Introduction: Primary hyperparathyroidism is the most common cause for hypercalcemia. Familial benign hypocalciuric hypercalcemia (FBHH) is an unusual autosomal dominant disease. The mutation in the calcium sensing receptor (CaSR) determines a shift to the right in the calcemia set-point that inhibits PTH secretion. Generally asymptomatic, these patients present with mild hypercalcemia and hypophosphatemia, normal or slightly increased PTH levels and hypocalciuria. Daily calciuria lower than 50 mg and calcium to creatinine clearance ratio below 0.01 favour FBHH hypothesis instead of typical primary hyperparathyroidism.
Family case report: We describe a family whose propositus was a 37-years-old male, referred to our Department due to diabetes secondary to alcoholic pancreatitis. His routine analysis revealed hypercalcemia (11.2 mg/dl; RR: 8.410.4). He didnt exhibit any cardiac, gastrointestinal or psychiatric symptom that could support a primary hyperparathyroidism hypothesis. Absence of ancestor family history suggesting hypercalcemia. The following investigation confirmed hypercalcemia (10.9 mg/dl), hypophosphatemia (1.7 mg/dl; RR: 2.74.5), high PTH (75 pg/ml; RR: 972) and regular magnesium, albumin and creatinine levels. He showed hypocalciuria (85.6 mg/24 h; RR: 100300) and a calcium to creatinine clearance ratio of 0.004. Cervical ultrasonography and 99 mTc-sestamibi scintigraphy did not display any abnormality. Bone mineral density was preserved at dual energy X-ray absorptiometry. The propositus has three children, two of them presenting hypocalciuric hypercalcemia. Genetic study has identified R648X mutation in the CASR gene (heterozigoty).
Conclusion: Family history and analytical abnormalities led to FBHH diagnosis, which was genetically confirmed.
We emphasize the need of ruling out FBHH through an investigation triggered by hypercalcemia. Propositus and affected relatives should be warned against undergoing parathyroidectomy, as long as it would be unnecessary (considerable renal reabsorption of calcium and subsequent hypocalciuria still remain after total parathyroidectomy) and hazardous.
Due to neonatal severe hypercalcemia risk, consanguineous relationships are strongly discouraged.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
05 - 09 May 2012
European Society of Endocrinology