complete and incomplete precocious puberty

1. PRECOCIOUS PUBERTY

2. 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.

4. Classification:
Complete
Central
( gonadotropin-dependent
puberty,
GDPP)
Peripheral
(gonadotropin-independent
puberty,
GIPP)
Incomplete
Premature
thelarche
Premature
pubarche
Premature
menarche

5. 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 of
gonadotropin-releasing hormone (GnRH) by the
hypothalamus.
 Although the onset is early, the pattern and timing of
pubertal events usually progresses in the normal
sequence.

6. Gonadotropin-dependent
precocious puberty
• Non- CNS lesion:
- Idiopathic
- Genetics
-Prolonged, untreated severe hypothyroidism
• CNS lesion:
-CNS tumour
- CNS irradiation
- hydrocephalus, cysts, trauma, CNS inflammatory disease,

7.  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

8. Causes of CNS lesion:
 Hypothalamic hamartomas are the most common
brain lesion causing true precocious puberty.
 Hamartomas are non-malignant tumours of the
tuber cinereum that consists of disorganized collection of
neurons and glias.
 ectopically located neural tissue containing GnRH-secretory
neurons and may function as an accessory
GnRH pulse generator
 Other tumour: astrocytoma, optic and hypothalamic
glioma

9. Causes of CNS lesion: (cont.)
Radiation therapy for leukemia or intracranial
tumours  irradiation is directed to the
hypothalamic area or to areas of the brain
anatomically distant from the hypothalamus 
increases the risk of precocious puberty

10. Clinical manifestations:
 Begin at any age, follows the sequence observed in normal
puberty
 In girls:
Breast enlargement comes first
Pubic hair may appear simultaneously but more often
laters
 Menarche is a late event ( irregular cycle and usually
anovulatory )
The pubertal growth spurt occurs early in female puberty

12.  In boys:
Testicular enlargement
( unnoticed)
Enlargement of penis
Axillary hair, acne, voice
deepens
Erections are common
spermatogenesis
observed as early as 5-6
yr of age

13.  In both gender:
Height, weight, and osseous maturation are
advanced
Without treatment, 30% early closure of the
epiphyses > height less than the 5th percentile as
adults
Emotional and mood swings are common

14.  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 hormone
deficiency may present

15. Gonadotropin-independent precocious
puberty ( GIPP)
 Independent of gonadotropin secretion and no
activation of the HPG axis
 aka precocious pseudopuberty
 caused by excess secretion of sex hormones
(estrogens or androgens) derived either from the
gonads or adrenal glands or from exogenous
sources

16. 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 estrogen
Adrenal pathology ( eg: androgen-secreting
tumour and CAH)
Teratoma
McCune-Albright syndrome

17. 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 pubertal
development 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 tumor
 Virilization 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?

18. 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-Albright
syndrome).

19. Investigations:
Serum LH
concentration
Proceed with GnRH stimulation test
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

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

21. Other investigations:
 Sex hormone
 To establish degree of biochemical pubertal enhancement
 Serum estradiol are low or undetectable in the early phase of sexual
precocity
 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 have
GDPP

22.  Several ix to identify the peripheral cause of
precocious 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

23. Management of GDPP:
 The treatment options depend upon the cause of the
precocious puberty
 If (GDPP) is caused by an identifiable central nervous
system (CNS) lesion therapy is directed toward the
underlying pathology
 For most patients with GDPP  primary treatment
option  gonadotropin-releasing hormone
(GnRH) agonist
 GnRH agonist administration  slows accelerated
puberty and improves final height

24.  The decision of whether to treat GDPP with a GnRH
agonist depends on:
- child’s age
- the rate of pubertal progression
- height velocity
- rate of bone age advancement.

25. 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.

26. Management for GIPP (cont.)
 A large functioning follicular cyst of the ovary 
Cysts develop and regress spontaneously
conservative 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

27. Incomplete precocious puberty
 Definition: isolated manifestations of precocity
without development of other signs of puberty.
Incomplete
Premature
thelarche
Premature
pubarche
Premature
menarche

28. 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

29. Premature pubarche
 Appearance of sexual hair before the age of 8 yr in girls or 9
yr in boys without other evidence of maturation
 Slowly progressive condition that requires no therapy
 Longitudinal observations suggest that ~50% of affected
girls are at high risk for
 Hyperandrogenism
 Polycystic ovary syndrome
 Metabolic syndrome

30. 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