congenital adrenal hyperplasia

Question 1

congenital adrenal hyperplasia (CAH)

Answer 1

-Caused by mutations in genes encoding enzymes involved in cortisol,aldosterone, and, rarely androgen synthesis.
-Patients affected by CAH exhibit glucocorticoid deficiency (decrease cortisol)
-Depending on the exact step of enzymatic block, they may also have excess production of mineralocorticoids or deficient production of sex steroids
-Decreased cortisol -> results in ACTH stimulation – b/o negative feedback
-21-Hydroxylase deficiency – commonest mutation
-Other: 11β-hydroxylasedeficiency and 17α-hydroxylasedeficiency

Question 2

presentation of CAH

Answer 2

-21β-hydroxylasedeficiency: MC
-Hypotension

-XX GENOTYPE
-Female pseudohermaphroditism: clitoromegaly and/or male external genitalia along with a uterus and ovaries
-Precocious puberty- early puberty
-Virilization, irregular menstrual cycles, infertility, hair
-diff dx- PCOS- do US

-XY GENOTYPE
-Normal male external genitalia at birth
-Precocious puberty

-11β-hydroxylase& 17α deficiency:
-Hypertension

-XX GENOTYPE
-Normal female external genitaliaatbirth
-Delayed puberty(primary amenorrhea) or sexual infantilism

-XY GENOTYPE
-Male pseudohermaphroditism:female external genitaliawith ablind-endingvaginaandintra-abdominaltestesatbirth
-Delayed pubertyor sexual infantilism

Question 3

signs and symptoms

Answer 3

-Adrenal crisis
-Failure to thrive
-Hypoglycemia
-Hyperpigmentation
-Gender dysphoria
-Infantswith21β-hydroxylasedeficiency can present with:
-boys with classic CAH usually present with life-threatening adrenal crisis in the first few weeks of life (salt-wasting crisis) -> shock -> screen for this

Question 4

diff dx

Answer 4

-Cushing Syndrome
-Primary adrenal insufficiency
-Precocious pseudo-puberty -elevatedGnRHlevels(early development of 2ry sexual characteristics)
-Polycystic Ovarian Syndrome- hyperandrogenism (hirsutism, acne, and, occasionally, virilization), oligoovulation/anovulation, and/or the presence of polycystic ovaries.
-Hyperprolactinemia

Question 5

diagnosis

Answer 5

-Measure steroids accumulating before the distinct enzymatic block, either in serum or in urine
-*Screening with 17-hydroxyprogesterone(by product of cortisol formation)- increased by 21 beta is not breaking it down!!!!!!
-decrease aldosterone in hypotension (21 beta) and hyperkalemia
-Hypocortisolism; levels remain low even after administration of cosyntropin.
-Neonatal Screening
-A simple-virilizing genotype manifests with precocious pseudo-puberty
-Advanced bone age in early childhood
-Men with nonclassic CAH are usually detected only through family screening
-CT imaging for CAH – abdomen; testes etc. – looking for adrenal hyperplasia

Question 6

tx

Answer 6

-Not only replacement of deficient hormones but you also need to control the increased ACTH which stimulates androgen excess
-Life long daily regimen:
-Hydrocortisone – to prevent crisis; any time of stress
-Prednisone – better for countering androgen excess in children
-Stress dosing with steroids- increase with sickness

-Regular and close monitoring
-Counseling for gender dysphoria

Question 7

specific tx

Answer 7

-21β-hydroxylase deficiency
-Lifelong fludrocortisone therapy (aldosterone substitution)
-Sodium chloride (salt) supplements, especially during infancy and childhood

-11β-hydroxylase deficiency
-Spironolactone to block mineralocorticoid receptors
-Reduced dietary sodium intake

-17α-hydroxylase deficiency
-Spironolactone to block mineralocorticoid receptors
-Estrogen replacement therapy for female genotype; may be started in early puberty
-Reduced dietary sodium intake