lecture

1. Puberty Disorders
Abdulmoein Eid Al-Agha, FRCPCH
Professor of Pediatric Endocrinology,
King Abdulaziz University Hospital,
Website: http://aagha.kau.edu.sa

2. Puberty
• Physiological transition from childhood to
reproductive maturity
• Associated with:
– Growth spurt
– Appearance of both primary and secondary
sexual characteristics in children
– Occurs between 8 and 13 yrs in girls
– Occurs between 9 and 14yrs in boys

4. Puberty: Influencing Factors
• Genetics: 50-80% of variation in pubertal
Timing.
• Environmental factors: nutritional status,
environmental hormonal disruptors ( for
example usage of plastics, nylon or food
products rich with estrogen.
• Obesity: as obese children tend to have
earlier puberty as their adipose tissues
produces Leptin peptide which has
stimulating effects on the hypothalamus.

5. • •

6. Puberty in Girls
Sexual Changes
- Shy and Isolated
- Breast enlargement
-Menstrual cycles
Psychological
Changes
- Very Sensitive
Somatic
Changes
- Acne and oily skin
- Increase body fat
in feminine areas
- Widening of pelvis
- Pubic and auxiliary hair growth
- Growth spurt
Increase Carrying angle

7. Secondary sexual Changes
• 5 stages from childhood to full maturity
described by Dr. Tanner (British citizen).
• Stage 1 is prepubertal, while stage 5 is full
adult.
• In females; 5 stages for breast development
and another 5 stages for Pubic hair.
• In males; 5 stages for genital development and
another 5 stages for Pubic hair.
• Secondary sexual characteristics
– starting age 8– 13 yrs in girls
– starting age 9 – 14yrs in boys

8. Tanner Stages Females

9. Puberty: Girls
• Breast enlargement (Thelarche) usually first
sign, Often begins unilateral then become in
both sides.
• Second stage is pubic & axillary hair
development (Adrenarche), in addition to
oily skin & hair with Acne ( this stage is
equally happened in both sexes) due to
adrenal androgens.
• Menarche usually 2-3 yrs after breast
development.
• Growth spurt peaks before menarche.

10. Puberty: Girls
Widening of pelvis & carrying angle.
Major increase in bone mineral density.
Increased adipose tissue with typical
female distribution (buttocks, upper thighs
& breast tissues).
 95% of growth happened < menarche
Menarche usually by age 13-14 years.
Increased in muscle bulk but not to same
extent as males.

11. Menarche
 During puberty estradiol levels fluctuate
widely (reflecting successive waves of
follicular development that fail to reach
ovulatory stage)
 Endometrium is affected by estradiol.
 Undergoes cycles of proliferation & regression
until point where withdrawal of estrogen
results in the first menstrual bleed (menarche)
 Increase of only 5% of final height after
menarche

12. Puberty in boys
Sexual
Changes
Testicular
enlargement
Spermatogenesis
Psychological
Changes
Aggressive
Positive self-
image and mood
Somatic
Changes
Growth spurt
Facial, pubic
and auxiliary hair
growth
Acne and oily skin
Voice change
Widening of
shoulders
Increased muscle
mass
Decreased
adipose
tissue
Gynecomastia(usually
disappearswithin 2 years)

13. Puberty: Boys
 First sign is testicular enlargement (often go
unnoticed ).
 Pre-pubertal testicular volume is 1-3 ml
 Puberty begins when testicular volume is 4ml
and above.
 Penile and scrotal enlargement occur approx
1 yr after testicular enlargement.
 Pubic hair appears at same time.

14. Tanner Stages Males

15. Orchidometer

16. Pubertal Growth Spurt: Boys
 Occurs later than in females by average 2
years.
 Testosterone less of a stimulus to GH
responsiveness than estradiol.
 Testosterone required in larger concentrations
to produce same anabolic effect.
 Greater and later growth spurt in boys.

17. Final adult height
• Puberty usually
completed within 3 - 4
yrs of onset
• Left wrist x-ray to
assess bone age
• Final adult height
results from complete
fusion of epiphyses
– Occurs approx 1-2 yrs
after menarche

18. Precocious Puberty
 In girls, defined as onset of puberty “breast
enlargement” before age of 8 years.
 In boys, defined as onset of puberty testicular
enlargement before age of 9 years.
 5 times more common in girls than boys.

19. Types
 Central, True, GnRH dependent.
 89-98% of cases (major type)
 Peripheral, Pseudo, GnRH Independent.
 10 – 15 % of cases (not major type)
 Isolated Forms:
 Isolated benign Thelarche.
 Isolated benign Adrenarche / Pubarche.

20. Central, True, GnRH dependent
 Result from premature activation of
Hypothalamus-Pituitary-Gonadal axis
 The pulsatile GnRH secretion leads to pulsatile
secretions of LH and FSH with subsequent
release of sex steroids
 Similar to normal mechanism but happened
earlier than expected age

21. Central, True, GnRH dependent
Etiology
„Idiopathic
most girls ( 90 %)
„Secondary
most boys ( 70-80%)

22. Central, True, GnRH dependent
CNS disorders
 Hypothalamic Hamartoma.
 Glioma, Astrocytoma, Craniopharyngioma, Ependymoma,
germinoma.
 CNS radiation therapy.
 Post trauma (surgery).
 Meningitis, encephalitis, Brain abscesses.
 Neurological insult & mental retardation.
 Hydrocephalus.
 Prolonged primary hypothyroidism.

23. Etiology of peripheral type
 Gonadal: McCune-Albright, tumor, cyst.
 Adrenal: non classical congenital adrenal
hyperplasia, tumors.
 Ectopic: hCG secreting tumors:
 Germinoma, Hepatoblastoma.
 Exogenous source of sex hormone
(contraceptive)
 Familial male dependent (Testotoxicosis)

24. Exogenous source of estrogens

25. McCune Albright Syndrome

26. Pubertal Delay
Definition:
 Girls:
 Lack of breast development by age 13 years.
 More than five years between breast growth and
menstrual period.
 Lack of pubic hair by age 14 years.
 Failure to menstruate by age 16 years.
 Boys:
 Lack of testicular enlargement by age 14 years.
 Lack of pubic hair by age 15 years.
 More than five years to complete genital
Enlargement.

27. TYPES
 Two major types:
 Hypogonadotrophic hypogonadism
 Hypothalamic -Pituitary defects
 Hypogonadotrophic hypogonadism
 Gonadal failure

28. Causes of Hypogonadotrophic
Hypogonadism
 Constitutional delay of growth &Puberty.
 Malnutrition.
 Excessive exercise.
 Isolated Gonadotropin deficiency.
 Brain tumors:
 Craniopharyngioma, Astrocytoma, Glioma,
histiocytosis X, germinoma, prolactinoma.
 Iron overload (hemosiderosis)
 GnRH receptor abnormalities.

29. Constitutional delay of Puberty
 Most common cause of pubertal delay.
 Physiological cause.
 Delayed puberty often found in siblings or
parents.
 Diagnosis of exclusion.
 Bone age is delayed & consistent with degree
of pubertal maturation (usually delayed by
2yrs or more.
 Often associated with constitutional short
stature.

30. Hypogonadotrophic hypogonadism
 Rare (~10%)
 Hypothalamic deficiency
 GnRH deficiency - may be isolated or associated
with other features e.g. anosmia (Kallman's
syndrome), cognitive impairment and dysmorphic
features (Prader-Willi syndrome).
 Pituitary deficiency
 Gonadotropin deficiency or more commonly associated
with any form of pan hypopituitarism.

31. Kallman Syndrome
 Syndrome of isolated Gonadotropin
deficiency.
 Present with anosmia or hypo-osmia.
 KAL-1 gene encodes protein (anosmin)
required for GnRH neurons to migrate from
olfactory placode to cribiform plate.
 Associated with harelip, cleft palate, and
congenital deafness

32. Kallman Syndrome

33. Syndromes associated with pubertal delay
 Prader-Willi syndrome.
 Laurence Moon syndrome.
 Septo-optic dysplasia.
 Bardet-Biedl syndrome.

34. Hypergonadotropic Hypogonadism
 Sex chromosome abnormalities:
 Klinefelter's syndrome in boys (47XXY)
 Turner's syndrome in girls (45XO)
 Gonadal dysgenesis with normal Karyotype
 Gonadal damage
 viral (e.g. mumps Orchitis)
 Iatrogenic (surgical, chemotherapy or
radiotherapy)
 Autoimmune destruction(often associated with
other autoimmune disease).
 Gametes generally more sensitive to damage that
steroid secreting cells

35. Klinefelter's syndrome

36. Turner syndrome

38. Chronic illness
 Delay in pubertal development is very
common in the presence of any serious
illness e.g. chronic renal failure, bowel or
liver diseases.
 Progress depends on the course of the
underlying disease.
 Endocrine causes of delay puberty
include hypothyroidism, GH deficiency
and excess glucocorticoid.

39. Learning Points (2)
 Idiopathic central precocious puberty in a
boy is very unusual so early puberty in
boys needs extensive investigation
which is usually unnecessary in early
puberty in a girl
 Delayed onset on puberty ( more than13
years in girls, 14 years in boys) is much
commoner in boys than girls and is
usually idiopathic