Acromegaly as a cause of 1,25-dihydroxyvitamin D-dependent hypercalcemia: case reports and review of the literature

Growth hormone excess has been associated with hypercalciuria and nephrolithiasis. Hypercalcemia in acromegaly is rare and usually due to coexistent primary hyperparathyroidism. To report two cases of 1,25-dihydroxyvitamin D (1,25 (OH)₂ D)-dependent hypercalcemia in cromegaly. A 50 year-old female with 2 years history of hypercalcemia presented with features of acromegaly. Serum calcium (Ca) was 10.9 mg/dl (8.6–10.2), parathyroid hormone (PTH) 20 pg/ml (10–65), PTH-related peptide undetectable, and 1,25 (OH)₂ D 119 pg/ml (15–75). Insulin-like growth factor 1 (IGF1) was 911 ng/ml (49–292) and growth hormone (GH) 14.5 ng/ml (0.03–10). MRI showed a 1.7 cm pituitary tumor. Transsphenoidal adenectomy (TSA) resulted in normalization of IGF1, GH, Ca, and 1,25 (OH)₂ D (50 pg/ml) and complete tumor resection. A 52-year-old female was diagnosed with visual field deficits on routine exam. MRI showed a 3 cm invasive pituitary macroadenoma. IGF1 was 416 ng/ml (87–238) and GH 75.8 (0–6.0) ng/ml. Incidentally, she was found with high Ca of 10.8 mg/dl (8.9–10.3) associated with PTH 19 pg/ml and 1,25 (OH)₂ D66 pg/ml. Postoperatively, IGF1 and GH remained abnormal (440 and 12.8 ng/ml, respectively), while MRI showed parasellar tumor residue. Ca remained high (10.1–11.1 mg/dl), along with elevated 1,25 (OH)₂ D level (81.3 pg/ml). In both cases, other causes of hypercalcemia were ruled out. We present 2 cases of 1,25 (OH)₂ D-dependent hypercalcemia associated with growth hormone excess. Complete resection of tumor produced biochemical remission of acromegaly and normalization of calcium and 1,25 (OH)₂ D levels, while incomplete resection was associated with persistent 1,25 (OH)₂ D-dependent hypercalcemia. Acromegaly should be considered a cause of 1,25 (OH)₂ D-dependent hypercalcemia.