Background: Humoral hypercalcemia due to high serum levels of Parathyroid Hormone-Related Protein (PTHrP) is very rare in the setting of benign disease. PTHrP has a significant impact on developmental stages of life and is expressed in a variety of tissues including placental tissue and mammary glands. Therefore, PTHrP has a large role in the homeostasis of calcium between the mother and fetus.
Clinical case: A 25 year old female presented to the emergency department six days post-partum of spontaneous vaginal delivery of twins at 28 and 4/7 weeks. Her chief complaints included bilateral leg pain, weakness, and difficulty ambulating for the previous two days. The patient reported complaints of recent fatigue, polyuria, and polydipsia. She was breastfeeding as well as pumping her breast milk and reported only taking pre-natal vitamins and occasional acetaminophen for headaches. Given her leg pain, venous Doppler studies of the lower extremities were ordered which revealed bilateral deep vein thromboses (DVT). A CT of the chest was also performed that revealed bilateral lower lobe pulmonary emboli (PE). Her calcium level prior to delivery was noted to be normal; however, on presentation she had hypoalbuminemia-corrected calcium of 17.14mg/dL (normal 8.5-10.1 mg/dL) and ionized calcium of 8.70 mg/dl (normal 4.60-5.40 mg/dL). Her alkaline phosphatase was 184 U/L (normal 35-120 U/L). Her remaining labs were all within normal limits. Her CT Chest did not reveal any signs of mediastinal masses. Due to her bilateral DVT and PE, she was started on a Heparin drip and admitted to the hospital. The patient was started on normal saline at 300mL/hr and 200 units of Calcitonin two times per day for her severe hypercalcemia.
Upon admission, her PTH was found to be extremely low. Levels of Vitamin D 1,25, angiotensin converting enzyme, vitamin A and serum urine protein electrophoresis were obtained in the workup for non-PTH mediated causes of hypercalcemia and all were within normal ranges. Her PTHrP was found to be elevated to 27.0 pmol/L (normal 0.0-3.4 pmol/L) endorsing a diagnosis of rare and benign Humoral Hypercalcemia of Pregnancy.
The patient was treated with intravenous fluids, six days of calcitonin, and one dose of pamidronate. Her calcium normalized and after six days she was clinically ready for discharge. During her hospital course, she was bridged to Coumadin for anticoagulation secondary to her DVT and PE. To date, the patient has been lost to follow up.
Conclusion: To our knowledge, this is the first case depicting the rare and benign entity of Humoral Hypercalcemia of Pregnancy in a twin pregnancy. This case demonstrates the importance of identifying the various etiologies of hypercalcemia that may be benign in etiology but can lead to potentially life-threatening calcium levels. Elevated PTHrP is known to be associated with certain malignancies; however it can also be related to peripartum physiology.
Published In/Presented At
Zamir, A., Manglitz, A., Perilli, G. (2016, April 1). Humoral Hypercalcemia of Twin Pregnancy: Not a Laughing Matter. Poster presented at: Endocrine Society 98th Annual Meeting and Expo, Boston, MA.
Medical Sciences | Medical Specialties | Medicine and Health Sciences | Obstetrics and Gynecology
Department of Medicine, Department of Medicine Faculty, Department of Obstetrics and Gynecology