Endocrine Abstracts

JOINT3625

Background: Congenital isolated hypogonadotropic hypogonadism (CIHH) is a disorder characterized by an impaired function gonadotropin-releasing hormone (GnRH). CIHH is associated with defects in 60 genes. CIHH prevalence varies from 1:4,000 to 1:10,000 newborns. “Red flags” include micropenis, cryptorchidism, deafness, anosmia, renal, skeletal, cardiac malformations, cleft lip and palate and etc.

Case report: The boy was born by a spontaneous delivery at 40 weeks of gestation. It was his mother’s first pregnancy which was complicated by chronic hypoxia. Neonatal weight was 3000 g. Neonatal length was 51 cm. His Apgar score were 8 and 9. Marriage was no closely related. At birth the patient was diagnosed with micropenis. The boy firstly was admitted at the age of 7 months complaining of micropenis. His length was 68.2 cm (-0.5 SDS), weight was 7.6 kg (-0.65 SDS). Psychomotor development was normal. Basal LH, FSH, testosterone were low. Triptorelin stimulated LH was 1.3 IU/l. hCG treatment (250 IU twice a week) was prescribed to increase penile length. At his second evaluation at the age of 13.7 years his height was 147.6 cm (-1.8 SD), his weight was 37.7 kg (-0.8 SD). The boy had severe scoliosis and multiple lentigines - dark brown and black skin spots up to 3 cm on the face, torso and hands. He was able to distinguish smells. His corpora cavernosa were 4 cm. The testicles were in the scrotum. The volume of the right testicle was 0.4 ml, the left one was 0.3 ml by ultrasound. Basal LH was 0.2 IU/l. Basal FSH was 0.7 IU/l. Total testosterone was 0.6 nmol/l. Patient had no multiple pituitary hormone deficiency.

Results: Triptorelin stimulated LH was 1.6 IU/l. CIHH was confirmed. Genetic tests revealed heterozygous previously reported pathogenic missense variant c.1016A>G: p.Tyr339Cys in 8 exon of gene FGFR1 (NM 023110.3, HG38, chr8: 38421862T>C, rs2150755221) associated with CIHH. Injections of testosterone 75 mg im/month were prescribed to initiate puberty.

Conclusion: This clinical case demonstrates extremely rare association of lentigo and normosmic congenital isolated hypogonadotropic hypogonadism. It’s the first Russian patient diagnosed with CIHH and lentigo. Due to micropenis the disease was diagnosed during mini-puberty via triptorelin test. Early diagnosis helped to effectively lengthen penis via hCG treatment at the first years of life. and to provide supportive counseling to family.