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J Clin Endocrinol Metab. 2009 Jul;94(7):2478-81. doi: 10.1210/jc.2009-0365. Epub 2009 Apr 28.

Hypothyroidism secondary to hypothalamic-pituitary dysfunction may be part of the phenotype in klinefelter syndrome: a case-control study.

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Department of Endocrinology and Medicine, Aalborg Hospital, Aarhus University Hospital, DK-9000 Aalborg, Denmark.



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.


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.


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 T(4) (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 T(3) was low in KS (P < 0.001), whereas no differences between groups were observed in TSH, free T(3), 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.


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.

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