3. Objectives:
At the end of this lecture participants will
be able to know:
• The pathophysiology of abnormal pubertal
development.
• The various medical disorders due to abnormal
pubertal development.
4. Puberty: Definitions
Pubertas = the period of human
development during which physical
growth and sexual maturation
occurs.
(spermatogenesis, ovulation ).
5. Peds 5
Puberty: Definitions
• Thelarche: breast budding, usual first
sign of puberty in girls
• Adrenarche: development of body odor
and fine pubic hair (occurs at 8-12 yrs
in females)
• Menarche: onset of menses, usually
occurs 2 yrs after thelarche (range 1-5
years)
6. • Pubarche – Appearance of pubic hair
• Spermarche – beginning of development of sperm
in boys' testicles at puberty
• Semenarche - The first ejaculatory experience of
boys
• Gonadarche – Earliest gonadal changes of
puberty
In boys- testicular enlargement
In girl -thelarche and growth acceleration
are usually the first evidence since ovarian growth
cannot be directly seen
8. Puberty: Pathophysiology
• Prepubertal stage: approximately 8 – 9 yr, the
hypothalamic-pituitary-gonadal axis is dormant as
reflected by immeasurable serum levels of LH,
FSH and sex hormones (estrogen, testosterone).
• In this phase activity of the hypothalamus and
pituitary gland is thought to be suppressed by
neuronal restraint pathway and by the negative
feed back provided in the young children by minute
levels of the circulating gonadal steroids.
9.
10. Puberty: Pathophysiology
• The physical changes of puberty are under the
control of the HPGA.
• The HPGA activity increases with the onset of
puberty ( spontaneous pulses of gonadotropins,
LH, SH),
• Plus increased peak LH and FSH levels in
response to GnRH stimulation
11.
12. Peds 12
Pubertal staging:
Sexual Maturity Rating (SMR)
Males
• Testicular
enlargement
• Penile enlargement
• Height growth spurt
• Pubic hair
Females
• Thelarche (breast
buds)
• Height growth spurt
• Pubic Hair
• Menarche
Changes are highly variable among individuals &
races. In girls 8 - 12 (mean 10) years, while in boys
10 - 14 (mean12) years.
13. Peds 13
Tanner Staging of
Breast Development
• Stage I: Preadolescent; elevation of papilla only
• Stage II: Breast bud; enlargement of areola (10-12.5yo)
• Stage III: Further enlargement and elevation of breast &
areola no separation of contour (11-13.5yo)
• Stage IV: Projection of areola and papilla to form second
mound (12-14yo)
• Stage V: Mature stage; projection of papilla due to
recession of areola to general contour (13.5-17yo)
14. Peds 14
Tanner Staging of
Male Genitalia
• Stage I: Preadolescent
• Stage II: Enlargement of scrotum and testes; skin
of scrotum changes texture (10.5-13)
• Stage III: Enlargement of penis (mainly in length);
further growth of scrotum & testes
(12.5-15y)
• Stage IV: Increased size of penis with growth in
breadth; more growth of testes/scrotum;
further darkening of scrotal skin
(12.5-15y)
• Stage V: Genitalia of adult size and shape (14-16y)
15. Peds 15
Tanner Staging of
Pubic Hair
• Stage I: Preadolescent: no pubic hair
• Stage II: Sparse growth of long, slightly pigmented
downy hair at base of penis or along labia
(male 13-14y; female 11-12y)
• Stage III: Darker, coarser, curled; hair spreads
sparsely over junction of pubes
(male 13-15y; female 11-13y)
• Stage IV: Hair resembles adult type; no spread to
thighs (male 13-15y; female 12-14y)
• Stage V: Adult in quantity and type with distribution
of the horizontal pattern
(male 14-16y; female 13.5-16y)
16. Conclusion
In adulthood, therefore, men are taller than
women by 12.5–14 cm (5–5.5 inches) due to
three factors:
● starting their pubertal growth spurt two years
later than girls
● having a more intense pubertal growth spurt than
girls
● being slightly taller than girls during childhood
16
17. Abnormal Puberty
Precocious Puberty: most commonly defined
as the onset of puberty before 8 years in girls
and before 9 years in boys.
Delayed Puberty: most commonly defined as
no pubertal changes in girls by age of 14 years.
In boys no pubertal changes by age of 15 years.
18. Precocious puberty
Premature sexual
development before
( 8 yr in female, 9 yr in male )
Dominant in girls whom
it is usually idiopathic.
rarer in boys in whom an
underlying lesion is likely.
Delayed puberty
Absence of pubertal
development
(14 yr in female, 15 yr in male)
Dominant in boys, in
whom constitutional delay
is much the commonest
cause
19. Peds 19
Precocious Puberty
Differential diagnosis: 2 main categories
– True precocious puberty: activation of H/P/G
axis
– Pseudo-precocious puberty: primary production
of sex steroids from gonads or adrenals without
activation of H/P/G axis
20.
21. Overview (1)
• The overall incidence: 1:5,000-1:10,000.
• The female : male ratio is 10:1.
• Before age 6 for African American girls or
age 7 for Caucasian girls.
• A serious CNS disorder may be associated
with precocious puberty .
22. Overview (2)
• isosexual precocity: early sexual development
consistent with the sex of the individual (i.e., feminization
of a female)
• heterosexual or contrasexual precocity:
precocious pubertal development that is limited to those
physical signs not characteristic for the sex of the
individual when presenting as isolated findings (i.e.,
virilization of a female).
• GnRH dependent and GnRH independent precocious
puberty (GIPP) : refer to those causes of precocity that do
or do not respond to GnRH analogue treatment,
respectively.
• Finally, central precocious puberty (CPP) refers to
precocity of CNS origin.
23. Overview (3)
• Incomplete precocious puberty: appearance of
one phase of the pubertal process:
- Isolated precocious thelarche,
- Isolated precocious adrenarche,
- Isolated menarche
• A GnRH challenge test: that demonstrates the pubertal
response of gonadotropins (i.e., LH response > FSH response) is
the hallmark of this diagnosis as is the usual ability to suppress
pubertal development with GnRH agonists.
24. Causes
Boys Girls
•Virilizing and feminizing
adrenal adenomas
•Activating LH receptor
mutations
•Germline defects causing
Leydig’s cell adenoma
•Somatic defects causing
testotoxicosis
•Drugs (e.g. oxymethalone)
•Feminizing and virilizing
adrenal adenomas
•Virilizing ovarian tumours
•Feminizing granulosa cell
tumours of ovary
•McCune–Albright syndrome
(caused by mosaicism
for activating GS-
mutation).
21/08/14 24
25. Iatrogenic sexual
precocity
• In prepubertal children, exogenous intake of
estrogen has been shown to cause precocious
pubertal development.
• A number of estrogen containing products have
been previously reported including hair products,
lotions, and creams.
• Ingestion of estrogen containing meat has also
been implicated. In actuality, these causes are
extremely rare today.
26. Peds 26
Precocious Puberty: Evaluation
–Labs
• Testosterone, estradiol
• GnRH challenge test (FSH, LH)
–X-ray
• MRI Brain
• CT abdomen
• Bone age
27. 21/08/14 27
Precocious Puberty: Evaluation
LHRH test which will show a pubertal LH
response in true precocious and early puberty.
Pelvic ultrasound in girls will show the
characteristic pubertal uterus and ovaries.
Cranial MRI, in which resolution is superior to a
computed tomography (CT) scan.
( sought out the cause )
28. 21/08/14 28
Treatment
The decision whether or not to medically treat precocious and
early puberty must take into account the girl’s height status,
learning ability, age of onset and intensity of the puberty, and the
feelings of the girl and her family.
Treatment of precocious and early puberty is with GnRH
analogue which, when given in pharmacological doses causes
downregulation of gonadotrophin secretion.
29. TREATMENT
Treatment with GnRH analogue probably
improves final height outcome in precocious
puberty but probably not in early puberty.
The main benefit of treatment is psychological
in preventing progression of pubertal signs and
menses. This can be particularly valuable in girls
with learning disability.
30. Peds 30
Delayed Puberty
• Lack of pubertal changes
– Girls >13 years, Boys >14 years
• More common in boys
• Differential is extensive, but 2 main
categories:
– Hypothalamic, pituitary, and gonadal
– Constitutional delay: most common
31. Central delay( low GNRH( Gonadal impairment ( high GNRH
(
Intact axis Impaired axis Boys Girls
Constitutional delay in
growth and
adolescence
Congenital
hypopituitarism
Anorchia Gonadal dysgenesis
(e.g. Turner syndrome)
Eating disorders
e.g. anorexia nervosa)
LHRH deficiency
–7isolated
–with anosmia (Kallmann
syndrome)
–Prader–Willi syndrome
Bilateral
cryptorchidism
Radiotheraphy e.g. total
body irradiation in
preconditioning
for bone marrow
transplant
Chronic illness Tumours adjacent to
hypothalamo
pituitary axis (e.g.
Craniopharyngioma
suprasellar germinoma
Klinefelter syndrome Galactosemia
Surgery and radiotherapy Prader–Willi syndrome
Noonan syndrome
Radiotherapy (e.g. for
testicular relapse in
leukaemia)21/08/14 31
Causes of delayed / abnormal puberty
