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Hypercalcemia in pregnancy in a patient with multiple previous miscarriages

Rabia Arfan, Alireza Mohammadi, Sriranganath Akavarapu, Wexham Park hospital, Frimley Health NHS Trust.

Hypercalcaemia during pregnancy is not very common and can result in foetal morbidity and miscarriages. If it is due to primary hyperparathyroidism, guidelines suggest parathyroidectomy if corrected calcium is above 2.75 mmol/L which is considerably lower than usual cut off of 3 mmol/L in non-pregnant patients. If surgery is needed the best time is the second trimester as general anaesthesia is safer. When a pregnant patient is diagnosed with hypercalcaemia every effort should be made to get the correct diagnosis as quickly as possible and plan the management properly.

A 36-years old, 14 weeks pregnant woman was referred to the endocrinology department urgently with a corrected calcium of 2.97 mmol/L and normal parathyroid hormone (PTH).  Her symptoms were urinary frequency and nausea. She had three previous miscarriages (2002- 10 weeks, 2007 – 6 weeks, 2017 – 6 weeks) and two normal births (2004 and 2008).

Blood test showed high corrected calcium level at least since 2011 (2.64 – 2.97 mmol/l) with normal PTH (3.2 – 5.2 pmol/l) and low phosphate (0.66-0.93 mmol/l). Her vitamin D levels were 70.3- 73.7 nmol/L). Her renal function and electrolytes including Mg were normal. Her urinary calcium was 1.24mmol/l in 24 hours but as urine volume was less than a litre the test was repeated.

She was regularly taking folic acid 400mcg and vitamin D 400 units once a day. Her father had ischaemic heart disease and type 2 diabetes, Mother had Crohn’s and B12 deficiency. Two sisters had B12 deficiency. Father, mother, mother’s sister, two sisters and one of her children had calcium level checked at some point and they were normal. The patient has been with a new partner and was extremely worried about another miscarriage.

At that time the main differential diagnoses were Primary hyperparathyroidism (hypercalcaemia with inappropriately normal PTH) which needed parathyroidectomy in 2^nd trimester and Familial Hypocalciuric Hypercalcaemia FHH (due to low urinary calcium with normal Vitamin D level) which could be monitored closely.

We repeated the tests and 24 hr Urinary calcium showed low calcium output again with Urinary Calcium Creatinine Clearance Ratio of 0.0044 which was in favour of Familial Hypocalciuric Hypercalcemia but on other hand all close family members had normal calcium which made it difficult to diagnose without further investigation. She had her genetic screening for FHH and her case was discussed with genetic lab to prioritise her test and get results in 1-2 weeks (usually it takes 8 weeks). When discussed with nuclear medicine team at Oxford, they advised not to do SESTAMIBI scan or CT scan in pregnancy rather consider MRI scan. Opinion was sought from the endocrinologists at Hammersmith Hospital about starting her on cinacalcet in order to reduce hypercalcemia related risk in pregnancy and decision was made not to give it as there was no outcome study on its effect in pregnancy and wait for the other investigations. She was seen by ENT colleagues (both at Wexham park Slough and John Radcliffe Oxford), Obstetrician and obstetric anaesthetist so she could have timely parathyroidectomy in case of negative genetic tests.

Her genetic screening showed heterozygous positive result for CASR on which basis she was given a diagnosis of FHH type 1 with mild hypercalcemia. She was monitored during rest of her pregnancy which remained uneventful except 2 episodes of constipation which needed admission and was treated by starting her on regular laxatives. She delivered normally in May 2018 and her daughter’s calcium levels post birth remained normal at 2.44 mmol/L.

The patient was continually involved in decision making throughout the management of her hypercalcemia in pregnancy.

This is an example of a complex endocrine case and highlighted the importance of good communication between various specialities within the hospital and also across different hospitals to ensure safe and successful outcome.