Overlap in Diagnosis of Familial Hypocalciuric Hypercalcemia (FHH) and Hyperparathyroidism in an Urban Minority Clinic

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 199-237-Disorders of Parathyroid Hormone & Calcium Homeostasis
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-221
Ronak S Chaudhari*1, Alejandra Borensztein2, Lewen Zheng3, Mary Ann Banerji4, Agnieszka Anna Gliwa5, Nathaniel Winer6 and Lisel Marva Loney-Hutchinson7
1SUNY Downstate Med Ctr, Brooklyn, NY, 2SUNY Downstate, New York, NY, 3SUNY Downstate Medical center, 4SUNY Downstate Medical Center, Brooklyn, NY, 5SUNY Downstate, Brooklyn, NY, 6SUNY Hlth Science Ctr Brooklyn, Brooklyn, NY, 7SUNY Downstate Medical Center, Trumbull, CT
Background:  In evaluating primary hyperparathyroidism (PHPT), a low urinary fractional calcium excretion distinguishes the rare genetic disorder of FHH with similarly elevated serum calcium and PTH. We report preliminary observational data on unexpectedly low urinary calcium excretion in the range of FHH in our minority population with hyperparathyroidism.

Methods:  Of a convenience sample of 23 cases with elevated calcium and parathyroid hormone levels, we found 14 with complete data (excluding secondary hyperparathyroidism). Parameters were analyzed in 3 groups based on published criteria of the Ca/ Cr clearance ratio: a ratio < 0.01, typical of FHH, an intermediate ratio between 0.01 to 0.02 and a ratio > 0.02, typical of primary hyperparathyroidism. Parameters included intact PTH, serum and 24 hr urine calcium & creatinine, 25-(OH) vitamin D (vit D), sestemibi scan, and calculated fractional urinary calcium and creatinine (Ca/Cr) clearance. All data are mean­+SD.

Results: The majority of cases were women without a family history of calcium disorders. Unexpectedly, most (8/14 or 67%)  had a Ca/Cr clearance ratio of 0.0072±0.002 (FHH range of < 0.01) with the following: age 70­±15, serum calcium 10.9±06mg/dl, PTH 130±46 pg/ml, vit D 38±23 nmol/L. 3/8 cases had evidence of parathyroid adenoma on sestemibi scan or surgery. 

4 of 14 patients (28%) had an intermediate range Ca/Cr clearance ratio of 0.015±0.005 with following: age 63±8, serum calcium 11.6±2.9 mg/dl, PTH 173±64 pg/ml & vit D 19.3±6 nmol/L. Only 2 patients (14%) had a Ca/Cr clearance ratio in range of hyperparathyroidism at 0.025±0.0006 with age 49, serum calcium 12.2±2 mg/dl, PTH 157±91 pg/ml, and vit D 48.5 nmol/L. One had a parathyroid adenoma removed surgically.

Discussion: Primary hyperparathyroidism (PHPT) is 3rd most common endocrine disorder and FHH is a rare genetic disorder caused by inactivating mutations of the calcium-sensing receptor. Both have elevated serum calcium and “normal” or elevated serum PTH levels.  Surgery is indicated for the former but not the latter and distinguishing them is important to avoid unnecessary surgery. Currently, the Ca/Cr clearance ratio is routinely used as a discriminator, while specific genetic analyses for FHH are rarely used.

 Our data demonstrate a much higher than expected frequency of low urinary Ca/Cr clearance in the FHH range and importantly indicate that this test alone does not distinguish these 2 entities in African American minorities.

Possible explanations include low vitamin D, deficient calcium absorption/intake, measurement error or coexistence of both FHH & PHPT. Finally, minority patients may have a uniquely high prevalence of the calcium sensing receptor mutation of FHH or other alterations of calcium handling in the kidney. These possibilities warrant detailed studies in a larger population.

Nothing to Disclose: RSC, AB, LZ, MAB, AAG, NW, LML

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm