生殖系統發育異常及 生殖內分泌學

1. 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

2. Gender Assignment p320 Duct system

3. Fig 22-5

4. Testis (Sex determine Region Y, SRY)

7. Congenitaluterine anomaly

8. 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

10. 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

11. Disorders of sex development (DSD) • Sex chromosome DSD

12. 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

14. 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

15. 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

16. 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

17. 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

18. 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

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

20. 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

21. 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

22. Sex hormone synthesis

23. Congenital adrenal hyperplasia

24. 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

25. 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

26. Androgen

27. 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

28. Androgen insensitivity syndrome Female Phenotypic spectrum Male

29. 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

30. Sex hormone synthesis

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

32. p320 Duct system

33. Hypothalamic-pituitary system FSH LH

34. Puberty

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

36. Gonadarche • Intrinsic suppression of GnRH↓ • Sensitivity to estrogen negative feedback↓ • Accelerated growth • Breast development • Menarche

37. Gonadotropin-releasing hormone(GnRH)

38. Two-cell theory

39. Adrenarche

40. 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

41. Timing of puberty • Genetic factor • Geographic location • Exposure to light • General health and nutrition • Psychologic factor

43. Tanner stages

44. Tanner stages

45. 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

46. 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

47. 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

48. 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

49. 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

50. Treatment • Treat intracranial or underline disease • Bone age • GnRH analogues • Aromatase inhibitor