Thyroid function in Klinefelter syndrome: a multicentre study from KING group

Abstract

The prevalence and the etiopathogenesis of thyroid dysfunctions in Klinefelter syndrome (KS) are still unclear. The primary aim of this study was to evaluate the pathogenetic role of hypogonadism in the thyroid disorders described in KS, with the scope to distinguish between genetic alterations or hormonal involvement. Therefore, we evaluated thyroid function in KS and in non-KS hypogonadal patients. Methods This is a case-control multicentre study from KING group: Endocrinology clinics in university-affiliated medical centres. One hundred seventy four KS, and sixty-two non-KS hypogonadal men were enrolled. The primary outcome was the prevalence of thyroid diseases in KS and in non-KS. Changes in hormonal parameters were evaluated. Exclusion criterion was secondary hypothyroidism. Analyses were performed using Student's t test. Mann-Whitney test and chi-square test. Results FT4 was significantly lower in KS vs non-KS. KS and non-KS presented similar TSH and testosterone levels. Hashimoto's thyroiditis (HT) was diagnosed in 7% of KS. Five KS developed hypothyroidism. The ratio FT3/FT4 was similar in both groups. TSH index was 1.9 in KS and 2.3 in non-KS. Adjustment for differences in age, sample size and concomitant disease in multivariate models did not alter the results. Conclusions We demonstrated in KS no etiopathogenic link to hypogonadism or change in the set point of thyrotrophic control in the altered FT4 production. These results suggest possible deiodinase impairment. The prevalence of HT in KS was similar to normal male population, showing absence of increased risk of HT associated with the XXY karyotype.

Autoimmune Thyroid Disease in Specific Genetic Syndromes in Childhood and Adolescence

“…The above findings may suggest an impaired hypothalamic-pituitary control of the thyroid function resulting in secondary thyroid insufficiency (120). Similar TSH but lower FT4 levels were also documented in KS patients when compared to non-KS hypogonadal men with similar testosterone levels (105). Further to the above, pubertal KS patients showed similar FT4 and TSH, but lower FT3 levels when compared to age-matched pubertal healthy boys, indicating a mixed form of hypothyroidism in KS boys during the pubertal development: both secondary and peripheral, the latter due to reduced deiodinase activity (106) ( Table 1).…”

“…Positive thyroid antibodies are found in 5.4-10% of children and 3.3-7% of adults with KS in different studies (103)(104)(105)(106). Most cases are euthyroid, whereas GD occurs only rarely in patients with the syndrome (107, 108) ( Table 1).…”

European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology

“…Development of teeth may be affected, imposing as taurodontism 190 and an increased risk of caries has been reported 191‐193 . Also, autoimmune disorders might be more frequent in KS, 194‐196 while thyroid functions do not seem to be affected in men with KS 197 …”

The Human Microbiota in Endocrinology: Implications for Pathophysiology, Treatment, and Prognosis in Thyroid Diseases

“…The relation between autoimmunity and other systemic diseases has been for a long time examined by worldwide literature (28)(29)(30), moreover focusing on new therapeutic implications in both surgical and medical field (31)(32)(33)(34)(35)(36)(37)(38). The pathogenesis of autoimmune disorders is due to genetic (4-7, 23-25, 39-41), stochastic (42), and environmental (43)(44)(45)(46)(47)(48)(49) factors.…”