PUBERTY AND ADOLESCENCE Definition Adolescence it is the
PUBERTY AND ADOLESCENCE
Definition � Adolescence : it is the period of life during which a dependent child becomes an independent adult. It includes physical , mental and sexual maturation. � Puberty : It is the period of life during which sexual maturation is complete and the individual becomes able to reproduce.
Timing � Pubertal changes typically take about 4. 5 Ys. The exact timing of puberty is determined mainly by genetic factor , however other factors are also important : � Geographical distribution. � Nutritional status. � Body weight ( body fat percent ) controlled by leptin. Leptin is a peptide secreted in adipose tissue acting on the nervous system to regulate eating behavior and energy balance. � General health. � Light exposure. � Psychological status.
Physiology of Puberty I. Hormonal changes 1. Prepubertal changes : Ø a. Adrenarche : The 1 st hormones to increase are adrenal androgens. A pituitary adrenal androgen stimulator may be the initiating factor for adrenarche. Ø b. Start of Gn. RH secretion due to : Ø * Decrease in the sensitivity of the hypothalamo-pituitary cells to the low estrogen levels during childhood. Ø * Hypothalamo-pituitary release from an intrinsic inhibitory factor that reduce levels of gonadotrophins and decreases the response to Gn. RH. GABAand neuropeptide Y are supposed factors. Ø c. Increased sensitivity of the hypothalamo-pituitary-ovarian axis hormones and increased bioactivity of gonadotrophins.
Physiology of Puberty 2. Pubertal changes � # Responding to the Gn. RH pulses , FSH and small amounts of LH are secreted and cause ovarian follicular growth. E 2 secreted from growing follicles will cause : � Development of secondary sexual characters. � Endometrial growth into proliferative type. � (-) ve feedback on Gn. RH & FSH secretion. At 1 st , the secreted E 2 don’t reach the level that cause (+) ve LH. This explains why the 1 st few cycles in the females life are normally anovulatory. � Prolactin seems to increase by the age of 14 – 15 due to the effect of DHEA , but this is not understood. � Leptin and puberty : � Leptin is a peptide secreted from adipose tissue , acting on the CNS to regulate eating behavior and energy balance. � It may have a role in puberty : Low leptin is associated with delayed puberty and high levels correspond to early menarche
II. Physical Changes 1. Growth spurt : • This is the 1 st clinical sign of puberty. It starts at 9. 5 – 14. 5 Ys age. • Growth spurt is supposed to be due to increased insulin like growth factor -1 ( formerly called somatomedin-c ) through which steroid hormones and GH can act. The increase in sex steroids causes increased GH secretion which in turn increases insulin like growth factors. However , the exact mechanism is complex and ill defined. Adrenal steroids appear to be less important. • Very small amounts of estrogen ( 100 ng / kg / day ) are sufficient to cause cortical bone growth while too little to cause breast budding , vaginal cornification or increase in SHBG. This explains why growth spurt precedes other pubertal changes.
2. Thelarche (Breast development) � It is usually the 1 st recognized sign and starts at 9 – 11 Ys age. � Breast enlargement is mostly due to fat deposition and duct system development as an effect of E 2 and GH. Glandular development is minimal at that age. � Marshall & Tanner ( 1969 ) staging : � B 1 : Infantile breast = Flat ( no palpable mass ) , areola < 2 cm. � B 2 : Breast elevates , papilla will form a small mount , areola enlarge and nipple develop. � B 3 : Breast becomes larger , round , papilla & areola enlarge. The nipple is at the mid point of the breast when seen from the side. � B 4 : The papilla & areola form a secondary mount over the round breast. � B 5 : Adult breast ( smooth rounded contour , secondary mount disappears , areola pigment and Montgomery glands appear in the areola ). The nipple is below the midpoint of the breast when seen from the side.
3 - Pubarche Ø It usually appears after breast budding and before axillary hair development. However , this relation is not constant. The mean age for pubarche is 12. 4 Ys. Ø It is under the control of both estrogens androgens. Ø Tanner staging : 1. P 1 : Infantile pattern ( no sexually stimulated hair ). Some nonsexual hair may be present. 2. P 2 : Sparse , coarse , long , slightly pigmented hair on labia majora. 3. P 3 : Hair spreads over mons. 4. P 4 : Adult hair but spreading over a smaller area than adult typically not on the inner side of the thigh. 5. P 5 : Inverted triangular pattern of adult hair spreading over the labia , mons & inner aspects of the upper things.
4. Axillary hair development � It is usually developed after breast and public hair ( but not always ). The mean age is 14. 4 Ys. � It is under the integrative control of both ovarian and adrenal steroids. The exact mechanism is unclear.
5. Genital organs A. The ovaries �There is increase in size and they become rounded ( in childhood they are elongated ). Vascularity also increase. �The primordial follicles start development when FSH start to increase in blood. Many follicles are seen in different stages of development on examination of ovarian biopsy.
B. The uterus � a. There is rapid growth and increased vascularity. The corpus grows faster than the cervix till the ratio become 2: 1 ( reversed infantile ratio ). Anteversion also occur. � b. Endometrial glands : � - In childhood , the glands are simple , tubular , lined cuboidal epithelium with compact stroma. � - At puberty , under the effect of ovarian hormones , the endometrium starts to develop into proliferative / secretory phases ( describe ). � c- Cervical glands : � - In childhood , the glands are simple , lined by cuboidal epithelium with no secretory activity. � - At puberty , the following changes occur : � + Glands proliferate to become racemose. � + Glands become lined with columnar epithelium. � + Glands start secretory activity. The cells appear clear and vacuolated. The properties of secretion are affected by ovarian hormones ( describe ).
C- The vagina � a. The vagina increases in length and fornices start to appear. � b. Rugae start to appear. � c. Vaginal epithelium starts to proliferate to become stratified squamous epithelium ( cornification ). � d. Glycogen content increases and p. H becomes acidic. � e. Vaginal epithelium shows some cyclicity during the ovarian cycle affected by ovarian hormones ( describe ). D- The vulva • The labia majora start to enlarge and accumulate fat , mons pubis becomes well prominent and will be later covered with hair. • Clitoris enlarges and becomes erectile and sensitive to erotic stimuli
6. Secondary sexual characters 7. Menarche � The female develops high pitched � It is usually a delayed event in pubertal voice. changes as it seems to be the final goal for such changes and the final sign that � Female distribution of the female is now reproductive. subcutaneous fat. ( breast , buttocks , thighs and waist ). The � The range of age of menarche is 9. 1 – 17. 7 Ys with mean of 12. 8 in USA , 13 Ys pelvis enlarges to allow pelvic in western Europe and 13. 5 in India. In organs to descend , widens and Egypt , the range is 10 – 16 Ys with mean takes the gynecoid shape. 12. 5 Ys. � The girl develops shyness & � Ovulation usually starts 12 – 18 months becomes secretive. At first , she after menarche as the 1 st few cycles lack LH surge due to underdevelopment of becomes of homosexual interest. the (+) ve feedback of E 2 on LH. After sometime , she becomes of However , ovulation may start even heterosexual interest. before menarche.
PUBERTAL ABNORMALITIES 1. 2. 3. Precocious puberty. Delayed puberty. Asynchronous puberty : Pubertal development that deviates from normal pattern : A. B. 4. Complete AIS. Incomplete AIS. Heterosexual puberty but at normal age : A. B. C. D. E. PCO is the most common type. CAH. Incomplete AIS. Androgen secreting tumor. Cushing syndrome.
PRECOCIOUS PUBERTY Definition § Pubertal changes before the age of 8 Ys. However , the American Academy of Pediatrics has found in recent studies than many normal children may start puberty before 8 , so pubertal changes before 6 years is certainly considered. Between 6 and 8 years , the condition is left for clinician experience ( Speroff, 1999) Others consider precocious puberty before 10 years ( Dewhurst, 1999)
Classification And Etiology A- Gn. RH dependent ( true precocious puberty or central precocious puberty ). 1. Constitutional and idiopathic 74 – 90 %. 2. CNS disorders 7 % a. CNS tumor as hamartomas ( most common ), craniopharyngioma, astroctyoma, teratoma, gliomas, pituitary tumors and neurofibromas. Skull tumors have also a role. b. CNS non tumors lesions : § - Abnormal skull development as in rickets. § - Infiltrative processes. § - Cerebral anomalies as hydrocephalus and arachnoid cysts near the 3 rd ventricle. § - After irradiation. § - Head trauma. § - Meningitis and encephalitis.
B- Gn. RH non dependent ( Peripheral or precocious Pseudopuberty ) : ( due to premature increase in sex steroids ) 1. Isosexual : a. Estrogen producing ovarian tumors 11 % b. Mc. Cune Albright syndrome ( autonomous ovarian hypersecretion ) 5%. c. Adrenal tumor secreting estrogens 1 %. d. Iatrogenic due to chronic administration of estrogens. 2 - Heterosexual : a. Delayed type of CAH. b. Virilizing ovarian tumors. c. Virilizing adrenal tumor. d. Iatrogenic.
II- Incomplete precocious puberty (Mostly idiopathic) 1. Thelarche ( may also be due to primary hypothyroidism ). 2. Pubarche. 3. Menarche. Constitutional precocious puberty : • Most common cause for precocious puberty and is familial. The signs may starts as early as 9 months age. There is complete precocious puberty , fertility can be attained at 5 Ys age , however , there is accelerated bone age and premature closure of epiphysis resulting in short stature.
Mc. Cune Albright Syndrome (Albright polyostotic fibrous dysplasia) � It consists of precocious puberty + Disseminated cystic bone anomaly + � � � Hyperfunctioning endocrinopathies. � The cause is supposed to be due premature autonomous activity of the ovary. � It is characterized by : The age is as early as 9 months age. The 1 st sign is commonly menarche. The eventual fertility is unaffected. Disseminated cystic bone lesions with easy fracture. The adult height is normal. Café au lait patches with various sizes and irregular borders in contrast to the smooth borders of neurofibromatosis patches. Cushing syndrome , gigantism , hyperthyroidism , hyperprolactinemia , intestinal polyps and cardiac arrhythmias may associate the condition. Treatment is by testolactone ( armoastase inhibitor ) or ( MPA ( depot ) to suppess LH.
Diagnosis I- History 1. Age and sequences of events : A. Normal events denotes idiopathic condition. B. Single event or absence of growth spurt denotes incomplete type. 2. Family history denotes constitutional type. 3. History suggestive of CNS disease A. B. C. D. History of head trauma or inflammations. Hydrocephalus. Difficult or instrumental head delivery. Visual or nervous disturbances.
4 - Exogenous drug intake 5 - Virilizing symptoms (in cases of heterosexual type) 6 - History suggestive of thyroid , adrenal or pituitary disorders
II- Examination 1. Weight, height and span. Span is the distance between the tip of the middle fingers measured when the patient extends her arm laterally while standing against a flat wall. Span is normally + cm from the height. 2. Funds examination for evidence of vascular disease or increased ICT 3. Field of vision for chiasmatic compression. 5. Thyroid examination 6. Abdominal examination : A. Breast examination. B. Axillary hair examination. C. Abdominal mass ( renal , liver , ovarian ). D. pubic hair examination. 7. Genital examination : A. B. 4. Patches of hyperpigmentation for Mc. Cune syndrome C. Detection of pubertal changes in the external genitalia. Detection of estrogenic effects in vaginal wall ( describe ). Bimanual ( abdominal-rectal ) examination for detection of uterine size and ovarian masses.
III- Special investigations 1. To diagnose precocious puberty A. B. C. D. 2 - Investigations to detect the cause a. Monitoring of pubertal LH response to acute I. V injection of Gn. RH. Normally LH should be lower than 8 m. IU/ml 40 min. After Sc injection of 100 ug of Gn. RH. b- Monitoring pubertal LH peaks during sleep. The occurrence of 2 or more spikes within 20 min. sleep = pubertal pituitary. � If a & b are (+) ve , the cause may be idiopathic or CNS lesion. To differentiate : Hormonal profile : Serum levels of LH , FSH, E 2, DHEAS, urinary 17 -ketosteroids are all in postpubertal range. However , due to overlap between pre-and post pubertal levels of LH , FSH and E 2 , low levels does not exclude precocious puberty as long as other sings are (+) ve. � CT scan on the hypothalamo-pituitary area and pineal gland. EEG & MRI may also be of help. Vaginal smear to detect estrogenic effect. � Plain X-ray skull , field of vision and fundus examination Left hand Roentgenogram for bone age . (retarded only in cretinism ). � Bone scanning or X-ray to detect fibrous dysplasia in Increase in bioactive LH. Mc. Cune Albright syndrome. If a , b , c & d are (+) ve , complete true � U/S or CT scan on the abdomen to measure uterine size precocious puberty is diagnosed , further and to detect hepatic , renal or ovarian tumors. investigations are needed to detect the � Pregnancy tests for detection of h. CG secretion. cause. � Thyroid function tests for diagnosis of hypothyroidism. If gonadotrophins are low and E 2 is high , pseudoprecocious puberty is diagnosed. In � Dexamethasone suppression test to differentiate between cases with premature adrenarche , only adrenal hyperplasia and tumors adrenal androgens are elevated.
Treatments I. If there is a cause , treatment is the treatment of the cause. II- If the condition is dysfunctional , medical treatment is advised. Good treatment should be characterized by the ability to stop or decelerate pubertal changes and is reversible when stopped. The following drugs are used aiming at decreasing gonadotrophin secretion : 1. LHRH ( Gn. RH ) analog 2 - Medroxyprogesterone acetate � Appears to be the best drug to treat precocious puberty. � It decreases day and night gonadotrophin pulses thus decreases ovarian steroidogensis. � It reverts all pubertal changes ( except adrenarche as it has different control system ) including bone growth. � Long acting drugs as goserelin or leuprolide once / month SC injection are usually given. The dose is controlled by E 2 level ( should be < 10 pg/ml serum ) or by absence of gonadotrophin response to exogenous Gn. RH. The drug is stopped when : Ø Bone age is matching with chronological age. Ø Epiphyseal closure has occurred. Ø The patient reaches 12 Ys old. � No side effects is reported except allergic reactions. � It is not effective in precocious pseudopuberty • • • It primarily acts by blocking gonadotrophin secretion. The usual dose is 100 – 200 mg/ 1 – 2 Ws. I. M , or 10 – 100 mg/day orally. The dose should increase till stoppage of pubertal changes and decrease of gonadotrophins. Although it can control menses and breast changes , bone growth is not controlled. Side effects are dose dependent and are mainly due to glucocorticoid like action. There is decreased ACTH and cortisol levels during treatment period , so the dose should be withdrawn gradually and give ACTH during the last month of treatment to prevent acute adrenal failure
3 - Cyproterone acetate • It decreases gonadotrophin release and inhibits steroid actions. • It controls menses , breast development and hair growth , however bone growth is not controlled. • The usual dose is 75 – 150 mg/m 2 / day. • It also decreases ACTH but clinically non significant. • It is not used in USA as MPA 4 - Danazol • It suppresses gonadotrophin peaks , competes with steroids , and decreases ovarian steroidogenesis. • It controls menses and breast development but due to its androgenic properties hair is not regressed and may even increase. Also bone growth is not controlled but as an androgen , adult height is better than without treatment. • Side effects are mainly due to its androgenic characters ( clitoromegaly , acne , deep voice ). These effects does not appear at doses less than 250 mg/m 2/day. � III- Psychic support & reassurance specially for cases with incomplete precocious puberty. � IV- Follow up of treatment and cases with incomplete type for the appearance of other pubertal changes
DELAYED PUBERTY Definition � Failure of appearance of any Etiology I. Hypergonadotrophic hypogonadism (FSH > 20 m IU/ml): Ys or more have passed since 1. Gonadal dysgenesis. the onset of pubertal 2. Non dysgenetic gonadal failure. secondary sex character by age of 13 or failure of menarche by age of 16 Ys or cases in whom 45 development without attainment of menarche
II- Hypogonadotrophic hypogonadism (LH < 6 m IU/ml) 1 - Constitutional. 2 - CNS disease ( destroying the hypothalamus ) : a. Tumors b. Malformations. c. Infections d. Infiltrations. e. Irradiation. 3 - Hypothalamic disorders : a. Kallmann's syndrome. b. Del Castillo syndrome. c. Anorexia nervosa. e. Leurance-Moon-Beidle Syndrome. 4 - Antidopaminergic and Gn. RH inhibiting agents specially psychotropic drugs and opiates. 5 - Pituitary causes ( destroying gonadotroph cells ) : a. Tumors b. Multiple or isolated pituitary deficiency. c. Empty sella syndrome. 6 - General disease : a. Rheumatic fever. b. T. B. c. Leukemia. d. Chronic nephritis. e. IDDM. f. CAH g. Cushing's disease. h. Thyroid diseases. i. Malnutrition.
III- Normogonadotrophic hypogonadism (not true delayed puberty but delayed menarche only) 1. Mullerian duct agenesis. 2. Mullerian duct discontinuity ( vaginal septa or imperforate hymen ). 3. Syndromes of androgen insensitivity. 4. Inappropriate positive feedback. N. B : The most causes for delayed puberty are : I. Gonadal failure II. Mullerian defects. III. Constitutional
Diagnosis I. History : Past history of disease , drug , irradiation or operation. Nutritional history. Mental history and learning progress. Family history about : 1. 2. 3. 4. A. B. Puberty milestones in older siblings , parents and aunts. Consanguinity. II. Examination : 1. 2. 3. 4. 5. 6. The exact events of puberty + Tanner staging for breast and public hair development. Weight , height and span. Neurological examination , smell , field of vision and fundus examination. Signs of general disease ( thyroid, adrenal, cardiac, hepatic, renal, nutritional. . . etc). Examination of genitalia for pubertal changes or anomalies ( imperforate hymen ). PR examination for hematocolpos , uterine size and ovarian mass.
III. Special investigations : 1. FSH assay to differentiate between hyper , Hypo and normogonadotrophic hypogonadism. 2. Karyotyping. 3. X-ray , CT scan or MRI for diagnosis of CNS lesions. 4. Bone age specially if retarded growth is evident. 5. Serum progesterone and 17 OH-progesterone for diagnosis of CAH. 6. Gonadal biopsy through laparotomy if FSH is high. N. B : Hypergonadotrophic hypogonadism = Primary ovarian failure. Hypergonadotrophic hypogonadism = Secondary ovarian failure. Treatment : 1. Treatment of the cause if evident. 2. In primary gonadal failure : ERT is given to maintain secondary sexual characters. The usual protocol is premarin 0. 3 mg/day for 6 months then increase to 0. 625 mg + 10 mg MPA in the last 12 days / month. No hope for fertility ( except by ovum donation ). 3. In secondary ovarian failure : ERT is given + gonadotrophin induction of ovulation if pregnancy is needed. 4. In XY cases , gonadectomy is done for fear of malignancies ( not after 30 Ys ). 5. In constitutional type , only reassurance is needed.
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