When nausea & vomiting of pregnancy becomes a tricky affair
The following case has been reported in the European Journal of Obstetrics and Gynecology and Reproductive Biology.

A 40-year-old primiparous woman, 27 weeks pregnant was admitted in the emergency department, because of weakness and weight loss of 20 kg. She had had progressive nausea, vomiting and epigastric pain, with polyuria and polydipsia, since early pregnancy. Following several earlier medical consultations for these complaints she was treated for anemia.

One day before admission the patient perceived reduced fetal movements. At presentation she was lethargic with low skin turgor. The fundus height corresponded to 27 weeks of pregnancy. Laboratory studies revealed severe hypercalcemia (calcium 4.05 mmol/l and albumin 27 g/l) and increased parathyroid hormone-related protein (PTH-rp) concentration (PTH-rp 5.9 pmol/l, reference values 0–0.6 pmol/l).

At this time, the fetus appeared viable, although a cardiotocogram revealed little variation. Lung maturation was induced by betamethasone in case delivery was necessary. Meanwhile, plasma calcium lowering treatment with hyperhydration and diuretics appeared ineffective, so pamidronate was administered, which normalized maternal calcium levels.

Two days later, the condition of the fetus worsened, making an emergency cesarean section necessary. A healthy baby girl with an Apgar score of 9 at 1 and 5 min was born and admitted to the neonatal unit where hypercalcemia was diagnosed (calcium 4.27 mmol/l and albumin 35 g/l). The child's plasma calcium levels normalized with standard medical care, and she was swiftly transferred to the infant ward.

Once the girl was born, an abdominal CT scan was performed revealing a large lesion in the liver surrounded by multiple smaller lesions. A subsequent liver biopsy demonstrated a poorly differentiated adenocarcinoma, probably primary intrahepatic cholangiocarcinoma based on immunohistochemistry (cytokeratin (CK)7 positive) and CK20, CEA, TTF-1, AFP, estrogen receptor negative with additional PTH-rp positive staining.

The patient's rapidly deteriorating condition precluded further therapy, and she died 3 months later at home.

Major takeaways:-
• The present case demonstrates that nausea and vomiting together with unexplained weight loss in a pregnant woman should always alert physicians to consider more unusual causes including rare entities such as undetected malignancy and hypercalcemia as a paraneoplastic syndrome.

• Nausea and vomiting are common symptoms related to pregnancy. However, in this patient these symptoms were the expression of severe hypercalemia by PTH-rp production related to thus far undetected cholangiocarcinoma.

• Co-existing symptoms like thirst, polyuria, fatigue, muscle weakness and lethargy had remained unrecognized.

• Increased production of PTH-rp as the cause of the humoral hypercalcemia of malignancy is frequently observed in patients with melanoma, lung, breast and renal cancers but PTH-rp may be secreted by virtually any type of tumor including cholangiocarcinoma.

• In normal physiology PTH-rp levels are low, produced by various cell types. PTH and PTH-rp have close homology and in part identical actions in elevating plasma calcium.

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