Thyroid Function and Structure IN Klinefelter Syndrome

Hypothyroidism Clinical Trial

— THINKS  

Official title:

Thyroid Function and Structure IN Klinefelter Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05581147
• Other study ID #: THINKS
• Status: Completed
• Start date: May 11, 2007
• Est. completion date: October 1, 2022

Study information

• Verified date: February 2024
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 354
• Est. completion date: October 1, 2022
• Est. primary completion date: October 15, 2019
• Gender: Male
• Age group: 1 Year to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Hypothyroidism
• Klinefelter Syndrome
• Syndrome
• Thyroiditis
• Thyroiditis, Autoimmune

Locations

Country	Name	City	State
Italy	'Sapienza' University of Rome	Roma

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	Through study completion, an average of 6 years
Primary	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).	Through study completion, an average of 6 years
Primary	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).	Through study completion, an average of 6 years
Secondary	Peripheral deiodinase 2 (DIO2) activity	The investigators will derive the the fT3/fT4 ratio as a surrogate marker of peripheral deiodinase 2 (DIO2) activity.	Through study completion, an average of 6 years
Secondary	Pituitary sensitivity sensitivity to thyroid hormones	The investigators will derive the fT4/TSH ratio as surrogate marker of pituitary sensitivity.	Through study completion, an average of 6 years
Secondary	Thyroid hormone resistance index	The investigators will derive the TSH*fT4 product as a surrogate marker of thyroid hormone resistance.	Through study completion, an average of 6 years
Secondary	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).	Through study completion, an average of 6 years
Secondary	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.	Through study completion, an average of 6 years
Secondary	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).	Through study completion, an average of 6 years
Secondary	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.	Through study completion, an average of 6 years
Secondary	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).	At study end (May 2022).