Improvement of Multifactorial Tremor in Klinefelter Syndrome With Testosterone Replacement Therapy

A man in his 50s with long-standing learning difficulties and schizophrenia currently treated with clozapine presented with gynaecomastia and a new right testicular mass. He was noted to have a severe tremor interfering with activities of daily living treated with combination levodopa + benserazide, primidone and topiramate. Investigations revealed elevated prolactin, gonadotropins, sex hormone binding globulin, total testosterone and oestradiol. Right orchidectomy revealed Leydig cell hyperplasia. Karyotyping diagnosed Klinefelter syndrome. Testosterone replacement therapy (TRT) was commenced, with subsequent marked improvement in his debilitating tremor. Tremor is a potentially disabling complication of Klinefelter syndrome with fewer than 50 cases reported in the literature. The pathophysiology of tremor in Klinefelter syndrome is unclear. Tremor in Klinefelter syndrome is often refractory to anti-tremor medical therapy; however, as reported in this case, testosterone therapy may improve tremor in Klinefelter syndrome. It is rare for TRT to significantly improve tremor as reported in this case.