Letter to the Editor: Distinguishing Typical Primary Hyperparathyroidism From Familial Hypocalciuric Hypercalcemia by Using an Index of Urinary Calcium
Year: 2015
Type: letter
Abstract: The recent update of the guidelines for asymptomatic primary hyperparathyroidism includes recommendations around using the urinary calcium clearance to creatinine clearance ratio (UCCR) (1, 2). UCCR is a calculation that has helped distinguish typical primary hyperparathyroidism (PHPT) from familial hypocalciuric hypercalcemia (FHH) (2–5). An empirical cutoff at 0.01 helps separate these diagnoses. A low value recommends further evaluations about FHH. Both diagnoses show overlaps around the cutoff (2–4). The gold standard for diagnosis of FHH is mutation in CASR, APP2S1, or GNA11 (2, 6, 7). Distinction between typical PHPT and FHH is important because patients with undiagnosed FHH might be referred for parathyroidectomy. However, the mild consequences of FHH rarely require intervention. Furthermore, parathyroidectomy in FHH is usually followed by persistent hypercalcemia (2, 5, 6). The article includes a flow diagram, highlighting UCCR to help distinguish typical PHPT from FHH among cases with asymptomatic hyperparathyroidism; a separate diagram guides genetic testing in the minority with likely syndromal hyperparathyroidism (2). In the subset with UCCR below 0.01, the main flow diagram depicts greater than 95% likelihood of FHH and indicates that DNA testing can be considered next. However, the depicted value of 95% for likelihood of FHH in the subset group below 0.01 is incorrect; thus, its attached suggestion is incomplete. A lower value than cited for likelihood of FHH in this subset has several implications about testing and about management. First, about testing, the UCCR alone does not give as powerful a separation between PHPT and FHH as suggested. Second, the physician may still consider DNA testing in this subset. The cutoff has enriched FHH by approximately 8-fold, although it still remains a minority diagnosis; serum calcium tests in first-degree relatives, especially young relatives, also assist the diagnosis of FHH in a proband (2, 5). Third, the physician also should manage for most likely PHPT in this subset, particularly if the family and DNA testing for FHH is not diagnostic, as is likely to occur. This work was supported by the intramural program of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Human Genome Research Institute. Disclosure Summary: The author has nothing to disclose. familial hypocalciuric hypercalcemia frequency primary hyperparathyroidism urinary calcium clearance to creatinine clearance ratio.
DOI: 10.1210/jc.2014-4221
Author: Stephen J. Marx
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: National Institutes of Health
OpenAlex ID: W2151621642