Disorders of puberty.pptx 2

Precocious puberty Delayed puberty 08/01/11

terms Pubarche – Appearance of pubic hair Thelarche - Appearance of "breast bud ", Tanner stage 2 breast development of first stage of secondary (postnatal) breast development, usually occurring at the beginning of puberty in girls, noticed as a firm, tender lump directly under the center of the nipple (papilla and areola ),may occur on one side first, or both sides simultaneously. 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 Adrenarche – Early sexual maturation stage, the result of the development of a new zone of the adrenal cortex, the zona reticularis, adrenal cortex secretes increased levels of androgens such as DHEA and DHEAS, but without increased cortisol levels Menarche - The first menstrual cycle , or first menstrual bleeding in female The average age of menarche is 11.75 years Spermache –beginning of development of sperm in boys' testicles at puberty Semenarche- The first ejaculatory experience of boys 08/01/11

08/01/11 Normal developmental sequence Thelarche 8-13 years Pubarche Menarche 2-3 years later Enlargement of testes Apperance of pubic hair

Pubertal staging - Sexual Maturity Rating (SMR) Secondary sexual development is assessed according to the method of James Tanner. GENITAL STAGING ● G1 – pre-pubertal penis, testes and scrotum; testes 4 mL in volume ● G2 – laxity, rugosity and reddening of the scrotum with testes enlarged to 4 mL or greater, but the penis remaining pre-pubertal ● G3 – enlargement of the penis with further development of the scrotum and testes ● G4 – further penile development with broadening as well as lengthening, further development of scrotum and testes, testicular volume usually 12 mL or greater ● G5 – adult development, testes 15–25 mL. BREAST STAGING ● B1 – no breast tissue present ● B2 – breast budding, often felt as a hard wedge of tissue underneath the areola ● B3 – definite breast mound but not adult size ● B4 – projection of the areola from the breast mound at a different angle ● B5 – adult PUBIC HAIR STAGING ● P1 – no pubic hair ● P2 – the beginnings of pubic hair which is fine, wispy and not readily visible from a distance ● P3 – adult-type pubic hair (coarse, dark, curly) with distribution limited to the symphysis pubis and labia majora ● P4 – near-adult in type and distribution ● P5 – adult, with extension to the thighs and lower abdomen 08/01/11

08/01/11 Milestones of puberty in relation to peak height velocity

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 08/01/11

Precocious ( early)puberty premature sexual development before 8 years in female 9 years 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 years in female 15 years in male Dominant in boys , in whom constitutional delay is much the commonest cause Overview Puberty - derived from the Latin pubertas = coming to the age of manhood defined as the period of human development during which physical growth and sexual maturation occurs. 08/01/11

Causes True precocious and early puberty Idiopathic – common in girls, rare in boys Tumours within hypothalamus , e.g. hypothalamic hamartoma Tumours adjacent to hypothalamus, e.g. optic glioma, suprasellar germinoma Central nervous system disorders e.g. hydrocephalus, cerebral palsy, learning disability Low-dose cranial irradiation e.g. cranial prophylaxis in childhood leukaemia Previous exposure to sex steroids (‘priming’), e.g. simple virilizing 21-hydroxylase deficiency, Precocious pseudopuberty Exaggerated adrenarche Incomplete sexual precocity in girls Isolated premature thelarche Thelarche variant Isolated premature menarche 08/01/11 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).

08/01/11 History and examination Breast and genital development in girls and boys- variable combination of pubic hair, increase in growth rate, moodiness, body odour, and sometimes acne. The family patterns of puberty (menarche in females, growth spurt and voice breaking in males) Family history of neurofibromatosis and café-au-lait patches Learning disability and CNS disorders, cranial irradiation, headache (suggestive of raised ICP ) Anthropometry -Child usually tall for age, height above the target range centiles. ( exception to this is the child with concomitant growth hormone deficiency. Bone age is advanced by 1 year) In boys - palpation of the testes will show bilateral enlargement to 4 mL or greater , with or without penile enlargement and pubic hair. In girls - will show at least stage B2 development in breast staging Examination of the fundi -optic nerve atrophy due to pressure from a pituitary lesion adjacent to the hypothalamo-pituitary axis (e.g. an optic glioma). Examination of skin for- caféau- lait patches (seen in neurofibromatosis and McCune– Albright syndrome).

08/01/11 CASE STUDY A girl of 8 years presents with a six-month history of breast development and mood swings. Always tall, she has been growing particularly fast recently. Her mother and older sisters experienced menarche at 11 years. Examination shows a tall girl with stage B2 breast development, no café-au-lait patches, and normal fundoscopy. TRUE PRECOCIOUS AND EARLY PUBERTY

CASE STUDY A girl of 3 years is referred with a three-month history of pubic hair development and aggressive behaviour. Examination shows a child of normal stature in relation to parental heights. There is clitoral enlargement, stage P3 pubic hair and a mass in the lower abdomen. Plasma androgens are elevated, LH and FSH completely suppressed. PRECOCIOUS PSEUDOPUBERTY 08/01/11

08/01/11 Treatment Treatment of precocious and early puberty is with GnRH analogue which, when given in pharmacological doses causes downregulation of gonadotrophin secretion. 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 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.

08/01/11 Investigations 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 t omography (CT) scan. ( sought out the cause )

08/01/11 Sexual precocity Premature sexual maturation, due to oestrogen or androgen excess, will cause increased height velocity with tall stature and bone age advance. Depending on the severityof the sexual precocity, adult final height may be compromised due to premature closure of the epiphyses, resulting in the paradox of tall stature during childhood and short stature in adulthood . Children with overgrowth disorders associated with learning disability are also prone to early puberty, which will compound the tall stature.

08/01/11 Causes of delayed / abnormal puberty 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)

08/01/11 HISTORY AND EXAMINATION Important aspects to consider are previous growth history, (ii) clues as to the cause of the delayed puberty (iii) the psychological effect of the problem. Growth pattern -Constitutional delay in growth and adolescence longstanding short, or borderline short, stature compounded by a deceleration in growth rate from the age of 9 or 10 years. History of asthma. Family history of pubertal delay . ( most but not all ) The presence of tiredness and lack of energy suspicion of an underlying chronic illness. Effect of illness -Enquire about school attendance and performance,participation in sporting activities, and leisure pursuits( the psychological impact of the pubertal delay ) Kallmann syndrome - screened for by asking the boy if he can smell toast burning or unpleasant odours, such as rotting eggs. Past medical history causative factors such as previous treatment for childhood cancer (e.g. chemotherapy and radiotherapy),

08/01/11 CASE STUDY A 14-year-old boy received total body irradiation prior to bone marrow transplant for leukaemia at 9 years. Pubertal staging is G4P4A2 but testicular volumes are smaller than normal at 6 mL, FSH elevated at 20 U/L. The family are asking about his prospects for fertility. Delayed/incomplete puberty

08/01/11 INVESTIGATIONS The diagnosis of CDGA can usually made clinically, and most boys do not require investigation Karyotyping chromosomesf or TS. If chronic systemic disease is suspected from the history and examination the patient must be investigated accordingly When hypogonadism is suspected assessment includes gonadotrophin and sex hormone measurement before and after stimulation with LHRH and hCG Pelvic ultrasound examination, Formal smelling test and cranial imaging.

08/01/11 MANAGEMENT OF DELAYED/INCOMPLETE PUBERTY Physiological delay Reassurance and counselling. Prediction of adult height, helpful in giving the family a realistic height prognosis. In boys with CDGA aged 11–13 years -the anabolic steroid oxandrolone in doses of 1.25–2.5 mg at night for 3 to 6 months enhances height velocity. Boys aged 13 years or more can be offered a course of intramuscular testosterone 100 mg monthly for 3 months to increase height velocity and genital maturation without causing final height impairment Girls with CDGA are difficult to treat because of the tiny doses of oestradiol required to initiate puberty. In selected cases ethinylestradiol 2g daily or on alternate days for a one to two year period can be considered provided the patient is under strict endocrine supervision.

Impaired gonadal axis Testosterone and oestrogen replacement obviously be necessary in cases such as craniopharyngioma, TS and anorchia where gonadotrophin or sex steroid secretion is absent Where the gonadal axis impairment is partial following total body irradiation or in Klinefelter syndrome, treatment may be unnecessary or supplementation rather than full replacement may be required. For boys -an effective testosterone regimen for induction is Sustanon® 100 mg intramuscularly once every 6 weeks for one year, 100 mg intramuscularly once every 4 weeks for a second year, then 250mg intramuscularly every 4 weeks for a further year. Thereafter a suitable maintenance treatment – testosterone tablets, patches, intramuscular injections or subcutaneous pellets For girls- an effective induction regimen ethinylestradiol 2g daily for one year, 4g daily for a further year, then 6, 8 and 10g daily for four months followed by norethisterone 5 mg daily for the first fivedays of each calendar month in order to shed the endometrial lining and cause a period. Thereafter the girl and her doctor/gynaecologist should choose anappropriate maintenance regimen such as the oral contraceptive pill, hormone replacement therapy (HRT) and various patch preparations.

08/01/11 Premature Pubarche (Adrenarche). This term applies to the appearance of sexual hair before the age of 8 yr in girls or 9 yr in boys without other evidence of maturation. It is much more frequent in girls than in boys and may occur more frequently in American black girls than in others. Hair appears on the mons and labia majora in girls, perineal and scrotal area in boys; axillary hair generally appears later. Adult-type axillary odor is common. Affected children are slightly advanced in height and osseous maturation. Premature adrenarche is an early maturational event of adrenal androgen production. This event coincides with precocious maturation of the zona reticularis, an associated decrease in 3β-hydroxysteroid-dehydrogenase activity, and an increase in C-17,20-lyase activity. These enzymatic changes result in increased basal and ACTH-stimulated serum concentrations of the Δ 5 -steroids (17-hydroxypregnenolone and DHEA) and, to a lesser extent, of the Δ 4 -steroids (particularly androstenedione) compared with age-matched control subjects. The levels of these steroids and those of DHEAS are usually comparable to those of children in the early stages of normal puberty. Premature adrenarche is a benign condition that requires no therapy. However, a subset of patients with precocious pubarche has one or more features of systemic androgen effect, such as marked growth acceleration, clitoral (girls) or phallic (boys) enlargement, cystic acne, or advanced bone age (>2 SD above the mean for age). In these patients with atypical premature adrenarche , an ACTH stimulation test with measurement of steroid intermediates (mainly serum 17-hydroxyprogesterone concentrations) is indicated to rule out nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. of fetal undernutrition

08/01/11 Premature Menarche. This is a very rare entity, much less frequent than premature thelarche or premature adrenarche, and is a diagnosis of exclusion. In girls presenting with isolated vaginal bleeding in the absence of other secondary sexual characteristics, more common causes such as vulvovaginitis, foreign body, or sexual abuse, and uncommon causes such as urethral prolapse and sarcoma botryoides must be carefully excluded. The majority of girls with idiopathic premature menarche have only 1–3 episodes of bleeding; puberty occurs at the usual time and menstrual cycles are normal. Plasma levels of gonadotropins are normal, but estradiol levels may be elevated, probably owing to bursts of ovarian activity. Occasional patients are found to have ovarian follicular cysts on ultrasound.

08/01/11 556.9Medicational Precocity A variety of medicaments can induce the appearance of secondary sexual characteristics that may be confused with precocious puberty Precocious pseudopuberty has occurred in both boys and girls from the accidental ingestion of estrogens (including contraceptive pills) and from the administration of anabolic steroids. Estrogens in cosmetics, hair creams, and breast augmentation creams have caused breast development in girls and gynecomastia in boys; estrogens are readily absorbed through the skin. The high prevalence of premature thelarche and precocious pseudopuberty in Puerto Rico for the last 2 decades has been attributed to contamination of meats, particularly chicken, with estrogens used in animal husbandry but has not been proved. Exogenous estrogens may produce an intense, dark brown color in the areola of the breasts that is not usually seen in endogenous types of precocity. The precocious changes disappear after cessation of exposure to the hormones. Recently, the widespread use of testosterone gel, which is applied to the skin for treatment of male hypogonadism, has resulted in virilization of children and women following skin contact at, and systemic absorption from, the area where the gel was applied.

08/01/11 McCune-Albright Syndrome (Precocious Puberty with Polyostotic Fibrous Dysplasia and Abnormal Pigmentation) This is a syndrome of endocrine dysfunction associated with patchy cutaneous pigmentation and fibrous dysplasia of the skeletal system. Although sexual precocity in girls was the major recognized endocrinopathy in the past, associated pituitary, thyroid, and adrenal aberrations are also recognized. The disorder is characterized by autonomous hyperfunction of many glands and is caused by a missense mutation in the gene encoding the α-subunit of G S , the G protein that stimulates cyclic adenosine monophosphate (cAMP) formation, resulting in the formation of the putative gsp oncoprotein. Activation of receptors (e.g., corticotropin [ACTH], TSH, FSH, LH receptors) that operate with a cAMP-dependent mechanism, as well as cell proliferation, ensue. Because the mutation is somatic, rather than genomic, it is expressed differently in different glands or tissues; hence, the variability of clinical expression in different patients.

Disorders of puberty.pptx 2

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Disorders of puberty.pptx 2