Pediatric Endocrinology

1. Pediatric Endocrinology Sexual Differentiation Normal v. Abnormal Sterling M. Tanner, M.D., J.D.. F.A.A.P.

2. Symbolism Mr Ducks Mr Knot os Mr Cm Wangs Cm Ed BD Eyes oIB Mr Ducks

3. Symbolism Mr Ducks Mr Knot os Mr Cm Wangs Cm Ed BD Eyes oIB Mr Ducks

4. Growth Related hGH GHRH IgF—1 IgF—BP3 BA v. CA -2.3 SD Acromegaly CAH Related P450c11 P450c21 17OH P 11 DOC DHEA DHEA S Androstenedione Pediatric Endocrinologyis all aboutSymbolism

6. “Andre the Giant” -- 7’4” – 500 pounds – Died at age 47 Big Foot and Six Million Dollar Man

7. Etiology • Adrenal Tumors • Carcinoma • Adenoma • Not Defined • Ectopic ACTH syndrome • Nodular Adrenal Hyperplasia • Undefined Adrenal Hyperplasia • ACTH Producing Tumor PRODUCING EXCESS CORTISOL

8. Clinical Symptoms Weight Gain 92% Growth Failure 84% Osteopenia 74% Fatigue 67% Hypertension 63% Delayed Puberty 60% Plethora 46% Acne 46% Hirsuitism 46%

9. Clinical Symptoms Continued Compulsive Behavior 44% Striae 36% Bruising 28% Buffalo Hump 28% Headache 26% Delayed Bone Age 11% Nocturia 8%

10. Treatment: 1. Find the Cause2. Remove It

11. Normal Sexual Differentiation Don’t have time to discuss in detail. H-Y Antigen on Short Arm of the Y Chromosome is Required. Pseduoautosomal Region of the Y Chromosome Recombination During Meiosis. Testes Determining Factor ZFY Gene Initially, but can have males with out it. SRY Gene now thought to be the Testes Determining Factor.

12. Virilization Don’t forget that virilization of the developing female (and less so the male) can occur with intrauterine exposure to Androgens or Prostaglandins.

13. Girls are GirlsandBoys are Boys (Usually)

14. Next We Will DiscussTwo Situationsthat are Reasonably Rare.But, you should be Aware that theyExist.

15. Girls are GirlsandBoys are Girls (Sometimes)

16. Complete Syndrome ofAndrogen Resistance Previously Called Testicular Feminization Syndrome Follows X-linked Pattern There is a Variable Defect Beyond Our Scope Phenotypic FemalesMales 1:20,000 to 1:64,000 “men”

17. Diagnosis Not usually suspected until puberty Normal external female phenotype No breast development No axillary or pubic hair Amenorrhea Physical Exam Reveals Either: Inguinal Hernia v. Labial Masses

18. Findings Structural Issues – No oviducts, no uterus Only lower 1/3 of vagina (vaginal pouch) Prepubertal testes normal  Lesions of Sertoli Cells Post-pubertal  Precancerous

19. Treatment Structural Issues -- Ethical Issues -- (Jewish, Catholic, Mormons) First Do No Harm Do you tell? At what age? Pure E2 replacement ↓LH Levels (LHRH)

20. Girls are GirlsandBoys are Girls Until Puberty then Boys are Boys

21. 5 alpha-ReductaseDeficiency No Androgen Resistance Dominican Republic & São Paulo All Newborns are Female huevo a los doce – “eggs at twelve” Raised Female until Puberty Then Progressive Virilization Can Reproduce, but ↓ Fertility

22. Girls are GirlsandBoys are ??? Beyond Our Discussion

25. Treatment Dependson Syndrome • Small Penis • Cryptorchidism • Hypogonadism

26. Kallmann Syndrome Most Common Isolated gonado- tropin deficiency 1:10,000 births 5:1 male:female 50% males born with microphallus Anosmia v. hyposmia also with variable expression Hypothalamic hypogonadism

27. Girls are ???andBoys are Boys Or “Super Boys” Except Lipoid Boys

28. ClassicCongenital Adrenal Hyperplasia Hundreds of Mutations Identified Congenital Lipoid Adrenal Hyperplasia 21 - Hydroxylase Deficiency 11 beta – Hydroxylase Deficiency 3 beta – Hydroxysteroid Dehydrogenase Def. 17 beta – Hydroxysteroid Dehydrogenase Def. Placental Aromatase Deficiency

30. ClassicCongenital Adrenal Hyperplasia Congenital Lipoid Adrenal Hyperplasia

32. ClassicCongenital Adrenal Hyperplasia Congenital Lipoid Adrenal Hyperplasia 21 - Hydroxylase Deficiency

34. ClassicCongenital Adrenal Hyperplasia Congenital Lipoid Adrenal Hyperplasia 21 - Hydroxylase Deficiency 11 beta – Hydroxylase Deficiency

36. ClassicCongenital Adrenal Hyperplasia Congenital Lipoid Adrenal Hyperplasia 21 - Hydroxylase Deficiency 11 beta – Hydroxylase Deficiency 3 beta – Hydroxysteroid Dehydrogenase Def.

38. ClassicCongenital Adrenal Hyperplasia Congenital Lipoid Adrenal Hyperplasia 21 - Hydroxylase Deficiency 11 beta – Hydroxylase Deficiency 3 beta – Hydroxysteroid Dehydrogenase Def. 17 beta – Hydroxysteroid Dehydrogenase Def.

40. ClassicCongenital Adrenal Hyperplasia Congenital Lipoid Adrenal Hyperplasia 21 - Hydroxylase Deficiency 11 beta – Hydroxylase Deficiency 3 beta – Hydroxysteroid Dehydrogenase Def. 17 beta – Hydroxysteroid Dehydrogenase Def. Placental Aromatase Deficiency

42. ClassicCongenital Adrenal Hyperplasia Congenital Lipoid Adrenal Hyperplasia 21 - Hydroxylase Deficiency 11 beta – Hydroxylase Deficiency 3 beta – Hydroxysteroid Dehydrogenase Def. 17 beta – Hydroxysteroid Dehydrogenase Def. Placental Aromatase Deficiency 5 alpha – Reductase Deficiency

44. 5 alpha – Reductase Partial Deficiency

46. What Do You See??