HypothyroidismTSHRNCT00747760
TSH Receptor Mutations Among a Consanguineous Community
An observational study of Hypothyroidism, run by HaEmek Medical Center, Israel at 2 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypothyroidism
- How many people
- 209 participants
- Where
- 2 sitesin 2 countries
- Study dates
- Dec 2005to Dec 2006
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Subjects belonging to extended family of the index case
Who may be able to join
- Subjects belonging to extended family of the index case
Who cannot join
None listed.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: The Prevalence of TSH Receptor Mutation Among the Arab Population of Israel
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.
Read the 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.
- Conditions
- Hypothyroidism
- Keywords
- TSH Receptor, resistance TSH, Hyperthyrortropinemia
- Medical subject headings
- Hypothyroidism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Extended family members | |
| 2 | Control- subjects from the same town without known thyroid diseases |
What is being measured
The primary outcome is the main question the study is designed to answer.
Two specific TSHR mutations
Measured: Finished
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2008 (estimated)
- Study startDec 2005
- Primary completionJul 2006
- Study completionDec 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HypothyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- HaEmek Medical Center, Israel
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Investigators
- Yardena Tenenbaum-Rakover, MD, Principal investigator, Ha'Emelk Medical Center,Afula, IsraelSamuel Refetoff, MD, Principal investigator, The University of Chicago, Chicago, Il, USA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00747760
- Sponsor's protocol ID
- 920050194
- Other IDs
- 066-2005
- Acronym
- TSHR
- Status last verified
- Sep 2008
- First submitted
- 4 Sep 2008
- Last updated
- 11 Sep 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 17456567
Study at a glance
From the registry record, last updated by the sponsor on 11 Sep 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Prevalence of TSH Receptor Mutation Among the Arab Population of Israel
- ClinicalTrials.gov ID
- NCT00747760
- Acronym / sponsor ID
- TSHR / 920050194
- Conditions
- Hypothyroidism
- Keywords
- TSH Receptor, resistance TSH, Hyperthyrortropinemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- HaEmek Medical Center, IsraelUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Dec 2005
- Primary completion
- Jul 2006 (actual)
- Study completion
- Dec 2006 (actual)
- First posted
- 5 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –Extended family members |
| 2 | – | –Control- subjects from the same town without known thyroid diseases |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Subjects belonging to extended family of the index case
Key inclusion criteria (1 listed)
- Subjects belonging to extended family of the index case
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Two specific TSHR mutations
Time frame: Finished
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Sep 2008.
- Background: PubMed 17456567Grasberger 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yardena Tenenbaum-Rakover, MD principal investigator
Ha'Emelk Medical Center,Afula, Israel
Samuel Refetoff, MD principal investigator
The University of Chicago, Chicago, Il, USA
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypothyroidism, run by HaEmek Medical Center, Israel at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Sep 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Two specific TSHR mutations (time frame: Finished). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00747760, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Sep 2008.