Adrenal incidentalomas (AI) are commonly found on imaging done for indications other than to assess the adrenal glands. Prevalence increases with age and is around 10% in people over 80 years. The majority of AIs are benign adenomas, with 20%-50% exhibiting mild autonomous cortisol secretion (MACS). Clinical guidelines recommend the use of dexamethasone to improve outcomes in patients with COVID-19 requiring oxygen. Benign adrenal adenomas protect against severe COVID-19. Reports for all computed tomography pulmonary angiogram (CTPA) scans at Sheffield Teaching Hospitals between 11 March 2020 and 10 November 2021 were assessed for details of AI. Scan requests mandated recording COVID-19 status. Patients with a positive COVID-19 test within 2 weeks before the CTPA were classed as COVID-19 positive for the analyses. Duplicate scans were removed. A total of 4307 CTPA scans were included. The median age was 65 (IQR 49-77) and the majority of patients were female (55.0%). Seventy-six (1.76%) patients had a benign adenoma. COVID-19 positivity was found in 897 (20.8%). The presence of a benign adenoma was associated with a 70% reduced odds of being COVID-19 positive (aOR 0.30, 95% CI 0.12-0.74, p = 0.01), adjusting for age and sex. Prevalence of adrenal adenoma was associated with significantly reduced odds of being SARS-CoV2 positive in an inpatient cohort. Secretion of mild excess cortisol (MACS) may be protective against developing severe COVID-19.

Mild autonomous cortisol secretion (MACS) is associated with increased cardiometabolic risk factors including hypertension, type 2 diabetes and dyslipidaemia. By using evening doses of metyrapone, a short-acting 11-β hydroxylase inhibitor, it has been shown that it is possible to reset the abnormal circadian cortisol rhythm in MACS. This study aimed to evaluate the tolerability and impact of this approach on cardiometabolic outcomes in patients with MACS. We conducted a single-centre retrospective, longitudinal review of patients with MACS who received evening metyrapone (250-500 mg at 6 PM and 250 mg at 10 PM) to evaluate adverse events, tolerability, and cardiometabolic outcomes (systolic and diastolic blood pressure, HbA1c, weight and non-HDL cholesterol) at 6 months, compared to controls. Age and sex-matched controls were identified from patients with adrenal incidentalomas and non-suppressed serum cortisol following 1 mg overnight dexamethasone suppression testing. Fifteen patients and 15 matched controls were identified. Over 6 months there were no adrenal crises. Metyrapone was stopped in 2/15 patients in view of side effects. In the metyrapone group compared to controls, there were significant decreases in systolic blood pressure (-17.7 (SE 5.8) vs. +8.7 (5.7)mmHg, p = 0.008, n = 9) and diastolic blood pressure (-9.9 (4.2) vs. +3.0 (3.6)mmHg, p = 0.024). The differences between groups for HbA1c, weight and non-HDL cholesterol were not statistically significant. Evening metyrapone was associated with significant reductions in systolic and diastolic blood pressure in patients with MACS, without causing adrenal insufficiency, indicating its potential safe clinical utility. A well-powered, controlled, prospective study is needed to validate these findings and comprehensively investigate the broader metabolic outcomes.

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. 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. 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). 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.

Primary aldosteronism (PA) is a common cause of hypertension in young women. However, there is a paucity of data regarding its impact during pregnancy. The primary objective of this study was to describe the occurrence of hypertensive disorders of pregnancy (HDP) in PA. This retrospective cohort study compared outcomes in pregnancies according to PA status. Pregnancies occurred between 2011 and 2022 at the Centre Hospitalier Universitaire de Sherbrooke. All selected pregnancies were screened for PA with an aldosterone-to-renin ratio (ARR) within a 5-year period. Pregnancies with more than two fetuses and with other endocrinopathies were excluded. To ascertain PA diagnosis, ARR measurements were conducted, followed by a confirmatory test if abnormal. Among 226 studied pregnancies, 15 (6.6%) were diagnosed with PA. In the PA group, pre-eclampsia was diagnosed in 46.7% of pregnancies (vs. 30.8%, p = 0.252), while gestational hypertension was diagnosed in 0.0% of pregnancies (vs. 16.6%, p = 0.136). Post-partum HDP occurred in 40.0% of pregnancies with PA (vs 19.4%, p = 0.093). Additionally, 40.0% and 13.3% of pregnancies with PA respectively required intravenous antihypertensive treatment (vs. 24.2%, p = 0.216) and intensive care admission (vs. 3.3%, p = 0.113). A trend towards an increased incidence of postpartum and severe pre-eclampsia was noted in the PA group.

Differentiating primary hyperparathyroidism (PHPT), normocalcemic PHPT (NPHPT), and vitamin D deficiency-related secondary hyperparathyroidism (VDSHPT) remains a diagnostic challenge. This study evaluated the utility of biochemical markers in distinguishing these conditions. In this cross-sectional study, 437 participants were categorised into PHPT (n = 161), NPHPT (n = 97), VDSHPT (n = 89), and control (n = 90) groups. Serum calcium, phosphate, chloride, PTH, and vitamin D levels were analysed, along with indices such as Ca/P, Cl/P, Ca × Cl/P, and the PF Index (Ca × PTH/P). Calcium levels were highest in PHPT (2.73 ± 0.17 mmol/L), while phosphate levels were lowest (0.70 ± 0.19 mmol/L) both p < 0.001. PTH levels were significantly elevated in PHPT, NPHPT, and VDSHPT versus controls (p < 0.001). Ca/P ratio was significantly higher in PHPT (4.17 ± 1.21, p < 0.001), as was the Ca × Cl/P ratio (448.5 ± 133.6, p < 0.001). No significant difference was found between NPHPT and VDSHPT groups in Ca/P (p = 0.63) and Ca × Cl/P (p = 0.74) ratios. Ca × Cl/P ratio exhibited the highest diagnostic accuracy for PHPT with a specificity of 89.2% and PPV of 82.2%. Ca/P ratio had the highest sensitivity (77.6%) and an NPV of 86.6%. PF Index (AUC: 0.851, 95% CI: 0.816-0.886) and Cl/P ratio (0.766, 95% CI: 0.711-0.820) showed moderate accuracy. In NPHPT, all markers had high sensitivity but poor specificity (1.6%-23.2%). The Ca × Cl/P and Ca/P ratios demonstrate substantial diagnostic value for PHPT, while biochemical markers exhibited limited specificity in NPHPT. These findings highlight their role in screening but emphasize the need for additional diagnostic approaches.

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. 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. 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). 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. The trial was registered at ClinicalTrials. gov under the identifier NCT02638077.

To clarify the link between environmental pollution and diabetes risk by focusing on pancreatic β-cells as key targets of environmental insults, with emphasis on the role of endocrine-disrupting chemicals (EDCs) in pancreatic dysfunction and diabetes pathogenesis. This narrative review synthesises recent research on EDCs, focusing on their effects on β-cells. The literature search included studies in English on EDCs, diabetes, and β-cell function, utilising Boolean operators to refine the search. EDCs impair β-cell function through mechanisms such as oxidative stress, mitochondrial damage, and epigenetic changes. These pollutants disrupt insulin synthesis, secretion, and β-cell survival, which is distinct from their general metabolic effects. Additionally, EDCs may interact synergistically with traditional diabetes risk factors, such as high-fat diets, amplifying the risk of diabetes. Environmental pollutants play a significant role in β-cell dysfunction and diabetes, offering new directions for research and prevention.

Hyponatremia remains a common and life-threatening complication in children with traumatic brain injury, subarachnoid haemorrhage, brain tumours and post neurosurgical states, yet distinguishing its two primary neurogenic etiologies-syndrome of inappropriate antidiuretic hormone secretion (SIADH) and cerebral/renal salt wasting (C/RSW)-remains difficult. Misdiagnosis may result in inappropriate treatment strategies with a significant risk of morbidity. While adult studies suggest diagnostic roles for fractional excretion of uric acid (FEurate), fractional excretion of phosphate (PEphosphate) and NT-proBNP level, no paediatric-specific guidelines or reference thresholds currently exist. To evaluate the diagnostic accuracy of FEurate, FEphosphate and NT-proBNP in distinguishing C/RSW from SIADH in hyponatremic children with neurologic conditions. A comprehensive literature search was performed across PubMed, Embase, Web of Science, Scopus and the Cochrane Library. Eligible studies included RCTs, systematic reviews, meta-analysis and prospective/retrospective studies involving paediatric patients diagnosed with SIADH or C/RSW using any of the three biomarkers. Systematic reviews were appraised using AMSTAR 2. Two reviewers independently assessed eligibility and extracted data. Out of 69 identified studies, there were only two prospective paediatric cohort studies reported on the use of biomarkers in C/RSW versus SIADH syndromes. Findings are limited by the absence of paediatric-specific cut-off values. Current evidence suggests that FEurate, FEphosphate and NT-proBNP may provide diagnostic clues, but each biomarker has limitations related to assay variability, age-dependent reference ranges, comorbidities and confounding medications. FEurate response to sodium correction appears most useful, though serial measurements are often required.

Data on bone health in patients with mild autonomous cortisol secretion (MACS) are limited and heterogenous. We sought to assess the prevalence of osteoporosis and symptomatic fragility fractures in patients with adrenal adenomas and hypercortisolism, and explore associations with the degree of cortisol excess and frailty. This multicenter cross -sectional study involved prospective enrollment of adults with nonfunctioning adrenal adenomas (NFA), MACS, Cushing syndrome (CS) and referent subjects without adrenal disorders during the study period (January 2019-September 2022). All participants completed a bone health questionnaire at enrollment and had dual-energy X-ray absorptiometry bone mineral density assessment within 12-months. Final analyses were adjusted for age, sex, body mass index, smoking status, alcohol use. Participants included 117 with NFA (median age 62 years, 80% women), 191 with MACS (median age 63 years, 74% women), 62 with CS (median age 50 years, 92% women), and 101 referent subjects (median age 59 years, 47% women). Both patients with CS (OR: 3.0, 95% CI: 1.1-8.3) and MACS (OR: 2.2, 95% CI: 1.9-4.9) had a higher prevalence of osteoporosis when compared to referents. Among patients with MACS, only those with post 1-mg dexamethasone suppression test (post-1mg-DST) cortisol > 83 nmol/L had a higher prevalence of osteoporosis when compared to referents (OR: 3.2, 95% CI: 1.4-7.5) and NFA (OR: 2.2, 95% CI: 1.1-4.4). For clinical fragility fractures, only patients with CS showed an increased prevalence when compared to referents (OR: 6.1, 95% CI: 1.7-26.4) and NFA (OR: 3.8, 95% CI: 1.3-11.2). Prevalence of clinical fragility fractures was similar to referents in patients with MACS (OR: 1.8, 95% CI: 0.6-6.9) and NFA (OR: 1.5, 95% CI: 0.4-6.1), and was not associated with post-1mg-DST cortisol or frailty in the MACS and NFA groups. Patients with CS, and those with MACS and post-1mg-DST cortisol > 83 nmol/L, exhibited a higher burden of osteoporosis. However, only CS was associated with an elevated risk of symptomatic fragility fractures.