Endocrine Abstracts

Gonadal dysgenesis with DAX1 duplication as the cause of XY disorder of sexual development is a rare condition. Duplication of this causes male to female sex reversal while mutation or deletion can cause adrenal hypoplasia congenita with hypogonadotropic hypogonadism. We present a case of 37-year-old lady who was referred to endocrine clinic with ongoing symptoms of fatigue. She was diagnosed with 46 XY gonadal dysgenesis when she presented with groin swelling at the age of 1 year and had bilateral gonadectomy which showed prepubertal testis at one side and short fallopian tube containing a streak gonad on the other side. She had a normal uterus and plasma testosterone response to hCG stimulation test indicated the presence of testicular tissue. She had a reduction surgery for clitoromegaly at the age of 12 years and puberty was induced with exogenous oestrogen. She has been on hormone replacement therapy since puberty. Chromosomal microarray test was performed to look for the cause of XY DSD and she was found to have DAX1 duplication (NROB1) gene and chromosome 46 XY inversion 9 (p11q21). Her symptoms of fatigue have been ongoing with marked exhaustion even in daily activities. She had surgery for repair of incarcerated left femoral hernia 2 years ago which showed part of uterus and fallopian tube in the hernia sac. She has been on different preparations of oestrogen replacement therapy with no significant improvement in her symptoms. She was also recently given the possible diagnosis of ME/CFS. Recently, she has been in touch with Daisy Network and found the support helpful emotionally. She is a non-smoker, takes minimal alcohol and her current BMI is 37.5 kg/m2. She is euthyroid, euadrenal and her current blood test showed FSH 13.5, LH 8.6, oestradiol 127. She is currently on oestrogel 6 pumps daily (increased by another department) and utrogestan 200 mg at night for 2 weeks every month. This case describes the challenging management of rare condition of hypogonadism in which ongoing symptoms of fatigue are present despite high dose of hormone replacement therapy. Whether the symptoms of fatigue are due to hormone deficiency related to DAX1 duplication or simply related to ME/CFS is unclear. The case also highlights the need for multidisciplinary approach including medical and psychological support.