Endocrine Abstracts

Autosomal dominant hypoparathyroidism (ADH) is caused by gain-of-function mutations in the calcium-sensing receptor (CaSR), increasing its sensitivity to extracellular calcium, suppressing PTH and resulting in hypocalcaemia. In contrast to idiopathic hypoparathyroidism, treatment to correct serum calcium results in high urine calcium excretion, causing nephrocalcinosis, stones and renal impairment. Unlike surgical hypoparathyroidism where calcium should be maintained, patients with ADH are treated symptomatically. Interactions of maternal and fetal physiology make pregnancy complex. As maternal gut calcium absorption increases markedly by 12 weeks, alongside increased serum concentrations of 1,25(OH)2D3 independent of PTH, maternal serum calcium should be maintained. Maternal hypocalcaemia can have severe adverse effects on pregnancy, including spontaneous abortion, premature labour and stillbirths. Fetal compensation to maintain its calcium level results in secondary hyperparathyroidism, causing skeletal undermineralization, fractures in utero or on delivery and neonatal rickets. Neonatal hypercalcaemia may result. Alfacalcidol and calcium supplementation are used in pregnant women with ADH to maintain calcium in the low-end normal range. We present a case of a 29-year old lady with ADH caused by a novel heterozygous CaSR missense mutation, p.(Asn855Asp). By time of genetic diagnosis she had had two successful pregnancies and was breastfeeding her second child whilst suffering from marked symptoms of hypocalcaemia, with serum calcium dropping to 1.84 mmol/l, necessitating alfacalcidol titration up to 3ug daily. Post-breast feeding, she became rapidly hypercalcaemic, serum calcium 2.66 mmol/l, and we reduced to 1ug alfacalcidol, her adjusted calcium remaining between 1.9 to 2.1 mmol/l at this dose. Currently, she is in her third pregnancy and alfacalcidol has again been titrated up. Due to nausea and vomiting she has limited dairy intake and does not tolerate calcium supplementation. Being unsure of the baby’s mutation status, we are trying to avoid hypocalcaemia and fetal secondary hyperparathyroidism, should the baby not have the mutation.