TSH Receptor Mutations Among a Consanguineous Community

Hypothyroidism Clinical Trial

— TSHR  

Official title:

The Prevalence of TSH Receptor Mutation Among the Arab Population of Israel

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00747760
• Other study ID #: 920050194
• Secondary ID: 066-2005
• Status: Completed
• Phase: N/A
• First received: September 4, 2008
• Last updated: September 10, 2008
• Start date: December 2005
• Est. completion date: December 2006

Study information

• Verified date: September 2008
• Source: HaEmek Medical Center, Israel
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Observational

Clinical Trial Summary

Resistance to thyrotropin (RTSH) is a condition of impaired responsiveness of the thyroid gland to TSH, characterized by elevated TSH, low or normal thyroid hormone levels, and hypoplastic or normal-sized thyroid gland.

The aim of the present study was to evaluate the clinical course over time,the genotype-phenotype association and the frequency of two different TSH-receptor (TSHR) mutations in a highly consanguineous population of the town of Um-El-Fahem.

Description:

Resistance to thyrotropin (RTSH) is a syndrome involving reduced sensitivity to TSH. It is characterized by elevated TSH, absence of goiter (normal or hypoplastic thyroid gland) and normal to very low levels of thyroid hormones. The TSH-receptor (TSHR) gene is located on chromosome 14q31 and it consists of extracellular, trans-membrane and intracellular domains. Mutation in the TSHR may cause either gain or loss of function of the receptor. Loss-of-function mutations are autosomal-recessively inherited and lead to a spectrum of phenotypes, ranging from mild euthyroid hyperthyrotropinemia to severe congenital hypothyroidism (CH). Insensitivity to TSH depends on both the severity and location of the TSHR mutations. Since the first report of familial euthyroid hyperthyrotropinemia caused by a TSHR mutation, several cases of loss-of-function mutations of the TSHR have been reported however only a few reports on the outcome of patients affected with TSHR mutations. Whether the condition of euthyroid hyperthyrotropinemia leads to clinical hypothyroidism, remains stable or normalizes over time has yet to be elucidated. We recently described a unique novel TSHR-inactivating mutation located at the third extracellular loop that preferentially affected the inositol phosphate (IP) pathway in three sisters of Arab-Muslim decent that presented with euthyroid hyperthyrotropinemia. Further analysis of the extended family revealed additional members with TSHR syndrome phenotype carrying two different TSHR mutations. All the affected subjects live in the same town. The aim of the present study was to evaluate the clinical course over time, the genotype-phenotype association and the frequency of these two different TSHR mutations among the highly consanguineous population of the town of Um El Fahem.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: December 2006
• Est. primary completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Subjects belonging to extended family of the index case

Exclusion Criteria:

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Hypothyroidism

Locations

Country	Name	City	State
Israel	Ha'Emek Medical Center	Afula
United States	Samuell Refetoff	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
HaEmek Medical Center, Israel	National Institutes of Health (NIH)

Countries where clinical trial is conducted

United States,  Israel, 

References & Publications (1)

Grasberger H, Van Sande J, Hag-Dahood Mahameed A, Tenenbaum-Rakover Y, Refetoff S. A familial thyrotropin (TSH) receptor mutation provides in vivo evidence that the inositol phosphates/Ca2+ cascade mediates TSH action on thyroid hormone synthesis. J Clin Endocrinol Metab. 2007 Jul;92(7):2816-20. Epub 2007 Apr 24. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Two specific TSHR mutations		Finished	No