Hyperprolactinemia caused by lactation and pituitary adenomas is associated with altered serum calcium, phosphate, parathyroid hormone (PTH), and PTH-related peptide levels.

PRL stimulates systemic release of PTH-related peptide (PTHrP) in animals. To determine whether hyperprolactinemia causes PTHrP release in humans, we studied the relationship between PRL and PTHrP in lactating women and patients with PRL-producing pituitary adenomas. Thirty-three lactating women and 16 patients with pituitary adenomas were paired with healthy age- and sex-matched controls. Serum total calcium, albumin, phosphate, PRL, intact PTH, and PTHrP were measured. Mean calcium and phosphate levels were higher in lactating women than in control subjects [2.39 +/- 0.01 vs. 2.35 +/- 0.01 mmol/L (P < 0.01) and 1.33 +/- 0.03 vs. 1.13 +/- 0.02 mmol/L (P << 0.001), respectively]. Mean PTH was lower (2.49 +/- 0.24 vs. 3.17 +/- 0.23 pmol/L; P < 0.04) and mean PTHrP was higher than control values (0.93 + 0.08 vs. 0.38 +/- 0.04 pmol/L; P << 0.001). PRL correlated negatively with PTH (P < 0.02) and positively with PTHrP (P < 0.05). Mean calcium, phosphate, and PTH levels were not different between patients with pituitary adenomas and control subjects. The mean PTHrP level was higher in patients with pituitary adenomas (0.75 +/- 0.10 vs. 0.39 +/- 0.07 pmol/L; P < 0.006) and fell significantly with therapy to normalize PRL (P < 0.03). We conclude that PTHrP levels are increased in hyperprolactinemia caused by lactation and pituitary adenomas. In lactating women, the increased PTHrP was associated with higher mean calcium and phosphate and lower PTH levels. The metabolic consequences of these abnormalities in hyperprolactinemia require further elucidation.

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