Precocious puberty

1. PRECOCIOUS PUBERTY
Soumya Ranjan Parida
Basic B.Sc. Nursing 4th
year
Sum Nursing College

2. Precocious Puberty
• Definition :-
Precocious puberty is generally defined as the onset of secondary
sexual characteristics before 8 years of age in girls and 9yrs in boys.
Menarche before the age of 10 yrs in girls is also considered as
precocious.
• Precocious puberty is divided into 3 groups –
1 Gonadotropin dependent ,or Central, or True.
2 Gonadotropin independent, or peripheral, or pseudo.
3 Mixed.
• True precocious puberty is due to activation of hypothalmic-pituitary-
gonadal axis and isosexual.
• Pseudoprecocious puberty is HPG axis independent and isosexual or
heterosexual.

3. Causes of Precocious Puberty
• Gonadotropin dependent puberty ( True precocious puberty )
Idiopathic
Organic brain lesions
Hypothalamic haratoma, Brain tumors, Hydrocephalus, Severe
head trauma, myelomeningocele.
Hypothyroidism, prolonged and untreated
• Combined Gonadotropin dependent and Gonadotropin
independent puberty.
Treated congenital adrenal hyperplasia.
McCune-Albright syndrome, late.
Familial male precocious puberty ,late.
• Incompelete ( Partial ) Precocious puberty.
Premature adrenache.
Premature thelarche.
Premature menarche

4. • Gonadotropin independent puberty ( precocious pseudopuberty )
Females
Isosexual (feminizing) conditions
McCune-Albright syndrome
Autonomous ovarian cysts
Ovarian tumors
Granulosa-theca cell tumor,teratoma,
chorioephithelioma, SCTAT,
Feminizing adrenocortical tumor
Exogenous estrogens
Heterosexual (masculinizing) conditions
Congenital adrenal hyperplasia
Adrenal tumor
Ovarian tumor
Glucocorticoid receptor defect
Exogenous androgens
Males
Isosexual (masculinizing )conditions
Congenital adrenal hyperplasia
Adrenal tumor
Leydig cell tumor
Familial male precocious puberty
Isolated
Associated with
pseudohypoparathyroidism
hCG-secreting tumor
Hepatoblastoma, CNS, Mediastinal tumor
Glucocorticoid receptor defect
Exogenous androgens
Heterosexual (feminizing) conditions
SCTAT,
Feminizing adrenocortical tumor
Exogenous estrogens

5. Physiology of puberty
• Prepubertal stage :-
- Early childhood to 8-9 yrs.
- Hypothalamus-pituitary-gonadal axis dormant.
- LH, Estrogen and testosterone are undetectable.
• Peripuberty :-
- 1-3 yrs before puberty.
- Low LH during sleep and pulsatile.
• Early Puberty :-
- Sustaind effect
• Mid Puberty :-
- LH pulse present in day and night.
- Occur at interval of 90-120 minutes

6. Physiology of puberty
• Age of onset of puberty :-
Girls –
Breast bud – 10-11 yrs.
Pubic hair – 6-12 months
Peak height velocity – 11-12 yrs.
Menarche – 2 - 2.5 yrs. ( 12.75 yrs )
Boys –
Testes growth – 9.5- 13.5 yrs. ( > 3ml or 2.5 cm.)
Thinning of scrotum –
Penile growth – 10.5 – 12.5 yrs.
Pigmentation of scrotum –
Pubic hair – 12 yrs.
Peak height velocity – 13 -14 yrs.

7. HypothalamusHypothalamus
Pituitary gland
FSH LH
Ovary OvaryTestes Testes
Follicular
development
Gametogenesis Luteinization Testosterone
GnRH
Gn
GC SC TC LC

8. Gonadotropin dependent Precocious puberty
• M : F 1:10
• Idiopathic – 90 %.
• Structural CNS abnormality may be present in 25-75 % of boys and
in some girls.
• Secondary sexual characteristics develop in boys and girls before
puberty.
• Height, weight and osseus maturation are advanced.
• Mental development is compatible with chronological age.
• Emotional behavior and mood swing are common.

9. Diagnosis
• Blood –
FSH, LH, Testosterone, Estradiol,
GnRH stimulation test.
DHEA, DHEAS, hCG.
T3, T4, TSH.
• X – ray –
Xray wrist & hand
USG abdomen
CT scan head
MRI brain

10. Treatment
• GnRH agonist-
• Leuprolide acetate 0.25 – 0.3 mg/kg, IM, once every 4 wks.
• Sterile fluid collection at local site, < 5% cases.
• IF side effects, Treatment is changed to SC injection of aqueous
Leuprolide, given once or twice daily ( total dose 60 µg/kg/d ).
• Treatment results in decrease in growth rate and osseous
maturation rate in both sexes.
• In girls, breast development may regress. Menses, if present,
cease. Ovarian and uterine size may decrease. Pubic hair remains
stable.
• IN boys, decrease in testicular size, regression in pubic hair,
decrease in frequency of erections.

11. Precocious puberty resulting from organic brain lesions
• Hypothalamic hamartoma are most common ( 70 %) oganic brain
lesions.
• Hypothalamus may be affeced by scarring, invasion or pressure and
interrupting pubertal restraint pathway.
• Neoplasms –
Astrocytoma, ependymoma, optic glioma, germinomas hCG
secreting (only boys).
• S / S –
DI, adipsia, hyperthermia, gelastic seizures, obesity,
cachexia and precocious puberty
• Treatment –
- GnRH analogs.
- Neurosurgical intervention only in intractable seizures.
- GH therapy, if associated GH deficiency

12. Precocious puberty & Hypothyroidism
• Precocious puberty in untreatedHypothyroidism is unphysiological
association. ( 50 %).
• In girls, breast enlargement, menstrual bleeding, large multicystic ovaries.
Only ovarian estrogen and no androgens.
• In boys, testicular enlargement, no testosterone secretion, no penile
enlargement, no pubic hair development.
• Enlargement of sella by MRI, increased TSH, low FSH, undectable LH.
• TSH intreract with FSH receptor ( specificity spillover ), thus inducing FSH
like effects in the absence of LH effects on gonads.
• Treated by thyroid hormone.

13. Gonadotropin secreting tumors
• Hepatoblastoma may be associated with isosexual precocious
puberty.
• All males, age b/w 4m - 8 yrs.
• Tumor cells secret hCG, which stimulates LH receptor in leydig cells
of testes and causing inerstitial cell hyperplasia without
spermatogenesis.
• High hCG, α FP & testosterone;
• Low FSH and LH.
• Mediastinal tumors, but not gonadal tumors, cause precocious
puberty in boys with Klinefelter syndrome.

14. McCune-Albright syndrome
Precocious puberty with polyostotic fibrous dysplasia and abnormal pigmentation
• Missense mutation in the gene encoding the α subunit of of Gs, the
G protein that stimulates the cAMP formation, resulting in the
formation of putative gsp oncoprotein.
• Activation of receptors, ACTH, TSH, FSH and LH occur.
• In girls, precocious puberty, suppressed LH and FSH, no GnRH
stimulation, estradiol N - high
• In boys, symmetrical testicular enlargement, phallus and pubic hair
enlargement, large seminiferous tubules and no leydig cell
hyperplasia.
• When bone age reaches pubertal age, true precocious puberty
overides the antecedent pseudoprecocious puberty.
• Extraglandular manifestion – Hyperthyroidism, Cushing
syndrome,gigantism or acromegaly, phosphaturia and rickets.

15. Familial male gonadotropin independent precocious puberty
• Autosomal dominant
• Testes only slightly enlarged, maturation of leydig cell and
seminiferous tubules are present.
• Low LH, not pulsatile, no response to GnRH stimulation.
• Missense mutation of the LH receptor leading to activation of cAMP
production.
• When osseous maturation reaches at puberty, pubertal
development is shifted to gonadotropin dependent one.
• Treatment –
Ketoconazole 600 mg/d tds
Spironolactone & aromatase inhibitors ( testolactone, letrozole,
anastrozole )

16. Incomplete ( Partial ) Precocious puberty
Premature Thelarche –
• Present at 2 yrs of age.
• Breast development is unilateral , asymmetrical and often fluctuates.
• Growth and osseous maturation are normal.
• Genitals show no estrogen stimulation.
• Basal FSH increased, FSH response to GnRH stimulation high.
• LH and estradiol less than normal.
Premature Pubarche ( Adrenarche ) –
• Appearance of sexual hair before puberty without any evidence of maturation
• 3β HSD decreased, C-17,20 lyase increased
• Premature Pubarche is a benign condition that requires no therapy.
Premature Menarche –
• Isolated vaginal bleeding without any sexual maturation.
• Gonadotropin normal, estradiol increased.
• Diagnosis of exclusion.

17. Medicational precocity
• Estrogens, anabolic steroids, testosterone gel.
• Exogenous estrogen may produce an intense, dark brown color in
the areola of the breasts that is not usually seen in endogenous type
of precocity

18. THANKS