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RecruitingNCT05581147THINKSUpdated Mar 30, 2025

Thyroid Function and Structure in Klinefelter Syndrome

An observational study in Klinefelter Syndrome, Thyroiditis, Autoimmune and Hypothyroidism, sponsored by University of Roma La Sapienza. Recruiting at 1 site in Italy. Open to male participants aged 1 Year to 80 Years. Per ClinicalTrials.gov, last updated 2025-03-30.

Sponsored by University of Roma La Sapienza · Observational

From the registry’s dates

  • Started May 2007; still recruiting 19 years 6 months later.
Study type
Observational
Model
Cohort
Time perspective
Retrospective
Enrollment
600
Ages
1 Year to 80 Years
Sex
Male
01

Study 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 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.

02

Conditions studied

  • Klinefelter Syndrome
  • Thyroiditis, Autoimmune
  • Hypothyroidism

Keywords

  • Klinefelter syndrome
  • Hypothyroidism
  • Thyroiditis
  • Puberty
  • Prepuberty
  • Testosterone
03

In context

Klinefelter Syndrome

47 studies on the registry are indexed under Klinefelter Syndrome; 17 are open to participants now.

This study's planned enrollment of 600 is above the median of 300 across 27 observational studies indexed under Klinefelter Syndrome.

Browse Klinefelter Syndrome studies →

Lead sponsor

University of Roma La Sapienza is the lead sponsor of 398 studies on the registry; 56 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Year to 80 Years
Sexes eligible
Male
Accepts healthy volunteers
No
Sampling method
Non-probability sample

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).

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion Criteria:

  • 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).
05

Study design

Observational model
Cohort
Time perspective
Retrospective
Enrollment
600 participants (estimated)
Patient registry
No

Groups and cohorts

  • 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

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: Through study completion, an average of 6 years

  2. 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).

    Time frame: Through study completion, an average of 6 years

  3. 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).

    Time frame: Through study completion, an average of 6 years

Secondary outcomes

  1. Peripheral deiodinase 2 (DIO2) activity

    The investigators will derive the the fT3/fT4 ratio as a surrogate marker of peripheral deiodinase 2 (DIO2) activity.

    Time frame: Through study completion, an average of 6 years

  2. Pituitary sensitivity sensitivity to thyroid hormones

    The investigators will derive the fT4/TSH ratio as surrogate marker of pituitary sensitivity.

    Time frame: Through study completion, an average of 6 years

  3. Thyroid hormone resistance index

    The investigators will derive the TSH\*fT4 product as a surrogate marker of thyroid hormone resistance.

    Time frame: Through study completion, an average of 6 years

  4. 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).

    Time frame: Through study completion, an average of 6 years

  5. 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.

    Time frame: Through study completion, an average of 6 years

  6. 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).

    Time frame: Through study completion, an average of 6 years

  7. 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.

    Time frame: Through study completion, an average of 6 years

  8. 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).

    Time frame: At study end (May 2022).

07

Study locations

1 of 1 sites recruiting
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 30, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05581147
Responsible party
Andrea M. Isidori (Full professor, University of Roma La Sapienza) — Principal investigator
First posted
Oct 14, 2022
Start date
May 11, 2007
Primary completion
Oct 15, 2019
Completion
Dec 1, 2026 (estimated)
Last update
Mar 30, 2025

Study contacts

Andrea M Isidori, MD, PhD
Contact
andrea.isidori@uniroma1.it
0039649970711
Andrea M Isidori, MD, PhD
principal investigator · andrea.isidori@uniroma1.it

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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