PARATHYROID PATHOPHYSIOLOGY: ESTROGEN AND PREGNANCY

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The relationship of estrogen and pregnancy to vitamin D metabolism and Ca homeostasis in patients with disorders of the parathyroid glands will be examined. Previous work has demonstrated that estrogen inhibits PTH-mediated bone resorption. Therefore, the hypocalcemic effect of estrogen in patients with normocalcemic pseudohyparathyroidism, if confirmed, would provide evidence that bone contributes to the maintenance of serum Ca in these patients. Paradoxically, it has been observed that certain patients with pseudohypoparthyroidism who have a hypocalcemic response to estrogen, may remain normocalcemic throughout pregnancy. Initial studies, which will be pursued in vivo and in vitro, suggest that serum 1,25-(OH)2 vitamin D concentration may increase during pregnancy because of placental production of this metabolite. Estrogens have been shown to stimulate renal synthesis of 1,25-(OH)2 vitamin D in chickens and in osteoporotic women, but it has not been established in humans whether this represents a direct effect or is mediated by secondary hyperparathyroidism accompanying the inhibition of bone resorption. Women with true PTH- deficient hypoprathyroidism, as confirmed by EDTA testing, will serve as a model for testing whether estrogen treatment has any direct effect in stimulating 1,25-(OH)2D vitamin D synthesis and fractional intestinal 47Ca absorption. If estrogen inhibits bone resorption, but stimulates synthesis of 1,25-(OH)2 vitamin D and intestinal Ca absorption, then postmenopusal women with primary hyperparathyroidism may achieve a more positive calcium balance during estrogen therapy. If positive Ca balance persists throughout estrogen therapy, then beneficial changes in bone density and bone histomorphometry may be observe. EAch of these skuppostions will be tested to determine if estsrogen treatment may be useful in those postmenopausal women who are suboptimal unwilling or failed surgical candidates.