An overview of normal and abnormal puberty

1. Puberty- Normal & Abnormal

2. MODULE 5:
PHYSIOLOGY OF PUBERTY

3. Learning outcomes
After working through the materials in this module, the students
should be able to:
1.Describe the role of the hypothalamic and pituitary gland hormones
in puberty.
2.Explain the factors that influence timing of onset of puberty.
3.Explain changes that occur in serum gonadotropins & sex steroids
during foetal, neonatal, childhood, early & late pubertal periods.
4.Describe the sequence of development of secondary sex
characteristics in males and females.
5.Describe differences in changes in growth between male & female
adolescents during puberty.
6.Describe physical changes occurring in the early, middle, and late
phases of puberty in both sexes and correlate these with hormonal
changes, using appropriate standards of comparison.
7.Describe precocious and delayed puberty

4. THE HUMAN LIFECYCLE
Infant Teenage Adult Old

5. THE HUMAN LIFECYCLE
New human life develops
from conception.
maturity and
old age
childhood
adolescence
young adulthood
infancy

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

7. Puberty
Puberty is the stage of physical
maturation in which an individual
becomes physiologically capable of
sexual reproduction.
The biological changes
somatic growth,
development of the sex glands,
(their endocrine and exocrine secretions)
sexual characteristics
and the capacity for reproduction.

8. FACTORS INITIATING
PUBERTAL DEVELOPMENT
adrenal
androgen
activity
Increased
neurotransmitt
er activity in
CNS
Maturation of
hypothalamus
• Nutrition
• Environment
• Genetics

9. Hypothalamic-pituitary-gonadal (HPG) axis
The HPG axis plays a pivotal role in every
phase of mammalian reproduction
including fetal development, puberty,
menstrual cycle, pregnancy, postpartum,
and menopause.
Fertility depends on precise hormonal
regulation of this axis.
Two of the most critical hormones,
luteinizing hormone (LH) and follicle-
stimulating hormone (FSH), are produced
exclusively in the gonadotrope cells of

10. Hypothalamic-pituitary-gonadal (HPG) axis
They are secreted into the blood stream, primarily in
response to gonadotropin-releasing hormone (GnRH)
from the hypothalamus.
Gonadal steroid hormones, such as oestrogen,
progesterone and testosterone, in addition to
peptide hormones, such as activin, inhibin, and
follistatin, modulate LH and FSH levels via feedback
to the anterior pituitary, as well as to the
hypothalamus.
LH and FSH regulate critical aspects of reproduction
in the gonads, including steroidogenesis,
gametogenesis and ovulation

11. Regulation of puberty onset and progression via the
HPG and the HPA axes

13. Fig 1.1 The growth and development from childhood to
adult.

14. Fig 1.1 The age of development of features of puberty.
Stages and testicular size show mean ages, and all vary considerably between
individuals. The same is true of height spurt, shown here in relation to other
data. Number 2 to 5 indicate stages of development.

15. Puberty- terms
What do you understand by the
terms below: -
puberty
thelarche
pubarche
adrenarche
gonadarche
menarche

16. Manifestations of
puberty in females
1. Menarche
2. Appearance of secondary sex characters
3. Physical development
4. Psychological changes.

17. Secondary sex characteristics
•development of the breast (thelarche)
• appearance of pubic hair (pubarche)
•appearance of axillary hair

18. Interval between breast budding &
menarche is about 2.5 years
Puberty
Thelarche (Breast
development)
Adrenarche
↑↑ activity of the
suprarenal cortex
↑↑ androgens
Appearance of
Pubic &axillary hair
Menarche
Onset of
menstruation/
periods

19. Causes of puberty
During childhood , the hypothalamus is
extremely sensitive to the negative feedback
exerted by the small quantities of estradiol &
testosterone produced by the child's ovaries.
As puberty approaches, the sensitivity of the
hypothalamus is decreased and subsequently,
there is increase in the pulsatile GnRH secretion .

20. The anterior pituitary responds by
progressive secretion of FSH and LH
associated with increased secretion of
growth hormone .

21. The ovaries respond to the increase
in gonadotrophins (LH & FSH)
secretion
By : follicular development &
estrogen secretion .

22. Estrogen causes development of genital
organs & appearance of secondary sexual
characteristics .
With increased estrogen secretion ,
menarche and cyclic estrogen secretion
occurs .

23. Fig 1.2. Variations in LH and FSH during different
life stages in the female

24. Fig 1.2b. Gonadotropin-releasing hormone (GnRH)

25. Buck Louis, G. M. et al. Pediatrics 2008;121:S192-S207
FIG 1.3 Regulation of puberty onset and
progression via the HPG and the HPA axes

26. Fig 1.4. Male and female hypothalamic-
pituitary-gonadal axis.

28. Genital organ changes
 Mons pubis, labia majora & minora:
Increase in size
 Vagina:
1. length: increase, appearance of the rugae
2. Epithelium: thick, stratified squamous., containing
glycogen
3. pH: acidic, 4-5

29. Genital organ changes
Uterus:
enlarge, Uterus / Cervix :1/1 then 2 / 1
Ovaries:
1.Increase in size, oval shape
2.300 thousands primary follicle at menarche ( 2 million
at birth)

30. Breast changes
•marked proliferation of duct system
•deposition of fat
•Acini develop under influence of
progesterone

31. TANNER & MARSHALL STAGES- BREAST

32. TANNER AND MARSHALL STAGES-PUBIC HAIR

35. Management
•Sex Education
•Esp. in schools girls
•Knowledge about STD,HIV,Pregnancy
•Contraceptive advise
•Menstrual hygiene education
•Nutrition –Adequate protein, increase
demand of calcium by 50% & iron by 15%
•HPV vaccination
.

36. Abnormalities of
puberty
1 - Precocious puberty .
2 - Delayed puberty .
3 - Growth problems :
during adolescence e.g. short stature or tall
stature , marked obesity and menstrual
disorders at puberty .

37. FEMALE PRECOCIOUS
PUBERTY

38. Definition
Appearance of
any secondary sexual characters
<8 years
or
occurrence of menstruation
<10 years of chronological age

39. Types:
1 True precocious puberty
• GnRH Dependent (Central, True or Complete)
• Premature maturation of hypothalamic-pituitary axis (HPO)
2 False (pseudo-precocious puberty)
& Incomplete precocious puberty
• GnRH Independent (Pseudo, Peripheral or Incomplete)
• Gonadotropin secretion independent of HPO axis

40. Types
•ISOSEXUAL
Features are due to excess production
of estrogen
•HETEROSEXUAL
Features due to excess production of
androgen ( ovarian or adrenal
neoplasm)

41. Etiology
TrUE precocious puberty
GnRH dependent
•Constitutional – McCune-Albright
Syndrome (MAS)
•Juvenile primary hypothyroidism
•Intracranial lesions (TIN) –
Trauma, Infection, Neoplasm

42. Pseudo-precocious Puberty
GnRH Independent Varieties
OVARY
•Granulosa cell tumor
•Theca cell tumor
•Leydig cell tumor
•Mc Cune
Albright
Syndrome
LIVER
hepatoblastoma
ADRENAL
•Congenital adrenal
hyperplasia
•Tumour
IATROGENIC
•Estrogen or androgen
excess

43. History
•Timing of pubertal developmental signs
•Normal tempocentral cause
•Rapid tempoTumors
•Family history
•Medications
•Review of symptoms (ROS): pain, neuro
symptoms, headaches, visual change

44. Exam
•Height and weight plots are CRITICAL!
•Visual fields
•Skin abnormalities?
•Thyromegaly?
•Tanner stage
•External genitalia normal?

45. External Signs…
Café Au lait spots
(in MAS)

46. Labs
•Labs
•LH, FSH,Estradiol
•HCG
•TSH
•DHEAS, testosterone, 17-OHP

47. Useful Imaging Studies
•X ray wrist-Bone Age
•Rule out tumor
•MRI Brain
•Pelvic Ultrasound
•CT scan abdomen

48. Sorting it out…
Type of
precocity
Gonadal
Size
FSH/LH Estradiol/
Testosterone
DHEAS GnRH
stimulation
Idiopathic
    Pubertal
Cerebral    
Pubertal
Gonadal 

 
Flat
Albright    
Flat
Adrenal
normal
  
Flat

49. Treatment
•Explanation & Reassurance
•Tx with drugs which inhibit the secretion of
gonadotrophins till appropriate age is reached
(a)Gonadotrophin releasing hormone analogues which
are given as daily nasal spray, intramuscular, or subcutaneous
injections every 4 weeks.
•GnRH agonist therapy - administration for GnRH dependent
cases
•Consult Endocrinologist
• Weight-based-Intramuscular, subcutaneous or intranasal
• Effects: can stop when reaches appropriate height, menses occur
1-2 years after cessation, puberty occurs at normal pace after
cessation, no BMD diminishment, fertility unchanged

50. Isolated Pubertal Signs
•Precocious Thelarche
•Precocious Adrenarche
•Precocious Menarche

51. Precocious Thelarche
•Isolated development of breast tissue before age
of 8 yrs
•Commonly idiopathic
•Unilateral or bilateral
•Requires no treatment

52. Precocious Adrenarche
•Due to early androgen activation
•Seen in certain ethnic groups, children with
neurological sequelae, obese kids
•Increased risk for PCOS

53. Precocious Menarche
•A diagnosis of exclusion!
•Rule out: infection, trauma, tumors, foreign
body
•True cases thought to be idiopathic
similar to precocious thelarche

54. Evaluation of Precocious puberty
Bone
Age
Normal
Accelerated
Delayed
Monitor bone age and
pelvic ultrasound
Evaluate hormonal
causes
High hormone levels
Low or normal hormone levels
Central precocious
cause-order MRI
brain
Pseudoprecocious cause
Ultrasound of ovaries/testes, MRI brain, CT abdomen, labs
for CAH
With Café-au-lait spots, need bone scan or skeletal
survey
Consider thyroid cause

55. Delayed Puberty
No Secondary Sexual Characteristics
14y or
No menstruation till age of 16y
42

56. DELAYED PUBERTY
•3 classifications
•Hypergonadotropic hypogonadism
•Hypogonadotropic hypogonadism
•Eugonadism

57. HYPERGONADOTROPIC HYPOGONADISM
•LH & FSH are raised .
•What causes it?
•Ovarian failure
•Gonadal dysgenesis
•Karyotypic abnormalities-Turner(XO)=McCune
(genetic disorder)
•Chemotherapy
•Radiation
•Surgery
•Galactosemia

58. HYPOGONADOTROPIC HYPOGONADISM
•LH & FSH are decreased
•Reversible
•Constitutional delay (most common)
•Central suppression
•Weight loss, chronic disease, anorexia
•Prolactinoma
•Primary Hypothyroidism
•CAH (Congenital adrenal hyperplasia)

59. HYPOGONADOTROPIC HYPOGONADISM
•Irreversible
•Kallman’s syndrome ( most common)
•Hypo pituitarism
•CNS lesions

60. EUGONADISM
•Normal levels of LH & FSH
•Structural abnormalities
•Mullerian agenesis
•Transverse Vaginal Septum
•Imperforate Hymen
•Karyotypic abnormalities
•Androgen Insensitivity syndrome/testicular
feminization syndrome