Endocrine Abstracts

An underlying genetic/endocrine cause for severe hypospadias is found in up to 20% of affected boys as described in the literature, with environmental and epigenetic factors also believed to play a role. We conducted a retrospective analysis of 65 boys with severe hypospadias (penoscrotal, scrotal, perineal) managed by Paediatric Urology at Barts Health NHS Trust, born between January 2010 and 2021 (38% white caucasian, 28% asian, 22% black and 12% other/undefined). Boys with hypospadias with microphallus and/or cryptorchidism had a significantly lower gestational age as compared to hypospadias alone (median 32.6 Weeks vs 38 weeks; P <0.05). A significantly lower birthweight SDS was seen in boys with hypospadias with both cryptorchidism and microphallus as compared to hypospadias alone (median −2.36SDS vs −1.24 SDS; P<0.05). 38 patients had a one stage and 23, a two-stage surgical repair, with complications described in 45% and 56% respectively, including urethral fistula and requirement for urethral dilatation. When cryptorchidism and/or microphallus were described there was a greater likelihood of referral to endocrinology (82% of individuals with additional features as compared to 12% referred with hypospadias alone, 22 referred in total). The diagnostic yield following biochemical/genetic testing was 14%. Genetic testing undertaken beyond karyotyping included the NHSE R146 DSD 35 gene panel and in those with additional clinical features, a microarray. Whilst 6% of boys had a positive family history of hypospadias, none went on to have an established diagnosis. DSD secondary to 17-hydroxylase deficiency (urine steroid profile and confirmed genetically), VACTERL association secondary to compound heterozygous variants in TRAP1 (100 000 genome project), and a heterozygous NR5A1 variant (DSD gene panel) were diagnosed in 3 boys, born at term with normal birthweight and normal inhibin B results. 3 further patients had low inhibin B (< 60 pg/mL), all with a history of IUGR, 2 with cryptorchidism and microphallus (diagnoses to be determined). Diagnostic yield is low for affected boys however there is growing consensus that even those with isolated severe hypospadias warrant further investigation. Importantly, when established, diagnoses allowed for appropriate management of associated comorbidities and genetic counselling. *denotes equal contribution