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Gender D evelopment Disoreders and Congenital A drenal H yperplasia

Gender D evelopment Disoreders and Congenital A drenal H yperplasia. Dr Olcay Evliyaoğlu. Genes involved in gonadal differentiation. Sertoli H. AMH. DMRT1 ve 2. Test e s. SOX 9. Leydig H. Test o steron e. WT1 LIM-1. SRY. Me s oderm. Bipotan tial gonad. SF1. DAX 1. WNT 4.

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Gender D evelopment Disoreders and Congenital A drenal H yperplasia

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  1. GenderDevelopmentDisoreders and Congenital Adrenal Hyperplasia Dr Olcay Evliyaoğlu

  2. Genes involved in gonadal differentiation Sertoli H. AMH DMRT1 ve 2 Testes SOX 9 Leydig H. Testosterone WT1 LIM-1 SRY Mesoderm Bipotantial gonad SF1 DAX 1 WNT 4 Estradiol Ovary

  3. Campomelic dysplasia SOX9 SRY SF 1 46, XY Gonadal Dysgenesis Adrenal insufficiency Del(2q) Del (9p) WT1 DMRT 1 - 2 Del (10g) Dennys-Drash sendromu Frasier sendromu WAGR sendromu Dup (X)p21 (DAX 1)

  4. Gonadal dysgenesis

  5. Disorders of steroid biosynthesis

  6. Adrenal cortex

  7. Embryology • Mesoderm........adrenal cortex • Ectoderm.........adrenal medulla • Fetal adrenal cortex at 5-6 weeks • Definite zone (outer layer) (glucocorticoidand mineralocorticoid) • Fetalzone (inner layer) (androgenicprecursors)

  8. At birth adrenal gland is the 0,5 % of the birth weight • Glomerulosa 15% • Fasiculata 75% • Reticularis 10%

  9. Fetalzone disappears at about 1 years of age • Glomerularisand fasiculata development continues untill3 years • Reticularisdevelopment continues untill15 years

  10. Congentital adrenal hyperplasia

  11. Lipoid congenital adrenal hyperplasia • stAR protein absent • No steroid hormone synthesis • High ACTH and LH • Increased LDL rec • Cholesterolincrease and is stored • Mitochondrialand cellular damage

  12. 21- hydroxylase deficiency • Expressed in zona fasiculata • 21- hydroxylase gene(CYP21) localized on 6p21.3 chrom • 1/5000- 1/15000 live birth

  13. 21- hydroxylase deficiencyClinical forms I- Classical A- salt loosing B- simple virilisingII- Nonclassical

  14. 21- hydroxylase deficiency- 95% of CAH cases

  15. 21-hydroxylase deficiency- 46,XX gender development disordermild cliteromegaly→phallus  penıs+ completelabioscrotalfusion (I – V Praderstaging)- ± salt wasting

  16. 21- hydroxylase deficiency- 46,XYacceleratedgrowthandvirilization± salt wasting

  17. 21- hydroxylase deficiency- 17 alfa - OHP significantlyhigh- Exaggerated 17OHP responseto ACTH stimulation

  18. 21 hydroxylasedeficiencyresulting in salt wasting- P450c21 activity is absentnearcomplete- Girlsarerecognized at birth.- BoysCan be overloolkedIf not recognizeddeathwith salt wastingSymptoms of salt wastingappearafterthefirst 10-14 days of life

  19. 11-beta hydroxylasedeficiency • Expressed in zona fasiculata • Glucocortikoiddeficiency + excessandrogen + hypertension

  20. 11-beta hydroxylasedeficiency- Cortisol↓- DOC ↑ 11 deoksicortisol ↑

  21. 3-beta hydroxysteroiddehydrogenasedeficiency • 46, XX fetushigh DHEAS • 46, XY fetuslowtestosterone

  22. 3-beta hydroxysteroiddehydrogenasedeficiency

  23. 17 alpfahydoxylase/ 17-20 liyasedeficiency-P450c17 absence increase in corticosterone-Corticosterone has glucocortikoidactivity.-DOC ↑, sodiumretantion , hypertension, hyperkalemia, plasma renin ↓

  24. Treatment • CAH • Glucocorticoidtreatment (hydrocortisone)10-15 mg /m2/ day • Fludrocortisone 0,1mg/ day

  25. Acute adrenal insufficiencytreatment • Fluidandelectrolytetreatment 400cc/m2 serum saline IV in 1 houror 20cc/kg serum saline IV in 1 hour • Fluidtreatmentaccordingtodehydrationdegree • Glucocorticoidtreatment • Hydrocortisone 100-75mg/m2/ dayhalf of it as bolus • Remaininghalf is addedto 24 hourfluid • 2. day 75mg/m2/ day oral • 3. day 50mg/m2/ day • 4. day 30 mg/m2/ day

  26. Mineralocorticoidtreatment • Fludrocortisone 0.1-0.15 mg/ day • Newbornsneedmoredose • Salt 1-2 gr/ day(1 gr salt 17mEq, dose can be increasedto 8mEq/kg)

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