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NORD is very grateful to Jerrold S. Olshan, MD, Director, Division of Pediatric and Adolescent Endocrinology/Diabetes, The Barbara Bush Children's Hospital at Maine Medical Center and Associate Professor of Pediatrics, Tufts University School of Medicine, for assistance in the preparation of this report.
Precocious puberty means an abnormally early onset of puberty. A sequence of events occurs during which a child develops into a young adult beginning at an unexpectedly early age. Glands that secrete growth and sex hormones begin to function abnormally early in life resulting in this condition. Often, the exact cause of precocious puberty is not known.
Precocious puberty (PP) is a statistical definition; that is, it is the onset of secondary sexual characteristics in children at an age that is two standard deviations younger than the mean age of pubertal onset. The actual age that defines sexual precocity is therefore dependent on the epidemiological data that one uses to define the average age of pubertal onset. Different populations and different time periods will therefore have differing definitions of PP. Classically, in North America, puberty is considered precocious if it begins before age 8 in girls or age 9 in boys. Recently, most likely because of increasing weight in the population, puberty appears to be having an earlier age of onset.
Secondary sexual characteristics include testicular enlargement (>3 ml) and/or pubic hair development in boys, and breast and/or pubic hair development in girls. Other signs suggestive of pubertal onset include acne, growth acceleration, voice changes, vaginal discharge or bleeding, and advanced skeletal maturation. There are many terms used to describe pre-pubertal children who have isolated signs of puberty. These children, however, do not necessarily meet the criteria for true precocious puberty. These terms include premature thelarche, premature adrenarche, premature pubarche and premature menarche. The terminology is often confusing as these are also referred to by some authors as incomplete precocious puberty. Precocious puberty can occur in several forms. Normally, the hypothalamus initiates puberty by stimulating the pituitary to release gonadotropins (FSH and LH), the hormones which control growth and function of the sex organs. When gonadotropins are released, synthesis and secretion of steroids (such as estrogen, progesterone or testosterone) occur, leading to development of secondary sexual characteristics. If this occurs prematurely, a child starts to develop secondary sexual characteristics and proceeds to sexual maturity at an unexpectedly early age. Since the maturing of one's bones is usually accelerated by this condition, early fusion of the growth plates occurs, resulting in shortening of adult stature. However, during childhood, children with precocious puberty are often taller than their peers.
CPP can be caused by CNS tumors (craniopharyngioma, glioma, etc.) and other CNS disorders including: hypothalamic hamartoma of the tuber cinereum, encephalitis, brain abscess, static encephalopathy, global delays, sarcoid or tubercular granuloma, head trauma, vascular lesion, cranial irradiation, or neurofibromatosis type 1 (usually associated with optic glioma). CPP can also follow the treatment of virilizing congenital adrenal hyperplasia or the treatment of other causes of gonadotropin independent precocious puberty (GIPP).
The causes of GIPP include gonadal, adrenal, ectopic, or exogenous sources of hormone production. Hypothyroidism may also cause GIPP which is felt to be mediated by TSH stimulation of the FSH receptor. Very rarely, ingestion of birth control pills, or other preparations containing estrogens, or meat containing high estrogen concentrations can cause this disorder. Hormone-secreting tumors of the ovary or adrenal glands are also associated with precocious puberty. Estrogen-secreting ovarian granulosa-thecal cell tumors are probably the most common form of sex steroid-secreting tumors among girls with this disorder. Human chorionic gonadotropin tumors of the ovary, such as choriocarcinomas or teratomas, may be associated with ovarian sex steroid stimulation and precocious puberty in girls. Benign ovarian cysts may be present in some female patients with PP.
This disorder is classically characterized among females by breast development beginning before the age of eight years in white girls, 6.8 years for Hispanic girls and 6.6 years for Black girls, or the onset of menstruation before the age of approximately ten years (white-10.6 years, Hispanic-10.0 years and black-9.7 years). Among males, precocious puberty can be defined as pubertal development beginning before the age of nine years for white males, 9.5 years for Hispanic males and 8 years for black males. Boys with this disorder tend to exhibit facial, underarm (axillary) and pubic hair, accelerated growth, and a deepening voice. Puberty may occur even before three years of age in some cases of this disorder.
CPP has an incidence of 1 in 5-10,000 children with a female to male ratio of greater than 20:1 although this ratio is debated. Eighty to ninety percent of girls with PP have idiopathic CPP whereas over 50% of boys have an identifiable etiology for PP.
Symptoms of the following disorders can be similar to those of precocious puberty. Comparisons may be useful for a differential diagnosis:
Pseudo-precocious puberty is characterized by high steroid levels due either to ingestion of steroids, hormone-producing tumors (usually of the ovaries or testes), or abnormalities of the adrenal gland which cause over-production of hormones. Although patients appear to be maturing sexually, ovulation or sperm production may not occur because the gonads are not mature. However, in children with precocious puberty, ovulation and sperm production can occur abnormally early in life.
The following disorders may precede the development of precocious puberty. They can be useful in identifying an underlying cause of some forms of this disorder:
McCune-Albright syndrome is characterized by an early (precocious) sexual development, a change in bone structure, pain, increasing deformity, and abnormal changes in skin pigmentation ("Coast-of-Maine" cafe-au-lait spots). This syndrome affects the endocrine and musculoskeletal systems. (For more information on this disorder, choose "McCune-Albright" as your search term in the Rare Disease Database.)
Congenital adrenal hyperplasia (CAH) is a group of disorders resulting from defective synthesis of the corticosteroid hormones of the adrenal gland. The adrenal gland becomes enlarged because it tries to produce more and more of the hormones to compensate for their lack of effectiveness. The adrenal gland produces "male" sex hormones (androgens) in both males and females; because these are overproduced in certain forms of CAH, the external genitalia of some females with this disorder can become masculinized to various degrees. Lack of glucocorticoids, especially cortisol, causes various kinds of metabolic problems. Low levels of mineralocorticoids, primarily aldosterone, causes salt and water imbalances. (For more information on this disorder, choose "Adrenal Hyperplasia" as your search term in the Rare Disease Database.)
Neurofibromatosis (NF) is a genetic disorder with highly variable manifestations which can affect many body systems. Symptoms usually begin during childhood. Early puberty can occur in this condition. The disorder tends to become more active at puberty, during pregnancy, and at menopause. Neurofibromatosis is characterized by multiple nerve tumors under the skin which can result in disfigurement, curvature of the spine and long bones, and other complications. (For more information on this disorder, choose "Neurofibromatosis" as your search term in the Rare Disease Database.)
Normal puberty begins when the pulsatile release of GnRH from the hypothalamus begins. This results in an increase in the frequency and magnitude of gonadotropin release, especially LH. Unfortunately, it is challenging to determine the initial clinical corollary to these biochemical events. It has been suggested that there is a continuum of sexual development in girls from uncomplicated premature thelarche to true precocious puberty; the former being more likely to develop in girls under 2 years of age. This spectrum exists both clinically and biochemically and emphasizes the need for the clinician to distinguish between patients when making decisions about treatment. The criteria for diagnosis and treatment of CPP need to be reached through a synthesis of clinical findings as well as laboratory evidence for activation of the hypothalamic-pituitary-gonadal axis. The gold standard for determination of pubertal gonadotropin secretion is the GnRH stimulation test. In boys, serum testosterone levels are useful for the diagnosis of PP. Diagnostic studies including head MRI, pelvic ultrasound, and skeletal age determination are frequently required in the work-up of children with CPP.
The aims of treatment are to arrest physical maturation, prevent early menarche, bring final adult height closer to genetic expectation and allow normal psychosocial development. Treatment with very potent, long acting GnRH analogues have resulted in significant improvement in height in many, although not all, children with PP caused by both organic conditions and idiopathic CPP. These can be given as subcutaneous injections, intra-nasally, and as subcutaneous implants. These GnRH superactive agonists work by first stimulating and then, after a few days, suppressing pulsatile LH and FSH release. This leads to suppression of gonadal steroid production. In general, girls who need treatment are those who progress rapidly through puberty, whereas girls who progress more slowly will likely have the unsustained or slowly progressive variety of precocious puberty and will often do well without intervention. The degree of bone age advancement is also helpful for determining the tempo of pubertal progression.
Genetic counseling will be of benefit for families of patients with male- limited precocious puberty (familial testotoxicosis) and other genetic forms of this disorder.
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Report last updated: 2012/03/22 00:00:00 GMT+0