Fertility considerations in Klinefelter Syndrome complicated by hypogonadotrophic hypogonadism.

Abstract

Background: Klinefelter syndrome (KS) remains underdiagnosed with less than 50% of men ever diagnosed and >90% of diagnoses only occurring when fertility is sought. MicroTESE (microscopic testicular sperm extraction) is now successful in 47-69% [1]. Optimal timing of the procedure is uncertain. Case:A14-year-oldmale studentwith a history of renal stones (normal genitourinary tract anatomy) and anxiety presented with a six-day history of new onset headaches and transient visual blurring. MRI scan showed a 2.1cm pituitary lesion with local mass effect and minimal compression of the optic chiasm. Pre-operative pituitary panel: FSH29.8 IU/L (1.2 - 5.2 IU/L);LH8.8 IU/L (2.0 - 8.0 IU/L); testosterone 10.9 nmol/L (0.7 - 17.6 nmol/L). Remainder of anterior pituitary function was normal; no AVP deficiency. On examination, Tanner stage P4 G4, testicular volumes 5-6ml (right) and 6-8ml (left) (expected range 15-20ml). Height 175cm(75th centile)andweight 60.1kg (63rd centile). Transsphenoidal resection (TSS) of the pituitary lesion was performed. Intraoperative appearances were suggestive of craniopharyngioma adherent to the pituitary stalk, with stalk transection to achieve complete resection. Post-operatively AVP-deficiency, hypocortisolism and secondary hypothyroidism required replacement therapy. Histopathology was subsequently consistent with Rathke's cleft cyst. Karyotype testing confirmed 47 XXY genotype (Klinefelter syndrome). Post-TSS FSH and LH levels were 0.7IU/L (1.2 - 5.2 IU/L) and 0.3 IU/L (2.0 - 8.0 IU/L); with testosterone <0.1 nmol/L (0.7 - 17.6nmol/L), consistent with hypogonadotrophic hypogonadism superimposed on a background of primary hypogonadism. Testosterone replacement therapy was commenced following discussion regarding potential future fertility options. Discussion(s): This diagnosis of KS highlights the importance of thorough assessment of pubertal development and testicular examination. Small testes with hypergonadotrophic hypogonadism in the context of pituitary pathology should trigger further assessment. Fertility preservationprocedures inprepubertal and adolescent boys with KS remain controversial [2]. This patient represents a unique scenario whereby he is LH and FSH deficient post TSS. Whilst prior treatment with hCG does not increase spermretrieval in non-mosaic KS [3] there may be a role for gonadotrophin therapy prior to undertaking microTESE in our patient. To date, there are no reported cases. .