Hypoparathyroidism with Normocalciuria Understanding the Course of Treatment

TANGARI SAREDO, A.; TILITZKY, S.V.; DEL REY, G.; GARRIDO, J.; BATTELLINI, M.; TOMBESI, X.; GOLDARACENA, C.; JIMÉNEZ, M.G.; NAVARRO, G.; MIAURO, J.

Playa del Carmen, Riviera Maya

Congreso; XXIV Annual Meeting of the Sociedad Latino-Americana de Endocrinología Pediátrica (SLEP); 2014

Sociedad Latinoamericana de Endocrinología Pediátrica (SLEP)

Autosomal dominant hypocalcemia (ADH) results from gain of-function mutations of the calcium-sensing receptor (CaSR) coding gene, which is expressed in the parathyroid and in kidney tubules. The activation of CaSR inhibits PTH secretion and reduces calcium reabsorption in the kidney, resulting in hypocalcemia, low or normal levels of PTH and hypercalciuria. Seldom ADH can present with normal urinary calcium (relative hypercalciuria).Objective: To present a patient with hypocalcemia and normal urinary calcium in who lack of response to treatment suggested diagnosis of ADH.Results: A 13-yrs-old girl was referred due to hypocalcemia which was discovered due family history of hypocalcemia. The girl was born at term after an uneventful pregnancy Parents werenot related. She had normal weigh and length at birth. Learning difficulties were noted. She didn?t referred dysesthesia, muscle cramps, or seizures. Family history: Her mother had calcificationin the basal ganglia discovered in a brain CT scan performed during a severe headache. Subsequent hypocalcemia was found. Physical examination of the girl revealed: height on 50thpc, BMI 17.2 (pc25). No dysmorphic features were present. Breast development Tanner IV. No clinical evidence of rickets. She had positive Trousseau?s sign at the first minute and positive Chvostek?s sign. Laboratory test results Ca T 6.8 mg/dl (8.5?10.5), plasma ionized calcium: 0.8 mmol/l (1.14?1.3) P 7.4 mg/dl (2.7?4.5) Mg 1.5 mg/dl (1.3?2.1) Albumin 4.4 gr/dl (3.5?5.0) PTH 9 pg/ml (12?72). Urinary Ca/creatinine ratio: 0.11 (NV?0.2), 25(OH)D: 25.8 ng/ml (NV:30?60) Bicarbonate 25.9 mEq/l (22?26), Na 138 mEq/l (132?145), K:4.25 mEq/l (3.5?5.1). She had normal kidney function and US. To rule out autoimmune polyendocrinopathy type 1 syndrome type the following determinations were made: ACTH16 pg/ml (0?46), Cortisol:9.7 ug/dl (7?24), TSH: 2.6 mUI/ml (0.3?5.0), T3:113.5 ng/dl (80?200) T4:6.21 ug/dl(4.5?13), freeT4:1.08 ng/dl (0.8?2.1). Celiac disease was ruled out. She had not radiologic evidence of rickets. DEXA scan at lumbar spine showed BMD: 1234 gr/cm2 (Z score + 1.1), andtotal body BMD: 1152 gr/cm2 (Z score +0.9). Echocardiogram was normal, ruling out congenital heart disease. Primary hypoparathyroidism was diagnosed. Treatment with intravenous calciumtransiently normalized serum calcium, but thereafter under oral supplementation with 5.5 gr/day of Ca2+ and calcitriol (2 ug/day) serum calcium was:7.0 mg/dl. The 24-hrs- urinary calcium:120 mg (60?240). Mother laboratories: Ca T 6.26 mg/dl (8.5?10.5) plasma ionized calcium: 0.68 mmol/l (1.12?1.32), P:3.5 mg/dl (2.7?4.5), Mg:1.9 mg/dl (1.3?2.1), PTH:27.4 pg/ml (15?68) Urine Ca/Cr ratio: 0.02, 25-OHVitamin D: 40.5 ng/ml (8.9?46.7). The lack of normalization of calcium suggested that the patient may had ADH. Genetic studies showed in the daughter: 2 mutations in compose heterozygous state: p.T151R and p.H429Y on CASR gene. Both of them have been described as cause of ADH. Her mother has only the mutation p.T151R in heterozygous state. DNA from the father was not available to perform the study. Conclusions: Persistent hypocalcemia under calcium supplementation and relative hypercalciuria suggested ADH despite the lack of absolute hypercalciuria. The genetic test was an important tool allowing the correct diagnosis, avoiding unnecessary excessive calcium load and lowering the risks of hypercalciuria.