Endocrine Abstracts

Introduction: Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder affecting the calcium-sensing receptor (CaSR) expressed in the chief cells of the parathyroid glands and in the renal tubules. The CaSR permits the parathyroid gland to sense variations in serum calcium thus regulating parathyroid hormone (PTH) secretion; it also regulates calcium excretion in the kidneys. In FHH, loss-of-function mutations in the CaSR result in a higher serum calcium due to enhanced PTH secretion, and hypocalciuria due to higher tubular reabsorption of calcium in the nephrons. It can sometimes be difficult to differentiate between primary hyperparathyroidism (PHPT) and FHH.

Case Presentation: A 26-year-old woman was referred to the endocrine clinic with longstanding severe asymptomatic hypercalcaemia. She has a background of emotionally unstable personality disorder (EUPD) and anorexia nervosa. Her most recent biochemistry demonstrated an adjusted calcium of 3.23mmol/l(2.2-2.6mmol/l) with normal albumin, PTH 6.1 pmol/l(1.6-6.9 pmol/l), vitamin D 27nmol/l(25-162nmol/l), and phosphate 0.7mmol/l(2.2-2.6mmol/l). A neck ultrasound was normal. A family history of hypercalaemia was noted. Genetic blood tests confirmed a mutation in the CASR gene in keeping with autosomal dominant FHH.

Discussion: Despite usually having a benign prognosis FHH can be associated with nephrolithiasis, chondrocalcinosis and pancreatitis. Interestingly it can also be linked to behavioural disorders and this lady has EUPD. Cinacalcet is an allosteric agonist of the CaSR thus mimicking the effect of calcium and decreasing PTH, used commonly in patients with PHPT where surgery is inappropriate. There are few studies that have evaluated the efficacy of cinacalcet in FHH so it is not routinely used. Some case reports have used surgery in patients with FHH and a parathyroid adenoma identified on ultrasound. It is unclear how to manage cases such as this where the patient is asymptomatic but the calcium is very high. Consideration should be made to replacing low Vitamin D as this can contribute to a high PTH. FHH is often underdiagnosed, as it can be difficult to distinguish from PHPT. A family history of asymptomatic hypercalcaemia or unsuccessful parathyroid surgery should raise suspicion of FHH. The calcium/creatinine clearance ratio can be helpful in differentiating FHH and PHPT; it is typically <0.01 in FHH and >0.02 in PHPT. This case highlights the importance of a thorough history and focused genetic testing; which is the definitive diagnostic test. Making the correct diagnosis can help to prevent morbidity by avoiding unnecessary investigations and interventions such as surgery.