Girls with congenital GnRH deficiency require enough sex hormone supplementation to maintain body levels in the expected pubertal levels necessary to induce ovulation, especially when fertility is a concern.Males with primary failure of the testes will be on lifelong testosterone.Pulsatile GnRH, weekly multi-LH, or hCG and FSH can be used to induce fertility in adulthood for both males and females. Genetic or acquired defect of the hormonal pathway of puberty (hypogonadotropic hypogonadism)
Boys aged >12 years old with hypogonadotropic hypogonadism are most often treated with short-term testosterone while males with testicular failure will be on life-long testosterone. Choice of formulation (topical vs injection) is dependent on the childs and familys preference as well as on how well they tolerate side effects. Although testosterone therapy alone will result in the start of puberty, to increase fertility potential, they may need pulsatile GnRH or hCG with rFSH. hCG can be used by itself in boys with spontaneous onset of puberty from non-permanent forms of hypogonadotropic hypogonadism and rFSH can be added in cases of low sperm count after 6 to 12 months of treatment.If puberty has not started after 1 year of treatment, then permanent hypogonadotropic hypogonadism should be considered.Girls with hypogonadotropic hypogonadism are started on the same sex steroid therapy as their counterparts with a constitutional delay, however doses are gradually increased to reach full adult replacement levels. Dosage of estrogen is titrated based on the womans ability to have withdrawal bleeds and to maintain appropriate bone density. Induction of fertility must also be done through pulsatile GnRH.
Hypogonadism can be differentiated between hyper- and hypo-gonadotropic hypogonadism by measuring serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) (gonadotropins to measure pituitary output), and estradiol in girls (to measure gonadal output). By the age of 10–12, children with failure of the ovaries or testes will have high LH and FSH because the brain is attempting to jump-start puberty, but the gonads are not responsive to these signals.Stimulating the body by administering an artificial version of gonadotropin-releasing hormone (GnRH, the hypothalamic hormone) can differentiate between constitutional delay of puberty and a GnRH deficiency in boys, although no studies have been done in girls to prove this. It is often sufficient to simply measure the baseline gonadotrophin levels to differentiate between the two.In girls with hypogonadotropic hypogonadism, a serum prolactin level is measured to identify if they have the pituitary tumor prolactinoma. High levels of prolactin would warrant further testing with MRI imaging, except if drugs inducing the production of prolactin can be identified. If the child has any neurological symptoms, it is highly recommended that the physician obtains a head MRI to detect possible brain lesions.In girls with hypergonadotropic hypogonadism, a karyotype can identify chromosomal abnormalities, the most common of which is Turner syndrome. In boys, a karyotype is indicated if the child may have a congenital gonadal defect such as Klinefelter syndrome. In children with a normal karyotype, defects in the synthesis of the adrenal steroid sex hormones can be identified by measuring 17-hydroxylase, an important enzyme involved in the production of sex hormones.