Sarcoidosis is a multisystem granulomatous disorder that most commonly involves the lungs and intrathoracic lymph nodes. Hypercalcemia is a recognized but uncommon manifestation of sarcoidosis and is typically mild; however, severe hypercalcemia as the initial presentation is rare and may pose a diagnostic challenge. We report a 66-year-old female patient with multiple comorbidities, including stage 4 chronic kidney disease, who presented with fatigue, decreased appetite, vomiting, and significant weight loss. Laboratory findings demonstrated severe hypercalcemia (15.7 mg/dL) with acute worsening of renal function. Parathyroid hormone (PTH) levels were inappropriately normal in this setting. Neck ultrasonography suggested a possible parathyroid lesion; however, technetium-99m sestamibi scintigraphy showed no focal uptake, excluding a functional adenoma. Further workup excluded malignancy and vitamin D intoxication. Elevated 1,25-dihydroxyvitamin D levels suggested extrarenal activation. Positron emission tomography-computed tomography (PET/CT) revealed widespread lymphadenopathy, and mediastinal lymph node biopsy confirmed noncaseating granulomas, establishing the diagnosis of sarcoidosis. The patient developed refractory hypercalcemia requiring aggressive medical therapy, denosumab, and one session of hemodialysis. Initiation of corticosteroid therapy resulted in rapid clinical and biochemical improvement. This case highlights severe vitamin D-mediated hypercalcemia as an uncommon presentation of sarcoidosis with acute kidney injury. Cases requiring both denosumab and hemodialysis are rarely reported. A systematic approach to evaluation is essential, particularly in distinguishing PTH-dependent from independent causes. Sarcoidosis should be considered in unexplained severe hypercalcemia, even in the absence of pulmonary manifestations, as early recognition and corticosteroid therapy can be highly effective.
Sabu et al. (2026) studied this question.