Female-pattern hair loss is common in obese women with polycystic ovary syndrome (PCOS), recently proposed as polyendocrine metabolic ovarian syndrome (PMOS) and is often associated with hypertriglyceridemia (TG), although the underlying mechanisms remain unclear. This study investigated how metabolic factors and androgens contribute to hair loss in female mice exposed to a high-fat diet (HFD). A controlled, parallel-group study using 8-week-old female C57BL/6 mice fed either an HFD (60% kcal fat) or a standard diet for 16 weeks. Mice were sacrificed at baseline and 4-week intervals for serial evaluation of metabolic, hormonal and skin changes (n = 6/group/time point). Hair loss was quantified from digital photographs using the ImageJ and further supported by histological examination. Circulating metabolic and hormonal profiles were measured. In dorsal skin, oxidative stress (malondialdehyde, MDA) and androgen-related markers-5-alpha-reductase type II (5αR2), dihydrotestosterone (DHT) and androgen receptor (AR)-were evaluated using immunohistochemistry, Western blot and enzyme-linked immunosorbent assay. From Week 12 onward, HFD-fed mice exhibited greater weight gain, pronounced dorsal hair thinning and elevated TG, insulin and free androgen index (FAI) levels. Skin MDA, 5αR2, DHT and AR levels also progressively increased. In the second experiment, 8-week-old female mice were assigned to four groups (n = 6/group): HFD with N-acetylcysteine (NAC), finasteride, spironolactone, or vehicle administered by oral gavage for 12 weeks. Compared with HFD-vehicle, antioxidant or anti-androgen co-treatment significantly lowered serum TG, tissue MDA and ameliorated hair thinning despite similar weight gain and 5αR2 levels. NAC reduced TG, FAI and decreased tissue MDA, DHT and AR. Finasteride lowered TG, MDA, DHT and AR, whereas spironolactone reduced TG and MDA. HFD-induced obesity exacerbates hair loss in female mice by enhancing oxidative stress and activating androgen signalling in the skin. Targeting these pathways, such as antioxidants and antiandrogens, may mitigate HFD-accelerated hair loss.

Polycystic ovary syndrome (PCOS) is a hormonal disorder marked by irregular menstrual cycles, elevated androgen levels, ovarian cysts, hirsutism, acne and other symptoms. While conventional medications such as Metformin and Spironolactone are commonly prescribed, they are often associated with undesirable side effects. As a result, there is growing interest in alternative treatments, particularly those involving medicinal plants. Vitex negundo L., a member of the Lamiaceae family, has demonstrated promising therapeutic effects against PCOS. However, its precise molecular mechanism of action remains unclear. To explore this, we conducted an untargeted metabolomics analysis using UPLC-MS/MS to identify bioactive compounds, followed by network pharmacology to elucidate potential mechanisms. Metabolite fingerprinting revealed 186 metabolites, among which 122 were identified as secondary metabolites. Network pharmacology analysis uncovered 910 potential targets associated with the identified compounds and 297 known PCOS-related disease targets, with 50 overlapping targets between the two datasets. Key hub targets identified included P53, ESR1, AKT1, STAT3, CTNNB1, ERBB2, BCL2, EGFR, MTOR and IL6. Furthermore, molecular docking highlighted several bioactive constituents-syringin, 4-(3,4-dihydroxyphenyl)-6,7-dihydroxynaphthalene-2-carboxylic acid, and Isovitexin-as potential lead compounds for PCOS treatment. Further evaluation of lead compounds can be conducted through in vitro and in vivo studies.

The renal distal convoluted tubule (DCT) plays a key role in magnesium homeostasis with genetic and drug-induced causes of hypomagnesemia affecting this segment. The importance of the renal TRPM6 channel subunit of the TRPM6/7 magnesium channel in magnesium homeostasis is unclear due to discrepant findings in knockout mice. Furthermore, the apical potassium channel Kv1.1 has been proposed to drive magnesium entry through TRPM6/7 along DCT, with limited experimental evidence. To clarify the roles of TRPM6 and Kv1.1 we generated mice with inducible DCT-specific TRPM6 knockout (DCT-TRPM6 KO) or renal tubule Kv1.1 knockout (tubule-Kv1.1 KO). Using a newly generated antibody, we found that TRPM6 expression is restricted to early DCT (DCT1), consistent with single cell transcriptomic data. DCT-TRPM6 KO displayed lower plasma [Mg[2+]] on diets with normal (0.21% w/w) or reduced (0.08% w/w) magnesium content. In contrast, plasma [Mg[2+]] did not differ to controls in tubule-Kv1.1 KO mice on diets containing 0.08% w/w or 0.04% w/w magnesium. There were no differences in other blood chemistry values for either knockout. GFR, lithium clearance, and natriuretic responses to furosemide, hydrochlorothiazide, or amiloride did not differ in tubule-Kv1.1 KO mice. Immunofluorescence and single molecule fluorescent in situ hybridization revealed Kv1.1 expression in mouse and human in glomeruli and along the S3 segment of the proximal tubule, but not along DCT. In summary, renal TRPM6 plays a critical role in magnesium homeostasis under baseline conditions. Kv1.1 is not expressed along DCT and is not required for magnesium homeostasis or normal renal function at baseline.

A rapid and sensitive direct injection (DI) method is proposed for the monitoring of 235 organic microcontaminants (OMCs), including those listed in the recently adopted Directive (EU) 2024/3019 and the 5th Watch List, in treated wastewater (WW) and drinking water (DW), using ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS/MS). No pre-concentration stages were applied thanks to the advantages of a state-of-the-art triple quadrupole (QqQ) instrument, minimizing sample handling up to a filtration step. The polarity switching mode was used for the analysis of the selected OMCs from different classes (pharmaceuticals, antibiotics, pesticides, artificial sweeteners, metabolites and transformation products) in a single injection. LC-MS/MS parameters, including injection volume, capillary voltage, source temperature and mobile phase composition, were optimized. The proposed method was successfully validated in urban WW effluents and DW at 10, 100 and 1000 ng/L. Trueness (average expressed as relative recovery) was in the range of 72-127% and inter and intra-day precision (expressed as relative standard deviation, RSD) was always ≤21%. Limits of quantification (LOQs) were in the range of 0.5-500 ng/L for WW and 0.1-100 ng/L for DW. The suitability of the method was demonstrated by analysing 28 WW samples from 2 wastewater treatment plants (WWTPs) and 10 DW samples from different locations. 150 OMCs with sum of concentrations ranging from 17.7 to 239.9 μg/L were detected in WW samples and 0.1 to 1.0 μg/L in DW samples, respectively. All of 12 compounds included in EU Directive 2024/3019 were detected in WW samples with individual concentrations ranging from 46 (metoprolol) to 6667 ng/L (hydrochlorothiazide).

Gordon syndrome (Pseudohypoaldosteronism type II) is a rare autosomal dominant disorder characterized by hyperkalemia, hypertension, and metabolic acidosis. Among the four causative genes, CUL3 mutations produce the most severe phenotype, yet endocrine manifestations beyond growth delay remain poorly described. We report a 22-year-old male who presented with chronic hyperkalemia, hypertension, insulin resistance with steatohepatitis, and testicular hypoplasia with elevated gonadotropins, consistent with compensated primary testicular dysfunction. Genetic analysis identified a de novo heterozygous CUL3 c.1207-26A>G splice-site mutation resulting in exon 9 skipping. Treatment with hydrochlorothiazide normalized blood pressure and serum potassium while improving metabolic and hormonal abnormalities. Notably, these improvements reversed upon treatment discontinuation. This case suggests that certain endocrine manifestations in CUL3-related Gordon syndrome may be secondary to chronic electrolyte imbalance rather than direct genetic effects, highlighting the importance of comprehensive endocrine evaluation and sustained thiazide therapy in affected patients.

A 54-year-old woman with recurrent hypertensive crises was found to have a lipid-rich right adrenal adenoma. Biochemical evaluation was inconclusive for both pheochromocytoma and primary aldosteronism (PA). While 68Ga-DOTATATE PET/CT showed no abnormal uptake in the adrenal adenoma, effectively excluding pheochromocytoma, 68Ga-Pentixafor PET/CT demonstrated focal uptake within the adenoma, suggesting an aldosterone-producing adenoma. Given the high clinical suspicion for PA and the invasive nature of adrenal vein sampling, medical therapy with spironolactone was initiated and resulted in a favorable clinical response. This case highlights the potential diagnostic value of CXCR4-targeted PET/CT in suspected PA.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome encompassing hypertensive left ventricular remodelling with diastolic dysfunction and systemic inflammation-driven endothelial dysfunction, with possible contributions from visceral adipose tissue-associated metabolic and proinflammatory alterations. However, conventional key risk factors for HFpEF, including advanced age, female sex, obesity, diabetes, and chronic kidney disease, are closely associated with mineralocorticoid receptor (MR) overactivation through several under-recognized mechanisms, i.e. renin-independent aldosterone excess, cortisol dysregulation, and ligand-independent activation. MR overactivation promotes myocardial hypertrophy and fibrosis, vascular remodelling, and systemic inflammation, all of which are hallmark features of HFpEF. Among patients with HFpEF, the steroidal MR antagonist (MRA) spironolactone has been suggested to reduce the risk of HF-related events, while the non-steroidal MRA finerenone has significantly reduced the primary composite of total worsening HF events and cardiovascular death. Across subgroups suggestive of MR overactivation, MRA therapy has shown generally consistent efficacy and safety, although greater adiposity may be associated with greater MRA efficacy. Given the continuum of MR activation across HF stages, early therapeutic intervention targeting MR overactivation may mitigate the risk of HFpEF development and progression. Furthermore, aldosterone synthase inhibitors and MR modulators, which also attenuate MR overactivation, are being evaluated for HFpEF prevention and treatment. This paper presents the mechanistic pathways linking MR overactivation to HFpEF and highlights the potential benefits of mitigating MR activation for its prevention and treatment, calling for renewed consideration of treatment strategies in clinical practice and trial design.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is an uncommon but recognized complication of herpes zoster (varicella-zoster virus, VZV) infection, and diagnostic uncertainty may arise when hyponatremia develops after antiviral therapy is initiated. We report an 89-year-old patient with hypertension, chronic kidney disease stage 3, hyperlipidemia, and prior left nephrectomy for renal cell carcinoma who presented with right neck and upper arm pain, weakness, and a unilateral dermatomal vesicular eruption consistent with herpes zoster. Oral acyclovir was started at 800 mg five times daily. During hospitalization, serum sodium declined from 136 mEq/L to a nadir of 123 mEq/L despite discontinuation of hydrochlorothiazide. The patient remained clinically euvolemic, with urine sodium of 134 mEq/L and urine osmolality of 570 mOsm/kg, supporting SIADH. Thyroid-stimulating hormone and morning cortisol were normal. Fluid restriction < 1.2 L/day was ineffective. As the patient became symptomatic, and hypertonic saline (with removal of fluid restriction) produced no improvement, a single dose of tolvaptan produced rapid correction of serum sodium and improvement in mentation. The patient was subsequently maintained on sodium chloride tablet supplementation, fluid restriction, and a high-protein diet, with serum sodium improving to 135-136 mEq/L. This case describes severe hypotonic euvolemic hyponatremia meeting biochemical criteria for SIADH in the setting of localized herpes zoster, after consideration of concurrent hydrochlorothiazide exposure and temporally associated oral acyclovir.

A survey of UK and Irish healthcare professionals was distributed via the UK Dermatology Clinical Trials Network, British Society for Paediatric and Adolescent Dermatologists, Irish Association of Dermatologists and other regional groups. The aim was to understand how healthcare professionals prescribe spironolactone for female patients, with a particular focus on those aged ≤ 18 years, as well as concerns regarding side effects and thoughts about a future clinical trial. A total of 116 responses were received from healthcare professionals, including dermatologists, dermatology nurses, paediatricians, general practitioners and pharmacists. The results showed that there is varied clinical practice and confidence among healthcare professionals treating this population with spironolactone, with the main safety concerns being around hormonal implications, future pregnancies and lack of long-term data.

Primary hyperparathyroidism occurs in up to 95% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only a few cases of parathyroid carcinoma have been reported, and only one case of intrathyroidal parathyroid carcinoma. We describe the case of a 41-year-old male with a history of MEN1 and primary hyperparathyroidism who developed hypercalcemia to 13.1 mg/dL (SI: 3.3 mmol/L) (reference range [RR], 8.6-10.3 mg/dL [SI: 2.2-2.6 mmol/L]) with parathyroid hormone (PTH) 454 pg/mL (SI: 48.1 pmol/L) (RR, 15-65 pg/mL [SI: 1.6-6.9 pmol/L]). Neck ultrasonography showed a highly suspicious intrathyroidal 3.6 cm nodule. The patient had a lobectomy, and final pathology showed a 3.1 × 1.6 × 1.2 cm parathyroid carcinoma. After the surgery, calcium dropped to 6.0 mg/dL (SI: 1.5 mmol/L) with PTH of 11 pg/mL (SI: 1.2 pmol/L) requiring oral calcium supplements, calcitriol, and hydrochlorothiazide. Laboratory tests at 12 months on these medications showed calcium of 9.3 mg/dL (SI: 2.3 mmol/L) and PTH 21 pg/mL (SI: 2.2 pmol/L) indicating recovery of parathyroid function without recurrence, and calcitriol was discontinued. This case illustrates that a high index of suspicion for malignancy should be maintained for intrathyroidal parathyroid adenoma in the setting of severe hypercalcemia, especially in MEN1.

Sulfonamides are widely prescribed in clinical practice. Although rare, these have been shown to trigger an idiosyncratic reaction characterized by an acute myopic shift, likely caused by ciliochoroidal effusion and anterior rotation of the ciliary body, resulting in forward displacement of the iris-lens diaphragm. We report the case of a patient who developed blurred vision and acute myopia on cycloplegic refraction after initiating hydrochlorothiazide. The symptoms resolved completely after discontinuation of the medication. Although most of the literature highlights this reaction in association with topiramate, it is important to note that any sulfonamide can potentially lead to a similar clinical presentation.