delayed puberty.pptx DELAYED PUBERTY IN PEDIATRICS AND EVALUATION AND MANAGEMENT

DELAYED PUBERTY

1. APPROACH TO DELAYED PUBERTY PRESENTER: DR P SUDHA RANI(2 ND YEAR POSTGRADUATE) MODERATOR: DR CH ANUSHA DEEPTHI (PROFESSOR IN DEPARTMENT OF PEDIATRICS)

2. CONTENTS DEFINITION ETIOLOGY EVALUATION EXAMINATION INVESTIGATIONS MANAGEMENT

3. DEFINITION Boys have no signs of testicular development by 14 years of age Girls have not started to develop breasts by 13 years of age, or there is no onset of menarche by the age of 15 years.

4. ETIOLOGY Constitutional delay in pubertal growth and development Familial Chronic illness-thalassemia, chronic renal diseases, chronic hepatic diseases, and celiac disease Endocrine- hypothalamus, hypopituitarism, suprasellar space occupying lesions, and hypothyroidism

5. ETIOLOGY CONT Abnormal development of the reproductive system—congenital anomalies Inability of the body to use androgen hormones (androgen insensitivity syndrome) Too much exercise—athletes and ballerinas Eating disorders

6. EVALUATION - HISTORY PATTERN NO PUBERTAL DEVELOPMENT Permanent hypogonadotropic hypogonadism Steroidogenic defect Classical turner Kallmann’s syndrome FAILURE OF PROGRESSION Mosaic turner Acquired ovarian or pituitary insult Hyperprolactinemia Klienfelter’s syndrome

7. HISTORY CONT Features of chronic systemic illness, hypopituitarism, hypothyroidism Family history of delayed puberty Central nervous system insult (radiotherapy, trauma, surgery, infections, birth asphyxia) Neurological deficits (seizures, focal deficits, raised intracranial pressure) History of exposure to alkylating agents, pelvic radiation, testicular trauma, infection Abnormal smell sensation – Kallmann’s syndrome

8. HISTORY CONT Deafness (Turner, CHARGE syndrome, pseudohypoparathyroidism) Developmental delay( Prader Willi syndrome, CHARGE syndrome) Tetany ( hypoparathyroidism) Alopecia, vitiligo, mucosal candidiasis, adrenal insufficiency- antiphospholipid syndrome Delayed puberty in family ( constitutional delay)

9. EXAMINATION Growth parameters Short stature : turner syndrome, hypopituitarism, celiac disease Tall stature: Klienfelter’s syndrome Body mass index low: malnutrition, malabsorption, anorexia nervosa Obesity: pseudohypoparathyroidism, Prader Willi syndrome, leptin deficiency

10. EXAMINATION Neurological examination including fundus examination Smell sensation( anosmia in Kallmann’s syndrome) Galactorrhea ( hyperprolactinemia) Midline defects hypopituitarism Dysmorphism suggestive of charge syndrome, Prader Willi syndrome, turner syndrome Pigmentation ( steroidogenic defect) Vitiligo, alopecia, ( autoimmune endocrinopathy)

11. EXAMINATION CONT Blood pressure ( hypertension in 17 beta hydroxylase deficiency) Testicular size enlarged : hypothyroidism, fragile x syndrome Atrophic radiation damage, Klienfelter’s syndrome, Prader Willi syndrome Midline defects CNS malformations Gynecomastia Klienfelter’s syndrome

12. EXAMINATION CONT Features suggestive of turner syndrome Deafness Broad carrying angle Webbing of neck Short 4 th metacarpal Features suggestive of Klienfelter’s syndrome Tall stature Atrophic testes Lower segment to upper segment ratio

13. INVESTIGATIONS Systemic evaluation Liver function test Renal function test complete blood examination Erythrocyte sedimentation rate Blood pH IgA tissue Thyroid profile

14. GONADOTROPIN Gonadotropin levels after bone age more than 12 years Follicle stimulating hormone less than 2mU/L; hypogonadotropic hypogonadism Follicle stimulating hormone more than 10mU/L: hypergonadotropic hypogonadism Follicle stimulating hormone 2-10mU/L intermediate

15. GONADOTROPIN RELEASING HORMONE(GNRH)/GNRH AGONIST STIMULATION TEST Gonadotropin releasing hormone(GnRH)/GnRH agonist stimulation test Indication: intermediate baseline gonadotropin levels Protocol: injection GnRH / triptorelin 100mcg subcutaneously Luteinizing hormone and FSH at 0 and 60 mins Interpretation: exaggerated response hypergonadotropic hypogonadism Blunted response: hypogonadotropic hypogonadism

16. EVALUATION OF HYPOGONADOTROPIC HYPOGONADISM REVERSIBLE: serum prolactin, thyroid profile, celiac serology IRREVERSIBLE: MRI hypothalamic pituitary region, pituitary function In boys: differentiation of constituitonal delay from permanent HH In boys investigations; Dehydroepiandrosterone sulfate : marker of adrenarche, puberty levels suggest permanent HH Gonadotropin releasing hormone agonist test blunted response suggest permanent HH

17. EVALUATION OF HYPOGONADOTROPIC HYPOGONADISM Human chorionic gonadotropin test: testosterone less than 300ng/dl 48 hours after 4000IU/m2 intramuscular human chorionic gonadotropin suggest permanent HH

18. EVALUATION OF HYPOGONADOTROPIC HYPOGONADISM IN GIRLS

19. EVALUATION OF HYPERGONADOTROPIC HYPOGONADISM Karyotyping: Atleast 50 metaphase phases to be studied in view of mosaicism if karyotype normal: Girls: screen for antiphospholipid antibody syndrome, serum calcium, phosphate, PTH Steroid metabolites Low levels of all metabolites StAR deficiency High deoxycoticosterone9 17 b hydroxylase deficiency) High androstenedione (17 b HSD deficiency)

20. MANAGEMENT SPECIFIC MEASURES Malnutrition: nutritional rehabilitation Eating disorders: behavioural disorders Systemic diseases: specific treatment Hyperprolactinemia: dopamine agonists- bromocriptine, cabergoline Hypopituitarism: hormone replacement Steroidogenic defects: hydrocortisone and hormone replacement Turner syndrome: growth promoting therapy Celiac disease: gluten free diet

21. PUBERTAL INDUCTION INDICATIONS: bone age more than 13 years Estrogen Progesterone: Indications: Withdrawl bleeding/ endometrial thickness more than 5mm Preparation: medroxyprogesterone acetate, norethisterone. Dose – about 10mg once a day for 10 days a month.

22. FERTILITY MANAGEMENT Hypogonadotropic Hypogonadism: cyclical hCG , human menopausal gonadotropin Hypergonadotropic hypogonadism: Ovarian extraction and cryopreservation: Turner’s syndrome Invitro fertilisation and embryo transfer

23. BOYS CONSTITUTIONAL DELAY OF PUBERTY AND GROWTH: Bone age more than 13 years. Injection of testosterone ester 100mg monthly for 3 doses. Repeat course for 3 months if no improvement Testosterone more than 300 ng/ Ml 1 month after injection suggests constitutional delay in growth and puberty.

24. PERMANENT HYPOGONADOTROPIC HYPOGONADISM PERMANENT HYPOGONADOTROPIC HYPOGONADISM: pubertal induction after bone age more of 13 years Injection testosterone ester 100mg monthly for 6 doses Gradually increase to adult dose Fertility management: human chorionic gonadotropin, Hmg treatment

25. Hypergonadotropic hypogonadism: pubertal induction: 100mg testosterone monthly, gradual build-up to adult dose Pubertal induction schedule for boys FERTILITY: difficult to achieve Sperm donation Testicular sperm extraction and intracytoplasmic sperm injection.

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