BACKGROUND Rabson-Mendenhall syndrome (RMS) is an extremely rare autosomal recessive disorder caused by pathogenic variants in the insulin receptor gene, leading to severe insulin resistance and compensatory hyperinsulinemia. Classical features include acanthosis nigricans, non-obese or underweight body habitus, hirsutism, dental abnormalities, dysmorphic features, and variable growth abnormalities. Early recognition may be difficult when the initial presentation is dominated by non-specific symptoms rather than classical metabolic complaints. CASE REPORT A 10-year-old Saudi girl presented to a family medicine clinic with intermittent bilateral leg pain and excessive hunger, without polyuria or polydipsia. Examination revealed extensive acanthosis nigricans, moderate hirsutism, deep voice, high-arched palate, and dental enamel defects. Laboratory evaluation showed severe hyperinsulinemia with insulin level of 3522.5 µU/mL, elevated HbA1c of 8.4% (68 mmol/mol), and biochemical hyperandrogenism. Although RMS is classically associated with growth restriction, the patient was tall for age and had a family history of tall stature, requiring cautious interpretation of growth-related findings. Whole-exome sequencing confirmed a homozygous pathogenic insulin receptor variant (c.433C>T, p.Arg145Cys), establishing the diagnosis of RMS. Treatment included vitamin D supplementation, metformin, basal-bolus insulin therapy, dapagliflozin, home glucose monitoring, diabetes education, dietary counseling, and multidisciplinary follow-up. Glycemic control remained suboptimal despite treatment intensification, reflecting the severe receptor-level insulin resistance associated with RMS. CONCLUSIONS In this patient, marked acanthosis nigricans, severe hyperinsulinemia, hyperglycemia, and hyperandrogenic features supported evaluation for a genetic insulin resistance syndrome despite the absence of classical diabetic symptoms.

Arginine vasopressin (AVP) deficiency, previously termed central diabetes insipidus, arises from impaired AVP synthesis or secretion by the hypothalamus and/or the posterior pituitary gland and presents with hypotonic polyuria and polydipsia. To differentiate AVP deficiency from AVP resistance and primary polydipsia, a stepwise diagnostic work-up is required. In recent years, copeptin, as a reliable surrogate marker of AVP secretion, has been incorporated into diagnostic algorithms, and copeptin-based stimulation tests have substantially improved diagnostic accuracy. Once AVP deficiency has been established, identification of the underlying cause is essential. A wide range of etiologies, including neurosurgical and traumatic injuries, granulomatous, inflammatory and autoimmune diseases, vascular events, infections, and genetic defects, require a diagnostic approach tailored to the suspected diagnosis. Evaluation should include a careful assessment of the patient's personal and family history, clinical examination, laboratory studies, imaging and, when indicated, tissue biopsy. In patients with apparently idiopathic AVP deficiency, a careful longitudinal follow-up is warranted, since it may represent the first manifestation of an underlying pathology. Treatment of AVP deficiency consists of desmopressin replacement combined with etiology-specific management.

In this case report, a 36-year-old Eritrean man presented with polyuria, polydipsia, fatigue and 5 kg weight loss. HbA1c was 97 mmol/mol, proinsulin C-peptide 266 and glucose 19.2 mmol/l without ketoacidosis. Type 1 diabetes was diagnosed, and insulin was initiated. Abdominal CT showed splenomegaly, cirrhosis and portal hypertension. Liver biopsy and positive serology and PCR confirmed schistosomiasis. After three months, glycaemia normalised without insulin, C-peptide increased and autoantibodies were negative. The diagnosis was revised to type 2 diabetes/flatbush diabetes.

Langerhans cell histiocytosis (LCH) is a rare clonal proliferative disorder of bone marrow-derived dendritic cells that is uncommon in adults. Its clinical presentation varies depending on the organ involved. Central nervous system (CNS) involvement poses a critical therapeutic challenge because of permanent neurological dysfunction. Here, we report two contrasting cases of adult-onset LCH with distinct clinical outcomes. Case 1 involved a 36-year-old woman presenting with a persistent headache. Neuroimaging revealed a solitary osteolytic lesion in the left parietal bone with dural thickening. Surgical resection was performed, and histopathological examination revealed characteristic Langerhans cells with positive S-100 immunostaining, confirming the diagnosis of LCH limited to the calvarium. The patient was treated with bisphosphonates and remained stable without systemic involvement. Case 2 involved a 26-year-old man presenting with cognitive impairment, somnolence, polyuria, and endocrine dysfunction. Magnetic resonance imaging revealed an enhancing hypothalamic lesion. Histopathological and immunohistochemical analyses confirmed LCH with CD1a and S-100 positivity. BRAF V600E mutation was not detected via pyrosequencing. Systemic chemotherapy with cladribine resulted in partial tumor regression; however, the cognitive dysfunction persisted. These contrasting cases highlight that disease distribution, particularly CNS involvement, influences therapeutic strategies and neurological outcomes in adult LCH. Our findings emphasize that early diagnosis and proactive systemic evaluation are essential as functional recovery remains limited once neurological damage occurs, even with successful cytoreductive therapy.

Arginine vasopressin deficiency (AVP-D) is an uncommon but clinically important cause of the polyuria-polydipsia syndrome. Establishing the diagnosis extends beyond confirming hypotonic polyuria and requires differentiation from primary polydipsia and arginine vasopressin resistance, together with identification of the underlying etiology. Unlike adults, children and adolescents with AVP-D frequently present with the earliest manifestation of an evolving neoplastic, infiltrative, inflammatory, congenital, autoimmune, or genetic disorder, making longitudinal clinical, endocrine, and magnetic resonance imaging (MRI) surveillance integral to the diagnostic process. Using three illustrative clinical cases, this review presents a practical approach to the evaluation of AVP-D, integrating clinical assessment, biochemical investigation, dedicated hypothalamic-pituitary MRI, and risk-adapted longitudinal surveillance. We discuss the strengths and limitations of the water deprivation test, the emerging role of copeptin-based diagnostics, and current evidence supporting arginine-, urea-, and glucagon-stimulated copeptin testing. Emphasis is placed on the longitudinal interpretation of MRI, consensus recommendations for PST, and the concept that idiopathic AVP-D should be regarded as a provisional diagnosis requiring continued etiological reassessment. Emerging biomarkers, including neurophysin I and oxytocin, may further refine the assessment of hypothalamic-neurohypophyseal dysfunction but remain investigational in children. Ultimately, AVP-D should be viewed not as the end of the diagnostic process but as its beginning, with clinical assessment, neuroimaging, endocrine evaluation, and structured surveillance integrated to achieve the earliest possible etiological diagnosis.

Background and Objectives: Given the limited therapeutic options for patients with persistent nocturia despite desmopressin treatment, we aimed to evaluate the short-term effects of add-on Gosha-jinki-gan therapy on hours of undisturbed sleep (HUS) and nocturia-related parameters in a real-world clinical setting. Materials and Methods: This retrospective study included 40 men aged ≥60 years with nocturnal polyuria who had ≥2 nocturnal voids or HUS ≤ 3 h despite desmopressin treatment. Add-on Gosha-jinki-gan (7.5 g/day) was initiated while concomitant medications were continued. Voiding diaries and validated questionnaires were assessed before treatment and at 1 and 4 weeks. Primary outcomes were the nocturnal voiding frequency, nocturnal urine volume, nocturnal polyuria index, and HUS. Secondary outcomes included the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Athens Insomnia Scale, and Patient Global Impression of Improvement (PGI-I). Results: The mean voided volume before desmopressin treatment was low (109.9 mL), suggesting reduced functional bladder capacity. Add-on Gosha-jinki-gan therapy was associated with a reduction in nocturnal voiding frequency (3.38 to 2.60 episodes/night, p < 0.0001) and nocturnal urine volume (p < 0.0001). The mean HUS increased from 116 to 186 min at 4 weeks (p < 0.0001), representing an extension of approximately 70 min and exceeding the clinically meaningful 3 h threshold. Sleep quality, assessed by the Athens Insomnia Scale, also improved significantly. No serious adverse events were observed. Conclusions: Add-on Gosha-jinki-gan therapy was associated with improvements in nocturia-related parameters and prolongation of HUS in patients with persistent nocturia despite desmopressin treatment. These findings should be considered preliminary and hypothesis-generating. Prospective controlled studies are required to determine whether add-on Gosha-jinki-gan provides benefits beyond desmopressin alone.

Background and Clinical Significance: Tenofovir disoproxil fumarate (TDF) is a widely prescribed nucleotide reverse transcriptase inhibitor (NtRTI) for HIV-1 infection. Though generally well-tolerated, proximal renal tubulopathy resulting in full-blown Fanconi syndrome remains a rare but severe complication (<0.1%). Case Presentation: We present the case of a 52-year-old female living with HIV-1 (diagnosed in 1999, CDC stage A3) who had been treated with a TDF-based antiretroviral regimen for 12 years. Upon admission, she complained of progressive bone pain and polyuria over the preceding six months. Laboratory investigations revealed profound hypokalemia, severe hypophosphatemia, hypouricemia, elevated alkaline phosphatase (ALP) and a decline in renal function (creatinine 1.3 mg/dL from a baseline of 0.7 mg/dL). Arterial blood gas (ABG) analysis showed a normal anion gap hyperchloremic metabolic acidosis alongside respiratory acidosis. Urinalysis demonstrated profound glycosuria in the setting of normal blood glucose levels, coupled with increased 24 h urinary excretion of potassium and phosphorus. A bone scintigraphy demonstrated a "super scan" pattern of metabolic etiology, establishing secondary osteomalacia driven by renal phosphate wasting. Secondary hyperparathyroidism and severe vitamin D3 deficiency were also recorded. The diagnosis of TDF-induced Fanconi syndrome was established. TDF was discontinued, and her antiretroviral regimen was modified to tenofovir alafenamide fumarate (TAF), emtricitabine (FTC), darunavir, and ritonavir, combined with vitamin D supplementation. Over a 6-month follow-up period, renal function normalized, electrolyte wasting resolved, and metabolic acidosis completely reversed. Conclusions: This case highlights that TDF-induced proximal tubulopathy can manifest even after a decade of uneventful therapy, particularly when co-administered with a boosted protease inhibitor.

Claudin-16 (CLDN16) and claudin-19 (CLDN19) are essential tight junction proteins in the kidney that are critical for magnesium homeostasis. Mutations in CLDN16 and CLDN19 cause Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC), a rare autosomal recessive tubular disorder. The disorder can progressively lead to severe complications, including end-stage renal disease. Affected individuals often present with polyuria, polydipsia, nephrolithiasis, hematuria, muscular tetany, seizures, and failure to thrive. Notably, CLDN19 mutations have also been associated with ocular abnormalities. We describe three patients with FHHNC and ocular involvement harboring a novel homozygous variant of uncertain significance (VUS) in the CLDN19 gene (c.-24_47dup). Our findings contribute to the expanding genetic landscape of this rare disorder and highlight the importance of early diagnosis and multidisciplinary management.