Miriam Martin, Corin Heim, Martin Mueller, Markus Mohaupt
More than 90% of cases of gestational hypercalcemia are caused by PHPT, which in turn is mostly caused (over 80%) by a single parathyroid adenoma. However, we have to consider a number of other possible etiologies. We need to consider the increased risk of maternal, neonatal, and fetal complications. The review illustrates the various clinical presentation and complex therapeutic management of gestational hypercalcemia, necessitating an interdisciplinary approach to the mother and child.
AIM: We aim to perform a narrative literature review of gestational hypercalcemia including calcium homeostasis in pregnancy. Additionally, we demonstrate the diagnostic and therapeutic challenges and pitfalls of gestational hypercalcemia.
METHODS: Literature review.
RESULTS: Gestational hypercalcemia is a rare yet life-threatening condition. The presentation of gestational hypercalcemia is nonspecific and mimics common pregnancy-related symptoms contributing to missed or late diagnosis. Common morbidities include nephrolithiasis and pancreatitis in the mother and adverse obstetrical outcomes such as fetal loss, fetal growth restriction, preeclampsia and preterm delivery. Severe cases of neonatal hypocalcemia due to fetal hypoparathyroidism may lead to tetany and even death. Despite these risks, only few guidelines in the management of gestational hypercalcemia exist. Causes of gestational hypercalcemia can be divided into parathyroid hormone (PTH)-dependent versus PTH-independent disorders. PTH-dependent etiologies display increased or inappropriately high PTH levels; primary hyperparathyroidism (PHPT) and familial hypocalciuric hypercalcemia (FHH) are the main contributors. PTH-independent disorders include pseudohyperparathyroidism, malignancy, and excessive calcium intake including calcium alkali syndrome. Granulomatous diseases, cytochrome P450 family 24 subfamily A member 1 (CYP24A1) mutations, and excessive calcium intake are the main contributors. In the presence of maternal hypercalcemia, hypercalciuria is a common laboratory finding. Extended laboratory work-up is the most useful paraclinical examination in gestational hypercalcemia of unknown cause. Only FHH is usually associated with low urinary calcium excretion. Marked sarcoidosis-associated hypercalciuria in pregnancy is attributed to the increase in both renal and ectopic calcitriol production, due to pregnancy and sarcoid granulomas, respectively.
CONCLUSION: More than 90% of cases of gestational hypercalcemia are caused by PHPT, which in turn is mostly caused (over 80%) by a single parathyroid adenoma. However, we have to consider a number of other possible etiologies. We need to consider the increased risk of maternal, neonatal, and fetal complications. The review illustrates the various clinical presentation and complex therapeutic management of gestational hypercalcemia, necessitating an interdisciplinary approach to the mother and child.