Endocrine Abstracts

JOINT2401

Introduction: Familial hypocalciuric hypercalcemia (FHH) is a benign, autosomal dominant condition with high penetrance. Heterozygous individuals typically present with mild hypercalcemia, hypocalciuria, inappropriately normal parathyroid hormone (PTH) levels, and elevated serum magnesium levels. FHH1, the most common form, results from inactivating mutations in the calcium-sensing receptor (CaSR) gene on chromosome 3q21. 1. Distinguishing FHH from asymptomatic primary hyperparathyroidism (PHPT) is critical, as FHH rarely requires parathyroidectomy and is not resolved by it. While typical biochemical findings can differentiate the two conditions, atypical presentations pose challenges. The calcium-creatinine clearance ratio (CCCR) aids diagnosis, with CCCR <0. 01 indicating FHH and >0. 02 suggesting PHPT. However, values between 0. 01–0. 02 create diagnostic uncertainty, and some PHPT cases may also present with CCCR <0. 01, as reported by Moore et al. This report presents a 14-year-old girl diagnosed with FHH despite a CCCR >0. 01, emphasizing the role of genetic testing in cases with overlapping biochemical features.

Case Presentation: A 14-year-old girl was referred for incidentally detected hypercalcemia during a routine evaluation. She had no history of polyuria, abdominal pain, weight loss, or bowel changes. Her clinical examination was normal, with no family history of hypercalcemia at initial assessment. Growth parameters were within normal limits (height: 163. 2 cm, weight: 58. 6 kg).

Investigations: • Adjusted Calcium: 2. 97–3. 20 mmol/l (elevated) (NR: 2. 20 – 2. 70)

• PTH: 7. 0–10. 1 pmol/l (unsuppressed in presence of hypercalcemia) (NR: 1. 3 – 9. 3)

• CCCR: 0. 0158

• Magnesium: 0. 89–0. 90 mmol/l (normal) (NR: 0. 7 – 1. 0)

• Vitamin D: 54 nmol/l (normal) (NR: 50 – 200)

Renal ultrasound showed no nephrocalcinosis. Normal neck ultrasound as well as Sestamibi scintigraphy scan ruled out parathyroid adenoma. Genetic testing identified a heterozygous pathogenic missense variant in the CASR gene, confirming FHH1. Following this, patient’s father was also found to have asymptomatic hypercalcemia, and his genetic test results for the identified mutation are pending.

Discussion: FHH shares biochemical overlap with PHPT but is typically benign, with low urinary calcium excretion and a CCCR <0. 01. Unlike PHPT, FHH does not lead to complications like osteoporosis or kidney stones.

Conclusion: This case underscores the importance of genetic testing in distinguishing FHH from PHPT, especially when CCCR results are inconclusive. A correct diagnosis ensures appropriate management, avoiding unnecessary procedures and anxiety.

Reference: 1. Moore, E. C., Berber, E., Jin, J., and Siperstein, A. (2020) ‘Calcium-Creatinine Clearance Ratio is not helpful in differentiating primary hyperparathyroidism from familial hypocalciuric hypercalcemia: A study of 1, 000 patients’, Surgery for Obesity and Related Diseases.