Relationship of Estrogen and Pregnancy to Calcium Homeostasis in Pseudohypoparathroidism*

Abstract

The relationship of estrogen administration and pregnancy to vitamin D metabolism and Ca homeostasis was examined in two young women with pseudohypoparathyroidism. Estrogen, which is believed to inhibit PTH-mediated bone resorption, caused a consistent dose-related reversible reduction of serum Ca in these patients. This finding supports the concept that PTH-mediated bone resorption may contribute to the maintenance of serum Ca in normocalcemic pseudohypoparathyroidism. Paradoxically, these two patients remained normocalcemic throughout pregnancy, a high estrogen state. They were studied during four pregnancies, and each time a similar pattern emerged. Despite a primary derangement of the renal 1 alpha-hydroxylase, serum 1,25-dihydrovitamin D [1,25-(OH)2D] concentration increased 2- to 3-fold, while the serum PTH level was nearly halved during pregnancy. After delivery, serum Ca and 1,25-(OH)2D decreased, and serum PTH rose appropriately. Placental synthesis of 1,25-(OH)2D may have contributed to the maintenance of normocalcemia in these patients.

Maternal Mineral and Bone Metabolism During Pregnancy, Lactation, and Post-Weaning Recovery

“…In both women the hypocalcemic symptoms promptly returned within 3 wk after delivery (they did not breastfeed) (110). These reports suggest that PTH-independent increases in intestinal calcium absorption and calcitriol synthesis occur during pregnancy in pseudohypoparathyroidism type I, and that the effects are sustained for some time after delivery.…”

“…Calcitriol doubled during the second and third trimester for two women in which pseudohypoparathyroidism improved and supplemental calcitriol was stopped (110). In one woman whose serum calcium was stable in the first two trimesters before hypocalcemia occurred in the third trimester, this was paralleled by increases in endogenous calcitriol during the first two trimesters and a decline to prepregnancy values in the third trimester (814).…”

“…The level of calcium intake is likely an important variable. In the four pregnancies in which pseudohypoparathyroidism objectively improved, 1 g supplemental calcium was taken throughout (110), whereas in four of the pregnancies where it worsened, the women took no supplemental calcium (793,814), and in the remaining three pregnancies the worsening occurred when the supplemental intake was 250 or 500 mg daily (668,676). In none of these pregnancies was the dietary intake of calcium reported.…”

“…Type I pseudohypoparathyroidism appeared to improve during pregnancy in two women who maintained 1 g supplemental calcium intake daily during four pregnancies, including that hypocalcemic symptoms abated, normocalcemia was achieved, PTH levels decreased to near-normal, calcitriol levels increased three-to fourfold, urinary excretion of calcium after a 1 g calcium load normalized (an indicator of normal intestinal calcium absorption), and supplemental vitamin D or vitamin D analogs were no longer required (110). In both women the hypocalcemic symptoms promptly returned within 3 wk after delivery (they did not breastfeed) (110).…”

Pseudohypoparathyroidism Type 1b in Pregnancy

“…Saito and Saito [4] described a case of PHP in which physiological adjustment of Ca metabolism became insufficient during the second half of pregnancy. In contrast, Breslau et al [5] reported two women with PHP in whom the level of 1,25(OH) 2 D became normal during pregnancy [5]. Thus, inconsistent effects of pregnancy on PHP have been reported.…”