$Unique_ID{BRK04136} $Pretitle{} $Title{Precocious Puberty} $Subject{Precocious Puberty Pubertas Praecox Gonadotropin-Independent Familial Sexual Precocity Familial Testotoxicosis Precocious Puberty Idiopathic Precocious Puberty Isosexual Precocious Puberty Heterosexual Precocious Puberty True Precocious Puberty Central Precocious Puberty Peripheral Precocious Puberty Male-Limited Precocious Puberty Gonadotropin-Dependent Precocious Puberty Gonadotropin-Independent Precocious Puberty McCune-Albright Syndrome Congenital Adrenal Hyperplasia Pseudo-Precocious Puberty Adrenogenital Syndrome Neurofibromatosis} $Volume{} $Log{} Copyright (C) 1988, 1989, 1992, 1993 National Organization for Rare Disorders, Inc. 528: Precocious Puberty ** IMPORTANT ** It is possible the main title of the article (Precocious Puberty) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names and disorder subdivisions covered by this article. Synonyms Pubertas Praecox Gonadotropin-Independent Familial Sexual Precocity Familial Testotoxicosis DISORDER SUBDIVISIONS: Precocious Puberty Idiopathic Precocious Puberty Isosexual Precocious Puberty Heterosexual Precocious Puberty True Precocious Puberty Central Precocious Puberty Peripheral Precocious Puberty Male-Limited Precocious Puberty Gonadotropin-Dependent Precocious Puberty Gonadotropin-Independent Precocious Puberty Information on the following diseases can be found in the Related Disorders section of this report: McCune-Albright Syndrome Congenital Adrenal Hyperplasia Pseudo-Precocious Puberty Adrenogenital Syndrome Neurofibromatosis General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section 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. The exact cause of Precocious Puberty is not known. Symptoms Precocious Puberty can occur in several forms. Normally, the hypothalamus initiates puberty by stimulating the pituitary to release gonadotropins, the hormones which control growth and function of sex organs. When gonadotropins are released, synthesis and secretion of steroids (such as estrogen, progesterone or testosterone) occurs, 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. This disorder is characterized among females by breast development beginning before the age of eight years, or the onset of menstruation before the age of ten years. Among males, Precocious Puberty begins before the age of ten years. Boys with this disorder tend to exhibit facial, underarm (axillary) and pubic hair, accelerated growth, a deepening voice and aggressive behavior. Puberty may occur before three years of age in some cases of this disorder. Premature release of the LH-RH hormone from the hypothalamus results in the secretion of the pituitary gonadotropin hormones, which in turn stimulate the gonadal sex steroids among young children with true Precocious Puberty. Since the aging of bones is usually accelerated by this condition, early fusion of the ends of the long bones or growth plates occurs, resulting in short adult stature. However, during childhood children with Precocious Puberty are taller than their peers. Among girls with Isosexual Precocious Puberty, feminizing changes occur, whereas Heterosexual Precocious Puberty is associated with masculinizing changes. Cerebral Precocious Puberty is caused by brain abnormalities, but closely resembles True Precocious Puberty. Idiopathic Precocious Puberty has no identifiable cause. Among females affected by Idiopathic Precocious Puberty, electrical brain activity abnormalities tend to occur. Electroencephalographic (EEG) tests identify these abnormalities. However, their significance is not well understood. Central Precocious Puberty is characterized by changes which affect the central nervous system. Gonadotropin-Dependent Precocious Puberty is characterized by high concentrations of gonadotropin hormones in girls. In males, Isosexual Precocious Puberty is independent of LHRH hormone release. Gonadotropin- Independent Precocious Puberty is marked by low levels of gonadotropin and usually affects males. Girls with McCune-Albright Syndrome may have either Gonadotropin-Dependent or Independent Precocious Puberty. Causes The exact cause of most cases of Precocious Puberty is not known. In some cases, puberty begins early as the result of a disorder affecting the endocrine glands. Male-limited Precocious Puberty is thought to be inherited through either a sex-linked autosomal dominant inheritance pattern or a sex linked recessive pattern. Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed "dominating" the normal gene and resulting in appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child. X-linked recessive disorders are conditions which are coded on the X chromosome. Females have two X chromosomes, but males have one X chromosome and one Y chromosome. Therefore in females, disease traits on the X chromosome can be masked by the normal gene on the other X chromosome. Since males have only one X chromosome, if they inherit a gene for a disease present on the X, it will be expressed. Men with X-linked disorders transmit the gene to all their daughters, who are carriers, but never to their sons. Women who are carriers of an X-linked disorder have a fifty percent risk of transmitting the carrier condition to their daughters, and a fifty percent risk of transmitting the disease to their sons. Less frequent causes of Precocious Puberty in girls include the presence of abnormal tumors of the hypothalamus as well as Neurofibromatosis, congenital brain lesions, postinfectious encephalitis, hydrocephalus, and craniopharyngiomas. Very rarely, ingestion of birth control pills, or other preparations containing estrogens, or meat containing high estrogen concentrations can cause this disorder. Primary hypothyroidism and McCune- Albright Syndrome often occur in conjunction with Precocious Puberty. Young girls with McCune-Albright Syndrome may develop either gonadotropin or gonadotropin-dependent forms of Precocious Puberty. 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-s 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. Affected Population Precocious Puberty affects females approximately twice as often as males. Approximately eighty percent of female cases have no known cause. Related Disorders 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. Adrenogenital Syndrome is a group of disorders caused by overdevelopment of the adrenal glands (adrenocortical hyperplasia) or malignant tumors in these glands. Masculinization of women or precocious sexual development of male children are the chief characteristics of this syndrome. These disorders are characterized by excessive or abnormal secretions of adrenocortical steroids. 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 (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 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. 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). Therapies: Standard Treatment of Precocious Puberty is structured according to the cause of the disorder. Girls with heterosexual precocious puberty caused by Congenital Adrenal Hyperplasia can be treated by glucocorticoid suppression of the hormone known as ACTH. Girls with Precocious Puberty in conjunction with McCune-Albright Syndrome can be treated with the aromatase inhibitor testolactone, which blocks the synthesis of estrogens. Gonadotropin- Dependent Precocious Puberty in girls can be treated with intranasal administration of the hormone suppressing drug nafarelin acetate. Some lesions of the hypothalamus, as well as ovarian tumors or cysts, can be treated surgically. Hormone sources originating outside the body can be eliminated, provided they are identified. Girls with Precocious Puberty caused by primary hypothyroidism have delayed epiphyseal closure of long bone ends and usually respond well to replacement levothyroxine. Genetic counseling will be of benefit for families of patients with male- limited Precocious Puberty (Familial Testotoxicosis) and other genetic forms of this disorder. Ortho's orphan drug Supprelin (histrelin acetate), has received approval from the FDA for treatment of Precocious Puberty. The drug has been shown to be effective in reducing early sexual changes in boys and girls and to slow accelerated bone maturation. It is given once a day by subcutaneous injection. The orphan product Leuprolide Acetate (Lupron Injection) has received approval from the FDA for treatment of Central Precocious Puberty. The product is manufactured by: Tap Pharmaceuticals, Inc. 2355 Waukegan Rd. Deerfield, IL 60015 Therapies: Investigational To slow the growth rate of males with Isosexual Precocious Puberty, a combination of the drugs spironolactone and testolactone has been used experimentally to restore the growth rate and rate of maturation to normal pre-pubertal levels. The drugs must be prescribed for at least six months. Long-term safety and effectiveness of this treatment has not yet been assessed. Children with Central Precocious Puberty may be treated with an orphan drug known as deslorelin (Somagard). For information on this drug, physicians can contact: Roberts Laboratories, Inc. Meridian Center III 6 Industrial Way West Eatontown, NJ 07724 (201) 389-1182 This disease entry is based upon medical information available through May 1993. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Precocious Puberty, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 The National Adrenal Diseases Foundation 505 Northern Blvd., Suite 200 Great Neck, NY 11021 (516) 487-4992 NIH/National Institute of Child Health & Human Development (NICHHD) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5133 Brain & Pituitary Foundation of America 1360 Ninth Avenue, Suite 210 San Francisco, CA 94122 (209) 227-5466 For genetic information and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MENDELIAN INHERITANCE IN MAN, 7th ed.: Victor A. McKusick; Johns Hopkins University Press, 1986. P. 628-629. INTERNAL MEDICINE, 2nd Ed.: Jay H. Stein, ed.-in-chief; Little, Brown and Co., 1987. P. 1975. TREATMENT OF PRECOCIOUS PUBERTY IN THE MCCUNE-ALBRIGHT SYNDROME WITH THE AROMATASE INHIBITOR TESTOLACTONE: P.P. Feuillan, et al.; N Engl J Med (October 30, 1986, issue 315 (18)). Pp. 1115-1119. INTRANASAL NAFARELIN: AN LH-RH ANALOGUE TREATMENT OF GONADOTROPIN- PUBERTY: T.H. Lin, et al.; J Pediatr (December 1986, issue 109 (6)). Pp. 954-958. CT OF CEREBRAL ABNORMALITIES IN PRECOCIOUS PUBERTY: K.G. Rieth, et al.; AJR (June 1987, issue 148(6)). Pp. 1231-1238. THE TREATMENT OF FAMILIAL MALE PRECOCIOUS PUBERTY WITH SPIRONOLACTONE AND TESTOLACTONE. L. Laue, et al.; The New Eng. J. Med (February 23, 1989, issue 320 (8)). Pp. 496-502.