Endocrine Abstracts

Introduction: Deficiency of 17-βHSD3 is a rare autosomal recessive disorder of sex development manifesting in XY karyotype individuals. The presentation can range from partial or incomplete virilisation at birth to primary amenorrhoea and virilisation at puberty of an externally phenotypically female individual.

Case reports: Case1 A 2-year-old girl presented with ambiguity of external genetalia. She had no significant past medical or surgical history. On exam she had cliteromegaly measuring 2.5 cm and bilateral inguinal mass consistent with gonads (Prader stage4). Pelvic MRI showed inguinal testis, normal adrenal gland, a blind vagina and absent internal female structures. The serum testosterone (T) was 0.9 ng/ml and rose to <3 ng/ml after HCG stimulation. The serum androstenedione(A) was 12 ng/ml (8–250). The T:A ratio was low 0.16 (<0.8). The karypotype was XY. Gene analysis revealed a homozygous mutation of the 17-βHSD3gene, c618C>A. She underwent bilateral orchidectomy at at the age of 3, genitoplasty at the age of 8 and was commenced on oral estrogen. This resulted in satisfactory breast development and sexual intercourse was more comfortable. Case 2: (Cousin of the first patient) A 7-year-old girl presented with inguinal hernia. On exam she had cliteromegaly (Prader stage1). Pelvic ultrasound and MRI showed inguinal testis and absent internal female structures. The karypotype was XY and gene analysis showed the same mutation as the first case (heterozygous). Case 3: A 16 year old woman presented with primary amenorrhoea, poor breast development, hirsutism and cliteromegaly. She had increased hair growth on her abdomen and face as well as increased muscle mass and deepening of her voice. Pelvic ultrasound and MRI showed uterine and ovarian agenesis. The karypotype was XY. The serum testosterone was 2.82ng/ml. The serum androstenedione was high at 9.6 ng/ml (three times the upper limit of normal). The T:A ratio was 0.3 (<0.8) after HCG stimulation. Diagnosis of 17-βHSD3 deficiency was confirmed with genetic mutation of the 17-βHSD3 gene.

Conclusion: We have described 3 patients with classic clinical and biochemical features of 17-βHSD3 deficiency in whom a mutation was identified in the 17-βHSD3 gene. Identification of affected individuals and molecular biologic studies may help elucidate the clinical conundrums of this disorder. For patients who have a female gender identity, management includes orchidectomy to reverse virilisation and to remove gonads with malignant potential. Estrogen replacement is provided to maximise female secondary sexual characteristics and to prevent bone loss.