COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

TSH Receptor Mutations Among a Consanguineous Community (TSHR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00747760
Recruitment Status : Completed
First Posted : September 5, 2008
Last Update Posted : September 11, 2008
National Institutes of Health (NIH)
Information provided by:
HaEmek Medical Center, Israel

Brief 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.

Condition or disease

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.

Layout table for study information
Study Type : Observational
Actual Enrollment : 209 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Prevalence of TSH Receptor Mutation Among the Arab Population of Israel
Study Start Date : December 2005
Actual Primary Completion Date : July 2006
Actual Study Completion Date : December 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothyroidism

Extended family members
Control- subjects from the same town without known thyroid diseases

Primary Outcome Measures :
  1. Two specific TSHR mutations [ Time Frame: Finished ]

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)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Subjects belonging to extended family of the index case

Inclusion Criteria:

  • Subjects belonging to extended family of the index case

Exclusion Criteria:

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00747760

Layout table for location information
United States, Illinois
Samuell Refetoff
Chicago, Illinois, United States, 60637-1470
Ha'Emek Medical Center
Afula, Israel, 18101
Sponsors and Collaborators
HaEmek Medical Center, Israel
National Institutes of Health (NIH)
Layout table for investigator information
Principal Investigator: Yardena Tenenbaum-Rakover, MD Ha'Emelk Medical Center,Afula, Israel
Principal Investigator: Samuel Refetoff, MD The University of Chicago, Chicago, Il, USA
Layout table for additonal information
Responsible Party: Dr Yardena Tenenbaum-Rakover, Director Pediatric Endocrine Unit, Ha'Emek Medical Center, Afula, Israel Identifier: NCT00747760    
Other Study ID Numbers: 920050194
First Posted: September 5, 2008    Key Record Dates
Last Update Posted: September 11, 2008
Last Verified: September 2008
Keywords provided by HaEmek Medical Center, Israel:
TSH Receptor, resistance TSH, Hyperthyrortropinemia
Additional relevant MeSH terms:
Layout table for MeSH terms
Thyroid Diseases
Endocrine System Diseases