Endocrine Abstracts

A 34-year-old male with two decades of gender identity issues considered gender reassignment and attended pre-orchidectomy sperm-banking when he was found to be azoospermic. He described a history of difficulty learning to play the piano and of deep-vein thrombosis at 19 years. He was 187 cm tall with a span of 189.7 cm, and exhibited L-sided undescended testis, R testis 1.8×2.5×3.7 cm, bilateral prominent gynaecomastia, a female body habitus, micropenis, bimanual synkinesia and anosmia (confirmed with smell-testing). Low serum levels of testosterone (8 nmol/l) and gonadotropins confirmed hypogonadotrophic hypogonadism, consistent with Kallmann syndrome, though research-based genotyping showed no sequence changes in FGF8, FGFR1, KAL1, PROK2 and PROKR2 genes. Bone-density was impaired (T-score spine −1.9; hip −1.6) and MRI showed bilateral absence of olfactory nerves and bulbs. Low vitamin-D (21 nmol/l) prompted replacement. Thrombophilia screen identified low activated protein C resistance and a heterozygous Factor-V-Leiden mutation.

He has declined testosterone treatment pending assessment by a gender dysphoria clinic, though the possibility of future oestradiol treatment could be complicated by his previous DVT and Factor-V-Leiden status. Two years after his presentation he developed recurrent episodes of ipsilateral weakness and parasthesia in his limbs. Inflammatory spine lesions were identified which 2 years later were associated with white matter lesions in his brain in keeping with a diagnosis of multiple sclerosis (MS).

The question of validity of gender dysphoria diagnosis necessarily arises in the context of a prepubertal/apubertal individual, though psychosexual assessment was reassuring in this respect. Although male MS patients have been found to have reduced gonadotrophins, testosterone and sperm counts, suggesting an acquired effect of MS on hypothalamic regulation of the gonadotroph axis, in this case congenital hypogonadotropic hypogonadism is the likely diagnosis.