生殖系統發育異常及 生殖內分泌學 台北榮民總醫院婦產部 何積泓醫師 2009/11/02

p320 Gender Assignment 1/4000 births Duct system

Fig 22-5 PAR: pseudoautosomal region, PAR1: short stature, AZF: spermatogenesis, TSPY: testicular malignancy,

Testis (Sex determine Region Y, SRY)

Congenital uterine anomaly

2006 第一次醫師考試 女性陰道發育時如發生Defective canalization 時可能會有下列何種結果？ 陰道縱向中隔 陰道橫向中隔 處女膜閉鎖 子宮內膜中隔

2006 第一次醫師考試 胎兒的性別發育過程當中，那個事件是最早發生？ 苗勒氏管（Müllerian duct）的退化 伏耳夫氏管（Wölffian duct）的退化 伏耳夫氏管的分化 苗勒氏管的分化

Disorders of sex development (DSD) Sex chromosome DSD

Klinefelter’s syndrome 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

1:2500

Mixed gonadal dysgenesis 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 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) 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

2003 第一次醫師考試 有關真性陰陽人（true hermaphroditism）之敘述，下列何者正確？ 只存在男性或女性之性腺組織 外性器官大部分明確 XY 基因型者，絕不會出現月經 缺乏乳房發育

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

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

Masculinizied females Congenital adrenal hyperplasia (AR) 21-hydroxylase (P450c21) deficiency 11β-hydroxylase (P450c11) deficiency 3 β-hydroxysteroid dehydrogenese deficiency Elevated androgens in maternal circulation Drug intake Maternal disease Aromatase (P450arom) deficiency CAH: 1/15000 births

2007 第一次醫師考試 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 10週開始腎上腺才開始作用,內生殖器官已經形成

2008 第一次醫師考試 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/dL。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 Androgen insensitivity syndrome Abnormal androgen synthesis Gonadotropin-resistant testis LH receptor mutation Leydig cell hypoplasia Absent or defect anti-müllerian hormone Persistent Müllerian duct syndrome Undescended testis

Androgen

Androgen insensitivity syndrome Testicular feminization syndrome 46,XY Gene defect of Xq12 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 結婚前做人工陰道

Androgen insensitivity syndrome Female Phenotypic spectrum Male

Abnormal androgen synthesis Defects in testicular steroidogenesis (AR) P450 side-chain cleavage 3β-hydroxysteroid dehydrogenase P45017α 17β-hydroxysteroid dehydrogenase 5α-reductase Lipoid congenital adrenal hyperplasia Steroidogenic acute regulatory protein (StAR) defect Impaired cholesterol transportation into mitochondria 性線切除

Sex hormone synthesis

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

p320 Duct system

Hypothalamic- pituitary system FSH LH

Puberty

Adrenarche Pubarche Adrenal androgen  pubic/axillary hair Independent from GnRH-pituitary-ovarian maturation (gonadarche) Adrenal androgen-stimulating factor Adrenal enzyme activity

Gonadarche Intrinsic suppression of GnRH↓ Sensitivity to estrogen negative feedback↓ Accelerated growth Breast development Menarche GABA, neuropeptide Y, melatonin

Gonadotropin-releasing hormone (GnRH)

Two-cell theory

Adrenarche

2006 第二次醫師考試 2008 第二次醫師考試 女性青春期發育順序，最常出現之順序為： 加速長高→乳芽發育→陰毛生長→初經 乳芽發育→陰毛生長→初經→加速長高 陰毛生長→乳芽發育→加速長高→初經 乳芽發育→加速長高→初經→陰毛生長

Timing of puberty Genetic factor Geographic location Exposure to light General health and nutrition Psychologic factor 盲女早熟

Tanner stages

Tanner stages

女性乳房發育，乳芽 (budding) 出現係在唐納分期 (Tanner Stage) 之第幾期？ 第一期 第二期 第三期 第四期 2

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

2005 第一次醫師考試 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

2005 第二次醫師考試 女性性早熟（precocious puberty）指青春期發育在幾歲之前開始？ 6 歲 8 歲 10 歲 12 歲

2007 第一次醫師考試 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 Treat intracranial or underline disease Bone age GnRH analogues Aromatase inhibitor

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

2005 第二次醫師考試 關於女性青春期發育遲緩（delayed puberty），下列敘述何者不正確？ 第二性徵到13 歲尚未出現 到16 歲還沒有初經 乳房開始發育兩年內尚未有初經 初經在其它第二性徵發育超過5年後尚未出現

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