Introduction: Disseminated histoplasmosis is a rare but important cause of adrenal insufficiency (AI), particularly in tuberculosis (TB)-endemic regions, where it may mimic granulomatous diseases. Adrenal involvement occurs in up to 80% of disseminated cases, although overt AI is less common. Reported cases described bilateral adrenal masses mimicking malignancy or TB, even in immunocompetent individuals. Addisonian crisis may be the initial manifestation, especially when the diagnosis is delayed. In TB-endemic settings, fungal infections are often overlooked, leading to delayed diagnosis and inappropriate therapy. Case: We reported a case of a 68-year-old male with underlying diabetes mellitus who presented with fever, cough, dysphagia, and weight loss for 1 month. He was empirically treated as smear-negative disseminated TB. On day 2 of therapy, he developed hypotension (80/50 mmHg), hypoglycemia (3.9 mmol/L), hyponatremia (Na 129 mmol/L), and hyperkalemia (K 5.1 mmol/L), suggestive of adrenal crisis, and was started on intravenous hydrocortisone. Serum cortisol prior to treatment was 61 nmol/L. Computed tomography (CT) imaging revealed bilateral lipid-poor adrenal lesions (right: 3.6 × 2.2 × 4.9 cm, Hounsfield Unit (HU) 36 and absolute washout 33%; left: 3.5 × 2.4 × 5.4 cm; HU 35 and absolute washout 17%), raising suspicion of infectious or malignant etiologies. Endoscopic ultrasound-guided biopsy demonstrated necrotizing granulomatous inflammation with budding fungal yeasts on Pituitary Apoplexy Score and GMS staining, consistent with Histoplasma capsulatum. TB and malignancy were excluded. He received amphotericin B for 14 days, followed by oral itraconazole for 1 year, and oral hydrocortisone replacement. At 1-year follow-up, adrenal lesions remained stable on CT images, and he continued to require hydrocortisone replacement. Conclusion This case highlights the importance of considering disseminated histoplasmosis as a differential diagnosis of bilateral adrenal masses with AI, especially with poor response to anti-TB therapy. Early tissue diagnosis is essential, as imaging findings are non-specific. Prompt recognition is critical to prevent life-threatening adrenal crisis and improve clinical outcomes.
Histoplasmosis ; Tuberculosis

Introduction: Vitamin D-dependent rickets type 2 (VDDR2) is traditionally defined by biallelic vitamin D receptor (VDR) mutations causing resistance to 1,25(OH)₂D. We describe a case of the classical VDDR2 phenotype with a single VDR mutation and an interesting physiological adaptation. Case: A female diagnosed with rickets at age three presented with a femoral fracture, severe short stature, hypocalcemia (2.1 mmol/L; NR 2.35–2.70), hypophosphatemia (0.8 mmol/L; NR 1.5–2.10), and evidence of renal phosphate wasting (TMP/GFR 0.5 mmol/L; NR 1.5–2.4). Biochemistry showed markedly elevated alkaline phosphatase (1,227 IU/L; NR 50–136) and secondary hyperparathyroidism (20.7 pmol/L; NR 0.8–7.8). Despite hypocalcemia, 1,25(OH)₂D was significantly elevated (>450 pmol/L; NR 60–150), consistent with VDDR2. There was no initial family history; however, subsequent evaluation of her mother—prompted by the patient’s diagnosis—revealed a similar biochemical profile, along with short stature (142 cm) and a history of multiple fractures. Genetic analysis in both individuals identified a heterozygous missense mutation in exon 10 of the VDR gene, affecting the ligand-binding domain, supporting a pattern of dominant inheritance. The patient was treated with cholecalciferol (1,200 IU daily), calcitriol (5–6 µg daily), and calcium carbonate (2,000 mg daily). Although biochemical responsiveness to therapy was evident, poor adherence resulted in suboptimal metabolic control throughout childhood and adolescence, including a second fracture at age 15 and a final adult height of 124 cm. Notably, calcium and phosphate levels progressively normalized after puberty, with sustained biochemical stability despite the patient omitting the treatment. Conclusion This case provides two important insights. First, it represents the fourth reported case worldwide demonstrating a dominant-negative effect of a VDR gene mutation, whereby a single mutant receptor interferes with wildtype VDR function. Second, it highlights postpubertal calcium adaptation, in which vitamin D–independent intestinal absorption may restore mineral homeostasis, and disease severity can attenuate over time through adaptive physiological mechanisms.
Calcium ; Mutation ; Vitamin D ; Rickets