Gender Assignment p 320 Duct system l Fig

Gender Assignment p 320 Duct system

l Fig 22 -5

Testis (Sex determine Region Y, SRY)

Congenital uterine anomaly

Disorders of sex development (DSD) l Sex chromosome DSD

Klinefelter’s syndrome l l l Most common sex chromosome aneuploidy (1: 500~1000) 47, XXY, 48, XXXY, or mosacism Hyalinized testes and male infertility Testosterone supplementation Testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) Sperm donation

Mixed gonadal dysgenesis l l 45, X/46, XY and variants Dysgenetic testes, sometimes ovarian-like stroma (like Turner’s syndrome) Female external genitalia, sometimes with Müllerian structures Gonadectomy and estrogen replacement

2009 第一次醫師考試 l 1. 2. 3. 4. 染色體為 45, X/46, XY 者，性腺容易長腫瘤， 但下列何者除外？ Gonadoblastoma Teratoma Dysgerminoma Yolk sac tumor

Ovotestitular DSD (Ture hermaphroditism) l l l Mixture of gonadal sex Ovotestis or one ovary + one testis Ambiguous external genitalia or significant hypospadia 46, XX, 46, XY, or chimerism Remove discordant gonad and dysgenetic tissue

Disorder of gonadol development l l Ovotesticular DSD Complete testicular dysgenesis l l l Anorchia l l l Swyer syndrome Mutation or deletion of SRY XY karyotype with female genitalia Remove gonad as soon as possible Vanishing testis syndrome Male genitalia without detectable testes 46, XX testicular DSD

Disorders of fetal endocrinology l 46, XX DSD l l l Masculinized females Female pseudohermaphroditism 46, XY DSD l l Incompletely masculinized males Male pseudohermaphroditism

Masculinizied females l Congenital adrenal hyperplasia (AR) l l Elevated androgens in maternal circulation l l l 21 -hydroxylase (P 450 c 21) deficiency 11β-hydroxylase (P 450 c 11) deficiency 3 β-hydroxysteroid dehydrogenese deficiency Drug intake Maternal disease Aromatase (P 450 arom) deficiency

2007 第一次醫師考試 l 1. 2. 3. 4. 懷孕時引起母親及女嬰男性化，最常見的原因為 何？ Dermoid cyst Luteoma Brenner tumor Yolk sac tumor

Sex hormone synthesis

Congenital adrenal hyperplasia

2008 第一次醫師考試 l 1. 2. 3. 4. 一位 21 歲女性，因陰蒂肥大求診，被診斷為 congenital adrenal hyperplasia（CAH），其血中 17 -hydroxyprogesterone（17 -HP）為 600 ng/d. L。下 列關於 CAH 之病因及治療的敘述，何者最適當？ 最常見為 21 -hydroxylase deficiency，治療最有 效為 cortisone 最常見為 11β-hydroxylase deficiency，治療最有 效為 dexamethasone 最常見為 21 -hydroxylase deficiency，治療最有效 為 dexamethasone 最常見為 11β-hydroxylase deficiency，治療最有 效為 cortisone

Incompletely masculinized males l l l Androgen insensitivity syndrome Abnormal androgen synthesis Gonadotropin-resistant testis l l l LH receptor mutation Leydig cell hypoplasia Absent or defect anti-müllerian hormone l l Persistent Müllerian duct syndrome Undescended testis

Androgen

Androgen insensitivity syndrome l l l l Testicular feminization syndrome 46, XY Gene defect of Xq 12 無子宮而陰道短，有睪丸但未下降 外觀為女性，無陰毛或寡陰毛 青春期後將性腺摘除，補充荷爾蒙 結婚前做人 陰道

Androgen insensitivity syndrome Female Phenotypic spectrum Male

Abnormal androgen synthesis l Defects in testicular steroidogenesis (AR) l l l P 450 side-chain cleavage 3β-hydroxysteroid dehydrogenase P 45017α 17β-hydroxysteroid dehydrogenase 5α-reductase Lipoid congenital adrenal hyperplasia l l Steroidogenic acute regulatory protein (St. AR) defect Impaired cholesterol transportation into mitochondria

Sex hormone synthesis

Summary: ambiguous genitalia l l l Rule out congenital adrenal hyperplasia Medical history and family history Palpation of gonad Pelvic ultrasonography / MRI Karyotype Gonadectomy

p 320 Duct system

Hypothalamicpituitary system FSH LH

Puberty

Adrenarche l l l Pubarche Adrenal androgen pubic/axillary hair Independent from Gn. RH-pituitary-ovarian maturation (gonadarche) Adrenal androgen-stimulating factor Adrenal enzyme activity

Gonadarche l l l Intrinsic suppression of Gn. RH↓ Sensitivity to estrogen negative feedback↓ Accelerated growth Breast development Menarche

Gonadotropin-releasing hormone (Gn. RH)

Two-cell theory

Adrenarche

Timing of puberty l l l Genetic factor Geographic location Exposure to light General health and nutrition Psychologic factor

Tanner stages

Tanner stages

Precocious puberty l l l Pubertal changes before age 8 Menarche before age 10 Gn. RH-dependent (80%) l l Idiopathic CNS problem (brain MRI) Hypothyroidism Gn. RH-independent l l Ovarian cyst or tumor Mc. Cune-Albright syndrome Adrenal tumor Ectopic gonadotropin production

2005 第一次醫師考試 l 1. 2. 3. 4. 少女性早熟（precocious puberty），第一步檢 查為何？ 血中性腺激素（gonadotropin） 雌激素 Dehydroepiandrosterone sulfate (DHEAS) 雄性素

2007 第一次醫師考試 l 1. 2. 3. 4. 一位6 歲小女孩，初經來潮，最可能為何？ Turner’s syndrome Kallmann’s syndrome Isolated gonadotropin deficiency 11 -β-Hydroxylase deficiency

Treatment l l Treat intracranial or underline disease Bone age Gn. RH analogues Aromatase inhibitor

Delayed puberty l l l No secondary sexual characteristics by age 14 No period by age 16 Constitutional delay (10 ~ 30 %) Hypergonadotropic hypogonadism (karyotype) Hypogonadotropic hypogonadism l l l Hypothyroidism Hyperprolactinemia Kallmann’s syndrome Intracranial lesion Anorexia / poor nutrition

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