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.
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 Type
OBSERVATIONAL
Enrollment
600
'Sapienza' University of Rome
Roma, Italy
RECRUITINGPeripheral 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
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
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
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
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
Thyroid hormone resistance index
The investigators will derive the TSH\*fT4 product as a surrogate marker of thyroid hormone resistance.
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Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: 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).
Time frame: At study end (May 2022).