CAH Flashcards
1
Q
summarise 11-beta hydroxylase deficiency
A
- CYP11B1
- DOC–> corticosterone
- 11- DOC –> cortisol
- reduced cortisol and MC synthesis
- similar symptoms to 21-OHD
- only difference is hypertension due to XS DOC
- elevated androgens (simple V/ salt wasting)
- 8q24.3
2
Q
summarise 17-alpha hydroxylase deficiency
A
- 150 cases (rare)
- CYP17A1 gene
- low cortisol
- low androgens
- hypergonadotrophic hydogonadism (LH,FSH)
- primary amenorrhea (46 XX)
- under V + (46 XY DSD)
- hypertension and hypoK –> DOC + corticosterone
- elevated LH/FSH
- 10q24.3
- adrenal + gonadal steroids
no preg-> 17preg-> DHEA
no prog–> 17prog–> androstenedione
3
Q
summarise sTAR deficiency
A
- deficiency in all adrenal and gonadal steroid synthesis
- sTAR gene
- impaired cholesterol transport from OMM-> IMM
- no pregnenelone
- massive adrenal hyperplasia and XS lipidaemia
- cell destruction
- XS ACTH (XS lipid)
- 46 XX DSD
- adrenal insufficiency in neonate
4
Q
summarise p450 scc deficiency
A
- CYP11A1 gene
- 7 cases
- used to be thought as not viable (preg depends on prog)
- manifests with STAR symptoms but no hyperplasia
- all adrenal/ gonadal steroids impaired
- 46 XX DSD–> severe insufficiency
- no chol–> pregnenolone
5
Q
summarise 3beta- hydroxysteroid dehydrogenase deficiency
A
- HSD3B2 gene
- abolished adrenal and gonadal steroid synthesis
- variety of disease expression, salt wasting–> simple V etc
- preg–> prog
- 17a preg-> 17a prog
- DHEA-> androstenedione
6
Q
summarise 21-OHD
A
- CYP21A2
- 90%
- n 6p21.3
- HLA region
- no 17aprog–> 11-DOC
- prog–> DOC
- reduced cortisol and MC
- salt wasting (75)
- simple V (25) –> both classic –> severe enzymatic deficiency where symptoms manifest in neonate/ infancy
- non classical (most common)–> mild enzymatic deficiency where symptoms manifest later in childhood / adolescence
- high 17OH prog and prog levels / A / T
- hyperplasia and XS ACTH
- 1/10,000 1/300 alaskan
7
Q
explain the simple virilizing form
A
- Loss of the negative feedback axis leading to enhanced drive by ACTH
- XS adrenal weak androgens (17a-OHP, Progesterone, T, androstenedione)
- Females often diagnosed at birth –>presence of virilization of an affected female fetus
- Clitoral enlargement/labial fusion/ urogenital sinal development–> sexual ambiguity at birth
- Males –> present as relatively normal / asymptomatic at birth –> skewed female/male ratio of diagnosis
- If undiagnosed -> premature epiphyseal closure and final adult height being diminished (follows XS growth acceleration)
- Present with signs of sexual precocity/pubic hair dev/
- Mention difference in development of male/female gonads
- Due to block in steroidogenic pathway, sex hormone precursors proximal to the block which do not require 21-OH for synthesis are secreted in XS response to XS ACTH (shunted into ZR )
8
Q
explain the salt wasting form
A
- Amongst classical patients -> 75%
- Unable to synthesize adequate amounts of aldosterone - severely impaired conversion of progesterone –> DOC
- Essential normal Na homeostasis , increased Na loss via kidney (DCT.CD) , colon and sweat glands
- Ensures tight regulation of circulating volume
- Unable to retain Na/ water (impaired effectiveness of renin-ag system)
- Present with hypoV, hypoT, hyperreninemia, polyuria, polydipsia
- Poor appetite, vomiting, lethargy, weight loss
9
Q
explain the non-classical form
A
- Most common form
- Phenotype correlates with PCOS, precocious puberty
- Present with some signs of androgen XS
- Females born with non-ambiguous genitalia and mild clitoromegaly
- Child hood signs –> Premature puberty , severe cystic acne, hirsutism and oligomenorrhea
- Infertility
10
Q
why do we get infertility ?
A
- Low fertility in females with 21OD (SW form)
- Increased progesterone levels
· Alters GnRH pulse generator
· Disrupt endometrial thickening
· Increase cervical mucus
Disrupts ovulation, embryo implantation
- Increased progesterone levels
