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.

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.

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.

This review highlights disorders of water and tissue perfusion in equids, specifically diabetes insipidus, the renin-angiotensin-aldosterone axis, and anhidrosis. The differences in renal versus central diabetes insipidus is discussed, as well as diagnosis and treatment of diabetes insipidus in equids. The physiology of the renin-angiotensin-aldosterone axis is reviewed, and recent research in the role of the renin-angiotensin-aldosterone axis in equids in certain states is emphasized. The proposed pathophysiology of anhidrosis in horses is discussed, as well as potential therapies.

Background Polyuria-polydipsia syndrome encompasses a heterogeneous group of disorders, including central diabetes insipidus (CDI), nephrogenic diabetes insipidus (NDI), and primary polydipsia. Despite presenting with similar clinical manifestations, these conditions differ markedly in their underlying pathophysiology, prognosis, and management. Distinguishing between them remains clinically challenging, particularly in patients with partial disease and in resource-limited settings where newer diagnostic biomarkers such as copeptin are not routinely available. This study highlights the diagnostic complexity and diverse etiologies of polyuria-polydipsia syndrome through a retrospective case series. Methods We conducted a retrospective observational study of patients presenting with polyuria-polydipsia syndrome at a tertiary care center over a five-year period. Clinical, biochemical, and radiological data were retrieved from medical records. Patients underwent diagnostic evaluation based on clinical indication, including assessment of serum and urine osmolality and a supervised water deprivation test with or without a desmopressin challenge, as appropriate. Additional imaging and genetic investigations were performed where clinically indicated. Patients were classified as having CDI, NDI, or primary polydipsia based on the available clinical, biochemical, radiological, and, where applicable, genetic findings in accordance with standard diagnostic criteria. Results A total of seven patients were included, demonstrating diverse etiologies: complete CDI (n = 1), CDI associated with pituitary stalk interruption syndrome (n = 1), partial CDI (n = 1), NDI with a possible CLCN5 gene variant (n = 1), primary polydipsia (n = 1), pheochromocytoma presenting as a diabetes insipidus mimic (n = 1), and CDI secondary to postoperative and post-radiotherapy craniopharyngioma with panhypopituitarism (n = 1). Despite similar presenting complaints, each case exhibited distinct biochemical and radiological profiles. The water deprivation test followed by a desmopressin challenge enabled definitive diagnosis. Etiology-specific management resulted in significant clinical improvement across the cohort. Conclusion Polyuria-polydipsia syndrome represents a diagnostically challenging entity with diverse underlying etiologies. A structured approach integrating clinical evaluation, biochemical testing, dynamic assessment, and imaging remains effective for accurate diagnosis, even in the absence of advanced biomarkers. Recognition of atypical and reversible causes is essential to avoid misdiagnosis and ensure appropriate, targeted management.