Precocious Puberty

Precocious puberty is puberty that begins before age 8 years for girls and before age 9 years for boys. ^{[1] [2]} The word “precocious” means developing unusually early. In some cases, these children will start puberty as early as 3 or 4 years old.

Types

• Central precocious puberty
• Peripheral precocious puberty

Normal puberty

Puberty is the process of biological change after which sexual reproduction is possible. Puberty is characterized by accelerated linear growth in the bones and the development of secondary sexual characteristics, which include axillary and pubic hair in both genders as well as breast development in females. In females, menarche ( the beginning of menstrual periods) is typically last in the sequence.

Normal puberty starts when a part of the brain called the hypothalmus releases a hormone called gonadotropin-releasing hormone (GnRH). GnRH signals the pituitary gland (a pea-sized gland near the base of the brain) to release two more hormones - luteinizing hormone (LH) and follicle-stimulating hormone (FSH). It is these hormones that then travel to different sites in the body to increase the production of sex hormones. LH and FSH signal the ovaries in girls to produce estrogen. In boys, LH and FSH signal the testes to make androgen (male) hormones. This causes the child’s body to go through the changes of puberty.

The normal sequence of hormonal stimulation that causes puberty is:

• Hypothalamus (GnRH) --> Pituitary (LH & FSH) --> Ovaries or Testes (Estrogen or Testosterone) --> Cause secondary sex characteristics (In Girls: breast growth, pubic hair and menses or In Boys: penis, testes growth, pubic, and body hair growth)

The normal physiologic sequence resulting from this cascade of hormonal signals is, in females breast development, followed by pubic and axillary hair growth in both genders, followed by a period of maximal bone growth velocity, and culminating in females in the onset of menstruation. Normal puberty occurs over a wide range of ages, and is influenced by weight and ethnicity.^[3]

Signs and Symptoms

Signs of precocious puberty include development of the following before age 7 in girls and before age 9 in boys.

In both girls and boys:

• Pubic or underarm hair
• Rapid growth
• Acne
• Adult body odor

In girls:

• Breast growth
• First period (menstruation)

In boys:

• Enlarged testicles and penis
• Facial hair (usually grows first on the upper lip)
• Deepening voice

Drawings of both Male and Female Sexual Development in the Tanner Stages

Causes

Premature Thelarche

Isolated development of one or both breasts without other signs of puberty. Breast buds form in girls as young as 1 to 4 years old. Sometimes the process is asymmetrical (unequal). Nipple development does not occur. The condition is not well understood, but is thought to be related to increased estrogen levels. It is most commonly seen in females who were very low weight at birth. Typically the condition regresses spontaneously (goes away on its own) and does not require treatment. It is very important to watch these children for other signs and symptoms of precocious puberty.

Premature Pubarche or Adrenarche

Premature Pubarche is isolated development of pubic hair without other signs of puberty. Premature Adrenarche is isolated development of axillary (underarm) hair without other signs of puberty. Typically the condition is not progressive in that no other symptoms occur. The cause is poorly understood but is probably related to increases production of hormones by the adrenal glands, DHEA and DHEAS. No treatment is necessary. It is important to rule out other conditions and to follow these children closely for other signs or symptoms of precocious puberty.

Central precocious puberty or GnRH Dependent puberty

Central simply means that the problem starts in the brain or spinal cord. GnRH-dependent means that inappropriate release of GnRH starts the process. The sequence of hormonal stimulation happens in the correct order. The hypothalamus releases GnRH which signals the pituitary to release LH and FSH, which in turn signals the ovaries or testes. This sequence just happens earlier than it should.

For 70% of children with central precocious puberty, there is no identifiable cause found. Puberty just starts earlier than normal. ^[4] In these children, the hypothalamus starts the process too early. In rare cases this may be familial (runs in the family). A high incidence of abnormal EEGs in these children have raised the question of a potential central nervous system disease as the cause. Advances in MRI technology has decreased the number of cases for which no cause can be found by diagnosing more central nervous system lesions (abnormalities).

In rare cases the following may be the cause of central precocious puberty^[5]:

• A tumor in the brain or spinal cord (central nervous system)
• An infection in the brain or spinal cord, such as encephalitis or meningitis
• A defect in the brain present at birth, such as hydrocephalus (excess fluid build-up in the brain) or a cyst (small fluid filled collection).
• Noncancerous tumors (hamartoma), (teratoma),(craniopharyngioma)
• Radiation to the brain or spinal cord
• Injury to the brain or spinal cord

It is not known with certainty how these central nervous system abnormalities cause the pubertal sequence to begin prematurely. In the case of hamartomas, it is known that they can produce GnRH.

Peripheral precocious puberty or GnRH-independent precocious puberty

This type of precocious puberty is less common than central precocious puberty. In this type, the cause is not due to premature release of GnRH by the brain. Instead, puberty starts early because of problems with the ovaries, testicles, adrenal glands or pituitary gland. GnRH-independent precocious puberty can be isosexual (pubertal changes are appropriate for the gender), or heterosexual (the child may have pubertal changes associated with the opposite gender). Some causes of GnRH-independent precocious puberty are:

• Congenital adrenal hyperplasia (abnormal adrenal gland function)can produce either iso or heterosexual precocious puberty
• McCune-Albright syndrome
• Tumors in the ovaries or in the testicles The most common type of ovarian tumor is the granulosa cell tumor.
• Adrenal gland tumors
• Hypothyroidism (very rare)
• A very rare gene defect in boys which can cause the early production of testosterone^[6]
• Iatrogenic caused by exposure to medications containing hormones such as oral contraceptives

Diagnosis

In children in which precocious puberty is suspected, most doctors will refer the child to a pediatric endocrinologist. A pediatric endocrinologist has additional training and specializes in the treatment of hormone-related conditions in children.

Tests

• Thorough history and physical exam, especially height
• Tanner Staging
• Basic blood tests to determine levels GnRH, LH, FSH and thyroid hormone levels
• Specialized blood tests include prolactin, estradiol, testosterone, DHEA or DHEAS, androstendione, 17-hydroxyprogesterone, GnRH stimulation test
• X-rays of the hand and wrist to determine the child’s bone age (which shows if the bones are growing too quickly)
• Magnetic resonance imaging (MRI) of the brain
• Neurologic and Ophthalmologic exams
• Electroencephalogram (EEG)
• CT scan of the abdomen to look for tumors or enlargement of the adrenal glands
• In girls, an abdominal ultrasound can to check for an ovarian tumor.

Treatment

Treatment consists of either:

Surgery

It may be necessary to remove the underlying cause (such as a tumor) through surgery. For example removal of an ovarian granulosa cell tumor, or a hypothalamic hamartoma is a curative procedure because the source of abnormal hormones is removed.

Medications

Goals of medical therapy include reducing secretion of GnRH, reducing or counteracting the effects of sex hormones, and decreasing the growth rate to normal to allow maximal height.

Using medications called LHRH analogues or GnRH agonists can decrease the abnormally high levels of sex hormones in the child's bloodstream and halt the process of early puberty.

Children with McCune-Albright syndrome may be treated with testolactone which prevent the conversion of inactive to biologically active estrogens. This reduces the frequency of menses and decreases the growth rate.

Human Growth Hormone

Other therapies

In addition to medical treatment, children with precocious puberty may also benefit from psychological counseling to address the emotional and social issues of being more sexually developed than their peers. Children and adolescents generally want to be the same as their peers, and early sexual development can make them appear "different." This can result in self-esteem problems, depression, acting out at school and home, and abuse of alcohol and illegal substances.

Clinical Trials

Clinical Trials on Precocious Puberty

References

1. ↑ Marshall, WA, Tanner, JM. Variations in pattern of pubertal changes in girls. Arch Dis Child 1969; 44:291.
2. ↑ Marshall, WA, Tanner, JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970; 45:13.
3. ↑ Sun, SS, Schubert, CM, Chumlea, WC, et al. National estimates of the timing of sexual maturation and racial differences among US children. Pediatrics 2002; 110:911.
4. ↑ Boepple, PA, Crowley, WF Jr. Precocious puberty. In: Reproductive Endocrinology, Surgery, and Technology, Vol 1, Adashi, EY, Rock, JA, Rosenwaks, Z (Eds), Lippincott-Raven, Philadelphia, 1996, p. 989.
5. ↑ Chemaitilly, W, Trivin, C, Adan, L, et al. Central precocious puberty: clinical and laboratory features. Clin Endocrinol (Oxf) 2001; 54:289.
6. ↑ Teles, MG, Bianco, SD, Brito, VN, et al. A GPR54-activating mutation in a patient with central precocious puberty. N Engl J Med 2008; 358:709.

External Links

Kids Health. Nemours Foundation: Precocious Puberty

Mayo Clinic:Precocious Puberty

NIH: Precocious Puberty

Lucile Packard Children’s Hospital: Early Puberty