2. Defination
• Precocious puberty is defined as onset of
secondary sexual characteristics before age of
8 yrs in girls and 9 years in boys
• The variation in the age of the onset of
puberty in normal children, particularly of
different ethnicities, makes this definition
somewhat arbitrary. It remains in use by most
clinicians.
3. CONDITIONS CAUSING PRECOCIOUS PUBERTY
CENTRAL (GONADOTROPIN DEPENDENT, TRUE PRECOCIOUS
PUBERTY)
• Idiopathic
• Organic brain lesions
• Hypothalamic hamartoma
• Brain tumors, hydrocephalus, severe head trauma, myelomeningocele
• Hypothyroidism, prolonged and untreated
COMBINED PERIPHERAL AND CENTRAL
• Treated congenital adrenal hyperplasia
• McCune-Albright syndrome, late
• Familial male precocious puberty, late
6. Approach to precocious puberty
Pointers in History:
o Age of onset
earlier the age of onset greater the like hood of
underlying organic disease
Idiopathic GDPP
onset after age of 6 yrs
slow progression
lack of neurological features
7. • hypothalamic hamartoma, a neuronal migration
defect is the commonest cause of organic central
precocious puberty
Early age of onset
rapid progression of puberty
Seizures and uncontrolled laughter
(gelastic epilepsy)
o SEX:
GDDP is 5 times more common in girls, most
often Idiopathic.
in boys, less common, usually ass. With
underlying pathology in 2/3rd
8. oPubertal progression:
in GIPP , there is deviation from the normal pubertal
progression
Normal pubertal progression:
In girls: Thelarche pubarche menache
In boys: testicular enlargement (>4ml) pubarche
development of ext. genitalia.
o Evidence of Linear growth accelaration:
precocity is ass. with growth spurt, except in
hypothyroidism and sellar mass with G.H deficiency.
o H/O past CNS infections, headaches, visual
disturbances, personality changes, developmental delay
and seizures points underlying neurological disorder.
9. o H/o of Drug exposure
o Symptoms suggestive of Hypothyroidism
o H/o of precocious puberty in boys and genital ambiguity
in girls in same family suggests Congenital adrenal
hyperplasia
o family H/O of precocious puberty limited to males would
suggest familial testotoxicosis.
10. Physical examination
• Height, weight, Height velocity (cm/yr)
• SMR staging (tanner’s staging )
testicular volume estimation
Pre-Pubertal testicular volume(<4ml) is characteristic of
C.A.H and adrenal tumours.
Unilateral testicular enlargement is seen in testicular
tumours.
Pubertal testicular volume Central precocious puberty
11. • Evaluate
Androgen effects
Acne
Hirutism
Increase muscle mass
clitoromegaly
Estrogen effects
Breast development
Changes in vaginal mucosa
• Inspection of skin
café au lait macules characteristic of McCune-Albright
syndrome and neurofibromatosis.
Hyper pigmentation + Hypertension C.A.H
• Neurological examination including fundus and perimetry
• Examination for signs of Hypothyroidism.
•Abdominal examination for adrenal and ovarian masses.
12. Investigations
Basic radiology :
Bone age for skeletal maturation
Advanced in all cases of precocious
puberty
Delayed Hypothyroidism
Normal incomplete precocious puberty
Pelvic and Abdominal Usg : to evaluate the size and
morphology of uterus, ovaries and adrenals.
13. Hormonal evaluation:
random S. Luteinizing hormone (LH) is good
screening test for central precocious puberty
levels of 0.3 IU/L or more are pubertal
If random s.LH levels < 0.3 IU/L
Stimulation test with Aqueous Leoprolide acetate
(GNRH) (20 mg/kg ) S.C/I.M
60 min s.LH value > 3.3 – 5.0 IU/L suggest GDPP (CPP)
14. CT or MRI Brain
Thyroid Function Tests – to R/O Hypothyroidism
Further tests for Gonadotropic independent precocious
puberty :
s.DHES (dehydroepiandrosterone sulfate)
Elevated in premature adrenarche.
Very high in virilizing adrenal tumours.
Basal serum 17-OH Progesterone
(and/or) to R/O C.A.H
ACTH stimulated 17-OH Progesterone
15. Serum/C.S.F hCG levels – if hCG secreating tumour is
suspected in boys with precocious puberty.
Testicular sonography – if tumours suspected
TFT
Skeletal survey : in suspected cases of Mc Cune –
Albright syndrome to look for fibrous dysplasia.
16. Management
Surgical :
tumours of ovaries, testes, adrenals – remove
surgically.
ovarian cysts > 3cm in size – Explore surgically.
surgery for Hypothalamic hamartomas is hazardous &
not recommended as they do not grow and become
malignant
germ cell tumours, pineal tumours , hCG producing
suprasellar tumours are treated with radiotherapy
17. Medical:
Progressive central precocious puberty
Indication of treatment :
predicted adult height is less
psychologically distressing to the child
rapid progression GnRH Agonists
Inj.Leuprolide (0.5 – 0.3 mg/kg/dose) either monthly
or 3 monthly depot
Acts by continuous stimulation of pituitary gonadotropes
thereby desensitization and decrease in release of L.H
18. Inj. Medroxy-progesterone at dose of 150/m2 I.M is
added every 15days for first 6 weeks , to counter the
possible stimulatory effect of GnRH agonist initiation.
the Rx is discontinued at chronological age of 11 yrs
(12yrs in boys) and Bone age of 12.5 yrs (17.5 yrs in boys).
Rx of gonadotropin independent precocious puberty :
Hypothyroidism – thyroxine replacement
Mc Cune Albright syndrome :
inhibiting estrogen production
Aromatase inhibitor- Anastrazole, Letrozole
Block estrogen action – Tamoxifen
Testotoxicosis - Antiandrogens
20. Hypothyroidism & precocious puberty
• Precocious puberty in a child with untreated hypothyroidism
and a prepubertal bone age presents a strikingly unphysiologic
association, yet it is common and occurs in as many as 50% of
children with severe hypothyroidism of long duration.
• The cause of the hypothyroidism is usually Hashimoto
thyroiditis, which often goes undiagnosed, especially in children
with special needs such as those with trisomy 21.
• Plasma levels of thyroid-stimulating hormone (TSH) are
markedly elevated, often >500 ?U/mL
21. Plasma levels of thyroid-stimulating hormone (TSH) are markedly
elevated, often >500 ?U/mL. and plasma levels of prolactin are
mildly elevated.
the massively elevated concentrations of TSH appear to interact
with the FSH receptor (specificity spillover), thus inducing FSH-like
effects in the absence of LH effects on the gonads
unlike in central precocious puberty, testicular enlargement
occurs without substantial testosterone secretion in boys.
Thus, the precocious puberty associated with hypothyroidism
behaves as an incomplete form of gonadotropin-dependent
puberty. Prolactin raise stimulate thelarche.
Treatment of the hypothyroidism results in rapid return to normal of the
biochemical and clinical manifestations. Macroorchidism (testicular volume
>30 mL) can persist in men despite adequate thyroxine therapy.
