We describe a patient with a malignant carcinoid tumor who presented with severe, intractable hypercalcemia that would not respond to conventional therapy with fluids and pamidronate. His plasma concentrations of parathyroid-hormone-related peptide (PTHrP) and interleukin-6 (IL-6) were elevated. The patient was treated with subcutaneous injections of octreotide with a good response, resulting in normocalcemia. Plasma PTHrP and IL-6 fell with the octreotide but remained elevated above the upper limit of normal. We conclude that although rare, hypercalcemia may be associated with carcinoid tumors and may be mediated through the secretion of cytokines and or PTHrP. Treatment with octreotide may be effective in treating hypercalcemia in such patients.
Pathogenic variants of CYP24A1 are associated with hypercalcemia due to disruptions in the ability of 24-hydroxylase to break down 1,25-dihydroxyvitamin D (1,25-DHVD). A case involving a heterozygous pathogenic variant of CYP24A1 and primary hyperparathyroidism leading to severe hypercalcemia has not been previously reported. A 23-year-old woman presented with fatigue and was found to be hypercalcemic at 13.8 mg/dL [reference range, 8.4-10.2 pg/mL]. Her parathyroid hormone (PTH) was 62 pg/mL [reference range, 19-88 pg/mL] and 1,25-DHVD was elevated to 242.7 pg/mL [reference range, 18-72 pg/mL]. Other laboratory workup was unrevealing. She had a bone scan, whole body CT scan, and thyroid ultrasound that were normal. Her 25-hydroxy-vitamin D to 24,25-dihydroxy-vitamin D ratio was elevated at 25.18 (normal, < 25). Because of concern for primary hyperparathyroidism, she was referred to an endocrine surgeon and underwent a parathyroidectomy with the removal of a 3.5-gram adenoma. Pathology showed a parafibromin-deficient parathyroid neoplasm. Genetic testing demonstrated a heterozygous pathogenic variant in CYP24A1. Three weeks after surgery, PTH was 14 pg/mL (1.48 pmol/L), calcium and 1,25-DHVD normalized. In summary, we report a case where a patient with severe symptomatic hypercalcemia was found to have primary hyperparathyroidism exacerbated by an underlying heterozygous pathogenic variant in CYP24A1.
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