Click here to view next page of this article

Precocious Puberty

The average age of onset of puberty in girls is about 10 ½. The first clinically detectable sign is typically breast development, with pubic hair starting about six months later precocious puberty, precoshous. Menarche is a late event in female development, typically occurring around 12 years and eight months, on average, and is typified by the first slide. The adolescent growth spurt typically occurs in females very early in the course of puberty, between around ages 11 and 13. Whereas the male one occurs later. Menarche occurs about 2 ¼ years after breast development, which is a restatement of what I just said. About 10 ½ to 12 years eight months.

As far as boys are concerned, the first sign of clinically detectable puberty in males is testicular enlargement, which occurs around 11 ½ or a year later than breast development. Again, pubic hair six months later and here’s the adolescent male growth spurt occurring between about 13 and 15. A word about adolescent gynecomasty. This is usually transient.

What about the term, adrenarche? Adrenarche refers to adrenal androgen secretion and its resultant physical signs. Better known as secondary sexual hair, pubic hair and axillary hair, and acne and odor under the arms. What causes adrenarche isn’t known. It may have something to do with ACTH but there may be a separate or additional factor. It can be determined by a chemical even before the presence of secondary sexual development by the measurement in the serum of adrenal-specific weak androgens known as DHEA or DHEA sulfate.

Now let’s talk about delayed puberty. What is the definition? Well, that would be, based on statistics, the appearance of secondary sexual characteristics; after 13 in females and 14 years in males.

Let’s talk about the differential diagnosis. The most common cause is constitutional growth delay. Remember we talked about that in the growth section, but again both growth and puberty tend to be delayed and the term we use for the patient is, "You are going to be a late-bloomer." This is a normal variant, it’s not a disease. Another entity that causes delayed puberty, which is much more significant.

Those are the congenital defects. How about acquired hypothalamic pituitary defects? Well, this can be a component of hypopituitarism which can be due to tumors, radiation, trauma, surgery or typically seen in females, anorexia nervosa can cause an acquired form of hypo-gonadotropic hypogonadism.

Okay, what about primary gonadal disorders? In other words, the gonadotropins are fine, it’s the end organ that is the problem. Well, we’ve talked about Turner’s syndrome with bad ovaries and Klinefelter’s syndrome with reduced testicular function. There can be autoimmune destruction in gonads. There can be systemic diseases, products or metabolites of which occur, say in galactosemia, which are toxic to the ovaries.

What about early puberty? This would be defined, again statistically, by the appearance of secondary sexual characteristics before age eight-years in Caucasian females and before age seven in African-American females, and before nine-years in males of either racial background. The reason it sounds funny is that there are no data that have been published.

What about central precocious puberty? The first two things I showed you were way variant of normal, this is not. This refers to the activation of the hypothalamic pituitary gonadal axis at an early age and in boys you would look for testicular enlargement. In girls, if you had an ultrasound machine, you’d look for ovarian enlargement or breast development is easier to do with a physical exam. If the patient turns out not to have central sexual precocity with some of these findings, then you have to look for another origin of the problem.

What about causes of central sexual precocity? Well, it’s frequently idiopathic as I mentioned. Where there are CNS lesions it can be pretty much from anything. Congenital defects such as hydrocephalus, sequelae of an old infection related to meningitis, encephalitis, there can be a tumor of the hypothalamus known as hamartoma. It actually functions like a normal hypothalamus insofar as making GNRH secretions, just ahead of schedule.

Other forms of precocious pseudo-puberty can occur if there is an HCG-secreting tumor, such as a hepatoblastoma or germ cell tumor which occurs with higher frequency in Klinefelter’s syndrome. HCG operates like LH. If there is LH effectively present, or HCG, it stimulates testes to make androgen and you get sexual precocity.

What about treatment? It depends upon the underlying etiology and on other factors insofar as exact age of the child, psychosocial ramifications, the height potential, etc. Why do we treat? Well, it’s important, among other things, to maximize final adult height because untreated some of these patients end up quite short, and very importantly are the psychological issues, for example with early menstruation and physical development which could make someone else think the child is older than they are and cause problems.

If you have central precocious puberty the treatment is with GNRH analogs, of which there are … I’m going to skip the brand names. But these work by shutting down the central axis basically after a short period of accentuation. There are depo forms that we use that are given every three to four weeks. If you have other forms of precocity, such as I mentioned familial testotoxicosis, there may be specific drugs.