Nausea and vomiting of pregnancy (NVP) is common, affecting up to 80% of pregnancies. The onset of symptoms typically begins around 4 to 5 weeks of gestation and improves by week 12, but can persist longer. A minority of these women, 0.3% to 1.5%, will have a severe form of NVP called hyperemesis gravidarum.6
This is a spectrum of disease manifested by these commonly accepted criteria: persistent vomiting, weight loss exceeding 5% of pre-pregnancy body weight, and ketonuria unrelated to other causes.7
This patient met the criteria for hyperemesis gravidarum due to persistent vomiting associated with weight loss and ketonuria.
The differential diagnosis for the non-specific complaint of nausea and vomiting is broad and makes a complete evaluation lengthy. In the pregnant woman, evaluation and diagnosis is targeted to disease severity and exclusion of other causes. It includes measurement of weight, blood pressure, heart rate, electrolytes, serum ketones, and urinalysis. Routine obstetrical ultrasound can exclude multiple gestation and hydatidiform mole which are both associated with increased incidence of hyperemesis. Although calcium levels are not part of the general evaluation, it is a selective test that can be considered on a patient-specific basis.
An elevated calcium level is particularly notable because total calcium levels are normally lower during pregnancy due to the increased calcium demands of fetal growth.8
Primary hyperparathyroidism is a rare complication of pregnancy, occurring in 0.5%–1.4% of all cases.9
It is the most common cause of hypercalcemia and further testing of serum PTH is indicated in cases of hypercalcemia in pregnancy. PTH is unaffected by pregnancy and a normal or elevated PTH level in the setting of hypercalcemia is diagnostic of primary hyperparathyroidism.10
Ionized calcium levels are unchanged by pregnancy and are also helpful to rule out a pseudohypercalcemia. Vitamin D levels (25-hydroxyvitamin D and 1,25-dihydroxyvitamin D) should also be measured to evaluate for vitamin D intoxication or granulomatous disease such as sarcoidosis. Malignancy as a cause of hypercalcemia should be explored, as well as contributing factors such as acute renal failure, immobilization, or other endocrinopathies as clinically indicated.
Medical treatments of hyperparathyroidism include intravenous fluids and correction of electrolyte abnormalities which are initial treatments and safe in pregnancy. Calcitonin, pregnancy category C, does not cross the placenta and has been used safely in pregnancy to suppress bone resorption and promote urine calcium excretion.11
Oral phosphate, pregnancy category C, is used to bind calcium but has not been well studied. Bisphosphonates, pregnancy category C, cross the placenta and may interfere with endochondral bone development.12
Cinacalcet, pregnancy category C, has been used safely in two patients.13
High-dose magnesium also acts on the calcium receptor to decrease PTH and serum calcium and is commonly used in preeclampsia. Ethical concerns have limited testing of these drugs in pregnant patients and their risks remain unknown. Watchful waiting is a reasonable treatment for patients with mild, asymptomatic hypercalcemia. However, parathyroidectomy is the only definitive treatment and is recommended for symptomatic patients or those with severe hypercalcemia, generally defined as greater than 11 mg/dL. Surgery is generally only recommended in the second trimester due to the increased risks of incomplete organogenesis during the first trimester and preterm labor during the third trimester.14
Although third-trimester parathyroidectomy is associated with a reported 58% fetal mortality,15
there have been several case reports of third-trimester parathyroid surgery without complications and it may be reasonable when the benefits outweigh the risks of surgery.16,17
The risk of inducing premature labor increases in the third trimester; the risk of spontaneous abortion from general anesthesia is reported to be minimal, particularly in extraperitoneal surgery.18
The maternal risks of parathyroidectomy are similar to non-pregnant patients including those risks associated with general anesthesia, injury of the recurrent laryngeal nerve, and post-operative hypocalcemia.19