Klinefelter SyndromeTHINKSNCT05581147
Thyroid Function and Structure in Klinefelter Syndrome
An observational study of Klinefelter Syndrome and Thyroiditis, Autoimmune, run by University of Roma La Sapienza at 1 site in Italy.
Trial summary
This is a longitudinal retrospective study for the evaluation of thyroid function and structure in patients with Klinefelter syndrome compared to healthy controls and patients affected by chronic lymphocytic thyroiditis. Read more about this study
- Who is it for?
- Ages 1 year to 80 years, men only
- Conditions the study is for
- Klinefelter Syndrome, Thyroiditis, Autoimmune, Hypothyroidism
- How many people
- 600 participants
- Where
- 1 siteItaly
- Study dates
- 11 May 2007to 1 Dec 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 1 year to 80 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Study population: The study will enroll three cohorts of patients: * Patients with a confirmed diagnosis of classic, non-mosaic 47,XXY Klinefelter syndrome; * Males with a diagnosis of chronic lymphocytic thyroiditis (CLT); adult male patients affected by CLT, defined by positivity to anti-thyroglobulin antibodies (Ab-Tg) and/or anti-thyroperoxidase antibodies (Ab-TPO); * Euthyroid, healthy controls with no clinical signs or symptoms of thyroidal or testicular disease and meeting the same inclusion and exclusion criteria described above (except for KS diagnosis and availability of thyroid US in pre-pubertal and pubertal children).
Who may be able to join
- Patients with a confirmed diagnosis of classic, non-mosaic 47,XXY Klinefelter syndrome based on a peripheral blood 97 karyotype analysis;
- Availability of thyroid function test results (TSH, fT3, and fT4) and/or thyroid US imaging;
- Availability of concurrent clinical data.
Who cannot join
- Presence of other known genetic conditions or chromosomal abnormalities;
- Use of levothyroxine or other drugs that are either active on the hypothalamic-pituitary-thyroid (HPT) axis or that may interfere with thyroid function tests;
- History of previous surgery or radiotherapy on the thyroid or pituitary glands;
- Current or previous T therapy (for the pre-pubertal and pubertal groups).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
'Sapienza' University of Rome
Roma, 00161
Andrea Isidori, MD, Ph.D., andrea.isidori@uniroma1.it
About this study
Official title: Thyroid Function and Structure in Klinefelter Syndrome (THINKS)
This is a longitudinal retrospective study for the evaluation of thyroid function and structure in patients with Klinefelter syndrome compared to healthy controls and patients affected by chronic lymphocytic thyroiditis.
Read the detailed description
This is a longitudinal retrospective study for the evaluation of thyroid function and structure in patients with Klinefelter syndrome compared to healthy controls and patients affected by chronic lymphocytic thyroiditis (CLT).
The investigators will retrospectively enroll patients with Klinefelter syndrome followed at the host institution and will retrieve data with regards to peripheral hormone levels (thyroid function) and ultrasonographic appearance (thyroid structure) according to pubertal status and gonadal status. Data will be compared with male age- and pubertal stage-matched euthyroid controls, as well as with male patients affected by CLT.
The primary outcome will be the thyroid function compared to healthy controls, by the assessment of peripheral blood TSH, free T3 (fT3) and free T4 (fT4) levels according to pubertal status (pre-pubertal, pubertal and adult subjects) as well as according to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving testosterone replacement therapy [TRT]).
Secondary Outcome Measures will be:
Thyroid function indexes (fT3/fT4 ratio, fT4/TSH ratio, TSH*fT4 product)
Quantitative ultrasonographic thyroid structure parameters, comprising: thyroid volume and echogenicity index, as well as the echotexture parameters of homogeneity and entropy evaluated by Gray Levels Co-occurrence Matrices (GLCM).
In vitro assay of testosterone and estradiol effects on deiodinase type 2 (DIO2) activity in a rat pituitary cell line.
- Keywords
- Klinefelter syndrome, Hypothyroidism, Thyroiditis, Puberty, Prepuberty, Testosterone
- Medical subject headings
- Klinefelter Syndrome, Thyroiditis, Autoimmune, Hypothyroidism, Thyroiditis
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 |
|---|---|---|
| Klinefelter syndrome | Males affected by 47,XXY non-mosaic Klinefelter syndrome. Subgroups according to pubertal stage: pre-pubertal, pubertal and adults. Subgroups according to gonadal status: eugonadal, hypogonadal and receiving testosterone replacement therapy (TRT). | |
| Healthy controls | Euthyroid, age- and pubertal stage-matched males Subgroups according to pubertal stage: pre-pubertal, pubertal and adults. | |
| Chronic lymphocytic thyroiditis | Adult males affected by chronic lymphocytic thyroiditis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peripheral blood TSH concentration
Thyroid function will be assessed by peripheral blood TSH levels, taking into account pubertal status (pre-pubertal, pubertal and adult subjects) as well as to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving TRT).
Measured: Through study completion, an average of 6 years
Peripheral blood fT3 concentration
Thyroid function will be assessed by peripheral blood free T3 (fT3) levels, taking into account pubertal status (pre-pubertal, pubertal and adult subjects) as well as to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving TRT).
Measured: Through study completion, an average of 6 years
Peripheral blood fT4 concentration
Thyroid function will be assessed by peripheral blood free T4 (fT4) levels, taking into account pubertal status (pre-pubertal, pubertal and adult subjects) as well as to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving TRT).
Measured: Through study completion, an average of 6 years
Secondary outcomes (8)
Peripheral deiodinase 2 (DIO2) activity
The investigators will derive the the fT3/fT4 ratio as a surrogate marker of peripheral deiodinase 2 (DIO2) activity.
Measured: Through study completion, an average of 6 years
Pituitary sensitivity sensitivity to thyroid hormones
The investigators will derive the fT4/TSH ratio as surrogate marker of pituitary sensitivity.
Measured: Through study completion, an average of 6 years
Thyroid hormone resistance index
The investigators will derive the TSH*fT4 product as a surrogate marker of thyroid hormone resistance.
Measured: Through study completion, an average of 6 years
Thyroid volume
The investigators will assess ultrasonography-derived thyroid volume (in mL) by the sum of the left and right lobe volumes, derived by the ellissoid formula (d1 x d2 x d3 x 0,5233).
Measured: Through study completion, an average of 6 years
Quantitative thyroid echogenicity
The investigators will assess the ultraonographic thyroid echogenicity index, derived by the histogram mean of thyroid parenchyma in a standardized scan, normalized by the histogram mean of the pre-thyroid muscles.
Measured: Through study completion, an average of 6 years
Thyroid echotexture (homogeneity)
The investigators will assess the ultrasonographic thyroid parenchymal echotexture via the analysis of Grey Levels Co-occurrence Matrices (GLCM) second-order parameter homogeneity (or IDM).
Measured: Through study completion, an average of 6 years
Thyroid echotexture (entropy)
The investigators will assess the ultrasonographic thyroid parenchymal echotexture via the analysis of Grey Levels Co-occurrence Matrices (GLCM) second-order parameter entropy.
Measured: Through study completion, an average of 6 years
In vitro assay of deiodinase type 2 (DIO2) activity
The investigators will assess in vitro modulation of DIO2 activity by sex hormones testosterone and 17-beta estradiol in a rat pituitary cell line (GH4C1) by using a thyroid hormone-responsive artificial promoter (TRE3Tk-Luc).
Measured: At study end (May 2022).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2022
- Study start11 May 2007
- Primary completion15 Oct 2019
- Study completion1 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Klinefelter SyndromeStudies 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
- Retrospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Roma La Sapienza
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Andrea M. Isidori, University of Roma La Sapienza
- Investigators
- Andrea M Isidori, MD, PhD, Principal investigator, andrea.isidori@uniroma1.it
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05581147
- Sponsor's protocol ID
- THINKS
- Acronym
- THINKS
- Status last verified
- Feb 2024
- First submitted
- 4 Oct 2022
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thyroid Function and Structure in Klinefelter Syndrome (THINKS)
- ClinicalTrials.gov ID
- NCT05581147
- Acronym / sponsor ID
- THINKS / THINKS
- Keywords
- Klinefelter syndrome, Hypothyroidism, Thyroiditis, Puberty, Prepuberty, Testosterone
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- University of Roma La SapienzaUniversity, hospital or other
- Study start
- 11 May 2007 (actual)
- Primary completion
- 15 Oct 2019 (actual)
- Study completion
- 1 Dec 2026 (estimated)
- First posted
- 14 Oct 2022 (actual)
- 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.
This is a longitudinal retrospective study for the evaluation of thyroid function and structure in patients with Klinefelter syndrome compared to healthy controls and patients affected by chronic lymphocytic thyroiditis.
Detailed description
This is a longitudinal retrospective study for the evaluation of thyroid function and structure in patients with Klinefelter syndrome compared to healthy controls and patients affected by chronic lymphocytic thyroiditis (CLT).
The investigators will retrospectively enroll patients with Klinefelter syndrome followed at the host institution and will retrieve data with regards to peripheral hormone levels (thyroid function) and ultrasonographic appearance (thyroid structure) according to pubertal status and gonadal status. Data will be compared with male age- and pubertal stage-matched euthyroid controls, as well as with male patients affected by CLT.
The primary outcome will be the thyroid function compared to healthy controls, by the assessment of peripheral blood TSH, free T3 (fT3) and free T4 (fT4) levels according to pubertal status (pre-pubertal, pubertal and adult subjects) as well as according to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving testosterone replacement therapy [TRT]).
Secondary Outcome Measures will be:
Thyroid function indexes (fT3/fT4 ratio, fT4/TSH ratio, TSH*fT4 product)
Quantitative ultrasonographic thyroid structure parameters, comprising: thyroid volume and echogenicity index, as well as the echotexture parameters of homogeneity and entropy evaluated by Gray Levels Co-occurrence Matrices (GLCM).
In vitro assay of testosterone and estradiol effects on deiodinase type 2 (DIO2) activity in a rat pituitary cell line.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Klinefelter syndrome | – | –Males affected by 47,XXY non-mosaic Klinefelter syndrome. Subgroups according to pubertal stage: pre-pubertal, pubertal and adults. Subgroups according to gonadal status: eugonadal, hypogonadal and receiving testosterone replacement therapy (TRT). |
| Healthy controls | – | –Euthyroid, age- and pubertal stage-matched males Subgroups according to pubertal stage: pre-pubertal, pubertal and adults. |
| Chronic lymphocytic thyroiditis | – | –Adult males affected by chronic lymphocytic thyroiditis |
Who may qualify
- Ages
- 1 year to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study will enroll three cohorts of patients: * Patients with a confirmed diagnosis of classic, non-mosaic 47,XXY Klinefelter syndrome; * Males with a diagnosis of chronic lymphocytic thyroiditis (CLT); adult male patients affected by CLT, defined by positivity to anti-thyroglobulin antibodies (Ab-Tg) and/or anti-thyroperoxidase antibodies (Ab-TPO); * Euthyroid, healthy controls with no clinical signs or symptoms of thyroidal or testicular disease and meeting the same inclusion and exclusion criteria described above (except for KS diagnosis and availability of thyroid US in pre-pubertal and pubertal children).
Key inclusion criteria (3 listed)
- Patients with a confirmed diagnosis of classic, non-mosaic 47,XXY Klinefelter syndrome based on a peripheral blood 97 karyotype analysis;
- Availability of thyroid function test results (TSH, fT3, and fT4) and/or thyroid US imaging;
- Availability of concurrent clinical data.
Key exclusion criteria (4 listed)
- Presence of other known genetic conditions or chromosomal abnormalities;
- Use of levothyroxine or other drugs that are either active on the hypothalamic-pituitary-thyroid (HPT) axis or that may interfere with thyroid function tests;
- History of previous surgery or radiotherapy on the thyroid or pituitary glands;
- Current or previous T therapy (for the pre-pubertal and pubertal groups).
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
Peripheral blood TSH concentration
Time frame: Through study completion, an average of 6 years
Thyroid function will be assessed by peripheral blood TSH levels, taking into account pubertal status (pre-pubertal, pubertal and adult subjects) as well as to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving TRT).
Peripheral blood fT3 concentration
Time frame: Through study completion, an average of 6 years
Thyroid function will be assessed by peripheral blood free T3 (fT3) levels, taking into account pubertal status (pre-pubertal, pubertal and adult subjects) as well as to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving TRT).
Peripheral blood fT4 concentration
Time frame: Through study completion, an average of 6 years
Thyroid function will be assessed by peripheral blood free T4 (fT4) levels, taking into account pubertal status (pre-pubertal, pubertal and adult subjects) as well as to gonadal status (eugonadal subjects, hypogonadal subjects and subjects receiving TRT).
8 secondary outcomes
Peripheral deiodinase 2 (DIO2) activity
Time frame: Through study completion, an average of 6 years
Pituitary sensitivity sensitivity to thyroid hormones
Time frame: Through study completion, an average of 6 years
Thyroid hormone resistance index
Time frame: Through study completion, an average of 6 years
Thyroid volume
Time frame: Through study completion, an average of 6 years
Quantitative thyroid echogenicity
Time frame: Through study completion, an average of 6 years
Thyroid echotexture (homogeneity)
Time frame: Through study completion, an average of 6 years
Thyroid echotexture (entropy)
Time frame: Through study completion, an average of 6 years
In vitro assay of deiodinase type 2 (DIO2) activity
Time frame: At study end (May 2022).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2025.
- Individual participant dataSharing planned: Undecided
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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.
Andrea M Isidori, MD, PhD principal investigator
andrea.isidori@uniroma1.it
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Klinefelter Syndrome and Thyroiditis, Autoimmune, run by University of Roma La Sapienza at 1 site in Italy.
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 3 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Andrea M Isidori, MD, PhD (0039649970711, andrea.isidori@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peripheral blood TSH concentration (time frame: Through study completion, an average of 6 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Mar 2025; AzTrials last refreshed its copy on 27 Oct 2026.