Pituitary deficiency and lack of gonads in an XY pseudohermaphrodite with beta 39/Lepore haemoglobinopathy

We describe the occurrence of hypothyroidism and hypogonadotropic hypogonad ism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 3 9/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was r eferred at age of 15 years because of delayed puberty. Complete endocrine e valuation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E-2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP a nd ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisoto pe scanning and gonadal vessels phlebography) did not show internal genital ia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome, SRY gene, and no detectable testes indicat e a condition of male pseudohermaphroditism associated with testicular regr ession. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposit ion in both organs. We cannot exclude congenital failure of testosterone sy nthesis and action in this case, because lack of gonads is an unusual findi ng in thalassemic hypogonadic subjects.