Being born small for gestational age (SGA) is frequently associated with unexplained disorder of sex development (non-specific DSD) in boys. Little is known about their future growth, puberty and testicular function. Our objective is to determine the long-term endocrine outcome of boys born SGA who have a non-specific DSD. Cases and controls were retrieved through the international DSD registry and retrospective data collected, based on a spreadsheet containing 102 items. 46,XY boys with a non-specific DSD (n = 179) were included. Males born SGA (n=115) were compared to males born appropriate for gestational age (AGA) (n=64). Their growth and pubertal development were compared. Serum LH, FSH, testosterone, AMH and inhibin B levels in infancy and puberty were analyzed to assess testicular function. At two years of age, 30% of boys born SGA had incomplete or absent catch-up growth. Boys born SGA also had higher LH during minipuberty and lower testosterone in stimulation tests (p=.037 and .040 respectively), as compared to boys with non-specific DSD born AGA. No differences were observed in timing or course of puberty or end-pubertal hormone levels. Almost one out of three SGA boys with a non-specific DSD experiences insufficient catch-up growth. In addition, our data suggest dysfunction of infantile Leydig cells or altered regulation of the hypothalamic-pituitary-gonadal axis in SGA boys during childhood. Sex steroid production during puberty seems unaffected. 

Subjects and controls were retrieved through the international disorders of sex development (I-DSD) Registry and retrospective data collected, based on a spreadsheet containing 102 items. Centralized data analysis was performed in Ghent, and uniformity was achieved in collaboration with the respective centre when needed.