Endocrine Abstracts

Familial hypocalciuric hypercalcaemia consists of 3 subtypes which are all inherited in an autosomal dominant manner and caused by inactivating mutations. FHH type 1 is most common (>65%) and is due to mutation in the calcium sensing receptor gene (CaSR), FHH2 due to GNA11 mutation and FHH 3 due to AP2S1 gene mutation (has been found in both kindreds from Oklahoma and Northern Ireland). FHH results in hypercalcaemia and hypocalciuria. It is usually asymptomatic, requiring no treatment. However FHH 3 is clinically the most severe form, and cases of osteomalacia, pancreatitis and nephrolithiasis have been reported requiring treatment with cinacalcet therapy.

Case: A 37 year old woman was referred for incidentally detected hypercalcaemia. Adjusted calcium 2.94 mmol/l, PTH 97ng/l, vitamin D 14 nmol/l and 24 hour urinary calcium (when vit D deficient) 3.28 mmol/ 24 hours. She had 1 previous adjusted calcium checked 2 years prior to referral at 2.91 mmol/l. A maternal aunt had a history of parathyroidectomy. Her parathyroid ultrasound and sestamibi scan were both negative for parathyroid adenoma. Due to her young age she had genetic analysis performed confirming pathogenic AP2S1 missense variant. Subsequent adjusted calcium levels rose to 3.08 mmol/l with symptoms of constipation and fatigue, therefore cinacalcet 60 mg od was commenced which successfully alleviated her symptoms and lowered her adjusted calcium to 2.34 mmol/l. Our patient now desires pregnancy and has been referred to clinical genetics with withdrawal of cinacalcet therapy.

Learning points: 1. FHH rarely requires treatment, if end organ damage due to hypercalcaemia occurs then treatment is with cinacalcet as parathyroidectomy is not curative. 2. Only 4 cases of FHH in pregnancy have been reported with no maternal pregnancy complications, however neonatal biochemistry will depend on the fetal genotype and referral to genetic counselling is recommended.