Somatic HRPT2 Mutation (Arg234X) of Parathyroid Carcinoma Associated with Slipped Capital Femoral Epiphysis: A First Case Report.

A 14-year-old boy was admitted to the orthopedic clinic of Rajavithi Hospital complaining of pain in the left hip. A year earlier, pain had developed in his left joint and had gradually increased in intensity in both hips. A month before he was referred, radiographs obtained at another hospital showed bilateral slipped capital femoral epiphysis (SCFE). The patient's biochemical laboratory data showed hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone (iPTH) compatible with primary hyperparathyroidism. HRPT2 gene analysis found heterozygosity for c. 700 C > T mutation (Arg234X) of HRPT2 gene at exon 7. This is the first report in the literature about somatic mutation of the HRPT2 gene of parathyroid carcinoma associated with slipped capital femoral epiphysis.

Comparison effect of loading calcitriol and titrating calcitriol treatment to control hypocalcemia after parathyroidectomy in chronic kidney disease: randomized control trial, open labeled.

BACKGROUND: Postoperative parathyroidectomy hypocalcemia probably results from acute reversal of the parathyroid hormone induced contribution of bone to maintain serum calcium concentration. OBJECTIVE: Compare the effective treatment of calcitriol regimens (loaded and titrated) in control hypocalcemic hyperparathyroid (HPT) patients who were referred for parathyroidectomy. MATERIAL AND METHOD: A randomized control, open labeled study of 25 patients who underwent parathyroidectomy in Rajavithi Hospital from August 2009 to September 2010 was conducted. The authors randomized 25 patients with chronic kidney disease in two treatment arms of calcitriol (A: Titrated dose regimen, B: Loaded dose regimen), that met criteria. Biochemical factors available within 2 weeks before and after surgery were recorded and analyzed. RESULT: No significant difference was observed in amount of calcium gluconate intravenous use, hypocalcemia and hospital admission durations between titrated and loaded regimen groups, i.e., p = 0.160, 0.645 and 0.460, respectively. Loaded regimen ameliorated the mean reduction of day 7 postoperative mean change of serum calcium level by 0.33±0.99 mg/dl and median change by 2.88 mg/dl (min, max = -0.80, 5.64) compared with titrate regimen mean change ofserum calcium level by 2.68±2.16 mg/dl; median change 0.28 mg/dl (min, max = -0.84, 1.80) with significance, p = 0.036. CONCLUSION: Loaded calcitriol regimen was superior to titrated calcitriol regimen compared with the control group the first 7 days postparathyroidectomy. Amount of calcium gluconate intravenous used, hypocalcemia and duration of hospital stay did not show any significance.

Role of loading calcitriol to control hypocalcemia after parathyroidectomy in chronic kidney disease.

OBJECTIVE: To compare the effective calcitriol regimens in hypocalcimic hyperparathyroidism (HPT) patients who were referred to parathyroidectomy. MATERIAL AND METHOD: Retrospective study of fifty patients who underwent parathyroidectomy in Rajavithi Hospital between September 2001 and August 2009 was performed. The authors defined three regimens of calcitriol (A; fixed dose regimen, B; titrated dose regimen and C; loading dose regimen) by reviewing 41 charts of patients with chronic kidney disease. Biochemical factors available within two weeks before and after surgery were recorded and analyzed. RESULTS: Postoperative hypocalcemia was a common complication found in 82.93% (n = 34/41) of patients with chronic kidney disease, 80.61% (n = 25/31) and 90% (n = 9/10) of secondary HPT and tertiary HPT, respectively. In multiple logistic regression analysis; calcium-phosphorus product was the independent predictor of postoperative hypocalcemia requiring intravenous calcium gluconate with statistical significance atp = 0.008, ROC analysis showed calcium phosphorus products more than 53 mg2/dl2 represented the best compromise between sensitivity (0.71) and specificity (0.67) by area under the curve = 0.755). The amount of intravenous calcium gluconate after parathyroidectomy in the loading calcitriol regimen (initial dose 2.25-4 mcg/day) was significantly lower than that in the titrated calcitriol regimen (0.75-1.5 mcg/day) (p = 0.001). CONCLUSION: Loading calcitriol regimen reduced hypocalcemic morbidity in postoperative parathyroidectomy in patients with chronic kidney disease.

Sensitivity of HRPT2 mutation screening to detect parathyroid carcinoma and atypical parathyroid adenoma of Thai patients.

OBJECTIVE: Detected HRPT2 mutation in parathyroid carcinoma or atypical parathyroid adenoma in sporadic hyperparathyroidism in Thai patients. MATERIAL AND METHOD: Samples of parathyroid carcinoma, typical (atypical) adenoma or hyperplasia were obtained for HRPT2 gene (17 exons) study since September 2001 to August 2010 both somatic and germline by SyBr Green PCR method. RESULTS: Parathyroid carcinomas and atypical parathyroid adenoma from 5 of 26 patients (10 of 32 samples) were tested for HRPT2 mutations. Only somatic HRPT2 mutations were found in tumor from 2 patients but three patients found both somatic and germline HRPT2 mutations. Exon 15 of HRPT2 gene was the best sensitivity (sensitivity 80.0%; p < 0.001, 95% CI 0.75-1.05) followed by exon 2 and exon 11 (sensitivity 60.0%; p = 0.007, 95% CI 0.60-0.99) to detected parathyroid carcinoma or atypical parathyroid adenoma. CONCLUSION: HRPT2 mutations by SyBr Green PCR sensitive method to detected parathyroid carcinoma or atypical adenoma from benign parathyroid tissues. Exon 15 was the best sensitive to detected parathyroid carcinoma or atypical adenoma. Genotyping of such family members for germline mutation would focus implementation of clinical and biochemical monitoring of carriers of these mutations.