BÜYÜME VE PUBERTE. Prof. Dr. Özer Açbay
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1 BÜYÜME VE PUBERTE Prof. Dr. Özer Açbay
2 Hormones in the anterior pituitary and the hypothalamus. Summary of the hormones produced in the anterior pituitary and the hypothalamic hormones that regulate their secretion. ACTH, adrenocorticotropin-releasing hormone; CRH, corticotropin-releasing hormone; FSH, follicle-stimulating hormone; GH, growth hormone; GHRH, growth-hormone-releasing hormone; GHS, growth hormone secretagogue; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; VIP, PHI-27, TRH, thyrotropin-releasing hormone; TSH, thyroid-stimulating hormone; VIP, vasoactive intestinal peptide.
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9 Stimulus Exercise Levodopa Tests to Provoke Growth Hormone Secretion Dosage Step climbing; exercise cycle for 10 min. <15 kg: 125 mg kg: 250 mg >30 kg: 500 mg Times Samples Are Taken (minutes) 0, 10, 20 0, 60, 90 Clonidine 0.15 mg/m 2 0, 30, 60, 90 Arginine HCl (IV) 0.5 g/kg (max 30 g) 10% arginine HCl in 0.9% NaCl over 30 min 0, 15, 30, 45, 60 Insulin (IV) unit/kg 0, 15, 30, 60, 75, 90, 120 Glucagon (IM) 0.03 mg/kg (max 1 mg) 0, 30, 60, 90, 120, 150, 180 GHRH (IV) 1 µg/kg 0, 15, 30, 45, 60, 90, 120
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15 Hedef Boyun Hesaplanması Düzeltilmiş Midparental Boy Kız çocuklar için : (Baba boyu - 13 cm) + (Anne boyu) 2 Erkek çocuklar için : (Anne boyu + 13 cm) + (Baba boyu) 2
16 Postnatal Büyümeyi etkileyen faktörler Endokrin GH ve IGF-1 Tiroid hormonları Sex Steroidleri Glikokortikoidler Genetik Sosyo-ekonomik Nutrisyonel Psikolojik Kronik hastalıklar
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21 Classification of Growth Retardation I. Primary Growth Abnormalities A. Osteochondrodysplasias B. Chromosomal abnormalities C. Intrauterine growth retardation II. Secondary Growth Disorders A. Malnutrition B. Chronic disease C. Endocrine disorders 1. Hypothyroidism 2. Cushing's syndrome 3. Pseudohypoparathyroidism 4. Rickets
22 5. IGF deficiency a. GHD due to hypothalamic dysfunction b. GHD due to pituitary GH deficiency c. GH resistance (1) Primary GH insensitivity (2) Secondary GH insensitivity d. Primary defects of IGF synthesis e. Primary defects of IGF transport and clearance f. IGF insensitivity (1) Defects of the type 1 IGF receptor (2) Postreceptor defects III. Idiopathic Short Stature A. Genetic short stature B. Constitutional delay of growth and maturation C. Heterozygous defects of the GH receptor
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24 Height is often below the fifth percentile, but growth rate is normal for skeletal age
25 Growth curves of two brothers demonstrating the effect of constitutional delay of growth and puberty (growth curve A) in contrast to an unaffected brother (growth cure B).
26 Criteria for Presumptive Diagnosis of Constitutional Delay of Growth and Maturation 1. No history of systemic illness 2. Normal nutrition 3. Normal physical examination, including body proportions 4. Normal thyroid and GH levels 5. Normal CBC, sedimentation rate, electrolytes, BUN 6. Height at the 3rd percentile, but with annual growth rate above the 5th percentile for age 7. Delayed puberty a. Males: failure to achieve Tanner G2 stage by age 13.8 years or P2 by 15.6 years b. Females: failure to achieve Tanner B2 stage by age 13.3 years 8. Delayed bone age 9. Normal predicted adult height a. Males: >163 cm (64 inches) b. Females: >150 cm (59 inches) BUN, blood urea nitrogen; CBC, complete blood count; GH, growth hormone.
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31 Puberte ilk seksüel matürasyon belirtilerinin başlamasından seksüel, fiziksel, mental ve emosyonel gelişimin tamamlanmasına kadar geçen zaman dilimidir
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33 Cardinal Hormonal Characteristics of Puberty Decreasing effectiveness of intrinsic CNS inhibitory influences and decreasing sensitivity of hypothalamic-pituitary unit to gonadal steroids (increased set-point) Increased amplitude and frequency of LH pulses (initially at night) Increased LH response to intravenous LHRH Increased estradiol secretion in girls and testosterone secretion in boys Increased GH secretion Increased serum IGF-I concentration Increased prolactin secretion in girls
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37 Stages of breast development according to Marshall and Tanner: Stage 1: preadolescent; elevation of papilla only. Stage 2: breast bud stage; elevation of breast and papilla as a small mound, enlargement of areolar diameter. Stage 3: further enlargement of breast and areola with no separation of their contours. Stage 4: projection of areola and papilla to form a secondary mound above the level of the breast. Stage 5: mature stage; projection of papilla only, resulting from recession of the areola to the general contour of the breast.
38 Stages of female pubic hair development according to Marshall and Tanner Stage 1: preadolescent; there is no pubic hair. Stage 2: sparse growth of long, slightly pigmented, downy hair, straight or only slightly curled, appearing chiefly along the labia. This stage is difficult to see on photographs. Stage 3: hair is considerably darker, coarser, and curlier. The hair spreads sparsely over the junction of the pubic region. Stage 4: hair is now adult in type, but the area covered by it is still considerably smaller than in most adults. There is no spread to the medial surface of the thighs. Stage 5: hair is adult in quantity and type, distributed as an inverse triangle of the classical feminine pattern. The spread is to the medial surface of the thighs but not up the linea alba or elsewhere above the base of the inverse triangle.
39 Telarj Adrenarj Pübarj Gonadarj
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41 Stages of male genital development and pubic hair development, according to Marshall and Tanner: Genital development Stage 1: preadolescent. Testes, scrotum, and penis are about the same size and proportion as in early childhood. Stage 2: the scrotum and testes have enlarged; the scrotal skin shows a change in texture and also some reddening. Stage 3: growth of the penis has occurred, at first mainly in length but with some increase in breadth; there is further growth of the testes and scrotum. Stage 4: the penis is further enlarged in length and breadth with development of the glans. The testes and scrotum are further enlarged. The scrotal skin has further darkened. Stage 5: genitalia are adult in size and shape. No further enlargement takes place after stage 5 is reached. Public hair development: Stage 1: preadolescent; there is no pubic hair. Stage 2: sparse growth of long, slightly pigmented, downy hair, straight or slightly curled, appearing chiefly at the base of the penis. Stage 3: hair is considerably darker, coarser, and curlier and spreads sparsely over the junction of the pubes. Stage 4: hair is now adult in type, but the area it covers is still considerably smaller than in most adults. There is no spread to the medial surface of the thighs. Stage 5: hair is adult in quantity and type, distributed as an inverse triangle. The spread is to the medial surface of the thighs but not up the linea alba or elsewhere above the base of the inverse triangle. Most men will have further spread of the pubic hair.
42 Timing of Sexual Maturity Stages in White Males Genital Stages Stage Mean age SD Pubic Hair Stages Stage Mean age SD
43 Prader's orchidometer.
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46 A diagram of the testis shows the relationship of Sertoli cells to germ cells. Evidence for the secretion of estradiol (E2) and gonadotropin-releasing hormone (GnRH) by the adult Sertoli cell is tentative, but the hormones have been suggested as local modulators of Leydig cell function. (ABP, androgen binding protein)
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49 Sexual Precocity Sexual precocity is defined as the appearance of any sign of secondary sexual maturation at an age more than 2.0 SD below the mean; in the past, the ages of 8 years in girls and 9 years in boys were considered the lower limits of the normal onset of puberty. Present data indicate that the limits in normal boys remain at 9 years but that the lower limit for white girls is 7 years and for black girls is 6 years, assuming that there is no sign or symptom of CNS disorders or other serious or chronic disease that might cause sexual precocious puberty. Girls had true precocious puberty five times more commonly than boys.
50 Classification of Sexual Precocity True Precocious Puberty or Complete Isosexual Precocity (LHRH-Dependent Sexual Precocity or Premature Activation of the Hypothalamic LHRH Pulse Generator) Idiopathic true precocious puberty CNS tumors Optic glioma associated with neurofibromatosis type 1 Hypothalamic astrocytoma Other CNS disorders Developmental abnormalities including hypothalamic hamartoma of the tuber cinereum Encephalitis Brain abscess Sarcoid or tubercular granuloma Head trauma Hydrocephalus Arachnoid cyst Myelomeningocele Vascular lesion Cranial irradiation True precocious puberty after late treatment of congenital virilizing adrenal hyperplasia or other previous chronic exposure to sex steroids
51 Males Incomplete Isosexual Precocity (Hypothalamic LHRH-Independent) Gonadotropin-secreting tumors hcg-secreting CNS tumors (e.g., chorioepitheliomas, germinoma, teratoma) hcg-secreting tumors located outside the CNS (hepatoma, teratoma, choriocarcinoma) Increased androgen secretion by adrenal or testis Congenital adrenal hyperplasia (CYP21 and CYP11B1 deficiencies) Virilizing adrenal neoplasm Leydig cell adenoma Familial testotoxicosis (sex-limited autosomal dominant pituitary gonadotropin-independent precocious Leydig cell and germ cell maturation) Females Ovarian cyst Estrogen-secreting ovarian or adrenal neoplasm Peutz-Jeghers syndrome In Both Sexes McCune-Albright syndrome Hypothyroidism Iatrogenic or exogenous sexual precocity (including inadvertent exposure to estrogens in food, drugs, or cosmetics)
52 Variations of Pubertal Development Premature thelarche Premature isolated menarche Premature adrenarche Adolescent gynecomastia in boys Macro-orchidism
53 Premature Thelarche Unilateral or bilateral breast enlargement without other signs of sexual maturation (e.g., sexual hair and growth of the labia minora and the uterus). The disorder usually occurs by age 2 (in over 80%) and rarely after age 4. The breast enlargement usually regresses in 6 months to 6 years after diagnosis but occasionally persists for years or lasts until the onset of normal puberty. Usually, significant nipple and areolae development is absent and estrogen-induced thickening and dulling of the vaginal mucosa are uncommon. Enlargement of the uterus on ultrasonography (>1.8 ml volume and length > 36 mm) is rare (V = longitudinal diameter anteroposterior diameter transverse diameter 0.523) is the most sensitive and specific discriminator between premature thelarche and early true precocious puberty and provides better early discrimination than the LH response to LHRH. Growth in stature is normal.
54 Premature Adrenarche Premature adrenarche is the precocious appearance of public hair or axillary hair, or both, and less commonly an apocrine odor, comedones, and acne without other signs of puberty black girls younger than 5 years of age white girls younger than 7 years of age boys younger than 9 years of age
55 Classification of Delayed Puberty and Sexual Infantilism 1. Idiopathic (Constitutional) Delay in Growth and Puberty (Delayed Activation of Hypothalamic LRF Pulse Generator) 2. Hypogonadotropic Hypogonadism: Sexual Infantilism Related to Gonadotropin Deficiency Central nervous system (CNS) disorders Tumors Craniopharyngiomas, Germinomas,, Hypothalamic and optic gliomas, Astrocytomas Pituitary tumors (including MEN-1, prolactinoma) Other causes Langerhans' histiocytosis Postinfectious lesions of the CNS Vascular abnormalities of the CNS Radiation therapy Lymphocytic hypophysitis Isolated Gonadotropin Deficiency Kallmann's syndrome LHRH receptor mutation Congenital adrenal hypoplasia (DAX1 mutation) Isolated LH deficiency Isolated FSH deficiency Prohormone convertase 1 deficiency (PCI) Idiopathic and Genetic Forms of Multiple Pituitary Hormone Deficiencies Including PROP-1 Mutation
56 Miscellaneous Disorders Prader-Willi syndrome Laurence-Moon and Bardet-Biedl syndromes Functional gonadotropin deficiency Chronic systemic disease and malnutrition Sickle cell disease Cystic fibrosis Acquired immunodeficiency syndrome (AIDS) Chronic gastroenteric disease Chronic renal disease Malnutrition Anorexia nervosa Bulimia Psychogenic amenorrhea Impaired puberty and delayed menarche in female athletes and ballet dancers (exercise amenorrhea) Hypothyroidism Diabetes mellitus Cushing's disease Hyperprolactinemia
57 3. Hypergonadotropic Hypogonadism Males The syndrome of seminiferous tubular dysgenesis and its variants (Klinefelter's syndrome) Other forms of primary testicular failure Chemotherapy Radiation therapy Testicular steroid biosynthetic defects Sertoli-only syndrome LH receptor mutation Anorchia and cryptorchidism Trauma/surgery Females The syndrome of gonadal dysgenesis (Turner's syndrome) and its variants XX and XY gonadal dysgenesis Familial and sporadic XX gonadal dysgenesis and its variants Familial and sporadic XY gonadal dysgenesis and its variants Aromatase deficiency
58 Other forms of primary ovarian failure Premature menopause Radiation therapy Chemotherapy Autoimmune oophoritis Galactosemia Glycoprotein syndrome type 1 Resistant ovary FSH receptor mutation LH/hCG resistance Polycystic ovarian disease Trauma/surgery Noonan's or pseudo-turner's syndrome Ovarian steroid biosynthetic defects
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