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Precocious puberty

Precocious puberty is puberty occurring at an unusually early age. 

In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. 

Uncommonly, precocious puberty is triggered by a disease such as a tumor or injury of the brain.

Early puberty can have adverse effects on social behavior and psychological development, can reduce adult height, and may shift some lifelong health risks. 

It is the early development of phenotypical sex organs before the age of 8 in girls and 9 in boys.

Girls as young as 8 are increasingly starting to menstruate, develop breasts and grow pubic and underarm hair.

These biological markers typically occurred only at 13 or older in the past. 

Causes: Idiopathic, brain damage, brain tumor.

Early pubic hair, breast, or genital development may result from natural early maturation or from several other conditions.

Hypothalamus or pituitary impairment can be the cause and is considered central.

Central precocious puberty (CPP) can be treated by suppressing the pituitary hormones that induce sex steroid production. 

Causes of central precocious puberty can include:

Damage to the inhibitory system of the brain

 

Langerhans cell histiocytosis

McCune–Albright syndrome

Brain tumors, 

Infection 

Trauma, 

Hydrocephalus, 

Angelman syndrome.

Precocious puberty is associated with advancement in bone age, which leads to early fusion of epiphyses.

Precocious puberty is associated with  reduced final height and short stature.

Precocious puberty in girls begins before the age of 8. 

The youngest mother on record is Lina Medina, who gave birth at the age of either 5 years, 7 months and 17 days or 6 years 5 months,  as mentioned in another report.

Secondary sexual development induced by sex steroids from other sources is referred to as peripheral precocious puberty or precocious pseudopuberty. 

Symptoms are usually as a sequelae from adrenal hyperplasia, because of 21-hydroxylase deficiency or 11-beta hydroxylase deficiency: hypertension, hypotension, electrolyte abnormalities, ambiguous genitalia in females, signs of virilization in females. 

Blood tests will typically reveal high level of androgens with low levels of cortisol.

Precocious puberty causes:

Endogenous sources

Gonadal tumors 

Adrenal tumors

Germ cell tumor

Congenital adrenal hyperplasia

McCune–Albright syndrome

Familial male-limited precocious puberty 

Exogenous hormones

Environmental exogenous hormones

As treatment for another condition

Patients with precocious puberty develop phenotypically appropriate secondary sexual characteristics. 

This is called isosexual precocity.

In some cases, a patient may develop characteristics of the opposite sex. 

This is called heterosexual or contrasexual precocity, and 

is rare in comparison to isosexual precocity.

Familial cases of idiopathic central precocious puberty have been reported.

Mutations in genes such as LIN28 and LEP and LEPR, which encode leptin and the leptin receptor,have been associated with precocious puberty. 

The gene MKRN3 on chromosome 15 on the long arm in the Prader-Willi syndrome critical region2, and is identified as a cause of premature sexual development or  enteral precocious puberty.

MKRN3 gene mutations acts as a brake on the central hypothalamic-pituitary access, allowing  early activation of the GnRH pathway and cause phenotypic central precocious puberty.

Breast development in girls and the appearance of pubic hair in both girls and boys are starting earlier than in previous generations.

Thresholds for evaluation are thought to minimize the risk of missing a significant medical problem:

Breast development in boys before appearance of pubic hair or testicular enlargement.

Pubic hair or genital enlargement in boys with onset before 9.5 years.

Pubic hair (pubarche) before 8 or breast development (thelarche) in girls with onset before 7 years.

Menstruation (menarche) in girls before 10 years.

Medical evaluation is sometimes necessary to recognize the few children with serious conditions.

 The majority entering puberty early are still medically normal. 

Early sexual development requires evaluation:

induces early bone maturation and reduce eventual adult height

indicates the presence of a tumor or other serious problem

cause the child, particularly a girl, to become an object of adult sexual interest.

Treatment

Surgical Care

When CPP is caused by a CNS tumor a resection should be attempted to the extent possible without impinging on vital structures such as the optic nerves. 

Radiation therapy is often indicated if surgical resection is incomplete. 

Unfortunately, removal of the tumor rarely causes regression of precocious puberty.

For patients with precocious puberty treatment with GnRH agonists is an option.

Adding  growth hormone to GnRH agonist therapy results  in significant height increase, as well as increases in predicted adult height and height standard deviation for bone age, in children with CPP. 

Treatment efficacy is greatest  in patients whose initial treatment began prior to age 10 years or whose therapy lasts more than 12 months.

However, the high cost of combined growth hormone–GnRH agonist therapy relative to its modest benefit has generally limited its use to children with a very poor adult height prediction.

Patients not treated with GnRH agonists

In many cases observing  the child with CPP, either because the age of onset is borderline (ie, 7-8 y), the child and family are coping well, or because the progression of puberty is not rapid and the bone age is only mildly advanced.

Continuous administration of GnRH agonists suppresses pituitary production of gonadotropins because they provide constant stimulus, whereas the pituitary responds only to pulsatile GnRH stimulation. 

GnRH agonists are safe and effective, resulting in decreased levels of LH, FSH, and sex steroids within 4 weeks after initiation of treatment.

Histrelin is a potent inhibitor of gonadotropin secretion when administered long-term.

The implant remains effective in suppressing puberty for at least 2 years. 

 Requires a surgeon to place and remove the implant.

Progestin agents were the mainstay of therapy, and work by providing feedback suppression of pituitary gonadotropin secretion. 

Progestin agents lack significant androgenic or estrogenic activity.

Medroxyprogesterone (Depo-Provera)

Inhibits secretion of pituitary gonadotropin,and Inhibits effect of LH. 

Medroxyprogesterone is effective at slowing breast growth and preventing or stopping menses when administered q3months.

Breakthrough bleeding may occur. 

Less used now due to relative ineffectiveness in reversing rapid advancement of skeletal maturation.

Treatment is with an aromatase inhibitor is an option.

Early puberty also puts girls at a higher risk for teasing or bullying, mental health disorders and short stature as adults.

African-American girls are prone to early puberty.

Early sexual maturation in boys can be accompanied by increased aggressiveness due to the surge of hormones that affect them.

Pubescent boys may face increased social pressure to conform to adult norms, are more likely to be sexually active and are more likely to participate in risky behaviors.

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