Thyroid Function and Structure in Klinefelter Syndrome

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.

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).