gender development disoreders and congenital adrenal hyperplasia dr olcay evliyaoğlu

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  • Gender Development Disoreders and Congenital Adrenal Hyperplasia Dr Olcay Evliyaolu

  • MesodermWT1LIM-1SF1Bipotantial gonadSRYSOX 9DMRT1 ve 2DAX 1WNT 4Testes OvarySertoli H.Leydig H.AMHTestosteroneEstradiol Genes involved in gonadal differentiation

  • 46, XY Gonadal Dysgenesis SOX9SRYDel(2q)Del (9p)Del (10g)Dup (X)p21(DAX 1)WT1SF 1Campomelic dysplasiaAdrenal insufficiencyDennys-Drash sendromuFrasier sendromuWAGR sendromuDMRT 1 - 2

  • Gonadal dysgenesis

  • Disorders of steroid biosynthesis

  • Adrenal cortex

  • Embryology Mesoderm........adrenal cortexEctoderm.........adrenal medullaFetal adrenal cortex at 5-6 weeksDefinite zone (outer layer) (glucocorticoid and mineralocorticoid)Fetal zone (inner layer) (androgenic precursors)

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

  • Fetal zone disappears at about 1 years of ageGlomerularis and fasiculata development continues untill 3 yearsReticularis development continues untill 15 years

  • Congentital adrenal hyperplasia

    Enzyme deficiencyGirls Boys Lab Lipoid formSexual infantilism salt wastingInsufficient virilisation Salt wasting All steroid hormones are lowLow response to ACTH stimACTH and PRA high3beta HSDVirilisation Salt wastingInsufficient virilisation Salt wasting Delta steroids are increasedACTH and PRA high21 hydoxylase def classical type Virilisation Salt wastingMacrogentaliaSalt wasting 17OH progesterone increasedAndrogens increased ACTH and PRA increased21 hydoxylase def late onset type Premature adrenarche, hirsutismus, menstrual irregularity ,acne,nfertilityPremature adrenarcheIncreased 7OHprogesterone response to ACTH11 beta hydorxylase deficiencyVirilisation , hypertensionMacrogenitalia,11deoksi cortcosterone increase11deokscortsol increasePRA suppresed17hydroxylase deficiencySexual infantilisim hypertension Insufficient virilisation hypertensionAndrostenedione/ testesterone increasedACTH high, PRA low

  • Lipoid congenital adrenal hyperplasiastAR protein absentNo steroid hormone synthesisHigh ACTH and LHIncreased LDL recCholesterol increase and is storedMitochondrial and cellular damage

  • 21- hydroxylase deficiencyExpressed in zona fasiculata21- hydroxylase gene(CYP21) localized on 6p21.3 chrom 1/5000- 1/15000 live birth

  • 21- hydroxylase deficiency

    Clinical forms

    I- Classical A- salt loosing B- simple virilising

    II- Non classical

  • 21- hydroxylase deficiency

    - 95% of CAH cases

  • 21- hydroxylase deficiency- 46,XX gender development disorder mild cliteromegaly phallus pens + complete labioscrotal fusion (I V Prader staging)- salt wasting

  • 21- hydroxylase deficiency

    - 46,XY accelerated growth and virilization salt wasting

  • 21- hydroxylase deficiency

    - 17 alfa - OHP significantly high- Exaggerated 17OHP response to ACTH stimulation

  • 21 hydroxylase deficiency resulting in salt wasting

    - P450c21 activity is absent near complete- Girls are recognized at birth.- Boys Can be overloolked If not recognized death with salt wastingSymptoms of salt wasting appear after the first 10-14 days of life

  • 11-beta hydroxylase deficiencyExpressed in zona fasiculataGlucocortikoid deficiency + excess androgen + hypertension

  • 11-beta hydroxylase deficiency

    - Cortisol - DOC 11 deoksicortisol

  • 3-beta hydroxysteroid dehydrogenase deficiency46, XX fetus high DHEAS46, XY fetus low testosterone

  • 3-beta hydroxysteroid dehydrogenase deficiency

  • 17 alpfa hydoxylase/ 17-20 liyase deficiency-P450c17 absence increase in corticosterone -Corticosterone has glucocortikoid activity.

    -DOC , sodium retantion , hypertension, hyperkalemia, plasma renin

  • Treatment CAHGlucocorticoid treatment (hydrocortisone)10-15 mg /m2/ dayFludrocortisone 0,1mg/ day

  • Acute adrenal insufficiency treatment Fluid and electrolyte treatment 400cc/m2 serum saline IV in 1 hour or 20cc/kg serum saline IV in 1 hourFluid treatment according to dehydration degree Glucocorticoid treatmentHydrocortisone 100-75mg/m2/ day half of it as bolusRemaining half is added to 24 hour fluid2. day 75mg/m2/ day oral3. day 50mg/m2/ day4. day 30 mg/m2/ day

  • Mineralocorticoid treatmentFludrocortisone 0.1-0.15 mg/ day Newborns need more doseSalt 1-2 gr/ day (1 gr salt 17mEq, dose can be increased to 8mEq/kg)