Endocrine Abstracts

A 35 year old gentleman with a history of 47 XXY Klinefelter Syndrome (KS) and previous orchidopexy presented to the endocrine service with a two-week history of left sided testicular pain. Examination revealed a tender left testicle. Testicular ultra-sound confirmed bilateral atrophic testes and a 5 mm hypoechoic lesion in the left upper pole. This patient presented with KS at the age of 15 years with gynaecomastia and elevated gonadotrophins. After urgent urological review a left radical inguinal orchidectomy was performed. Histology revealed a sex cord-stromal tumour, 20 mm in maximum measurement. The major pattern was multifocal Leydig cell tumour with additional glandular ductal components. There was no normal testicular histology and no evidence of malignancy. The patient remains clinically well six months post-operatively.

Discussion: KS is the most common sex chromosomal disorder in males, caused by the inheritance of at least one additional × chromosomes from either parent. Its prevalence is 1 in 660. Discovered in 1942 by Harry Klinefelter, it is characterised by gynaecomastia, aspermatogenesis and elevated gonadotrophins. Sex cord stromal tumours (SCST) are rare, accounting for only 5% of all testicular tumours in general populations. These tumours occur most commonly between 40 and 50 years of age and rarely metastasise. Patients who develop metastasis have an estimated prognosis of two years. Leydig cell tumours are the most common type of SCST. Approximately 30% present with virilising or feminising symptoms due to excess androgens or oestrogens. Two large epidemiological studies (Swederlow et al. 2005 and the Danish Cytogenic Registry), have demonstrated that KS is not associated with an increased risk of testicular tumours. Despite a 37% prevalence of crypto-orchidism, few testicular cancer cases are seen. These same studies confirmed the greatly elevated risk of lymphoma and breast cancer iin KS patients. Mediastinal germ cell tumours are also observed in KS patients despite being extremely rare in the general population. Two theories exist to explain the discrepancy between the perceived and the actual risk of testicular cancer in this group. One possible explanation is an unknown immunological process which has a net protective effect against testicular cancer. The second hypothesis postulates that patients with undiagnosed KS present with testicular cancer, however the diagnosis of KS is missed due to phenotypical variability and under-recognition. This case highlights the phenotypic variability and complexity of KS. In summary, greater awareness of KS, its potential complications and various manifestations, is needed to optimise patient outcomes.