Clinical trial NCT05581147: Thyroid Function and Structure in Klinefelter Syndrome
Official title: Thyroid Function and Structure in Klinefelter Syndrome (THINKS)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Klinefelter Syndrome
Thyroiditis, Autoimmune
Hypothyroidism
Keywords: Klinefelter syndrome
Hypothyroidism
Thyroiditis
Puberty
Prepuberty
Testosterone
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2022-10-14
Enrollment: 600
Sex: MALE
Minimum age (years): 1
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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).

Brief 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.

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.

Eligibility criteria: 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:

* 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).

Primary outcomes:
measure: Peripheral blood TSH concentration
timeFrame: Through study completion, an average of 6 years
measure: Peripheral blood fT3 concentration
timeFrame: Through study completion, an average of 6 years
measure: Peripheral blood fT4 concentration
timeFrame: Through study completion, an average of 6 years
Secondary outcomes:
measure: Peripheral deiodinase 2 (DIO2) activity
timeFrame: Through study completion, an average of 6 years
measure: Pituitary sensitivity sensitivity to thyroid hormones
timeFrame: Through study completion, an average of 6 years
measure: Thyroid hormone resistance index
timeFrame: Through study completion, an average of 6 years
measure: Thyroid volume
timeFrame: Through study completion, an average of 6 years
measure: Quantitative thyroid echogenicity
timeFrame: Through study completion, an average of 6 years
measure: Thyroid echotexture (homogeneity)
timeFrame: Through study completion, an average of 6 years
measure: Thyroid echotexture (entropy)
timeFrame: Through study completion, an average of 6 years
measure: In vitro assay of deiodinase type 2 (DIO2) activity
timeFrame: At study end (May 2022).
Other outcomes:
Locations:
city: Roma
country: Italy
facility: 'Sapienza' University of Rome
Study officials:
affiliation: andrea.isidori@uniroma1.it
name: Andrea M Isidori, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: