Hypercalcemia of benignancy
Ajit Kashyap, Kuldip Anand & Surekha Kashyap
A 49-year old woman presented with four months history of drowsiness and weakness. She had twelve years history of intermittent menorrhagia, and was treated with iron and folic acid tablets, with partial relief. Clinically she was dehydrated, drowsy, pale and had pedal edema. Pelvic examination revealed a uterine mass 16 centimeter in diameter. Investigations- hemoglobin 9.0 gm/dl, peripheral smear microcytic, hypochromic anemia,serum albumin- 2.8 g/dl (3.64.7 g/dl), serum calcium- 15.9 mg/dl(8.510.4), serum phosphorus- 3.1 mg/dl (2.5 to 4.5 mg/dl), alkaline phosphatase- 176 U/l (30 to 130 U/L),serum creatinine, vitamin D, and urine 24 hours calcium were normal;serum PTH - 4 pg/mL (12 to 56) and serum PTHrP- 8.8 pmol/L (<1.6 pmol/L). The chest radiograph and electrocardiogram were normal. She was managed with intravenous fluids, frusemide and intravenous pamidronate. Her sensorium improved over next four hours and serum calcium level decreased to 12.6 mg/dl. CT pelvis suggested a uterine leiomyoma. Three weeks later patient had an abdominal hysterectomy. A 4.3 kg histopathologically confirmed leiomyoma was removed. Postoperatively the serum calcium levels decreased gradually. The immunohistocytochemical staining of leiomyoma was positive for PTHrP. The serum calcium levels were normal, PTHrP decreased and became undetectable, and the parathyroid hormone levels increased to normal levels ten weeks after leiomyoma removal. The history, clinical profile, biochemical values, and hormonal profile are consistent with the diagnosis of recently described syndrome of humoral hypercalcemia of benignancy, with uterine leiomyoma being the cause of PTHrP-induced hypercalcemia in this patient.
Uterine leiomyomas show over expression of PTHrP gene. Other tumours known to be associated with this syndrome are ovarian dermoid cyst, intestinal leiomyoma, mammary hyperplasia, and pheochromocytoma.