Dual Pathology Contributing to Severe Hypercalcemia: Primary Hyperparathyroidism in the Setting of Suspected Familial Hypocalciuric Hypercalcemia — ASN Events
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Dual Pathology Contributing to Severe Hypercalcemia: Primary Hyperparathyroidism in the Setting of Suspected Familial Hypocalciuric Hypercalcemia (#447)

Hari Haran R 1 , Anna Mclean 1 , Ashim Sinha 1
  1. Cairns Hospital, Cairns, QLD, Australia

Background: Distinguishing familial hypocalciuric hypercalcemia (FHH) from primary hyperparathyroidism (PHPT) is essential, as parathyroidectomy is generally ineffective in FHH. Diagnosis becomes challenging when urinary calcium excretion is borderline in the setting of significant PTH dependent hypercalcemia.

 

Case Presentation: A 42-year-old gentleman presenting with severe PTH dependent hypercalcemia and a 20-year history of elevated serum calcium. Initial investigations demonstrated an ionised calcium of 1.96 mmol/l (reference 1.6-1.32 mmol/l) and parathyroid hormone (PTH) of 13.9 pmol/l (reference 1.6-6.0 pmol/l). His symptoms were longstanding fatigue and bone pain, without nephrolithiasis, osteoporosis or fragility fractures. Family history was significant for hypercalcemia affecting his father and paternal aunt.

The calcium- to – creatinine ratio, calculated using the Hammersmith equation was 0.010, within the borderline range for FHH. Sestamibi scintigraphy and 4D CT demonstrated a concordant right parathyroid adenoma measuring 10 x 8 x 4 mm. Genetic testing identified a heterozygous CASR missense variant (c.1801A>G; p. Lys601Glu), classified as a variant of unknown significance. Given the severity of hypercalcemia and concordant localisation studies, he underwent subtotal parathyroidectomy with subtotal parathyroidectomy. Histopathology confirmed a parathyroid adenoma measuring 12 mm. However, postoperative ionised calcium and PTH remained elevated at 1.55 mmol/l and 13.2 pmol/l. He has subsequently been referred for genetic counselling to facilitate interpretation of the CASR variant and consideration of family segregation studies.

 

Conclusion: This case highlights the possibility of dual pathology contributing to hypercalcemia, with PHPT occurring in the setting of suspected FHH. Persistent postoperative hypercalcaemia should prompt reconsideration of an underlying inherited disorder, particularly in patients with a strong family history of hypercalcaemia. Genetic counselling and family segregation studies will be essential to clarify the pathogenicity of novel CASR variants and guide diagnosis, management and screening of at-risk relatives.