MASSIVE VIRGINAL BREAST HYPERTROPHY AS A CAUSE OF RECURRENT HUMORAL HYPERCALCEMIA DUE TO PARATHYROID HORMONE-RELATED PROTEIN (PTHrP) SECRETION

Abstract

Humoral hypercalcemia associated with certain neoplasms is caused by their secretion of a parathyroid-like 16-18 kd peptide, PTHrP. PTHrP also is expressed by keratinocytes, placenta, fetal parathyroids, and lactating mouse mammary tissue. We report a 15 y old female who presented with massive virginal breast hypertrophy and symptoms of urinary frequency, fatigue, and personality changes attributable to hypercalcemia. At 13 1/2 y she had a successful liver transplant for α1-anti-trypsin deficiency. This was followed by rapid breast growth; 6 months later she had menarche and then regular menses. At 15 y symptomatic hypercalcemia was documented -serum Ca 16 mg/dl, P 2.7 mg/dl, alk phosphatase 151 U/l, PTH 5 pg/ml (n=10-65), and PTHrP 9.4 pmol/L (n=<1.5); 1,25(OH)2D 28 pg/ml (20-76) unlike the usually elevated level with PTH excess. The hypercalcemia responded promptly to saline diuresis. Imaging studies failed to show a parathyroid abnormality or tumor. She had three subsequent episodes of symptomatic hypercalcumin 4 - 5 days prior to menses; PTHrP levels were undetectable between episodes. Following an extensive reduction mammoplasty, the hypercalcemia has not recurred. Studies of PTHrP mRNA in the tissue are in progress. In summary, benign breast hypertrophy can cause secretion of PTHrP which results in hypercalcomia. The cyclical occurrence and its temporal relationship to the menstrual cycle suggests that changes in circulating ovarian sex steroids may have affected PTHrP synthesis.