TSH Receptor Mutations Among a Consanguineous Community (TSHR)

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
HaEmek Medical Center, Israel
ClinicalTrials.gov Identifier:
NCT00747760
First received: September 4, 2008
Last updated: September 10, 2008
Last verified: September 2008
  Purpose

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.


Condition
Hypothyroidism

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Prevalence of TSH Receptor Mutation Among the Arab Population of Israel

Resource links provided by NLM:


Further study details as provided by HaEmek Medical Center, Israel:

Primary Outcome Measures:
  • Two specific TSHR mutations [ Time Frame: Finished ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Blood samples were taken with EDTA and Genomic DNA was extracted from peripheral mononuclear cells using the Blood Amp Kit (QIAGEN Inc., Valencia, CA)


Enrollment: 209
Study Start Date: December 2005
Study Completion Date: December 2006
Primary Completion Date: July 2006 (Final data collection date for primary outcome measure)
Groups/Cohorts
1
Extended family members
2
Control- subjects from the same town without known thyroid diseases

Detailed 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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Subjects belonging to extended family of the index case

Criteria

Inclusion Criteria:

  • Subjects belonging to extended family of the index case

Exclusion Criteria:

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00747760

Locations
United States, Illinois
Samuell Refetoff
Chicago, Illinois, United States, 60637-1470
Israel
Ha'Emek Medical Center
Afula, Israel, 18101
Sponsors and Collaborators
HaEmek Medical Center, Israel
Investigators
Principal Investigator: Yardena Tenenbaum-Rakover, MD Ha'Emelk Medical Center,Afula, Israel
Principal Investigator: Samuel Refetoff, MD The University of Chicago, Chicago, Il, USA
  More Information

Publications:
Responsible Party: Dr Yardena Tenenbaum-Rakover, Director Pediatric Endocrine Unit, Ha'Emek Medical Center, Afula, Israel
ClinicalTrials.gov Identifier: NCT00747760     History of Changes
Other Study ID Numbers: 920050194, 066-2005
Study First Received: September 4, 2008
Last Updated: September 10, 2008
Health Authority: Israel: Ministry of Health

Keywords provided by HaEmek Medical Center, Israel:
TSH Receptor, resistance TSH, Hyperthyrortropinemia

Additional relevant MeSH terms:
Hypothyroidism
Thyroid Diseases
Endocrine System Diseases

ClinicalTrials.gov processed this record on August 18, 2014