ABSTRACT
Congenital isolated hypogonadotropic hypogonadism (CIHH) is a well-known cause of absent pubertal development in both boys and girls and results from inadequate secretion of the two pituitary gonadotropins, luteinizing hormone and follicle-stimulating hormone, with consequent impairment of normal testicular or ovarian function. Mutations in the genes whose actions determine any one or more of these pathways could theoretically underpin congenital forms of hypogonadotropic hypogonadism. Prepubertal diagnosis in boys with CIHH is rarely made before puberty, although the presence of neonatal unilateral or bilateral cryptorchidism or micropenis or hyposmia/anosmia may suggest the diagnosis. Difficulties arise in partial forms of CIHH when gonadotropin and inhibin B levels can be in the reference range. Renal ultrasound examination can reveal malformation or unilateral agenesis in patients with X-linked KAL1 but is invariably normal in other causes of CIHH. Rapid progress has been made in unraveling the genetic basis of CIHH.
