Delayed Puberty

Puberty begins when pulsatile hypothalamic gonadotropin-releasing hormone (GnRH) stimulates pituitary luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These gonadotropins activate the gonads, which then produce testosterone or oestradiol and support gamete development. Delayed puberty occurs when this sequence has not begun within the expected developmental window: no testicular enlargement to at least 4 mL by age 14 years in a boy, or no breast development by age 13 years in a girl. The first useful clinical split is whether the gonads are failing or are not receiving adequate hypothalamic-pituitary stimulation. Low sex steroids with high LH and FSH indicate hypergonadotropic hypogonadism, or primary gonadal failure. Low sex steroids with low or inappropriately normal LH and FSH indicate a hypogonadotropic pattern; the differential then includes constitutional delay of growth and puberty (CDGP), functional suppression from illness or undernutrition, pituitary disease, and congenital hypogonadotropic hypogonadism (CHH). CDGP is common and often familial, but it is a diagnosis of exclusion. CHH is a deficiency of GnRH production, release, or action and may be permanent, although endogenous reproductive function later returns in approximately 10%...