1. Gender Development Disoreders and Congenital Adrenal Hyperplasia
Dr Olcay Evliyaoğlu

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

5. 46, XY Gonadal Dysgenesis SOX9 SRY SF 1 Del(2q) Del (9p) WT1 Del (10g)
Campomelic dysplasia
SOX9
SRY
SF 1
46, XY
Gonadal
Dysgenesis
Del(2q)
Adrenal insufficiency
Del (9p)
WT1
DMRT 1 - 2
Del (10g)
Dennys-Drash sendromu
Frasier sendromu
WAGR sendromu
Dup (X)p21
(DAX 1)

6. Gonadal dysgenesis

7. Disorders of steroid biosynthesis

8. Adrenal cortex

9. Embryology Mesoderm........adrenal cortex
Ectoderm adrenal medulla
Fetal adrenal cortex at 5-6 weeks
Definite zone (outer layer) (glucocorticoid and mineralocorticoid)
Fetal zone (inner layer) (androgenic precursors)

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

11. Fetal zone disappears at about 1 years of age
Glomerularis and fasiculata development continues untill 3 years
Reticularis development continues untill 15 years

12. Congentital adrenal hyperplasia
Enzyme deficiency
Girls
Boys
Lab
Lipoid form
Sexual infantilism
salt wasting
Insufficient virilisation
Salt wasting
All steroid hormones are low
Low response to ACTH stim
ACTH and PRA high
3beta HSD
Virilisation
Delta steroids are increased
21 hydoxylase def classical type
Macrogenıtalia
17OH progesterone increased
Androgens increased
ACTH and PRA increased
21 hydoxylase def late onset type
Premature adrenarche, hirsutismus, menstrual irregularity ,acne,ınfertility
Premature adrenarche
Increased 7OHprogesterone response to ACTH
11 beta hydorxylase deficiency
Virilisation , hypertension
Macrogenitalia,
11deoksi cortıcosterone increase
11deoksıcortısol increase
PRA suppresed
17’hydroxylase deficiency
Sexual infantilisim hypertension
hypertension
Androstenedione/ testesterone increased
ACTH high, PRA low

14. Lipoid congenital adrenal hyperplasia
stAR protein absent
No steroid hormone synthesis
High ACTH and LH
Increased LDL rec
Cholesterol increase and is stored
Mitochondrial and cellular damage

16. 21- hydroxylase deficiency
Expressed in zona fasiculata
21- hydroxylase gene(CYP21) localized on
6p21.3 chrom
1/ /15000 live birth

17. 21- hydroxylase deficiency Clinical forms I- Classical A- salt loosing B- simple virilising II- Non classical

18. 21- hydroxylase deficiency - 95% of CAH cases

19. 21- hydroxylase deficiency - 46,XX gender development disorder mild cliteromegaly →phallus  penıs + complete labioscrotal fusion (I – V Prader staging) - ± salt wasting

31. 21- hydroxylase deficiency - 46,XY accelerated growth and virilization ± salt wasting

32. 21- hydroxylase deficiency alfa - OHP significantly high - Exaggerated 17OHP response to ACTH stimulation

33. 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 wasting Symptoms of salt wasting appear after the first days of life

38. 11-beta hydroxylase deficiency
Expressed in zona fasiculata
Glucocortikoid deficiency + excess androgen + hypertension

39. 11-beta hydroxylase deficiency - Cortisol ↓ - DOC ↑ 11 deoksicortisol ↑

40. 3-beta hydroxysteroid dehydrogenase deficiency
46, XX fetus high DHEAS
46, XY fetus low testosterone

41. 3-beta hydroxysteroid dehydrogenase deficiency

42. 17 alpfa hydoxylase/ liyase deficiency -P450c17 absence  increase in corticosterone -Corticosterone has glucocortikoid activity. -DOC ↑, sodium retantion , hypertension, hyperkalemia, plasma renin ↓

43. Treatment
CAH
Glucocorticoid treatment (hydrocortisone)10-15 mg /m2/ day
Fludrocortisone 0,1mg/ day

44. Acute adrenal insufficiency treatment
Fluid and electrolyte treatment
400cc/m2 serum saline IV in 1 hour or
20cc/kg serum saline IV in 1 hour
Fluid treatment according to dehydration degree
Glucocorticoid treatment
Hydrocortisone mg/m2/ day half of it as bolus
Remaining half is added to 24 hour fluid
2. day 75mg/m2/ day oral
3. day 50mg/m2/ day
4. day 30 mg/m2/ day

45. Mineralocorticoid treatment
Fludrocortisone mg/ day
Newborns need more dose
Salt 1-2 gr/ day (1 gr salt 17mEq, dose can be increased to 8mEq/kg)