Precocious Puberty and normal puberty

1. Precocious Puberty
Kelvin Philip Group 99
I.M Sechenov, Moscow.

2. Normal Puberty
The stage of physical maturation in which an
individual becomes physiologically capable of
sexual reproduction
Triggered by increased secretion of LH.
Results from changes in the hypothalamus that
allow increased secretion of GnRH to stimulate the
secretion of LH

4. The
Reprodcutive
System
Functional by the end of the first trimester of fetal life
Become briefly inactive around the time of birth
Resume hormonal activity until several months after birth
The brain begin to suppress the activity of the arcuate nucleus.
Gonadotropin and sex steroid levels fall to low levels for
approximately another 8 to 10 years of childhood.
Normal puberty happens when there is de-inhibition of the pulse
generator in the arcuate nucleus.

5. Onset of normal
puberty
Girls : 10- 14 years old
Boys : 12-16 years old
With this disease puberty could begin as early as
age 6 or 7 in girl
For boys puberty could begin as early as before
age 9.

6. Phases of puberty
Adrenarche
- Stage of maturation of the cortex of adrenal
glands
- Increase adrenal androgen secretion
Gonadarche
- Earliest gonadal changes
- Ovaries and testes begin to grow
- Increase production of sex hormones

7. Thelarche
-First stage of secondary breast develpment
-Usually noticed as firm, tender lump directly in the
center under the nipple(papilla and areola)
-Referred to as breast bud (Tanner stage 2)
Pubarche
-First appearance of the pubic hair
-Results from increased levels of androgens from
adrenal glands or testes.
Menarche
-First menstrual bleeding
-Possibility of fertility

9. Tanner Stages
Develop as a way to classify the time, course, and
progress of changes that occur during puberty.
Based upon attainment of secondary sex
characteristics, which include genital development
in males, breast development in females, and
pubic hair development in both genders.

10. Female Breasts
Tanner Stages Breast
1 Preadolescent. Elevation of the
papilla only
2 -A small mount is formed by the
elevation of the breast and papilla
-Areolar diameter enlarges
3 Further enlargement of breast and
areola.
4 Projection of the areola and papilla
to form a secondary mound above
the level of the breast
5 -Mature breast
-Areola recessed to the general
contour of the breast.

11. Male genitalia
Tanner
Stages
Genitalia
1 -The penis , testes and
scrotum are of childhood size
2 -Enlargement of scrotum and
testes
- Scrotal skin reddens
3 -Further growth of the
testes and scrotum.
-Enlargement of penis,
mainly in length
4 -Further growth of the
testes and scrotum.
-Enlargement of penis,
mainly in breadth
5 Adult genitalia

12. Pubic Hair
Tanner Stages Female Male
2 Sparse growth of long, slightly pigmented,
downy hair, straight or only slightly
curled, primarily along the labia.
Sparse growth of long, slightly pigmented,
downy hair, straight or only slightly
curled, primarily at the base of penis.
3 Hair is darker, coarser, and more curled. Hair is darker, coarser, and more curled.
4 Adult type hair, does not extend onto the
thighs
Adult type hair, does not extend onto the
thighs
5 Hair is adult in quantity and type, with
extension to the thighs.
Hair is adult in quantity and type, with
extension to the thighs.

13. Growth Spurt
Growth spurt/Peak height velocity
 Female:
 Happens in earlier stages of puberty
 Average age: 12.1
 Male:
 Happens in later stages of puberty
 Average age: 14.1
 Boys have greater velocity at the maximum pubertal growth rate

14. Hormonal changes
Increase in:
 Testosterone
 Estrogen
 Prolactin
 Growth Hormone
 Insulin

15. Precocious Puberty
onset of secondary sexual characters before the age of 8 years in
girls and 9 years in boys.
Two types :
-central-gonadotropin dependent or true. Stems from
hypothalamic-pituitary-gonadal activation with ensuing sex
hormone secretion and progressive sexual maturation. Most
common. Puberty starts too soon but pattern and timing of
processes are normal.

16. Rare Causes of Central Precocious Puberty
Idiopathic - 90% of girls
Tumor in brain or spinal cord - Hypothalamic hamartoma
Brain defect present at birth
Injury to brain or spinal cord, severe head trauma, hydrocephalus,
myelomeningocele
McCune-Albright syndrome
Genetic disease, affects bones and skin color, causes hormonal
problems
Congenital adrenal hyperplasia
Group of inherited disorders, causes abnormal hormone production by
adrenal glands
Hypothyroidism
Condition where thyroid doesn’t produce enough hormones

17. peripheral- gonadotropin independent. some of the secondary sex
characters appear, but no activation of the normal hypothalamic-pituitary-
gonadal interplay. May be isosexual or heterosexual (contrasexual)
Less common
Occurs without the hormone in your brain that usually causes puberty to start
(Gn-RH)
Caused by the release of estrogen or testosterone into the body because of
problems with the ovaries, testicles, adrenal glands or pituitary gland
•

18. Other causes
Little evidence, but these may be contributing factors to precocious puberty:
-Environmental Factors
1) Increase in hormones found in food
2) Exposure to household toxins (BPA)
Obesity
~106 lbs is the weight when puberty starts
-Leptin, a hormone involved in puberty, is secreted in fatty tissue (more fatty
tissue=more leptin=earlier puberty)

19. Hypothalamic
Hamartoma
In hypothalamic hamartoma remain static in size or grow slowly, -
no signs other than precocious puberty.
For symptomatic , manifestations may be present for 1-2 years
before the tumor can be detected radiologically
Include diabetes insipidus, adipsia, hyperthermia, unnatural
crying or laughing (seizures), obesity, and cachexia.
Visual signs (proptosis, decreased visual acuity, visual field
defects) may be the first manifestation of an optic glioma.

20. Mental development is usually compatible with chronological age.
Emotional behavior and mood swings are common, but serious
psychological problems are rare
Natural course- rapid- most common pattern. characterized by
rapid physical and osseous maturation, leading to a loss of height
potential.
Slow-this pattern characterized by parallel advancement of
osseous maturation and linear growth, with preserved height
potential.
spontaneously regressive or unsustained central precocious
puberty – marks the need for longitudinal observation

21. How it affects the child
With this disease the kids usually do not achieve
their full height, they may be taller when younger
compared to their peers but when older they are
short
Girls can become more emotional, moody, and
irritable at a younger age.
Boys can become more aggressive and develop a
sex drive that is very inappropriate for their young
age.

22. Symptoms for girls
Breast development can happen as early as between
6 months and 3 years.
Pubic or underarm hair development at a very young
age
A growth “spurt” before all of their peers, they may
seem taller at a younger age
Menstruation begins earlier
Acne at a young age
Also mature body odor at a young age

23. Presentation
GIRLS- The average age at onset girls is about 3 yr, vaginal
bleeding as early as 4 mo of age and secondary sexual
charecters at 6 mo of age.
Estradiol levels vary from normal to markedly elevated (>900
pg/mL), are often cyclic, and can correlate with the size of the
cysts.

24. When to consult
• Boys: Girls:
Age: < 9.5 years old
• Physical Features:
- secondary sex characteristics
Tanner Stage 2 - 5
Age: < 8 years old
• Physical Features:
- breast growth
Tanner Stage 3-5
If at Tanner Stage 2, there
must be other features
(e.g. a recent growth spurt).

25. Lab Diagnosis
With sensitive assays, serum LH concentrations are undetectable
in prepubertal children but become detectable in 50-75% of girls
and a higher percentage of boys with central sexual precocity.
Measurement during sleep increases diagnostic power and
reveals the pulsatile LH secretion.
GnRH stimulation test. Predominant LH response over FSH after
iv administration of GnRH or agonist like Leuprolide. However in
girls, LH:FSH ratio can remain low until mid-puberty. In such girls
with “low” LH response, the central nature of sexual precocity can
be proved by detecting pubertal levels of estradiol (>50 pg/mL),
20-24 hr after stimulation with leuprolide.

26. A CT Scan of the brain or the abdomen can be used
Also an MRI of the brain or the abdomen can be used
to diagnose the problem.
Pelvic ultrasound reveals progressive enlargement of
ovaries followed by uterus to pubertal size.
Osseous maturation advances.
An MRI scan usually shows normal enlargement of the
pituitary gland, during puberty; it may also reveal CNS
pathology.

27. Treatment
The goal of the treatment is to stop or reverse
sexual development and stop the rapid growth and
bone maturation.
hormone (GnRH) analogues.
Usually results in a decrease in growth
Combining growth hormone (GH) to GnRH
treatment results in a better outcome
final height in girls

28. • There is a currently approved hormone treatment is with drugs called LHRH
analogs: synthetic hormones that block the body’s production of the sex
hormones that are causing the early puberty.
• LHRH Analogues: Drugs that act like luteinizing hormone releasing hormone
(LHRH) are known as LHRH analogues. These drugs turn off the signal for
testosterone production by the testicles. By turning off the signal, hormone
levels are reduced and cancer cells are not exposed to male hormones.
LHRH analogues are given as a small injection under the skin of the
abdomen every month or every three months.

29. Long term GnRH agonists, (leuprolide) (Lupron Depot Ped), in
a dose of 0.25-0.3 mg/kg (minimum, 7.5 mg) i.m. once every 4
wk.
- Other preparations : (D-Trp6-GnRH [Decapeptyl], goserelin
acetate [Zoladex]) are approved for treatment of precocious
puberty in other countries.
Alternatively, histrelin (Supprelin LA), a subcutaneous 50 mg
implant with effects lasting 12 mo, is approved by the FDA .
Intranasal and subcutaneous injection formulae are also
available.
IUGR at greater risk of short stature as adults and require
more-aggressive treatment of precocious puberty, possibly in
conjunction with human growth hormone (hGH) therapy.

30. After treatment
In girls, breast size may decrease or there will be
no further development.
In boys, the penis and testicles may shrink and go
back to the expected size for their age.
In both, the growth height comes to a halt and the
behavior goes back to normal according to their
age.

31. Incomplete Partial
Variants
Isolated manifestations of precocity without development of other
signs of puberty.
Premature thelarche- isolated breast development that most often
appears < 2 yr of life. Sporadic and asymmetric. ; activating
mutations of the GNAS1 gene encoding the α-subunit of the GS
protein have been described in some patients without other signs of
McCune-Albright syndrome.
Menarche occurs at the expected age, and reproduction is normal.
Basal serum levels of FSH and the FSH response to GnRH
stimulation >normal girls
Plasma LH and estradiol are consistently < limits of detection.
Ultrasound examination of ovaries show a few small (<9 mm) cysts.

32. However, In some girls, breast development is associated with
definite evidence of systemic estrogen effects, such as growth
acceleration or bone age advancement. Pelvic sonography shows
enlarged ovaries or uterus. This condition, referred to as
exaggerated or atypical thelarche, differs from central
precocious puberty because it spontaneously regresses.
PREMATURE PUBARCHE(ADRENARCHE)-appearance of
sexual hair before the age of 8 yr in girls or 9 yr in boys without
other evidence of maturation.
Girls >boys. Associated with reduced 3β-hydroxysteroid
dehydrogenase activity, and an increase in C-17,20-lyase activity.
Leads to increased DHEA, androstenedione and 17HOP

33. Although it has been considered a benign condition, longitudinal
observations suggest that approximately 50% of girls with premature
adrenarche are at high risk for
-hyperandrogenism and
-polycystic ovary syndrome,
alone or more often in combination with other components of the
metabolic syndrome (insulin resistance possibly progressing to type 2
diabetes mellitus, dyslipidemia, hypertension, increased abdominal fat) as
adults.
Premature Menarche-is a diagnosis of exclusion. In girls with isolated
vaginal bleeding in the absence of other secondary sexual characters,
more common causes such as vulvovaginitis, a foreign body, or sexual
abuse, and uncommon causes such as urethral prolapse and sarcoma
botryoides(embryonal rhabdomyosarcoma) must be carefully excluded.

34. The majority of idiopathic premature menarche have only 1-3
episodes of bleeding; puberty occurs at the usual time, and
menstrual cycles are normal. Plasma levels of gonadotropins are
normal, but estradiol levels may be elevated, probably owing to
episodic ovarian estrogen secretion. Occasional patients are
found to have ovarian follicular cysts on ultrasound.

35. Early breast development
Increased height velocity and
advanced bone age
yes
Associated sec.sexual characters , axillary and pubic hair
yes
no
age
<2years
Infantile mamoplasia
>2 year
Pelvic ultrasound evaluation of gonads and
uterus
Pubertal
GnRH stimulation
test
Prepubertal
Premature thelarche

36. GnRH stimulation test
LH response
Suppressed
GnRH independent PPGnRH dependent CPP
MRI CNS imaging
Abnormal
Idiopathic CPP
no yes
Organic CPP
TSH, T4, hCG,ovarian,
adrenal imaging