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Hypothyroidism Secondary to Hypothalamic-Pituitary Dysfunction May Be Part of the Phenotype in Klinefelter Syndrome: A Case-Control Study

Department of Endocrinology and Medicine (A.-M.B.B., P.L.), Aalborg Hospital, Aarhus University Hospital, DK-9000 Aalborg, Denmark; Medical Department M (Diabetes and Endocrinology) (A.B., C.H.G.), Aarhus University Hospital, DK-8000 Aarhus, Denmark; and Department of Clinical Genetics (A.B.), Vejle Hospital, Kabbeltoft DK-7100, Denmark

Address all correspondence and requests for reprints to: Peter Laurberg, Department of Endocrinology, Aalborg Hospital, DK-9000 Aalborg, Denmark. E-mail: peter.laurberg{at}rn.dk.

Context: Klinefelter syndrome (KS) may involve a number of abnormalities besides the characteristic testicular insufficiency. Some studies have suggested that thyroid abnormalities may be common, but this has not been clarified.

Design: A case-control study of men with KS (n = 75) compared with age-matched men from the general population (n = 75) was organized, and thyroid function, thyroid volume by ultrasonography, and thyroid antibodies were examined.

Results: Men with KS were on average taller and heavier and tended to have a higher body mass index than the men in the control group. Serum free T₄ (fT4) was lower in men with KS than controls [mean (SD): 16.3 (2.35) vs. 17.6 (1.75) pmol/liter; P < 0.001], with clustering in or just below the lower part of the reference range for the assay. The ratio fT4 to free T₃ was low in KS (P < 0.001), whereas no differences between groups were observed in TSH, free T₃, TSH to fT4 ratio, thyroid volume, or the prevalence of thyroid antibodies. No difference in any of the variables were observed between testosterone-treated and untreated KS men. Adjustment for differences in height, weight, and concomitant disease in multivariate models did not alter the results.

Conclusions: Men with KS had a general shift toward lower values in distribution of serum fT4 with no compensatory increase in serum TSH. The most likely mechanism is a decrease or change in set point of thyrotroph control of thyroid function.