Primary Hyperparathyroidism in Pregnancy: A Diagnostic and Therapeutic Challenge

Abstract

The risk of severe complications arising from primary hyperparathyroidism (pHPT) is increased during pregnancy. Gestational pHPT often goes undiagnosed, and by the time it is diagnosed, a majority of women have endured one or more failed pregnancies. During pregnancy, active transport of calcium ions from the mother to the fetus leads to suppression of the fetal parathyroids. When the prenatal pool of calcium is depleted, the newborn may develop neonatal hypocalcemic tetany. The mother, in turn, may suffer from worsening hypercalcemia and a hypercalcemic crisis after delivery. Awareness and confirmation of the diagnosis may be crucial for the outcome. The only definitive treatment of pHPT is parathyroidectomy, which should be recommended in most cases. Our two cases illustrate both the importance of and the difficulty in detecting pHPT during pregnancy, as well as some of the serious complications that may occur during pregnancy and after delivery.

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

“…Conversely, rapid placental calcium transfer and uptake of calcium by the fetal skeleton during the third trimester may help protect against severe hypercalcemia in the mothers. Loss of outflow to the placenta likely explains why hypercalcemic crises have occurred after delivery of the placenta (612,662,701,795). Physical inactivity and bedrest will add an additional component of skeletal resorption.…”

“…In up to 15% of cases women presented with pancreatitis during the second or third trimester (153,186,205,429,508,511). Hypercalcemic crises have occurred during the third trimester (153,186,662,795), which coincides with peak release of PTHrP by the placenta and breasts. There are risks to the fetus and neonate that must be considered, including miscarriage, stillbirth, and hypoparathyroidism, and these are discussed in more detail in the companion review (492).…”

“…A retrospective review found significantly fewer neonatal deaths and complications in surgically treated mothers compared with the medically managed group (466). The second trimester is considered to have a lower risk of anesthetic or surgical complications, precipitated delivery, and neonatal death, compared with surgery during the third trimester (153,236,508,824), although individual case reports have supported the apparent safety of third trimester surgery (354,662,711,802).…”

“…Severe hypercalcemia, also termed a parathyroid crisis, has occurred during the postpartum interval in women with primary hyperparathyroidism who were not operated on during pregnancy, and in some women who go on to breastfeed (54,153,186,612,662,795). The sudden rise in serum calcium likely results from several factors, including abrupt loss of the placenta (a significant route of calcium loss), the initiation of low estradiol and PTHrP-induced skeletal resorption to support milk production, the effect of low estradiol to increase skeletal sensitivity to excess PTH, and physiological resorption induced by physical inactivity and bedrest during the puerperium.…”

Parathyroid Function and Disease during Pregnancy, Lactation, and Fetal/Neonatal Development

“…142,[145][146][147][148][149] Severe hypercalcemia or parathyroid crisis has also occurred during the third trimester. 147,148,150,151 Fractures are uncommon, likely reflecting the short duration of pregnancy and young age of most pregnant women, but they have occurred during pregnancy with marked hyperparathyroidism or parathyroid carcinoma. 152, 153 The overall impression is that pregnancy may predispose to more severe hypercalcemiarelated manifestations of primary hyperparathyroidism, although reporting bias must also be considered.…”