CD-ROM Today 1996 January/CD-ROM Today 1996 January.iso/dp/0413/04136.txt

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$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
     [phone]

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
     [phone]

     The National Adrenal Diseases Foundation
     505 Northern Blvd., Suite 200
     Great Neck, NY  11021
     [phone]

     NIH/National Institute of Child Health & Human Development (NICHHD)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

     Brain & Pituitary Foundation of America
     1360 Ninth Avenue,  Suite 210
     San Francisco, CA  94122
     [phone]

For genetic information and genetic counseling referrals, please
contact:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY  10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

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.