Delayed Puberty Onset and Hypogonadism

Delayed puberty is defined as the absence of any sign of puberty in a child at a chronologic age 2–2.5 standard deviations above the mean age of pubertal development for a given population. Following a period of quiescence in childhood, normal puberty is initiated by the release of tonic inhibition of pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus leading to increased GnRH secretion. These pulses cause secretion of luteinizing hormone (LH) and follicular-stimulating hormone (FSH) from the pituitary gland. These pituitary gonadotropins then circulate to the gonads and stimulate production of sex steroids. The differential diagnosis of pubertal delay is extensive but can most easily be divided into four categories. The first group represents variations in pubertal timing termed self-limited delay (previously referred to as constitutional delay of growth and puberty). Functional disorders, such as chronic illness, can cause a temporary suppression of the axis. Finally, more permanent causes include hypogonadotropic hypogonadism, in which hypothalamic or pituitary failure results in deficiency of circulating gonadotropins, and hypergonadotropic hypogonadism which results from primary gonadal failure, with subsequent lack of negative feedback of sex steroids at the hypothalamic and pituitary levels resulting in elevated serum gonadotropin levels. Sex hormone replacement with exogenous testosterone therapy in boys and estradiol and progestin therapy in girls remains the first line treatment in hypogonadism.