Background and Clinical Significance: IgG4-related disease (IgG4-RD) is a chronic fibroinflammatory, immune-mediated multisystem disorder that can mimic neoplastic, infectious, or autoimmune conditions. Among its head-and-neck manifestations, IgG4-related dacryoadenitis and sialadenitis, historically referred to as Mikulicz disease, should be distinguished from the classical Mikulicz syndrome, which describes secondary lacrimal and salivary gland enlargement due to other systemic disorders. Renal involvement, most commonly in the form of IgG4-related tubulointerstitial nephritis (IgG4-TIN), is less frequent but carries major prognostic implications because delayed diagnosis may lead to irreversible kidney damage. Case Presentation: A 49-year-old man with no relevant past medical history presented with a 2-year history of intermittent polyuria and foamy urine. Laboratory testing revealed advanced kidney dysfunction, with serum creatinine of 4.2 mg/dL, estimated glomerular filtration rate of 16 mL/min/1.73 m2, and proteinuria of 2874 mg/day. Physical examination showed bilateral parotid enlargement, upper eyelid edema, lacrimal gland enlargement, and sicca symptoms, raising suspicion for IgG4-related dacryoadenitis and sialadenitis (Mikulicz disease). Further work-up demonstrated marked eosinophilia, polyclonal hypergammaglobulinemia, and significantly elevated serum IgG4 levels (3180 mg/dL), while infectious serologies and autoimmune studies were negative. Kidney biopsy revealed plasma cell-rich tubulointerstitial nephritis with lymphoplasmacytic and eosinophilic infiltrates, interstitial fibrosis, tubular atrophy, and more than 40 IgG4-positive plasma cells per high-power field, supporting the diagnosis of IgG4-related tubulointerstitial nephritis in the setting of systemic IgG4-RD. Treatment with prednisone followed by mycophenolate mofetil led to improvement in glandular manifestations and a partial reduction in proteinuria, but renal recovery remained incomplete. The patient subsequently developed a severe pulmonary infection complicated by sepsis and oligoanuric acute kidney injury superimposed on chronic kidney disease, and ultimately progressed to end-stage kidney disease requiring chronic maintenance hemodialysis. Conclusions: This case highlights that a Mikulicz disease phenotype may represent the initial manifestation of systemic IgG4-RD and should prompt evaluation for extraglandular involvement, particularly renal disease. In patients with glandular enlargement, eosinophilia, hypergammaglobulinemia, and unexplained renal dysfunction, IgG4-RD should be actively considered. Kidney biopsy remains essential for diagnostic confirmation and prognostic assessment, as delayed recognition may result in irreversible renal damage and progression to end-stage kidney disease.

Diabetes insipidus (DI) is a heterogeneous disorder characterised by polyuria and polydipsia due to impaired arginine vasopressin (AVP) secretion or action. We describe a 36-year-old pregnant woman who presented at 28 weeks' gestation with weakness, severe hypokalaemia from renal potassium wasting, hypernatraemia and polyuria with dilute urine. Vasopressinase-mediated DI was suspected; there was no response to AVP, but desmopressin (dDAVP) produced a rapid clinical improvement, confirming the diagnosis. However, postpartum recurrence of symptoms prompted further evaluation, with imaging suggestive of lymphocytic infundibuloneurohypophysitis, necessitating reinitiation of dDAVP. This case highlights the diagnostic complexity of DI in pregnancy and the need to remain vigilant for central causes, even when vasopressinase-mediated DI is initially suspected.

Within a 2-year period, 5 adult, single-housed, northern tree shrews (Tupaia belangeri) presented for a range of clinical signs including lethargy, hindlimb lameness, decreased visual acuity, polyuria, and polydipsia. Diagnostic findings, including point-of-care blood glucose and ketone measurements, urine dipstick analysis, insulin, fructosamine, and glycosylated hemoglobin levels, and gross and histopathologic lesions, were consistent with a diagnosis of type 2 diabetes mellitus. Although spontaneous diabetes mellitus has been reported in other members of the order Scandentia, to our knowledge, this represents the first published case series describing naturally occurring type 2 diabetes mellitus in the northern tree shrew.

Fulminant type 1 diabetes (FT1D) is a rare immune-related adverse event associated with nivolumab, and its clinical characteristics remain unclear. This study aims to characterize the clinical features of nivolumab-associated FT1D and to generate evidence to inform its diagnosis and prevention. A systematic search of databases was conducted to identify clinical cases of nivolumab-associated FT1D reported through March 31, 2026. Clinical data for the patients were extracted and subjected to statistical analysis. A total of 59 patients were included, with a median age of 59 years (range 22, 87). The median time to onset of FT1D was 90 days (range 9, 1988) after the initial administration of nivolumab, with a median treatment cycle of 6 cycles (range 1, 136). Polyuria (45.1%), polydipsia (31.4%), weight loss (29.4%), thirst (23.5%), nausea (23.5%), vomiting (21.6%), and fatigue (19.6%) were the main symptoms. The median plasma glucose level at the diagnosis of FT1D was 594 mg/dL (range 208.8, 1652.4), and the median HbA1c was 7.2% (range 5.4, 8.9). Glutamic acid decarboxylase antibody positivity was detected in 23.6% of patients. Following nivolumab discontinuation and initiation of intensive insulin therapy, glycemic control was satisfactorily achieved. FT1D is a rare immune-related adverse event associated with nivolumab. Close plasma glucose monitoring should be maintained both during nivolumab therapy and after drug discontinuation. The possibility of FT1D should be considered in patients presenting with hyperglycemic symptoms and diabetic ketoacidosis. Nivolumab-associated FT1D requires long-term maintenance insulin therapy.

Immune checkpoint inhibitor-related diabetes mellitus is a rare but clinically important endocrine adverse event that characteristically presents with abrupt-onset diabetic ketoacidosis, disproportionately normal or near-normal glycated haemoglobin, and evidence of autoimmune beta-cell destruction. We report the case of a 58-year-old woman receiving atezolizumab and bevacizumab for hepatocellular carcinoma who developed new-onset polyuria and polydipsia followed by diabetic ketoacidosis within weeks of commencing immunotherapy. Biochemical evaluation confirmed endogenous hyperinsulinaemia-unrelated hyperglycaemia with strongly positive islet autoantibodies, including glutamic acid decarboxylase (158 IU/mL) and zinc transporter 8 (1,467 U/mL), alongside a urinary C-peptide/creatinine ratio of 0.59 nmol/mmol, consistent with early but rapidly evolving beta-cell failure. She was treated with standard diabetic ketoacidosis care, transitioned to a basal-bolus insulin regimen with continuous glucose monitoring, and discharged with coordinated oncology-endocrinology follow-up. Atezolizumab was held during acute decompensation with plans for re-initiation once metabolic stability was achieved. This case adds to the growing literature on programmed death-ligand 1 inhibitor-induced diabetes in the hepatocellular carcinoma population, where such events are incompletely characterised. Clinicians managing patients on atezolizumab-based regimens should maintain a low threshold for glucose monitoring and early ketone testing in the presence of osmotic symptoms.

Renal water reabsorption is classically regulated by vasopressin V2 receptor (V2R) signaling through cyclic AMP and protein kinase A, driving apical accumulation of aquaporin-2 (AQP2). However, collecting duct water handling is also modulated by vasopressin-independent mechanisms. Here, we examined intracellular soluble urate as a vasopressin-independent regulator of AQP2 trafficking. Intracellular urate accumulation in collecting duct cells was mediated by enhanced apical urate uptake via GLUT9b and reduced apical urate efflux through ABCG2, triggering phosphodiesterase-4 activation, reduced cAMP, and downstream AMP-activated protein kinase (AMPK) activation. The resulting AQP2 accumulation at the apical membrane was independent of V2R signaling, required ongoing endocytosis and was associated with features of post-endocytic apical trafficking of internalized AQP2. In vivo ABCG2 inhibition with probenecid increased apical AQP2 abundance and markedly attenuated tolvaptan-induced polyuria in both wild-type and Pkd1RC/RC autosomal dominant polycystic kidney disease (ADPKD) mice in a uricase-independent manner, while preserving tolvaptan's ADPKD-modifying efficacy. In a Phase 2 trial with tolvaptan-treated ADPKD patients, probenecid reduced urine volume and nocturia frequency. Together, these findings support a vasopressin-independent urate-AMPK-AQP2 pathway that regulates renal water handling and, in a preclinical ADPKD model, can uncouple cyst growth attenuation from the dose-limiting aquaretic effects of V2R antagonism.

Granulomatosis with polyangiitis (GPA) is a systemic necrotizing vasculitis associated with anti-neutrophil cytoplasmic antibodies (ANCA). Although pituitary involvement is rare, it represents a clinically relevant manifestation that may present as a sellar mass mimicking a pituitary neuroendocrine tumour (PitNET), leading to diagnostic delay and inappropriate management. We report the case of a male patient who initially presented at 24 years of age with recurrent epistaxis and nasal crusting, with histopathological evidence of chronic granulomatous inflammation of undetermined aetiology. Four years later, he developed headache, diplopia, bitemporal hemianopia, polyuria, and polydipsia. Magnetic resonance imaging revealed a pituitary mass with suprasellar extension. Endocrine evaluation demonstrated hypopituitarism and arginine vasopressin (AVP) deficiency. The patient underwent transcranial resection under the presumptive diagnosis of a non-functioning PitNET; however, postoperative imaging showed lesion progression. Further investigation revealed positive C-ANCA and systemic features consistent with GPA. Histopathological reassessment with immunohistochemistry supported the diagnosis of granulomatous hypophysitis in the context of GPA. Induction therapy with cyclophosphamide achieved initial disease control, but pituitary relapse occurred during maintenance therapy with azathioprine, prompting treatment escalation to rituximab. Rituximab led to reduction of the pituitary mass and sustained clinical stability over four years. Persistent hypopituitarism required long-term hormone replacement. Pituitary involvement in GPA is an uncommon but important diagnostic challenge and may closely mimic a PitNET. This case highlights the need for careful integration of systemic clinical features, endocrine findings, imaging, and histopathological reassessment when evaluating sellar masses. Immunosuppressive therapy with cyclophosphamide and rituximab was effective in controlling pituitary involvement, although permanent pituitary hormone deficiencies may persist despite disease control.

Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes characterized by hyperglycemia, high-anion-gap metabolic acidosis, and ketonemia. Hypernatremia in DKA is uncommon and typically reflects disproportionate free water loss. Arginine vasopressin resistance (AVP-R), previously known as nephrogenic diabetes insipidus, may occur in the setting of hypokalemia, leading to polyuria, hypotonic urine, and worsening hypernatremia. We report the case of a 14-year-old previously healthy female who presented with new-onset severe DKA complicated by profound acidosis, hyperglycemia, hypokalemia, and hypernatremia. Despite standard DKA management, she developed persistent polyuria and rising serum sodium levels. Urine studies demonstrated dilute urine with inappropriately elevated pH, raising suspicion for hypokalemia-induced AVP-R. Management included aggressive potassium repletion, careful adjustment of intravenous fluids, and adjunctive desmopressin therapy. This approach resulted in normalization of electrolyte abnormalities, resolution of polyuria, and full clinical recovery. This case highlights the importance of recognizing hypokalemia-induced AVP-R as a reversible cause of refractory hypernatremia in DKA and underscores the need for individualized fluid and electrolyte management beyond standard treatment protocols.