When 'benign' hypercalcaemia isn't benign: FHH presenting with marked hypercalcemia and recurrent pancreatitis in a young man with a CASR variant — ASN Events
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 When 'benign' hypercalcaemia isn't benign: FHH presenting with marked hypercalcemia and recurrent pancreatitis in a young man with a CASR variant (#442)

Divia Dr Mohandas 1 , Matthew Dr Luttrell 1 2
  1. ENDOCRINOLOGY, NEPEAN HOSPITAL, Kingswood, NSW, Australia
  2. ENDOCRINOLOGY, Wollongong Hospital , Wollongong, NSW, Australia

Background: Familial hypocalciuric hypercalcaemia (FHH) is an autosomal dominant disorder caused most commonly by inactivating variants in the calcium-sensing receptor (CASR) gene. It is typically characterised by lifelong mild hypercalcaemia, hypocalciuria and normal or mildly elevated parathyroid hormone concentrations, with few clinical complications (1,2). We describe an atypical case of severe FHH complicated by recurrent pancreatitis, diagnostic uncertainty with suspected coexistent primary hyperparathyroidism (PHPT), and successful treatment with cinacalcet.

Case: A 27-year-old man presented with recurrent alcohol-associated acute pancreatitis and persistent severe hypercalcaemia (peak corrected calcium 3.46 mmol/L). Biochemistry demonstrated an inappropriately normal PTH, hypophosphataemia and a low urine calcium-to-creatinine clearance ratio (0.04), suggesting FHH. Neck ultrasound, sestamibi scintigraphy and 4D CT demonstrated concordant localisation of bilateral parathyroid lesions, raising concern for dual pathology. Genetic testing identified a CASR variant of uncertain significance, while MEN testing was negative. Following multidisciplinary review, four-gland exploration was performed with excision of an enlarged right inferior gland; histology demonstrated hyperplasia. Persistent postoperative hypercalcaemia supported FHH as the predominant diagnosis. Cinacalcet was commenced and titrated to 60 mg twice daily, reducing serum calcium from 3.2–3.3 mmol/L to 2.7–2.9 mmol/L. During treatment adherence, pancreatitis admissions ceased for approximately two years, recurring only during periods of medication interruption.

Conclusion: Although FHH is generally considered a benign disorder, severe hypercalcaemia and recurrent pancreatitis have been reported rarely (2,3). This case demonstrates the diagnostic challenge of distinguishing FHH from PHPT when severe hypercalcaemia and concordant localisation studies suggest dual pathology. It also highlights the potential for alcohol excess to act synergistically with hypercalcaemia in precipitating pancreatitis and supports the use of cinacalcet in selected patients with complicated FHH.

References
1.Hannan FM, Kallay E, Chang W, Brandi ML, Thakker RV. Nat Rev Endocrinol. 2019;15:33–51.
2.Marx SJ. J Clin Endocrinol Metab. 2018;103:426–429.
3.Horiuchi K, et al. Endocrinol Diabetes Metab Case Rep. 2014;2014