Abstract 106: Hypogonadism due to isolated luteinizing hormone receptor defect

Background: The human luteinizing hormone/chorionic gonadotropin receptor (LHCGR) belongs to G-protein coupled class A receptor with 12 Exons, 699 amino acids and molecular weight of 85-95KDa, the gene is located on chromosome 2p21. Mutations of LHCGR have been divided into two types based on the severity of the disease. Type 1 LCH (most severe form) causes male to female DSD, absence of sexual maturation at puberty, milder forms of resistance can present with micropenis and/or hypospadias or only infertility called type 2 LCH. Aims and Objectives: In this study we aim to describe a case with type 2 LCH and systematically review the literature of type 2 LCH cases with available genotype data. Results: Mr. AS presented from southern India born of third degree consanguineous marriage presented with micropenis at the age of 18 years. He had uneventful birth and was reared as a male. External genitalia showed Pubic hair stage 2, stretched penile length of 3.5 cm, bilateral testicular volume of 8 cc with no breast development. Karyotype of the patient was 46 XY and Hormonal evaluation (18 years) showed luteinizing hormone (LH) 19.92 mIU/ml, Follicular stimulating hormone (FSH) 7.62 mIU/ml, testosterone (T) 0.114 ng/ml, stimulated T 0.118 ng/ml, dihydrotestosterone (DHT) 0.199 ng/ml. Imaging showed small sized bilateral testes in the scrotum (right 2.5x1.6 cm, left 2.6x1.9 cm), with visible prostate gland, epididymis and no mullerian structures. Genetic analysis by next generation sequencing showed homozygous pathogenic mutation c.391T>C (p.Cys131Arg) in Exon 5 suggestive of leydig cell hypoplasia. He was treated with Inj testosterone and Inj Human chorionic gonadotropin (HCG) with which he had clinical improvement in terms of virilization and increase in testicular volume. Conclusion: Leydig cell hypoplasia is a rare cause of hypogonadism.