or adjuvant therapy with anthracyclines and/or trastuzumab will be eligible. The intervention includes three supervised out of five weekly aerobic and resistance exercise. A total of 284 participants will be randomized 1:1 to intervention or control arms. Results will be disclosed at completion. We expect a structured exercise program may reduce the incidence of CTRCD associated with anthracycline and/or HER2 antibody and provide a potential non-pharmacological therapy that could also enhance cardiometabolic markers and quality of life among this population. NCT06881940 (registered March 18th, 2025).

Cancer risk in acromegaly remains debated, with studies showing both increased and similar risk compared to the background population. We conducted a nationwide cohort study examining the risk of cancer and benign colorectal lesions in acromegaly patients. The study included acromegaly patients diagnosed in Denmark (1977-2021, n = 809, median follow-up 12.2 [IQR: 5.6-21.7] years (range: 0.04-44.0) and controls matched on sex and birth year (n = 80 900). All diagnoses of acromegaly were biochemically validated. We investigated the occurrence of cancer diagnoses, benign colorectal lesions, performance of colonoscopies and mortality with time-to-event statistics and logistic regression. Overall cancer risk was not clearly increased (IRR: 1.10 [0.93;1.30], P = .27), but patients with acromegaly had an increased risk of colorectal cancer (IRR: 1.78 [1.22;2.60], P < .01) and thyroid cancer (IRR: 3.68 [1.16;11.66], P = .03). Colorectal cancers were more often localized (IRR: 2.00 [1.21;3.30], P = .007) as compared to controls, and the use of endoscopic colorectal procedures was increased (IRR: 2.85 [2.54;3.19], P < .01). The incidence of benign colorectal lesions was elevated in acromegaly patients (IRR: 2.32 [1.96;2.76], P < .01) and dominated by tubular adenomas (43.6%) and hyperplastic polyps (33.2%). Fecal immunochemical test (FIT) screening and clinical suspicion guided the use of colonoscopies, rather than systematic colonoscopy screening. All-cause mortality was elevated in acromegaly (IRR: 1.18 [1.02; 1.36], P = .03), but cancer-specific mortality was not (IRR: 0.95 [0.72;1.25], P = .72). Acromegaly carries an increased risk of colorectal cancer, but neither overall cancer risk nor cancer-specific mortality is increased.

Hyperparathyroidism (HPTH) is a common feature in patients with X-linked hypophosphatemia (XLH), especially when treated with vitamin D analogs and phosphate supplements. Although the exact mechanism is not clear, it is assumed that prolonged intake of phosphate supplements stimulates parathyroid hormone (PTH) secretion. We prospectively assessed the effect of burosumab on PTH levels in children with XLH. Thirty-seven children (8.8 &#xb1; 3.2 years) were switched from phosphate supplements and vitamin D analogs to burosumab and completed at least 3 years of therapy. Biochemical parameters of calcium-phosphate homeostasis were measured at baseline and prospectively every 6 months. Target serum phosphate under burosumab was >1.2&#x2005;mmol/L (>3.7&#x2005;mg/dL). After 3 years of treatment, there was a global increase of PTH levels from 39.1 &#xb1; 18.2 to 54.8 &#xb1; 27.6&#x2005;ng/L (P = .001) (normal range 18.5-88&#x2005;ng/L). Four of 37 subjects (10.8%) developed secondary HPTH after 3 years. None developed tertiary HPTH. Subjects who developed HPTH had higher serum phosphate at M36 (1.33 vs 1.19&#x2005;mmol/L, P = .11, respectively), in comparison with those without HPTH. A significant increase in PTH was correlated with the increase in serum phosphate >1.3&#x2005;mmol/L (P = .012); serum phosphate positively and independently correlated with PTH in logistic regression analysis (odds ratio = 2.1, 95% CI = 1.1-3.8, P = .021). We suggest that higher serum phosphate levels in the context of prolonged treatment with burosumab may stimulate PTH secretion in some patients with XLH, leading to HPTH. Careful follow-up and preventive measures to limit the development of secondary HPTH should be applied in treated children.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been in use for twenty years. There have been concerns about their safety in patients with neuroendocrine neoplasms (NENs). The reports of GLP-1 receptor (GLP-1R)-driven proliferation of C-cell neoplasms in rodent studies had led to the black-box warning against their use in patients with medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2). In this review, we have attempted to evaluate the physiological and pathological expression of GLP-1 receptors (GLP-1R) in various endocrine organs and summarise the preclinical and clinical evidence regarding the effect of GLP-1RA exposure and risk of NENs. GLP-1R expression has not only been found in nonneoplastic tissues such as neurohypophysis, duodenal glands and pancreatic islets but also in neuroendocrine tumours (NETs). Preclinical studies have demonstrated the proliferative effects of GLP-1RA in cell lines representing pancreatic NETs (panNETs) and small intestinal NETs. The available data from retrospective studies, randomized trials and cancer registries provide conflicting data and does not support a generalized increase in NENs with the use of GLP-1RA. Some epidemiological studies have even shown survival benefits associated with GLP-1RA use. In addition, significant gaps in evidence remain, such as lack of data regarding certain tumour subtypes, long-term prospective studies with NENs as the clinical endpoint and uncertainty regarding patients with multiple endocrine neoplasia type 1 (MEN1). Hence, the initiation of GLP-1RA therapy in patient with predisposition to NEN where a contraindication does not exist, should be approached cautiously with careful monitoring for long-term adverse effects.

Hyponatremia is the most common electrolyte disorder. While overly rapid correction can cause osmotic demyelination syndrome (ODS), hyponatremia itself is linked to neurocognitive impairment. Despite this, the neurological burden remains underappreciated, and subclinical neuronal and astrocytic injury due to hyponatremia or its correction may be more frequent than recognized. Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are biomarkers of neuronal and astrocytic injury. Whether hyponatremia and its treatment are associated with changes in serum NfL and GFAP levels. Two randomized, double-blind, placebo-controlled trials. Study 1: healthy adults underwent experimentally induced hyponatremia within 8&#x2005;hours. Study 2: hospitalized patients with hyponatremia were treated over 4 days. Biomarkers were measured at baseline and follow-up and analyzed as age- and BMI-adjusted Z-scores (for GFAP, also sex-adjusted). In healthy adults, blood sodium decreased by a median of 7&#x2005;mmol/L [-8(-)-6] within 8&#x2005;hours, associated with an increase in NfL (+0.48 Z-units [0.09-0.78]) and GFAP (+1.02 Z-units [0.84-1.39]). Patients with hyponatremia showed a baseline sodium of 126&#x2005;mmol/L [122-127], which increased by 4&#x2005;mmol/L [2-6] within 24&#x2005;hours. NfL increased from a Z-score of 1.90 [1.06-2.51] by +0.21 [-0.03-0.66]; GFAP increased from 0.16 [-0.55-0.58] by +0.46 [0.12-0.81]. In multivariable models predicting biomarker Z-scores on day 5, both baseline biomarker levels and the degree of sodium increase within 24&#x2005;hours were significant predictors. Hyponatremia and its correction are associated with measurable neuronal and astrocytic injury. NfL and GFAP may serve as early indicators of osmotic brain stress, suggesting ODS may represent only the visible part of a broader spectrum of cerebral vulnerability.

Rare diseases affect a small percentage of the population but collectively impact millions worldwide. In the Middle East, the challenges are intensified by regional factors such as high rates of consanguinity, sociocultural stigma, limited diagnostic capacity, and inadequate healthcare infrastructure. These challenges often lead to delayed diagnoses, restricted access to treatment, and poor quality of life for affected individuals and their families. The Rare Advocacy Council conducted two 1.5-hour virtual expert panels involving 14 regional and international stakeholders (5 clinicians, 4 patient advocates, and 5 international academic experts) to identify and prioritize the challenges of managing rare diseases in the Middle East region. Discussions were organized across four domains: disease recognition and diagnosis, the patient journey and continuum of care, access to timely diagnostics, and access to adequate treatment, followed by structured online voting (involving only clinicians and patient advocates; n&#x2009;=&#x2009;9), discussions focused on prioritization, and a descriptive follow-up survey to identify the most critical barriers and propose actionable solutions. Key challenges identified included the lack of national disease registries, limited public awareness, underrepresentation of patient voices in decision-making, fragmented multidisciplinary care, and restricted access to diagnostics and advanced therapies. Top priorities included developing national registries, enhancing media-driven education, strengthening collaboration among care providers, and improving treatment accessibility through policy reforms. Effective management of rare diseases in the Middle East requires a coordinated, patient-centered approach. Strengthening health system infrastructure, investing in education, and aligning policy with patient needs are essential for sustainable improvement. Collaborative action among policymakers, healthcare providers, and advocacy groups can significantly advance care delivery and improve outcomes for individuals living with rare diseases.

Esophageal adenocarcinoma (EAC) represents one of the most increasing malignancies in Western countries. The disease is multifactorial, involving modifiable risk factors and genetic susceptibility variants. These variants can be aggregated to a polygenic risk score (PRS) that reflects individual genetic risk. Investigation of the effects of lifestyle factors, PRS, and co-medication on EAC age at onset (AAO) is critical for shaping prevention strategies. A detailed questionnaire was used to assess pre-diagnostic exposure to lifestyle factors and clinical information from a large German EAC cohort. Linear regression analysis was performed to identify factors associated with EAC AAO in 1742 EAC patients. PRS was available for 1190 patients. Subgroup analyses were conducted to estimate the effects of the analyzed factors on AAO according to age group (early vs. late onset), sex, and prior diagnosis of Barrett's esophagus (BE). Earlier AAO was significantly associated with gastroesophageal reflux (GER), smoking and a higher PRS, whereas later AAO was associated with physical activity and higher consumption of fish and fruits. Among co-medication, combined use of proton pump inhibitors (PPIs) and acetylsalicylic acid (ASA) showed the most significant effect on AAO, whereas the use of PPIs and ASA alone showed weaker effects. This study represents the largest questionnaire-based analysis to date investigating factors influencing EAC development. Our findings show that the combined use of PPIs and ASA, both cost-effective medications, is associated with delayed EAC onset. In addition, lifestyle and genetics contribute to EAC AAO.

To investigate life situation and social wellbeing over time, including perceived disease limitations, and quality of life (QoL) in patients with congenital adrenal hyperplasia (CAH). A retrospective cross-sectional follow-up study including a structured interview and survey questionnaires on QoL and play-behavior as children. Seventy-five patients with CAH due to 21-hydroxylase deficiency (50 females and 25 males, age range 20-60 years) and a control group of 20 healthy females were followed-up. A lifeline describing the participants' self-reported life situation and social wellbeing was compiled using a numeric rating scale. The lifeline was divided into 8 time periods (range 4-31 years). For a subgroup that previously participated in an observed play-behavior study during childhood the retrospective play-behavior questionnaire was validated. QoL was assessed using the AddiQoL questionnaire. A genotype-dependent difference in lifeline scores over time was seen during school age with the lowest social wellbeing scores among participants with severe forms of CAH. Females scored lower than males, irrespective of severity, and lower than the control group. Females with CAH reported more perceived social limitation than males. QoL scores correlated with the mean levels of lifeline scores, suggesting that children with poor wellbeing may be at risk of lower QoL as adults. A genotype-dependent difference in social wellbeing was seen at an early age, with lower scores in participants with the severe form of CAH. Patients with poor wellbeing as children may be at risk of reduced QoL as adults.

The cytochrome P450 side-chain cleavage enzyme (P450scc), encoded by the CYP11A1 gene, regulates the first and rate-limiting step of steroidogenesis. c.1351C > T (p.R451W) is the most commonly identified pathogenic variant in the CYP11A1 gene, and is associated with a mild P450scc deficiency. Long-term follow-up data of affected individuals are insufficient. To investigate the long-term growth, pubertal development, and adrenal and gonadal functions of patients with homozygous CYP11A1 c.1351C > T (p.R451W) variant. Retrospective follow-up data were obtained from the medical records of patients managed at tertiary pediatric endocrinology centers. Twenty-two patients (16 males) from 16 families were included. The median age at presentation was 4.8 &#xb1; 4.2 years (range: 1-14.6 years), and the mean follow-up period was 7.8 &#xb1; 5.2 years (range: 0.5-17.9 years). Primary adrenal insufficiency (PAI) was present in all cases. Three patients were diagnosed during family screening. Mineralocorticoid (MC) deficiency was detected in 20 patients (83%), and recovered in 2 cases during follow-up. One patient with no MC deficiency at presentation had developed a salt-wasting crisis during acute illness. None of the 46,XY cases showed atypical genitalia; 3 had micropenis, 1 had cryptorchidism, and 2 patients required sex steroid therapy because of subsequent hypergonadotropic hypogonadism later. Mild P450scc deficiency due to p.R451W variant in the CYP11A1 gene is associated with late onset PAI with variable MC and sex hormone deficiency. The growth is consistent with genetic potential, and pubertal onset and progression are normal in affected patients, while long-term follow-up is required with regard to the risk of gonadal failure.

Transsphenoidal surgery is the first-line treatment for Cushing's disease (CD), but long-term remission rates and predictors of outcome vary. This study analyzes 20 years of neurosurgical experience, including surgical strategies, endocrine outcomes, and remission predictors. Between 2004 and 2024, 346 patients with confirmed CD underwent 376 pituitary surgeries at the University Hospital of T&#xfc;bingen. Data on demographics, tumor imaging, surgical technique, remission, recurrence rates, postoperative complications, and improvement of comorbidities were analyzed. Early remission was achieved in 81.9% at discharge and 89.8% at first follow-up. During long-term follow-up (mean 109.7 months), a recurrence rate of 9.4% occurred. Primary surgery achieved higher remission rates than repeat surgery (94.1% vs 70.5% at first follow-up; 86.1% vs 57.4% long-term, both P < .001). Preoperative predictors included detectable microadenoma on magnetic resonance imaging (MRI) (P = .001) and smaller adenoma size (mean 7.5&#x202f;mm vs 12.6&#x202f;mm, P = .001). Invasive adenoma growth on MRI correlated with lower remission rates. Intraoperative factors associated with remission included shorter surgical duration (82.1 vs 101.3&#x2005;min, P < .001), clear adenoma visualization (P < .001), histopathological confirmation (P = .003), use of selective adenomectomy (P < .001), and absence of intraoperative invasiveness (P = .003). Remission correlated with greater improvement in hypertension (P < .001), diabetes mellitus type 2 (P = .030), and weight loss (P < .001), while new pituitary hormone deficiencies occurred mainly after extensive surgery. Transsphenoidal surgery remains an effective and safe treatment for CD, with high remission rates and long-term control, strongly associated with tumor characteristics and surgical approach.

Primary aldosteronism (PA) is a common, treatable cause of hypertension for which screening is widely recommended but rarely performed in clinical practice. However, real-world screening and diagnosis patterns across the entire hypertensive population remain unknown. This study aimed to delineate the 22-year state of nationwide PA screening and diagnosis rates among all hypertensive population in Taiwan. In this nationwide retrospective cohort study from 2001 to 2022, we identified all patients with hypertension using a national health insurance database. We calculated annual PA screening and diagnosis rates, with particular focus on high-risk subgroups, including patients with resistant hypertension, early-onset hypertension, hypokalemia, and other comorbidities warranting screening. Among 7.8 million patients with hypertension, a total of 4.4% received PA screening during the study period. The annual PA screening rate increased from 0.26% in 2001 to 0.75% in 2022 (P < .001) yet remained markedly low. In 2022, only 1.0% of patients with resistant hypertension, 3.2% with early-onset hypertension, and 3.6% with hypokalemia underwent screening. The diagnostic yield of PA showed a slight decrease over time, fluctuating between 8.0% and 6.7% (P = .006). Despite an increase in PA screening over the past 2 decades, absolute rates remain critically low, falling far short of guideline recommendations, even in high-risk groups. Our findings quantify a major implementation gap between evidence and clinical practice. As international guidelines are shifting toward broader and simpler screening protocols, there is an urgent need to improve the detection of this common and actionable condition.

Congenital hyperinsulinism (HI) is a rare disorder characterized by severe, recurrent hypoglycemia. Subtotal pancreatectomy remains a treatment option for diffuse HI, but post-surgery quality of life is largely undescribed. This mixed-methods study utilized quantitative data from the HI Global Registry, including individuals with diffuse HI and &#x2265;75% pancreatectomy (n&#xa0;=&#xa0;34). Of these, 13 (38%) completed qualitative interviews to capture the patient and caregiver perspectives. This is the first study to investigate long-term clinical and lived impacts of pancreatectomy for diffuse HI as reported by affected families. Most participants underwent subtotal pancreatectomy before two months of age (24, 71%). Only three (9%) had normal glucose status at discharge. At follow-up by median (range) age 9 (1.5-32) years, diabetes was reported in 15 (44%), pancreatic insufficiency in 14 (41%), and 24% reported ongoing medication use for hypoglycemia. Continuous glucose monitoring data demonstrated suboptimal time in range, regardless of diabetes status. Interviews revealed variability in surgical decision-making based on preoperative medical management, genetics, and imaging of the pancreas. Hospitalization and post-discharge periods were described as stressful and challenging to mental health for caregivers. At follow-up, children reported less perceived burden than caregivers. Of the six parents interviewed whose children have transitioned to diabetes, four stated that diabetes was easier to manage than HI, although hypoglycemia could still be frequent. Subtotal pancreatectomy for diffuse HI may be necessary when medical therapy is not sufficient to prevent severe hypoglycemia. However, surgery was not curative and was associated with life-long consequences and management.

Most neuroendocrine neoplasms (NENs) are sporadic and occur predominantly in older patients. Early-age disease onset has been increasingly observed in NENs. We aimed to assess the clinical features and outcomes of young adults with sporadic NENs. This is a retrospective study that gathered 20 institutions from 12 countries under the auspices of Women in NET (WiN) ENETS group. Young patients aged 18-40 years diagnosed with sporadic NENs (well and poorly differentiated) from 2010 to 2020 were enrolled. Patients with appendiceal and type 1 gastric NETs, hereditary syndromes, synchronous malignancy, pheochromocytoma, paraganglioma, and medullary thyroid cancer were excluded. Descriptive statistics, comparisons between groups, survival, and Cox multivariable analysis were performed. Overall, 478 young patients with sporadic NENs were enrolled. Localised (62%, n = 249), well-differentiated (92%, n = 433), non-functioning tumours (81%, n = 384), and women (58%, n = 277) were more prevalent. The pancreas was the most common primary site (33%, n = 159). Metastatic disease at diagnosis was more often found in men than women (47%, n = 78 vs. 33%, n = 78, P = .004). Five-year overall survival was 82%. Overall survival was significantly longer in women than men (P = .019), as well as in rectal (P = .00245) and lung (P = .0027) primary tumours compared to pancreatic NENs. The multivariable analysis identified stage, Ki-67, morphology, and gender as independent predictors of survival. Young patients with NENs often present with well-differentiated and localised tumours, thereby increasing the probability of curative surgical resection. Prospective research into molecular biology is needed to identify distinct NEN features in young adults and determine risk factors to tailor effective treatment strategies.

The 1-mg dexamethasone suppression test (DST) may be affected by dexamethasone (DEX) exposure and assay-related variability. We aimed to define pragmatic post-DST DEX benchmarks and to compare the diagnostic performance of cortisol measured by chemiluminescent immunoassay (CLIA) vs liquid chromatography-tandem mass spectrometry (LC-MS/MS). Consecutive real-world observational study. Post-test cortisol was measured by CLIA, while cortisol, cortisone, and DEX were quantified by LC-MS/MS on stored samples. Diagnoses were clinically adjudicated. ROC analyses and DeLong tests compared AUCs. The study involved 636 participants: 351 controls (55.2%), 135 non-functioning adrenal incidentaloma (21.2%), 14 aldosterone-cortisol cosecretion (2.2%), 116 mild autonomous cortisol secretion (18.2%), and 20 overt Cushing's syndrome (3.2%). Lower-tail DEX values were uncommon and even below lower-tail thresholds, DST results often remained clinically interpretable. DEX was higher in obesity than BMI <30&#x2005;kg/m2 (4.87 &#xb1; 2.26 vs 4.40 &#xb1; 2.44&#x2005;ng/mL; P = .030). For predicting overt hypercortisolism, AUCs were 0.976 (CLIA cortisol), 0.974 (LC-MS/MS cortisol), and 0.959 (LC-MS/MS cortisone), without significant pairwise differences. For the diagnosis of all forms of hypercortisolism, AUCs were 0.961 (CLIA cortisol), 0.951 (LC-MS/MS cortisol), and 0.931 (cortisone). LC-MS/MS cortisol optimal cut-offs were close to CLIA practice. Very low post-DST DEX concentrations are rare, and DST interpretation often remains informative even when DEX is below conventional thresholds, supporting a selective rather than routine use of DEX measurement. LC-MS/MS cortisol provides excellent discrimination with thresholds close to CLIA practice; cortisone appears best suited as an adjunct marker.