Administration of GH to patients with normal GH responsiveness to secretagogues is controversial, but, as noted earlier, diagnostic tests are imperfect; if the patient is growing extremely slowly without alternative explanation, GH therapy is sometimes used. GH is effective in increasing the growth rate and final height in Turner syndrome and in chronic renal failure; GH also is used for treatment of short stature and muscle weakness of Prader-Willi syndrome. Other indications include children born small for gestational age who have not exhibited catch-up growth by 2 years of age and the long-term treatment of idiopathic short stature with height 2.25 SDs or less below the mean. Psychological support of children with severe short stature is important. Although there is controversy, marital status, satisfaction with life, and vocational achievement may be decreased in children of short stature who are not given supportive measures.
The staging of pubertal changes and the sequence of events are discussed in Chapter 67. The onset of puberty is marked by pubarche and gonadarche. Pubarche results from adrenal maturation or adrenarche and is marked with the appearance of pubic hair; other features include oiliness of hair and skin, acne, axillary hair, and body odor. Gonadarche is characterized by increasing secretion of gonadal sex steroids as a result of the maturation of the hypothalamic-pituitary-gonadal axis. These sex steroids differ by gender, consisting of testosterone from the testes and estradiol and progesterone from the ovaries. In males physical signs are pubic hair, axillary hair, facial hair, increased muscularity, deeper voice, increased penile size, and increased testicular volume. In females the physical signs are breast development, development of the female body habitus, increased size of the uterus, and menarche with regular menstrual cycles. The third component is the growth spurt of puberty.
Hypothalamic gonadotropin-releasing hormone (GnRH), produced by cells in the arcuate nucleus, is secreted from the median eminence of the hypothalamus into the pituitary portal system and reaches the membrane receptors on the pituitary gonadotropes to cause the production and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) into the circulation. The hypothalamic-pituitary-gonadal axis is active in the fetus and newborn but is suppressed in the childhood years until activity increases again at the onset of puberty.
In females FSH stimulates the ovarian production of estrogen and, later in puberty, causes the formation and supportof corpus luteum. In males LH stimulates the productionof testosterone from the Leydig cells; later in puberty, FSHstimulates the development and support of the seminiferous tubules. The gonads also produce the protein inhibin.Both sex steroids and inhibin suppress the secretion of gonadotropins. The interplay of the products of the gonadsand GnRH modulates the serum concentrations of gonadotropins. GnRH is released in episodic pulses that vary duringdevelopment and during the menstrual period. These pulsesensure that gonadotropins are released in a pulsatile manner. With the onset of puberty, the amplitude of the pulses ofgonadotropins and, in turn, the sex steroids increases, firstat night and then throughout the day. Adrenarche generallyoccurs several years earlier than gonadarche and is heraldedby increasing circulating dehydroepiandrosterone (DHEA)or androstenedione. Serum DHEA increases years before theappearance of its effects.