1. Puberty

2. Definition of puberty
It is the physiological stage that leads to reproductive capability manifested by spermatogenesis in the male and ovulation in the female.

3. Conditions influence the age onset of puberty
Socioeconomic conditions
Nutritional status
States of health
Chronic disease
Altitudes
Genetic factors
Strenuous physical activity

7. Female secondary sex characteristics
Breast enlargement the first sign of puberty in % 85 girls
Pubic hair
Axillary hair
Vagina and uterus
Menarche (stage 4), mean age 12.8 years

8. Male secondary sex characteristics
External genitalia
Pubic hair
Axillary and facial hair
Voice change
Spermarche

9. Changes in body size and shape
1. Stature: PVH F stage III
M stage IV
2. Bone age
3. Body composition
4. Body build proportions
5. Strength

11. Precocious puberty
Appearance of any sign of secondary sexual maturation at an age more than 2SD below the mean.
The age of 7y in girls and 9y in boys

12. Precocious puberty True P. puberty Pseudo P. puberty
Contrasexual precocity

13. True precocious puberty
Idiopathic true precocious puberty
CNS tumors
Other CNS disorders
After late treatment of C.A.H.
or previous chronic exposure to gonadal steroids

14. Idiopathic precocious puberty
Most often sporadic, rarely A.R.
Is more common in girls
Progression of secondary sexual maturation is often more rapid than normal puberty
There is increased risk for the development of Ca. of breast in adulthhood
Ht. velocity, somatic development, skeletal maturation are increased .

15. Treatment of true P.P Medroxyprogesterone acetate Cyproterone acetate
The drug of choice is LHRH agonists

16. Objectives of the managements and treatment of T.P.P
Detection and treatment of an expanding intracranial lesion
Arrest of premature sexual maturation
Regression of secondary sexual characteristics
Attainment of normal mature height
Reduction of risk of sexual abuse
Prevention of pregnancy in girls
Preservation of future fertility
Diminish the increased risk of breast cancer

17. Action of LHRH agonists in TPP
A selective highly specific
Pharmacological clamp on the secretion of gonadotropin
Chronic administration induces desensitization of the pituitary gonadotrope to the action of endogenous LHRH.
As a consequence:
Inhibition of pulsatile secretion of LH and FSH
Inhibition of gonadotropin secretion

18. Indications for therapy with LHRH agonists in T.P.P
In children with endocrine features of T.P.P
Rapid advancement over a period of 6 mo to 1 y
A serum testosterone concentration > 1ng/mL in boys less than 8 y of age
Onset of menarche in girls less than 9 y of age

19. Side effect of LHRH agonists
Erythema (most common), sterile abscess and hematoma at the site of injection
Anaphylactic reaction (rare)
Asthma attack (nasal route)
Bone demineralization in girls
Antibody formation
Acceleration of sexual precocity
Diarrhea, constipation

20. Pseudo-precocious puberty (In boys)
Gonadotropin – secreting tumors
Inside CNS
Outside CNS
2. Increase androgen secretion by adrenal or testis
C.A.H.
Virilizing adrenal tumor
Leydig cell adenoma
Familial testotoxicosis

21. Pseudo-precocious puberty (In girls)
Estrogen – secreting ovarian or adrenal neoplasm
Ovarian cyst
Peutz – jeghers synd.

22. Pseudo – precocious puberty (In both sexes)
McCune – Albright synd.
Hypothyroidism
Iatrogenic or exogenous

23. McCune – Albright synd. Café au – lait spots
Polystotic fibrous dysplasia
Endocrine hyperfunction

24. Contrasexual precocity
Feminization in boys and virilization in girls

25. Feminization in males Adrenal neoplasm Chorioepithelioma
11-β hydroxylase def.
Late-onset C.A.H.
Testicular neoplasm (peutz-jeghers synd.)
↑Extraglandular conversion adrenal androgens to estrogen
Iatrogenic (exposure to estroges)

26. Virilization in girls C.A.H. (21-, 11-, 3  HSD def.)
Virilizing adrenal neoplasm
Virilizing ovarian neoplasm
Iatrogenic (exposure to androgens)

27. Variation of pubertal development
Premature thelarche
Premature adrenarche
Premature menarche
Adolescent gynecomastia in boys

28. Classification of delayed puberty
Idiopathic
Hypogonadothropic hypogonadism
Hypergonadothropic hypogonadism

29. Hypogonadoropic hypogonadism
CNS disorders
Tumors
Congenital malformations
Radiation therapy
Head trauma
Other causes

30. Classification of delayed puberty
Isolated gonadotropin deficiency
Kallmann syndrome with hyposmia or anosmia
Congenital adrenal hypoplasia
Other disorders
Idiopathic and genetic forms of multiple pituitary Hormone deficiencies
Miscellaneous disorders
Prader-willi syndrome
Laurence-moon-biedl syndrome

31. Characteristics of isolated gonadotropin deficiency
Males more commonly affected
Familial or sporadic
Height normal
Eunuchoid skeletal proportions
Delayed bone age
Small testes: diameter ≤ 2.5 cm
Normal adrenarche
Examine for anosmia or hyposmia (kallmann syndrome)
Look for associated malformations (facial, skeletal, renal)

32. Features of Kallmann syndrome
Clinical
LHRH deficiency: absent or arrested puberty
Anosmia or hyposmia
In infancy: microphallus, cryptorchidism
Normal stature and growth in childhood
Normal adrenarche
Eunuchoid proportions
Associated midline defects
MRI: aplasia or hypoplasia of olfactory bulbs
Cont.

33. Features of Kallmann syndrome
Prevalence: approximately 1 in 7500 males, 1 in females
Inheritance: sporadic and familial cases; genetic heterogeneity X linked
X-linkes recessive
X chromosome deletion: Xp22.3
Autosomal (Dominat, recessive)
Anatomy: developmental field defect
Aplasia or hypoplasia of olfactory bulb

34. Classification of delayed puberty
Functional gonadotropin deficiency
Chronic systemic disease and malnutrition
Hypothyroidism
Diabetes mellitus
Cushing disease
Hyperprolactinemia
Anorexia nervosa
Psychogenic amenorrhea
Delayed puberty and/or menarche, especially in female athletes and ballet dancers
Cont.

35. Classification of delayed puberty
Hypergonadotropic hypogonadims
Males
Klinefelter syndrome
Other forms of primary testicular failure
Chemotherapy
Radiation therapy
LH resistance
Testicular biosynthetic defects
Anorchia and cryptorchidims
Cont.

36. Classification of delayed puberty
Females
Turner syndrome
46 XX and 46 XY gonadal dysgenesis
Other forms of primary ovarian failure
Premature menopause
Radiation therapy
Chemotherapy
Autoimmune oophoritis
Polycystic ovary disease
Galactosemia

37. Endocrine diagnosis of constitutional delayed adolescence and hypogonadotropic hypogonadism
No single test reliably discriminates between the two diagnoses
Onset of puberty in boys is indicated by testes > 2.5 cm in diameter
Serum testosterone concentration > 50 ng/dl
Pubertal LH response to LHRH bolus
Pubertal pattern of LH pulsatility

38. Endocrine and imaging studies in delayed adolescence
Initial assessment
Plasma testosterone or estradiol
Plasma FSH and LH
Plasma thyroxine (and prolaction)
Bone age and lateral skull roentgenograph
Test of olfaction
Cont.

39. Endocrine and imaging studies in delayed adolescence
Follow-up studies
Karyotype (short, phenotypic females)
MRI and/or CT scan
Pelvic sonography (females)
LHRH test
hCG test (males)
Pattern of pulsatile LH secretion
Visual acuity and visual fields

40. Objectives in management and treatment and therapy of delayed adolescence
determine site and etiology of abnormality induce and maintain secondary sexual characteristics induce pubertal growth spurt
prevent the potential short-term and long-term
Psychological, personality and social handicaps of delayed puberty
Ensure normal libido and potency
Attain fertility
Cont.

41. Therapy of delayed puberty
Reassurance and follow-up
Repeat evaluation (including serum testosterone or estradiol) in 6 mo
Psychosocial handicaps, anxiety, highly concerned:
Therapy for 4 mo with
Boys: testosterone enanthate 100 mg IM every 4 wk at y of age.
Girls: ethiyl estradiol 5-10 ug daily by mouth or conjugated estrogens 0.3 mg daily by mouth at 13 y of age

42. Hormonal substitution therapy in boys with hypogonadism
Goal: to approximate normal adolescent development when diagnosis is established
Initial therapy: at 13 y of age, testosterone enanthate 50 mg IM every month for about 9 mo (6-12 mo)
Over the next 3 to 4 y: gradually increase dose to adult replacement dose of 200 mg every 2-3wk
Begin replacement therapy in boys with suspected hypogonadotropic hypogonadism by bone age < 14 y
To induce fertility at appropriate time: pulsatile
LHRH or FSH and hCG therapy

43. Hormonal substitution therapy in girls with hypogonadism
When diagnosis of hypogonadism is firmly established begin hormonal substitution therapy at 12-13y
Goal: to approximate normal adolescent development
Initial therapy: ethinyl estradiol 5 ug by mouth or conjugated estrogen 0.3 mg (or less) by mount daily for 4-6 mo.
After 6 mo of therapy begin cyclic therapy:
Estrogen: first 21 d of month
Progestogen: 12th to 21st day of month