Disorders of puberty

1. Disorders of puberty Department of Pediatrics Soochow University Affiliated Children’s Hospital

2. Aim and claim • Understanding the normal development of child • Familiar with the causes of precocious puberty • Get hold of the clinical features and diagnosis and management of precocious

3. General concepts • Puberty is defined as the acquisition of reproductive capability. • In clinical practice it is marked by the acquisition of secondary sexual characteristics • Between the age of 8-18 years children acquire secondary sexual characteristic and undergo the bodily changes which we loosely call puberty • Some do earlier than others • Some go through the changes in about 2 years,while others may take three times as long

4. General concepts • it is important to recognize the apparently Beneficial changes which take place at puberty such as rapid increase in size, strength and endurance; the development of gonads from their infantile to mature state. All these changes and there interactions constitute puberty.

5. Normal puberty • Secondary sex characteristics in girls: Breast development at the age abort 8-13 years, the vagina（阴道） begins to increase in length, the uterus （子宫）and ovarian（卵巢） follicles（卵泡） increase in size, the pubic hair（阴毛） appears,menarche（月经） occurs. • Secondary sex characteristics in boys: the external genitalia begin to enlarge at the age about 9-14 years from infantile to mature, represented by enlargement of the testes（睾丸） and scrotum（阴囊） and penis（阴茎）,pubic hair appears, voice change,sperm produce.

6. Features of puberty • Females breast development is first sign, height spurt reaches maximum before menarche, menarche occurs between 11 and 15 years • Males testicular growth is first sign, maximum height spurt reached 2 years after females

7. The stages of female and male sexual development(1-5）

8. 乳房发育的分期 • Stage 2 - Breast bud with areola widening • Stage 3 - Enlargement of breast and widening of areola. No separation of contours • Stage 4 - Secondary mound develops with separation • Stage 5 - Mature breast

10. 睾丸测量装置

11. Between early childhood and approximately 8-9 yr of age (prepubertal stage), the hypothalamic-pituitary-gonadal axis（下丘脑-垂体-性腺轴） is dormant, as reflected by undetectable serum concentrations of luteinizing hormone (LH) and sex hormones (estradiol in girls, testosterone in boys). In this phase, the activity of the hypothalamus and pituitary may be suppressed by poorly characterized neuronal restraint pathways.

23. The feature of puberty • At about same time as secondary sex characteristics are developing, children experience a dramatic acceleration of their growth—growth spurt. • Change in body proportions(legs trunk and sitting height) • The skull forward growth, skeletal maturetion, lymphoid tissues development • GnRH (from hypothalamus),FSH,LH (from pituitary) have sure pulsatile secretion • Sex steroids modulate the adolescent growth spurt and ultimately bring about cessation of growth

24. Disorder of puberty • During normal puberty,secondary sex characteristics are acquired and reproductive capacity is attained. • Puberty may be precocious or delayed.

25. Disorder of puberty Definition of precocious puberty: • Precocious puberty refers to the development of secondary sexual characteristics before the age of 8 year in girls or 9 year in boys.

26. Cause of precocious puberty • Gonadotrophin-dependent/ True precocious puberty （促性腺激素依赖性） idiopathic, familial, CNS lesions, e.g. postirradiation, surgery, tumours,hydrocephalus. • Gonadotrophin-independent / precocious pseudopuberty （促性腺激素非依赖性） McCune-Albright syndrome , (polyostotic fibrous dysplasia of bone, café-au-lait spots ,Excessive oestrogen in girls or excess testorsterone in boys isseen together with no LH or FSH response to LHRH) tumours of adrenals or gonads , CAH.

27. True precocious puberty is always isosexual and stems from hypothalamic-pituitary-gonadal activation. The gonadotropin-mediated increase in the size and activity of the gonads leads to increasing sex hormone secretion and progressive sexual maturation. In precocious pseudopuberty, some of the secondary sex characteristics appear, but there is no activation of the normal hypothalamic pituitary-gonadal interplay. In this latter group, the sex characteristics may be isosexual（同性） or heterosexual（异性） (“contrasexual”)

28. Conditions causing precocious puberty: • GONADOTROPIN-DEPENDENT PUBERTY (TRUE PRECOCIOUS PUBERTY) • Idiopathic • Organic brain lesions • Hyoothalamic hamartoma • Brain tumors, hydrothephalus, severe head trauma, myelomeningocele • Hypothyroidism, prolonged and untreated • COMBINED GONADOTROPIN-DEPENDENT AND GONADOTROPIN-INDEPENDENT PUBERTY • Treated congenital adrenal hyperplasia • McCune-Albright syndrome, late • Familial male precocious puberty, late

29. GONADOTROPIN-INDEPENDENT PUBERTY(PRECOCIOUS PSEUDOPUBERTY) • Females • isosexuol (feminizing) conditions • McCune-Albright syndrome • Autonomous ovarian cysts • 0varian tumors • Granulosa-theca cell tumor associated with 0llier disease • Teratoma, chorionepithelioma

30. Sex-cord tumor with annular tubules (SCTAT) associated with Peutz-Jeghers syndrome • Feminizing adrenocortiral tumor • Exogenous estrogens • Heterosexuol (masculinizing) conditions • congenital adrenal hyperplasia • Adrenal tumors • Ovarian tumors • Glucocorticoid receptor defect • Exogenous androgens

31. Males • isosexuol (norulinizing) conditions • Congenital adrenal hyperplasia • Adrenocortical tumor • Leydig cell tumor • Familial male precocious puberty • isolated • Assoriated with pseudohypoparathyroidism • HCG-secreting tumors • Central nervous system

32. Hepatoblastoma • Medjastinal tumor associated with Klinefelter syndrome • Teratoma • Glucocorticoid receptor defect • Exogenous androgen • Heterosexual (feminizing) conditions • Feminizing adrenocortical tumor • SCTAT associated with Peutz-leghers syndrome • Exogenous estrogens

33. INCOMPLETE (PARTIAI) PREOCIOUS PUBERTYPremature thelarche（单纯乳房发育） Premature adrenarche（单纯肾上腺初现）Premature menarche（单纯月经来潮）

34. Central precocious puberty(CPP) Precocious puberty is termed ‘central’ when it is caused by the premature activation of the hypothalamo-pituitary- gonadal axis.It is also to describe this condition as idiopathic precocious puberty(also not all causes of central precocious puberty are idiopathic).

35. Clinical manifestation Sexual development may begin at any age and generally follows the sequence observed in normal puberty. In girls, the first sign is development of the breast; pubic hair may appear simultaneously but more often appears later .Maturation of the external genitalia, the appearance of axillary hair, and the onset of menstruation follow. The early menstrual cycles may be more irregular than they are with normal puberty. The initial cycles are usually anovulatory, but pregnancy has been reported as early as 5.5yr of age.

36. Clinical manifestation In boys, enlargement of the testes is followed by enlargement of the penis, apperance of pubic hair,and acne. Erections are common, and nocturnal emissions may occur. The voice deepens, and linear growth is accelerated, testicular biopsies have shown stimulation of all elements of the testes, and spermatogenesis has been observed as early as 5-6yr of age. In affected girls and boys, height, weight, and osseous maturatron are advanced. The increased rate of bone maturation results in early closure of the epiphyses, and the ultimate stature is less than it would have been otherwise.

37. without treatment, approximately 1/3 of girls and an even larger percentage of boys achieve a height less than the 5th percentile as adults. Mental development is usually compatible with chronological age. Emotional behavior and mood swings are common, but serious psychologic problems are rare.

39. 男孩，8岁 外生殖器发育 阴毛发育 身高蹿长 ——中枢性性早熟

41. CPP Children with suspected CPP should be investigated in order to answer two question: • To confirm the dependence of the pubertal maturation on hypothalamo-pituitary function. • To exclude an intracranial tumour.

42. CPP • An assessment of physiological Gn secretion is the most helpful investigation. • Patients have a nomal pubertal LH and FSH response after an LHRH test, The bone age is usually advanced. • Pelvic ultrasound assessment is useful in girls. • CT or MRI scanning of the brain is advisable.

43. Disorder of puberty • Precocious puberty is more common in girls.It is usually due to early onset of normal puberty.(80%) • In boys, It is usually due to an intracranial tumour(40%)

45. Disorder of puberty • Precocious puberty should be differentiated from: • Premature thelarche: isolated breast development in a very young girl.a non-progressive,benign condition. • Premature adrenarche: isolated early appearance of pubic hair in either sex. a benign self-limiting condition due to early maturation of adrenal androgen secretion, but an adrenal tumour may need to be excluded

46. CPP The problems associated with Icpp are in three areas: • Premature sexual development, especially menarche at primary school. • Psychological disturbance, especially masturbation in boys • Impaired growth prognosis

50. Treatment of children with cpp • Treatment depends on cause. It may be necessary to attempt to reduce the rate of skeletal maturation to avoid early cessation of growth and a reduction in adult height. • GnRH analogues are useful in treatment with cpp and have no known side effects. • GnRHa are effective at suppressing the secondary sexual characteristics of puberty and the first few years of use are to improve height prognosis