1. Puberty
Done by: Samir Alaidaroos,Ahmed Alamoudi,Yousef Alsawwaf Wael Bakhamees, Adel almuzaini

2. OBJECTIVES:
Describe the normal sequence of puberty and recognize deviation from the normal.
Define precocious puberty and develop an approach tohistory and physical examination.
To define delayed puberty and develop an approach to history and physical examination.
Appreciate the impact of delayed and precocious puberty on both the patients and their family.

3. Normal Puberty

4. Puberty
The stage of physical maturation in which an individual becomes physiologically capable of sexual reproduction.
Triggered by increased secretion of Luteinizing Hormone(LH).
Results from changes in the hypothalamus that allow increased secretion of GnRH to stimulate secretion of LH

6. Phases of Puberty Adrenarche Gonadarche
Stage of maturation of the cortex of adrenal glands
↑ adrenal androgens secretion
 Gonadarche
Earliest gonadal changes
Ovaries and testes begin to grow
↑ production of sex hormones

7. Thelarche Pubarche First stage of secondary breast development
Usually noticed as a firm, tender lump directly under the center of the nipple(papilla & areolla)
Reffered as breast bud(Tanner stage 2)
Pubarche
First appearance of the pubic hair
Results from ↑ levels androgens from adrenal glands or testes

8. Menarche
First menstrual bleeding in females
Possibility of fertility

9. Puberty in female:
The onset of puberty in females start at age of years old
First sign of puberty is Breast development

10. Preadolescent. Elevation of the papilla only
Female: Breast
Tanner Stages
Breast 1
Preadolescent. Elevation of the papilla only 2
-A small mount is formed by the elevation of the breast and papilla
-Areolar diameter enlarges 3
Further enlargement of breast and areola. 4
Projection of the areola and papilla to form a secondary mound above the level of the breast 5
-Mature breast
-Areola recessed to the general contour of the breast.

11. Other changes in female
Growth spurt/Peak height velocity
Female:
Happens in earlier stages of puberty
Average age: 12.1
Vagina
Becomes thicker and duller pink in color
Uterus, ovaries and follicles in the ovaries
Increase in size
Menstrual and fertility

12. Other changes in female
Body shape and fat distribution:
Pelvis and hip widen
More fat distributed to breasts, hips, buttocks, thighs, upper arm and pubis.
Body odor and acne

13. Hormonal Changes in female
Increase in:
Estrogen
Prolactin
Growth hormone

14. Puberty in Male The onset of puberty in males start at 12-16 years old
The first sign of puberty is the increase of testicles size and genitalia.

15. Male: Genitalia Tanner Stages Genitalia 1
-The penis , testes and scrotum are of childhood size 2
-Enlargement of scrotum and testes
- Scrotal skin reddens 3
-Further growth of the testes and scrotum.
-Enlargement of penis, mainly in length 4
-Enlargement of penis, mainly in breadth 5
Adult genitalia

16. Other Changes in male Growth spurt/Peak height velocity
Happens in later stages of puberty
Average age: 14.1
Boys have greater velocity at the maximum pubertal growth rate
Body and Facial hair
Voice change
Same time as growth of penis

17. Other changes in male Musculature and body shape
Body oHeavier bones, nearly twice skeletal muscle
Muscle develops mainly during the later stages of puberty
odor, sweat glands, sebaceous glands and acne
About the same time as facial and axillary hair growth

18. Hormonal Changes in male
Increase in:
Testosterone
Growth Hormone

19. PRECOCIOUS PUBERTY

20. Patient :
On examination there were no palpable masses in her abdomen. No signs of other endocrinopathies were observed.
An 4 year old Saudi female presented with her mother to the outpatient endocrinology clinic complaining of ‘period-like’ light red discharge gushing out of her vagina once every three weeks for three months, her mother is concerned that her daughter is getting her period too early. The history revealed that the girl has bone pain in her limbs, and on examination multiple cafe au lait marks were observed in addition to tanner stage 1 pubic hair and tanner stage 3 breasts.

21. Patient :

22. Definition
Precocious puberty is defined as the onset of secondary sexual characteristics before 8 yr of age in girls and 9 yr in boys.

24. Classification Incomplete Complete Central
(gonadotropin-dependent puberty, GDPP)
Peripheral
(gonadotropin- independent puberty, GIPP)
Incomplete
Premature thelarche
Premature pubarche
Depending on the primary source of hormonal production, this may be classified as

26. 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.

27. Gonadotropin-dependent precocious puberty ( GDPP):
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

28. Causes: Non- CNS lesion: - Idiopathic - Genetics
- Prolonged, untreated severe hypothyroidism
CNS lesion:
- CNS tumour
- CNS irradiation
hydrocephalus, cysts, trauma, CNS inflammatory disease

29. 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
There is usually hypothalamic signs:
diabetes insipidus
hyperthermia
unnatural crying or laughing(gelastic seizures)
cachexia
interrupting CNS inhibitory pathways to the hypothalamus usually in very young children

30. CNS lesion (cont.):
Other tumour: astrocytoma, optic and hypothalamic glioma
In optic glioma : proptosis
In irradiation of brain : signs of growth hormone deficiency may present

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

32. Clinical manifestations (cont.):
In girls (somatic changes):
pubic & axillary hair
acne
body odour
oily skin and hair

34. Clinical manifestations (cont.):
In boys (physical changes):
Testicular enlargement (unnoticed)
Enlargement of penis
Erections are common
spermatogenesis observed as early as 5-6 yr of age
Somatic changes:
Axillary hair, acne, voice deepens

35. Clinical manifestations (cont.):
In both gender (skeletal and emotional):
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

36. Gonadotropin-independent precocious puberty ( GIPP):
Independent of gonadotropin secretion and no activation of the Hypothalamic pituitary gonadal axis
Also know as precocious pseudopuberty
caused by excess secretion of sex hormones (estrogens or androgens) derived either from the gonads or adrenal glands or from exogenous sources

37. Causes of GIPP : Girls Boys Ovarian cysts Leydig cell tumour
Ovarian tumours
Human chorionic gonadotropin (hCG) secreting germ cell tumors
Granulosa theca cell tumor
Familial precocious puberty

38. Other causes of GIPP: Both in boys and girl: Exogenous estrogen
Increase in hormones found in food
Adrenal pathology ( eg: androgen-secreting tumour and CAH)
Teratoma
McCune-Albright syndrome

39. McCune-Albright syndrome
McCune-Albright syndrome is a genetic disease caused by mutations in the GNAS1 gene.
A small number, but not all, of the patient's cells contain this faulty gene (mosaic pattern).
This disease is not inherited.

40. McCune-Albright syndrome
 (MAS) consists of at least 2 of the following 3 features: 
polyostotic fibrous dysplasia
café-au-lait skin pigmentation
autonomous endocrine hyperfunction
which leads to precocious puberty

41. McCune-Albright syndrome
Other possible manifestations include the following:
Cushing syndrome
Growth hormone (GH) excess (gigantism and acromegaly)
Ovarian cysts
Pituitary tumors
Thyroid tumors

42. Peripheral type (GIPP)
Central type (GDPP)
Peripheral type (GIPP)
H-P-G Axis
Activated
Suppressed
LH and FSH
Adult values
Pre-Pubertal
Sex steroids
High
Gonads
Pubertal size
Small in size (unless tumor)

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

44. 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.
Management: reassurance and monitoring regularly for any other sign of pubertal advancement

45. 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

46. Patient :
On examination there were no palpable masses in her abdomen. No signs of other endocrinopathies were observed.
An 4 year old Saudi female presented with her mother to the outpatient endocrinology clinic complaining of ‘period-like’ light red discharge gushing out of her vagina once every three weeks for three months, her mother is concerned that her daughter is getting her period too early. The history revealed that the girl has bone pain in her limbs, and on examination multiple cafe au lait marks were observed in addition to tanner stage 1 pubic hair and tanner stage 3 breasts.

47. Patient :

48. Investigations Bone Age 7 Years old FSH & LH Low T3%T4&TSH Normal ACTH
Supressed
GNRH
High
ESTROGEN
High
IGF-1

49. DELAYED PUBERTY

50. Patient :
On examination, he was on the 90th percentile of height and the 50th percentile for weight, and his testes were found to be bilaterally small. His upper to lower ratio is 0.8.
A 18 year old Saudi male came to the endocrinology outpatient clinic complaining of looking boyish compared to his peers. History revealed that he had never grown facial, axillary or pubic hair, his voice had not changed, and he noticed bilateral small enlargements in his nipples. His mother claimed no complications during her pregnancy of him, and that he did not miss his early developmental milestones, however she was concerned of the female figure of his body that started noticing around the age of 13.

51. Patient :

52. Definition
Its defined when there is no sign of pubertal development by age 13 in girls and by age 14 in boys.

53. Low gonadotropin secretion
Types
Low gonadotropin secretion
(hypogonadotropic hypogonadism).
High gonadotropin secretion
( hypergonadotropic hypogonadism).

54. Constitutional delay of growth and puberty/familial
The commonest , more common in males.
usually familial , having occurred in the parent or sibling of the same sex.
Could be induced by dieting and excessive physical training.
delayed sexual maturation , and delayed in skeletal maturity on bone age.
Legs are longer in comparison to the back ( eunuchoid body habitus).
The deceleration (nadir) before their pubertal growth spurt is prolonged in the affected children as opposed to their peers , this cause them to eventually reach the target height.

55. Hypogondatropic Hypogonadism ( Low gonadotropin secretion)
Hypogondatropic Hypogonadism hinders the spontaneous entry into gonadarche , while adrenarche usually occur to some degree.
During childhood and early puberty they have normal proportions and growth.
When they reach adulthood enuchoid proportions may occur because their bones grow longer than normal ( Upper to lower ratio less than 0.9)

56. Hypogondatropic Hypogonadism ( Low gonadotropin secretion)
Isolated gonadotropin deficiency e.g Kallman Syndrome.
Idiopathic hypopituitarism
Hypothalamic-Pituitary tumors.

57. Isolated gonadotropin deficiency
Inability to release gonadotropins but no other pituitary abnormalities, is indicative of Isolated gonadotropin deficiency.
Patients grow normally but they fail to achieve the accelerated growth characteristic of the normal growth spurt.
An example is Kallmann Syndrome , this syndrome typically feature anosmia.

58. Hypothalamic-Pituitary tumors.
CNS Tumors: Pituitary adenoma, germinoma, glioma, prolactinoma, craniopharyngioma.

59. Systemic medical conditions:
Anorexia nervosa
Athletic Amenorrhea
Chronic illness
Hypothyroidism.

60. Hypergonadotropic Hypogonadism ( High gonadotropin secretion)
Characterized by elevated gonadotropin and low sex steroid levels , a result of primary gonadal failure. Associated Conditions: 1- Ovarian Failure 2- Testicular Failure

62. Ovarian Failure
A Common cause is turner syndrome or the syndrome of gonadal dysgenesis.
The karyotype is classically 45,XO.
Patients with other types of gonadal dysgenesis and galactosemia, also patients treated with chemotherapy or radiation for malignancy may also develop ovarian failure.

65. Testicular Failure
Klinfelter Syndrome ( seminiferous tubular dysgenesis) is the most common cause.
Karyotype is 47,XXY.
Clinical presentation: hypogonadism (small testes, azoospermia, oligospermia), gynecomastia in late puberty, Eunchoid body.
Leydig cell function maybe spared, however Seminiferous tubular function is characteristically lost.
LH levels may be normal or elevated , while FSH levels are unmistakably elevated

67. Patient :
On examination, he was on the 85th percentile of height and the 50th percentile for weight, and his testes were found to be bilaterally small. His upper to lower ratio is 0.8
A 18 year old Saudi male came to the endocrinology outpatient clinic complaining of looking boyish compared to his peers. History revealed that he had never grown facial, axillary or pubic hair, his voice had not changed, and he noticed bilateral small enlargements in his nipples. His mother claimed no complications during her pregnancy of him, and that he did not miss his early developmental milestones, however she was concerned of the female figure of his body that started noticing around the age of 13.

68. Patient :

69. Examination
The vitals were normal. His height was 187cm, significantly taller than both his parents, and he had a tanner stage 2 penis with small testicles, in addition to tanner stage 3 breasts. He had no thyroid enlargement or ocular abnormalities. His bone age was 14.

70. Investigations Karyotype 47 + XXY FSH High T3%T4&TSH Normal Prolactin
Low
Testosterone
Normal LH

71. IMPACT ON PATIENTS & PARENTS

72. The impact of Precocious puberty on both the patient and family
Even when it's happening to average 12-year-olds, puberty can be a confusing time. It can be all the more stressful for younger kids with early puberty. Adolescent with Precocious puberty may go through social and emotional stress due to: Girls : 1. Short stature 2. Shyness 3. Inability to cope with menstruation and they are at risk of sexual child abuse 4. Behavioral problems

73. Boys :
Short stature
Aggressiveness and inappropriate sexual drive .
Behavioral problems

74. The impact of delayed puberty on both the patient and family
Adolescent with delayed puberty may go through social and emotional stress due to: 1. Physical appearance: - Short stature: to their lack of sexual development. - Lack secondary sexual characteristics. 2. Being bullied at school: - Reluctance to go to school - Fear of the journey to and from - Things go missing – money, school clothes, lunch boxes - Bruises and scratches.

75. Thank you!

76. Done by: Sameer Alaidroos Ahmed Al-amoudi Yousef Alsawaf
Wael Bakhamees
Adel Almuzaini

77. References UPTODATE MEDSCAPE NELSON PEDIATRICS BMJ BESTPRACTICE
PROF.AGHA LECTURES
ILLIUSTRATED