Calcium confusion during pregnancy
Authors: Dr Felicity Coad; Dr Iona Thorne; Dr Maria Mouyis; Professor Catherine Nelson-Piercy; Dr Anita Banerjee
Contact: [email protected]; Obstetric Medicine Registrar Guy’s and St Thomas’ hospital
Hypercalcaemia in pregnancy is uncommon. Differentials include primary hyperparathyroidism but it can be caused by excess PTH-rP (parathyroid hormone related peptide) production from placental tissue or mammary glands. If left untreated it can be hazardous resulting in adverse effects for mother and baby. We report a 51-year old egg-donor pregnancy presenting with hypercalcemia due to presumed humeral hypercalcaemia of pregnancy.
Background: 51 years old African-Caribbean lady of normal BMI (23kg/m2), three previous early pregnancy losses including spontaneous delivery of 14/40 embryo in 2016. This pregnancy was an IVF pregnancy with donor egg and she had a cerclage in situ. She has diet controlled gestational diabetes mellitus.
Past medical and surgical history: fibroids and previous myomectomies in 2006 and 2008
Medications on admission: folic acid 5mg OD, pyridoxine (vitamin B6), cholecalciferol 800 IU daily
Presentation to hospital: She presented to our maternity assessment unit at 34/40 feeling generally unwell and dizzy. She was admitted to the antenatal ward because of high blood pressure (BP), proteinuria (PCR 44), abnormal liver function tests and an acute kidney injury (AKI). A renal ultrasound scan showed mild left hydronephrosis and right pelvic dilatation. The presumed diagnosis was pre-eclampsia. She was given nifedipine and magnesium (BP 200/98 mmHg with brisk reflexes) and a plan for urgent caesarean section with a senior clinician (previous myomectomy) was made. The estimated blood loss from delivery was 800mls.
Day 1 post caesarean section she became drowsy and confused. Her confusion screen identified a corrected calcium of >5 mmol/l (2.15-2.55 mmol/l). An ECG showed characteristic isothermic non-ischaemic J waves (figure 1). She was treated with isotonic saline. Her corrected calcium, AKI and confusion resolved with fluids alone. Her serum PTH was inappropriately low initially but rebounded with a low corrected calcium (figure 2).
She suffered with auditory and visual hallucinations at night for days after her caesarean. She was referred to our mental health team for counselling and to discuss her experience during the peri-partum period.
Further investigations were requested to investigate causes including occult malignancy or excessive PTH-rP. A PTHrP was sent to a specialist lab in France but the result was normal (<1.40 pmol/l).
With the aid of further imaging and blood tests we ruled out multiple myeloma, lymphoma and other solid organ malignancies, sarcoidosis, vitamin D intoxication and Milk-Alkali syndrome.
Hypercalcaemia during pregnancy can be caused by a number of conditions, most commonly primary hyperparathyroidism (incidence 0.5-1.4% (1) in pregnancy). Malignancies including lymphoma or multiple myeloma are also important causes. Left untreated, hypercalcaemia can lead to serious morbidity and mortality in both mother and fetus and requires thorough investigation and prompt management.
After excluding other differential diagnoses, this patient was diagnosed with a PTHrP-associated hypercalcaemic crisis during pregnancy. Following delivery, she recovered rapidly with intravenous fluids alone. She went on to develop ‘hungry bone’ syndrome with low calcium. This occurs where PTH remains suppressed for a period of time following removal of the hormone stimulating hypercalcaemia.
PTHrP is a protein with some homology to parathyroid hormone (PTH), which binds and activates PTH receptor-1 (PTHR1) causing bone resorption and renal tubular calcium reabsorption. This in turn causes hypercalcaemia and suppression of PTH through negative feedback (2). PTHrP is produced by many different tissues including mammary and placental tissue. It has a number of developmental functions for the growing fetus and enables chondrocyte differentiation and maturation. PTHrP produced by the placenta increases placental calcium transport (3).
In this woman, the hypercalcaemia was not diagnosed until after delivery, therefore PTHrP was only tested postnatally. Her post-delivery PTHrP was not elevated suggesting a probable placental source.
Hypercalcaemia in pregnancy is uncommon. Thorough investigation for occult malignancy is necessary before diagnosing humeral hypercalcaemia of pregnancy.
1. Primary hyperparathyroidism in pregnancy — a review of literature. Komarowska, Hanna, et al. 2017, Ginekol Pol, Vol. 88, pp. 270-275.
2. Parathyroid Hormone-Related Protein (PTHrP):: A Nucleocytoplasmic Shuttling Protein with Distinct Paracrine and Intracrine Roles. Jans, David A, Thomas, Rachel J and Gillespie, Matthew T. s.l. : Vitamins & Hormones, 2003, Vol. 66, pp. 345-384.
3. Pediatric Endocrinology Fourth Edition. CHAPTER 8 - Disorders of calcium and phosphorus homeostasis in the newborn and infant. Root, Allan W. Fourth. s.l. : Elsevier , 2014. pp. 209-276.
Dr Louise Oliver
Dr Paul Carrol
Dr Anand Velusamy