ESPE Abstracts

A child with ambiguous genitalia (Prader IV) was born at term from non-consanguineous parents. Otherwise, medical history was normal. Penile length was < 1.5 cm with penoscrotal hypospadia. Testes were inguinal and < 0.5ml. Karyotype was XY and analysis of gonadal and adrenal steroids by TMS showed undetectable testosterone and dihydrotestosterone (DHT) and normal adrenal steroids. Testosterone and DHT rose spontaneously during “Minipuberty” at 1.5 month and showed a low normal increase after 5000 IU HCG. Normal analysis for SRD5A2, HSD17B3, and NR5A1 and no sign for other androgen synthesis defects were encountered. A heterozygous defect in Desert Hedgehog (DHH) gene with rest activity (Tajouri et al.2018) was detected. Inhibin B was 331 ng/l and AMH > 20 µg/l. To improve situation for orchidopexy, correction of hypospadia and increase of penile length, GnRH agonist was started and topical DHT. Penile length increased to 2.5 cm while testes remained at 0.5 ml. Orchidopexy was performed at 8 and 11months. Gonadotropins and testosterone initially being in the range for mini puberty, fell after 7 months stayed low while inhibin B increased from 56 to 144 ng/l but AMH remained low. To improve testicular growth, HCG 500IU 2x/week and 75IU FSH/week were given instead of GnRH agonist for 6 mo. Testosterone increased from undectable levels to 350 ng/dl and testicular volume to 1 ml. It fell to pretreatment volume after the stop of treatment. Topical DHT was continued to an age of 3.5yrs. Penile length at 2y 10mo was 3cm. Between 3 and 7 years, situation was constant. Inhibin B increased from 50 to 95 ng/ml and AMH from 69 to 112 µg/l. At the age of 7y 5mo testicular volume was 0.7 ml on ultrasound. After a loss to follow up until 11yrs, the patient presented a penile length of 4 cm with a G3 appearance and 3 ml testicular volume. FSH was 5.1 U/l, LH 4.2 U/l, testosterone 350 ng/dl, inhibin B 233 ng/L and AMH 28.3 µg/l as signs of spontaneous puberty. This patient with compound heterozygous mutations in DHH has a considerable rest activity. Although there were clear signs of insufficient testicular development and androgen action at birth, mini-puberty as well as puberty started spontaneously and early development responded to systemic testicular and local penile treatment. Efforts to support gonadal function seem to be mandatory. Ref.: (Tajouri et al.2018)