Endocrine Abstracts

Introduction: Pats with Klinefelter Syndrome (KS) have elevated morbidity and mortality due to several reasons. Yet, there is no connection between KS and male-to-female sex change.

Case: A 74-year-old man was sent for endocrine work-up prior to surgery due to gynecomastia. The patient had lived as a man-to-woman transgender for many years. He was told not to qualify for a transgender surgical approach when he was 55 years old. He took estradiol substitution for several years, but by age 60 after developing recurrent severe pulmonary embolism he stopped substitution. After that he lived ‘asexual’ and bilateral, non-painful gynecomastia developed. Gonadal examination revealed small testes, bilateral Gynecomastia (Tanner IV) and signs of chronic venous insufficiency. The biochemical analyses showed hypergonadotropic hypogonadism with otherwise normal values. The molecular analyses revealed a 47XXY Karyotype. Osteodensitometry showed low peak bone mass. We started topical testosterone replacement and calcium/vitamin D3 substitution.

Discussion: KS affects about 1 in 660 men, but remains often undetected with only about 25% of patients receiving the correct diagnosis. Age at diagnosis is around 35. The phenotype is thought to be linked to non-inactivated genes from the extra X-chromosome, but alternative mechanisms are possible.

The excess morbidity and mortality may be explained by endocrine dysfunction and diseases of the cardiovascular and of respiratory systems. Only few studies have examined the association of KS and transsexuality. One study found an association of gender dysphoria with KS. Yet, no significant increase in KS was reported in previous studies looking at men-to-female transgender populations. Still, this hypothesis has to our knowledge not systematically been investigated to make firm conclusions.

Thus, in patients with male-to-female sex change, further work-up towards KS should only be envisaged if there is additional clinical suspicion – such as small testes or hypergonadotropic hypogonadism as found in our case.