In the prepubertal child, the hypothalamic-pituitary-gonadal (H-P-G) axis is functional and extremely sensitive to negative feedback inhibition by low circulating levels of sex
steroids. This feedback system may be under the control of unknown CNS inhibitory mechanisms. Clinical signs of puberty are preceded by increased pulsatile secretion of hypothalamic
gonadotropin-releasing hormone (
GnRH) followed by increased pituitary responsiveness to
GnRH.
Gonadotropin secretion, particularly LH, increases in both sexes, especially during sleep, resulting in gonadal stimulation, secretion of sex
steroids, and progressive physical maturation. When any phase of the H-P-G axis malfunctions, abnormal puberty can result. Abnormal puberty may be precocious or delayed. When puberty is precocious it may be isosexual or heterosexual, complete or partial, intermittent (unsustained), or progressive. True (
central) precocious puberty is usually progressive, and hormonally reflective of normal puberty, although occurring at an earlier age, whereas intermittent or unsustained
precocious puberty usually is associated with immature patterns of
gonadotropin secretion, or with complete
gonadotropin suppression as in
precocious pseudopuberty (ovarian or adrenal
tumors). Cranial axial tomography,
gonadotropin response to
GnRH, and pelvic ultrasound in girls are useful tools to aid in the differential diagnosis of these conditions. Intermittent, or unsustained, puberty in girls is usually self-limited, requiring no medical or surgical intervention. True progressive central precocity may now be managed with
GnRH analogues, which effectively arrest pubertal changes as well as slow rapid linear growth and skeletal maturation. Although a maturation lag usually explains most patterns of
delayed puberty, it is often challenging to exclude other conditions that may contribute to slow pubertal progression, such as
chronic illness, excessive exercise, emotional stress,
anorexia, or
drug use. Elevated serum
gonadotropin levels direct further evaluation toward etiologies of gonadal failure, including
gonadal dysgenesis,
Klinefelter syndrome, and
chemotherapy/irradiation damage. Both low
gonadotropins and absence of or immature
gonadotropin response to
GnRH administration after a bone age of 11 years in girls and 13 years in boys point toward
hypopituitarism or isolated
hypogonadotropic hypogonadism. Management with administration of gradually incremented amounts of sex
steroids at an appropriate psychologic age usually leads to enhanced linear growth, physical maturation, and improved self-esteem.