TSH Receptor Mutations Among a Consanguineous Community

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

209 participants

Study Classification

OBSERVATIONAL

Study Start Date

2005-12-31

Study Completion Date

2006-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Hypothyroidism

Keywords

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TSH Receptor, resistance TSH, Hyperthyrortropinemia

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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1

Extended family members

No interventions assigned to this group

2

Control- subjects from the same town without known thyroid diseases

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* Subjects belonging to extended family of the index case

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Responsible Party

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Ha'Emek Medical Center, Afula, Israel

Principal Investigators

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Yardena Tenenbaum-Rakover, MD

Role: PRINCIPAL_INVESTIGATOR

Ha'Emelk Medical Center,Afula, Israel

Samuel Refetoff, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Chicago, Chicago, Il, USA

Locations

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Samuell Refetoff

Chicago, Illinois, United States

Site Status

Ha'Emek Medical Center

Afula, , Israel

Site Status

Countries

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United States Israel

References

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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. doi: 10.1210/jc.2007-0366. Epub 2007 Apr 24.

Reference Type BACKGROUND

PMID: 17456567 (View on PubMed)

Other Identifiers

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066-2005

Identifier Type: -

Identifier Source: secondary_id

920050194