Clinical and molecular genetics of parathyroid neoplasms.

Metabolic Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bldg. 10 Room 8C-101, 10 Center Dr. MSC 1752 Bethesda, MD 20892-1752, USA.
Best Practice & Research: Clinical Endocrinology & Metabolism (Impact Factor: 4.91). 06/2010; 24(3):491-502. DOI: 10.1016/j.beem.2010.01.003
Source: PubMed

ABSTRACT Primary hyperparathyroidism (HPT) results from the excessive secretion of parathyroid hormone from parathyroid tumours. While most HPT is sporadic, it is associated with a familial syndrome in a minority of cases. The study of these syndromes has helped define the pathophysiology of both familial and sporadic parathyroid neoplasms. Investigation of kindred with multiple endocrine neoplasia type 1 (MEN1) and the hyperparathyroidism-jaw tumour syndrome (HPT-JT) led to the discovery of the tumour suppressor genes MEN1 and HRPT2. We now recognise that somatic mutations in MEN1 and HRPT2 tumour suppressor genes are frequent events in sporadic parathyroid adenomas and carcinomas, respectively. Parathyroid tumours in the MEN2A syndrome result from mutational activation of the RET oncogene. The CCND1/PRAD1 oncogene was discovered by analysis of sporadic parathyroid tumours. Studies of familial isolated HPT and analysis of chromosomal loss and gain in parathyroid tumours suggest that other genes relevant to parathyroid neoplasia await identification.

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    ABSTRACT: Objective: Asymptomatic primary hyperparathyroidism (PHPT) is a common clinical problem. The purpose of this report is to provide an update on the use of diagnostic tests for this condition in clinical practice. Participants: This subgroup was constituted by the Steering Committee to address key questions related to the diagnosis of PHPT. Consensus was established at a closed meeting of the Expert Panel that followed. Evidence: Each question was addressed by a relevant literature search (on PubMed), and the data were presented for discussion at the group meeting. Consensus Process: Consensus was achieved by a group meeting. Statements were prepared by all authors, with comments relating to accuracy from the diagnosis subgroup and by representatives from the participating professional societies. Conclusions: We conclude that: 1) reference ranges should be established for serum PTH in vitamin D-replete healthy individuals; 2) second- and third-generation PTH assays are both helpful in the diagnosis of PHPT; 3) normocalcemic PHPT is a variant of the more common presentation of PHPT with hypercalcemia; 4) serum 25-hydroxyvitamin D concentrations should be measured and, if vitamin D insufficiency is present, it should be treated as part of any management course; 5) genetic testing has the potential to be useful in the differential diagnosis of familial hyperparathyroidism or hypercalcemia.
    Journal of Clinical Endocrinology &amp Metabolism 08/2014; 99(10):jc20141414. DOI:10.1210/jc.2014-1414 · 6.31 Impact Factor
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    ABSTRACT: Objective: Primary hyperparathyroidism (PHPT) is one of the most frequently diagnosed endocrine disorders, but few studies focused on hospital management of the disease in Europe. We investigated the frequency of hospital admission for diagnosis and surgical treatment for PHPT in Italy. Design: retrospective study. Methods: We retrieved data from the "Record of Hospital Discharge" (SDO) of the Italian Health Ministry, from the year 2006 to 2011 and analyzed the codes corresponding to PHPT-related diagnoses and surgical procedures. Results: Overall, 46,275 hospitalization episodes for PHPT were identified during the entire period [69% in women and 31% in men); mean age 63.3±39.8 years]. Patients' mean age significantly increased during the years (p<0.001). The mean length of stay was 8.2±10.5 days (28% of the episodes requiring less than 3 days of stay). Admissions for surgical procedures were 12,457 accounting for 26.9% of the total hospitalizations. There was a trend to a significant increase in the percentage of surgery (p<0.05). The mean hospitalization rate for PHPT was 12.9/100,000 inhabitants/year and the trend showed a significant decrease during the period 2006-2011 (p<0.0001). The mean hospitalization rate for PHPT surgery was 3.65/100,000 per year, significantly increasing over time (p<0.001). Conclusions: PHPT considerably influences the Italian Hospital healthcare system. We observed a tendency to a decrease in the frequency of hospitalization during the period 2006-2011, most probably because of economic issues, a concomitant increased age of patients, and, interestingly, also a progressive increase in the percentage of surgical treatment among patients admitted for PHPT.
    European Journal of Endocrinology 07/2014; 171(4). DOI:10.1530/EJE-14-0493 · 3.69 Impact Factor
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    ABSTRACT: This study reported a family with primary hyperparathyroidism due to parathyroid carcinoma and investigated the pathological and genetic features of family members. Three members of the family had clinical manifestation of primary hyperparathyroidism and tumors in the neck. All three patients underwent parathyroidectomy, thyroidectomy and level-VI neck dissection and were definitively diagnosed based on pathology. The index case was a patient that was found to have parathyroid carcinoma on the right side and parathyroid adenoma on the left side. The other two patients had local tumor recurrence and metastasis to distant organs. A germline mutation in the HRPT2 gene (Arg91Pro) was identified in all of the patients in this family. Study of the literature indicated that this is the first report of familial parathyroid carcinomas with an HRPT2 gene missense mutation. Results also indicated that HRPT2 may play an important role in the development of parathyroid carcinoma.
    02/2012; 1(1):27-9. DOI:10.5582/irdr.2012.v1.1.27


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