Hypoparathyroidism and pseudohypoparathyroidism in pregnancy: an Italian retrospective observational study

Abstract

Background Hypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacological management, and potential adverse events during pregnancy and post-partum in pregnant women with HypoPT or pseudo-HypoPT. This was a retrospective, observational, multicenter, study involving nine Italian referral centers for endocrine diseases affiliated with the Italian Society of Endocrinology and involved in “Hypoparathyroidism Working Group”. Results This study identified a cohort of 28 women (followed between 2005 and 2018) with HypoPT (n = 25, 84% postsurgical, 16% idiopathic/autoimmune) and pseudo-HypoPT (n = 3). In HypoPT women, the mean calcium carbonate dose tended to increase gradually from the first to third trimester (+ 12.6%) in pregnancy. This average increase in the third trimester was significantly greater compared to the pre-pregnancy period (p value = 0.03). However, analyzing the individual cases, in 44% the mean calcium dosage remained unchanged throughout gestation. Mean calcitriol doses tended to increase during pregnancy, with a statistically significant increase between the third trimester and the pre-pregnancy period (p value = 0.02). Nevertheless, analyzing the individual cases, in the third trimester most women with HypoPT (64%) maintained the same dosage of calcitriol compared to the first trimester. Both mean calcium carbonate and calcitriol doses tended to decrease from the third trimester to the post-partum six months. Most identified women (~ 70%) did not display maternal complications and (~ 90%) maintained mean serum albumin-corrected total calcium levels within the low-to-mid normal reference range (8.5 ± 0.8 mg/dl) during pregnancy. The main complications related to pregnancy period included: preterm birth (n = 3 HypoPT women), and history of miscarriages (n = 6 HypoPT women and n = 2 pseudo-HypoPT women). Conclusion This study shows that mean serum albumin-corrected total calcium levels were carefully monitored during pregnancy and post-pregnancy, with limited evaluation of other biochemical parameters, such as serum phosphate, 24 h urinary calcium, 25-OH vitamin D, and creatinine clearance. To avoid complications in mothers affected by (HypoPT) or (pseudo-HypoPT) and offspring, intense biochemical, clinical and pharmacological monitoring during pregnancy and breastfeeding is highly recommended.

Approach to the Patient: Management of Parathyroid Diseases Across Pregnancy

“…This in turn, may lead to fetal hyperparathyroidism and demineralization of the fetal skeleton and increased risk of intrauterine fractures, low birth weight and fetal death ( 6 , 9 ). While earlier case reports and case series suggested a relatively high risk of pregnancy complications for women with HypoPT, recent larger national registry studies documented a relatively low risk of adverse pregnancy outcomes ( 21 , 22 , 24 ). The largest registry study from Sweden included 97 women with HypoPT and reported on an increased risk of induction of labor (odds ratio 1.87; 95% CI, 1.13-2.94) and lower birth weight (−188 g; 95% CI, −312.2 to −63.8) when compared with age-matched controls, but there was no increased risk for other relevant outcomes, such as small for gestational age, malformations, or perinatal death ( 21 ).…”

“…In the peripartum period and, in particular, immediately after delivery and during lactation, the requirements for active vitamin D and calcium supplements significantly decrease and may increase the risk of maternal hypercalcemia, as reported in some case series ( 22 , 23 , 25 ). Thus, frequent biochemical monitoring, weekly within the first month after birth and then every 4 weeks during lactation should be performed.…”

“…Pregnancy-associated increases in endogenous calcitriol, estrogen, and PTHrP may theoretically lower treatment requirements for women with HypoPT. In some, but not all, reports on this topic there is a trend for a reduced requirement for calcium and active vitamin D supplements, but roughly half of the patients do not have to change their doses to achieve their treatment goals, and a few patients may have even increased requirements during pregnancy ( 22 , 23 , 25 ). Interestingly, there is some evidence that hypoparathyroidism-related clinical manifestations such as paresthesia, cramps, and tetany, may improve during pregnancy, but the data on this topic are inconsistent ( 22 , 23 ).…”

“…In some, but not all, reports on this topic there is a trend for a reduced requirement for calcium and active vitamin D supplements, but roughly half of the patients do not have to change their doses to achieve their treatment goals, and a few patients may have even increased requirements during pregnancy ( 22 , 23 , 25 ). Interestingly, there is some evidence that hypoparathyroidism-related clinical manifestations such as paresthesia, cramps, and tetany, may improve during pregnancy, but the data on this topic are inconsistent ( 22 , 23 ). Due to the uncertainties regarding potential changes in dose requirements during pregnancy, careful biochemical monitoring should be done all 3 to 4 weeks throughout pregnancy and if changes in the treatment are made, an additional follow-up visit should be performed after 1 to 2 weeks ( 2 ).…”

Pseudohypoparathyroidism during pregnancy and the postpartum period: A case series of five patients

“…It is important to adjust medicine dosage in time to maintain calcium homeostasis for both maternal and fetal health. However, according to the limited previous case reports, the change in serum calcium level in PHP patients during pregnancy is inconsistent and the requirements of medication can change dramatically ( 3 ). Some patients had improved outcomes during pregnancy with abated hypocalcemic symptoms, normocalcemia, decreased to near-normal PTH level, and discontinuation of supplemental vitamin D agents ( 4 ), while other reports showed that the dose of calcium and/or active vitamin D had to be increased in PHP women during pregnancy ( 5 – 7 ).…”