Recurrent severe hypercalcemia in a nasopharyngeal carcinoma survivor

Hypercalcemia is a potentially life-threatening metabolic disorder with diverse etiologies. In oncology patients, it is often attributed to malignancy-related mechanisms, such as parathyroid hormone-related peptide (PTHrP) secretion. However, non-malignant causes, like calcium-alkali syndrome (CAS) and adrenal insufficiency, should not be overlooked. We report a 60-year-old man with nasopharyngeal carcinoma (NPC) treated with cranial radiotherapy, stage 3 chronic kidney disease (CKD), and multiple comorbidities, who presented with recurrent severe hypercalcemia (11.0-14.9 mg/dL) and hyperphosphatemia. Initial suspicion focused on paraneoplastic hypercalcemia; however, parathyroid hormone (PTH) and PTHrP levels were suppressed, alkaline phosphatase and bone turnover markers [N-terminal propeptide of type I procollagen (PINP) and beta-C-terminal telopeptide of type I collagen (β-CTx)] were consistently low, along with paradoxically elevated urinary calcium and phosphate excretions. This profile suggested a low-turnover, non-parathyroid, non-malignant etiology. A detailed history revealed chronic ingestion of calcium-fortified supplements via gastrostomy, implicating CAS as the primary cause. Persistent hypotension and biochemical abnormalities prompted an endocrine evaluation, revealing secondary adrenal insufficiency confirmed through consistently low cortisol and adrenocorticotropic hormone (ACTH) levels and ACTH stimulation testing. Positron emission tomography (PET) imaging demonstrated increased uptake at the skull base, suggestive of radiation-induced damage to the hypothalamic-pituitary axis. Discontinuation of calcium/vitamin D supplementation and initiation of low-dose prednisolone and fludrocortisone led to resolution of hypercalcemia and renal impairment. This case highlights the importance of recognizing dual non-malignant etiologies in cancer survivors with suppressed PTH/PTHrP and persistent hypercalcemia, particularly when urinary calcium excretion remains high despite renal impairment.