Precious puberty

2. Precocious
Puberty
H.Delshad M.D
Endocrinologist

3. PUBERTY
It is a physiological phase
lasting
2 to 5 years
during which the genital
organs mature

4. Is the onset of pubertal development at an
earlier age than is expected based upon
established normal standard
Early onset of puberty before
► 8 years of age in girls
► 9 years of age in boys
Several factors affect the age of onset of puberty: Familial
pattern, environmental factors, ethnicity, chronic disease.
Puberty
Precocious

5. Sequence of pubertal events in Girls and
Boys
The mean age of onset of puberty is about 10.5 years of
age in girls and 11.5 years in boys

6.  In a population-based study, breast and/or
pubic hair development was present at
age 8 in:
 48 percent of African-American
 15 percent of White girls.
 At 7 years of age, the proportions were
27 and 7 percent, respectively.
Pediatrics 1997; 99:505
Herman-Giddens ME, et al.
Difficult to ascertain the early age
limit because

7. Epidemiology
 The prevalence is difficult to estimate
 It has been reported at 1 in 5000 children
 In a population-based study that reviewed
data from Danish national registries from
1993 to 2001, the incidence of precocious
puberty was:
○ 20 per 10,000 girls
○ < 5 per 10,000 boys.
Teilmann G, et al. An epidemiologic study based on national registries.
Pediatrics 2005; 116:1323.

8.  In the US: the number of girls diagnosed
with precocious puberty is rising and its
onset is decreasing:
□Over the past 40 years: 0.5 to 1.0 years
□With black girls maturing 0.5 to 1.0 year
earlier than white girls.
Kaplowitz P. Pubertal development in girls: secular trends.
Curr Opin Obstet Gynecol 2006;18(5): 487-91.
Epidemiology

9. Trends in age at OGS and PHV.
Age at onset of pubertal growth spurt ( OGS) in boys (A) and girls (B),
Age at peak height velocity ( PHV) in boys (C) and girls (D)

10. Epidemiology
 There is a strong female predominance of
precocious puberty.
 In a retrospective review from a tertiary care
center the female to male ratio was 23:1.
 About half of the 197 girls and one quarter of the
boys had GDPP.
 An etiology was found in all 16 boys and only in
6 girls (3 percent).
Pescovitz OH , et al. The NIH experience with precocious puberty: Pediatr 1986; 108:47.
Bridges NA, et al . Sexual precocity: sex incidence and aetiology.
Arch Dis Child 1994; 70:116.

11. Types:
1 - True precocious puberty
2 - Pseudo precocious puberty
3 - Incomplete precocious
puberty

12. Central Precocious Puberty
 Idiopathic (90%)
 Organic brain lesions:
Inflamation,
Malformation
Trauma
Chemotherapy
Radiotherapy
Brain tumor:
 Hypothyroidism
 Gain-of-function mutations in GPR54
Hamartomas, Astrocytoma, Ependymoma, Pinealomas, Gliomas

13. Gain-of-function mutations in
GPR54
The pathogenesis of ICPP is currently unclear.
The kisspeptin/G protein-coupled receptor 54 (GPR54) signaling pathway
initiates the onset of puberty, which is probably closely associated with the
occurrence and development of ICPP.
The early diagnosis of PP and evaluation of therapeutic effects is very
important.
Plasma kisspeptin levels rise at the initiation of pubertal development, and the kisspeptin
levels of girls with PP decline following treatment with GnRH.
Detection of kisspeptin can contribute to the early diagnosis of ICPP and may be used as
an indicator of therapeutic effects in the treatment of precocious puberty.

14. Pseudo -Precocious puberty in Female
Isosexual
A girl who feminizes early is defined as
having isosexual precocious puberty.
 Heterosexual
A girl who virilize early is defined as having
heterosexual precocious puberty.

15. Pseudo -Precocious puberty in Female
 Iso sexual ( feminizing ) conditions
Mc cune – Albrightsyndrome
Autonomous ovarian cyst
Ovarian tumors
Feminizing adrenocortical tumor
Exogenous estrogens
 Hetrosexual (masculinizing)
Congenital adrenal hyperplasia
Adrenal tumor
Ovarian tumor
Glucocorticoid receptor defect
Exogenous androgens.

16. Pseudo -Precocious puberty in Male
Isosexual
A boy who virilize early is defined as having
isosexual precocious puberty.
 Heterosexual
A boy who feminizes early is defined as having
heterosexual precocious puberty.

17.  Isosexual
Congenital adrenal hyperplasia
Adrenocortical tumor
Leydig cell tumor
Familial male precocious puberty
HCG secreting tumor
Teratoma
Glucocorticoid receptor defect
Exogenous androgen
 Hertrosexual
Feminizing adrenocortical tumor
Exogenous estrogens
Pseudo -Precocious puberty in Male

18. Thelarche and
vaginal bleeding
A- at 2 ½ yrs
B- at 3½ years
C- at age 8 years
Idiopathic Precocious Puberty

20. peripheral precocious puberty, café-au-lait
spots and firbous dysplasia of bones

21. Three years old boy with hypothalamic hamartoma
Female with central precocious puberty due to
intracranial Hamaratoma
Brain Tumor &
Precocious Puberty

22. Male with central precocious
puberty with sixth nerve palsy
secondary to intracranial
astrocytoma

23. Testitoxicosis:
Mutations in LH receptor
Constitutively active Leydig
cell receptor
Adenyl cyclase stimulation
Testosteron

24. Ambiguous Genitalia
Hetrosexual (masculinizing) precocious puberty

25. Premature Thelarche
Premature Pubarche
Premature Adrenarche
Incomplete Precocious Puberty

26. Premature Pubarche
 50% of pt. with premature pubarche
progress to PCOD
 Late onset CAH may have a similar
presentation
 CPP can occur secondry to late Dx or
inadequate Rx of CAH

27. Premature Menarche
 Uncommon
 Role out serious cause of bleeding
 Neonatal period :
withdrawal of estrogen produced by the fetoplacental unit
 Childhood
 Vulvovaginitis
 Foreign body in the vagina
 Trauma
 Sexual abuse
 Vaginal tumors

28. Approach to precocious puberty
History
Physical examination
Laboratory
Bone age
Sonography
MRI of brain

29. 1. History:
● It excludes iatrogenic source of estrogen or androgen.
● It differentiates between isosexual and heterosexual
precocious puberty.
● Onset & progression of symptom
(N tempo CPP, Abrupt & rapid estrogen sec Tr)
● Hx of CNS trauma or infection
● Symptoms associated with neurological dysfunction
● Symptoms associated with endocrine dysfunction
● Exposure to exogenous steroids
● Hx of abdominal pain or swelling
● Family Hx  early puberty, short stature
Diagnosis of precocious puberty

30. 2. Physical examination:
● It diagnoses McCune-Albright syndrome.
● Neurologic and ophthalmologic examinations
exclude organic lesions of the brain.
● Boys: Testes > 4ml
● Girls: Breast development
● Pubic/axillary hair
Diagnosis of precocious puberty

31. Diagnosis of precocious puberty
3. Hormonal assay
●FSH, LH : Pubertal level in GDPP , Low in GIPP
●Sex hormones : Pubertal level in GDPP and in GIPP
- Estradiol > 9 pg/ml
-Testosterone : 20 – 1200 ng/dl
● Kisspeptin level
●17α-hydroxy progesterone : elevates in CAH
●TSH : elevated in hypothyroidism
●hCG : elevated in Germ cell tumors
●LHRH Test : pubertal response, LH > 7 IU/L in GDPP

32. Kisspeptin level of girls with ICPP at the time of diagnosis and after 6
months of treatment, and those of girls in PT group and control group.
CPP, idiopathic central precocious puberty; PT, premature thelarche.
Kisspeptin

33. GnRH STIMULATION TEST
■ 6 Y old with CPP
□14 Y old with normal
puberty
▲ 16 Y old with
craniopharyngioma
5 Y old prepubertal

34. Diagnosis of precocious puberty
4. X-ray examination
To determine bone age : bone age> height age> chronological age
Estrogen stimulates growth of bone but causes early fusion of the epiphysis.
So the child is taller than her peers during childhood, but is short during
adult life.
Hypothyroidism is the only condition of precocious puberty in which bone age is
retarded
5. Ultrasonography
To diagnose ovarian or adrenal tumor.
6. CT or MRI
To diagnose an organic lesion of the brain, or adrenal
tumor.

35. Precocious puberty in boys
Testicular enlargement
Yes No
TFT Testosterone
GnRH test : pubertal
1st Hypothroidism GDPP
Plasma /
or urine
androgens
Plasma
Testos.
17-OH Prog. Marginal
Elevation
In androgen
Virilising
Adrenal
tumors
Testotoxicosis CAH Precocious
adrenarche

36. Is diagnosed after
excluding all other
causes.
Idiopathic precocious
puberty:

38. Consensus Statement on the Use
of GnRH Analogs in Children
ESPE – LWPES GnRH Analogs
Consensus Conference Group
European Society for Pediatric Endocrinology(ESPE)
Lawson Wilkins Pediatric Endocrine Society( LWPES)
• 3- days conference in Nov. 2007
• 30 participants from North America and Europe
• Articles written in English with long-term outcome data
published between 1990 and 2007
Pediatrics 2009; 123: e752-e762

39. Use of GnRH for conditions other
than CPP
 Gonadal Protection for Children Undergoing
Chemotherapy
Routine use of GnRH as for gonadal
protection in children undergoing
chemotherapy cannot be suggested.

40. Use of GnRH for conditions other
than CPP
 Increasing AH of Children With Idiopathic Short
Stature
GnRH therapy alone in children with ISS and
normally timed puberty is minimally effective in
increasing AH, may compromise BMD, and cannot
be suggested for routine use .
Combined GnRH and GH therapy leads to a
significant height gain but may have adverse
effects.
Routine use of GnRH in children with ISS being
treated with GH cannot be suggested .

41. Use of GnRH for conditions other
than CPP
 Increasing AH of Children Born Small for
Gestational Age
Routine use of the combination of GnRH and
GH in children born SGA cannot be
suggested .
 Increasing AH of Children With Severe
Hypothyroidism
Routine use of combined therapy with GnRH
and Levothyroxine cannot be suggested .

42. Use of GnRH for conditions other
than CPP
 Increasing AH of Children With GH Deficiency
Routine use of combined therapy with GnRH and GH
in GH-deficient children with low predicted AH at onset
of puberty cannot be suggested .
 Increasing AH of Children With Congenital Adrenal
Hyperplasia
Additional studies are needed to determine if GnRH
therapy alone or in combination with GH should be
used in children with CAH and low predicted AH.
Routine use of GnRH for CAH cannot be suggested