PRECOCIOUS PUBERTY

Definition of precocious puberty

Precocious puberty is defined as the onset of secondary

sexual characteristics before 8 yr of age in girls and 9 yr in

boys.

Classification:

Complete

Central

( gonadotropin-dependent puberty,

GDPP)

Peripheral

(gonadotropin-independent puberty,

GIPP)

Incomplete

Premature thelarche

Premature pubarche

Premature menarche

Gonadotropin-dependent precocious puberty ( GDPP)

also known as true precocious puberty

early activation of the entire hypothalamic-pituitary-gonadal (HPG) axis

is caused by the secretion of high-amplitude pulses ofgonadotropin-releasing hormone (GnRH) by thehypothalamus.

Although the onset is early, the pattern and timing ofpubertal events usually progresses in the normalsequence.

• Non- CNS lesion:- Idiopathic- Genetics-Prolonged, untreated severe hypothyroidism

• CNS lesion:-CNS tumour- CNS irradiation- hydrocephalus, cysts, trauma, CNS inflammatory disease,

Gonadotropin-dependent precocious puberty

condition occurs at least 5- to 10-fold more frequently in girls than in boys

Approximately 90% of sexual precocity in girls is idiopathic

75% of boys have a structural CNS abnormality

Causes of CNS lesion:

Hypothalamic hamartomas are the most commonbrain lesion causing true precocious puberty.

Hamartomas are non-malignant tumours of thetuber cinereum that consists of disorganized collection ofneurons and glias.

ectopically located neural tissue containing GnRH-secretory neurons and may function as an accessoryGnRH pulse generator

Other tumour: astrocytoma, optic and hypothalamicglioma

Causes of CNS lesion: (cont.)

Radiation therapy for leukemia or intracranialtumours irradiation is directed to thehypothalamic area or to areas of the brainanatomically distant from the hypothalamus

increases the risk of precocious puberty

Clinical manifestations:

Begin at any age, follows the sequence observed in normalpuberty

In girls:

Breast enlargement comes first

Pubic hair may appear simultaneously but more oftenlaters

Menarche is a late event ( irregular cycle and usuallyanovulatory )

The pubertal growth spurt occurs early in female puberty

In boys:

Testicular enlargement( unnoticed)

Enlargement of penis

Axillary hair, acne, voicedeepens

Erections are common

spermatogenesisobserved as early as 5-6yr of age

In both gender:

Height, weight, and osseous maturation areadvanced

Without treatment, 30% early closure of theepiphyses > height less than the 5th percentile asadults

Emotional and mood swings are common

In intracranial lesion ( eg: hamartoma ) :

Hypothalamic signs:

diabetes insipidus

hyperthemia

unnatural crying or laughing(gelastic seizures)

cachexia

In optic glioma : proptosis

In irradiation of brain : signs of growth hormonedeficiency may present

Gonadotropin-independent precocious puberty ( GIPP)

Independent of gonadotropin secretion and noactivation of the HPG axis

aka precocious pseudopuberty

caused by excess secretion of sex hormones(estrogens or androgens) derived either from thegonads or adrenal glands or from exogenoussources

Causes of GIPP :

Girls Boys

Ovarian cysts Leydig cell tumour

Ovarian tumours Human chorionic gonadotropin(hCG) secreting germ cell tumors

Granulosa theca cell tmour Familial male-limited precocious puberty

Both in boys and girl:Exogenous estrogenAdrenal pathology ( eg: androgen-secreting tumour and CAH)TeratomaMcCune-Albright syndrome

How to approach:

Onset of age? Is the cause of precocity central or peripheral? Need to ask the

pattern of pubertal development in GDPP normal pubertaldevelopment but at an earlier age

How quickly is the puberty progressing?rapid bone maturation suggest either GDPP or GIPP

Presence of headaches or seizures ? CNS lesion Previous history of CNS disease or trauma? Are the secondary sexual characteristics virilizing or feminizing? feminizing in Sertoli cell tumorVirilization in CAH Any exposure to exogenous sex steroids?? (medicinal or cosmetic

sources) Timing of pubertal onset in his or her parents and siblings? family

history of similar symptoms?

Physical examination:

Measurements of height, weight, and calculation of height velocity (cm/yr)

Pubertal staging:

In girls :

- Breast staging, pubic hair,

In boys:

- Testicular volume? Penile size? Pubic hair?

Abdominal examination:

Palpate for mass ( in ovarian cyst and tumour)

Neurological examination (neurological deficit?)

Eye examination :

Fundoscopy :look for papilledema ( in CNS lesion)

Visual field

Look for signs of virilization in female? Ambigious genitalia? Hirsutism?

Dermatological exam to evaluate for cafe-au-lait spots( in McCune-Albrightsyndrome).

Investigations:

Serum LH concentration

If basal level of LH are low or

intermediate

If LH and FSH levels not increase with

GnRH stimulation

( GIPP)

If LH and FSH levels increase with GnRH

stimulation

( GDPP )

If basal level of LH are markedly elevated

Confirm GDPP

Proceed with GnRH stimulation test

** Patients with GDPP must proceed with brain imaging to exclude any CNS lesionContrast-enhanced MRI is use to detect any hypothalamic and infundibular lesion

Other investigations:

Sex hormone

To establish degree of biochemical pubertal enhancement

Serum estradiol are low or undetectable in the early phase of sexualprecocity

Serum testosterone levels are detectable or clearly elevated

Thyroid function test

- To be done if there is any clinical evidence of hypothyroidism

Radiographic assessment of bone age:

- If the patient has a normal bone age, he or she is unlikely to haveGDPP

Several ix to identify the peripheral cause ofprecocious puberty ( GIPP ):

- Serum testosterone and estradiol- Serum LH and FSH- Renal profile (check on dehydration or electrolytes

imbalance) in aldosterone deficiency- Serum cortisol to screen for Cushing syndrome- Abdominal and pelvic ultrasound to identify

presence of ovarian cysts or tumour- Ultrasound of testes possibility of Leydig cell

tumour

Management of GDPP:

The treatment options depend upon the cause of theprecocious puberty

If (GDPP) is caused by an identifiable central nervoussystem (CNS) lesion therapy is directed toward theunderlying pathology

For most patients with GDPP primary treatmentoption gonadotropin-releasing hormone(GnRH) agonist

GnRH agonist administration slows acceleratedpuberty and improves final height

The decision of whether to treat GDPP with a GnRHagonist depends on:

- child’s age

- the rate of pubertal progression

- height velocity

- rate of bone age advancement.

Management for GIPP

GIPP does not respond to GnRH agonist therapy. Instead, treatment is directed at the underlying pathology:

Children with tumors of the testis, adrenal gland, and ovary treated by surgery.

Those with hCG-secreting tumors require some combination of surgery, radiation therapy, and chemotherapy depending upon the site and histologic type.

Management for GIPP (cont.)

A large functioning follicular cyst of the ovary Cysts develop and regress spontaneouslyconservative management

Children whose sexual precocity is caused by exposure to exogenous sex steroids exposure identified and removed

Children with identifiable defects in adrenal steroidogenesis ( CAH ) glucocorticoid therapy

Incomplete precocious puberty

Definition: isolated manifestations of precocity without development of other signs of puberty.

Inco

mp

lete Premature

thelarche

Premature pubarche

Premature menarche

Premature thelarche

Transient condition of isolated breast development that most often appears in the first 2 yr of life, often persists for 3-5 yr, and is rarely progressive

mostly idiopathic

either remit spontaneously or are very slowly progressive.

no other signs of pubertal development and their growth rate is normal.

Serum estradiol : usually normal

Mx: reassurance and monitoring regularly for any other sign of pubertal advancement

Premature pubarche

Appearance of sexual hair before the age of 8 yr in girls or 9yr in boys without other evidence of maturation

Slowly progressive condition that requires no therapy

Longitudinal observations suggest that ~50% of affectedgirls are at high risk for

Hyperandrogenism

Polycystic ovary syndrome

Metabolic syndrome

Premature menarche

Diagnosis of exclusion

Isolated vaginal bleeding in the absence of other secondary sexual characteristics

Very rare

Carefully exclude: Vulvovaginitis

Foreign body

Sexual abuse