Steroid therapy

Question 1

How is cortisol controlled and produced?

Answer 1

Circadian/Stress - POMC -> ACTH -> Adrenal cortex fasciculata->Cortisol (Feedback on ACTH and POM)

Question 2

What two produce does ACTH control?

Answer 2

Controles cortisol and andregens (these dont feedback on it, zona reticulatis)

Question 3

What controlled and regulated aldosterone?

Answer 3

Hyper K, Hypo Na, BP low, low renal BF -> RAAs -> Zone glomerulosa-> aldo

Question 4

How essential are the adrenal steroids to life?

Answer 4

Cortisol is essential for life-Addison’s crisis can kill, need for stress response
Aldosterone-Promote Na retention and K+ loss -but not essentia
Adrogens from adrenal-unsure if have a big role

Question 5

What receptors can Aldo and cortisol bind to? Where are they found? What prevents cortisol acting as Aldo? How does it stand up in disease?

Answer 5

MR-aldo+Cortisol (Only in kidney-Cortisol has high affinity for it, but enzyme 11BHSD degrades it in the kidney-but overwhelmed in Cushings-hypokalemia
Gr-only Cortisol (Wide distrib, but cortisol has low affinity

Question 6

What is hydrocortisone, Predinsolone, Dexamethosone, Fludrocortosone? How do they differ and whem whould You use them?

Answer 6

Glucocoticoid used as replacement for Cortisol-has affinty for MR and GR (same as coertisol in high dose
Predinsolone-Glucosteroid-GR but weak MR affinity
Dexamethosone-Gluco-only GR
Fludrocortisone-Aldosterone analogue

These can all help treat Adrenal failure

Question 7

What are the different routes of administration for corticosteroids?

Answer 7

1-Oral- Hydrocortisone, predinisolone, dexamethasone, Fludrocorstisone
2-Parenteral-I.V/IM (acute)
Hyhdrocortisone, dexamethasone => Hydro at these dose usually also bind MR, which is good in acute cases of primary adrenal failure)

Question 8

How do corticosteroids distribute in your body? How long to they act for?

Answer 8

Bound to Cortisol binding globulin in blood

Hydro-only 8h-needs more than once a day
Predinosolone-12h-thats good
Dexamethasone-40h-very loong

Question 9

What are the 4 main disease treated with corticosteroids replacement therapy

Answer 9

1) Primary adrenal failure-Duh
2) -Secondary adrenocorticol failure (ACTH failure) (low cortisol but aldo in normal-replace that only)-hydro, predni
3) addisonian crisis-give sodium drip and large dose of hydro-acts on GR and MR (and possibly bit of glucose on top)
4) Congenital adrenal hyperplasia-lack of enzymes needed-95% 21 hydroxylase deficiceny-Replace cortisol and aldo-but need to supress sex hormones-cortisol lvls will help achieve that, but hard (dexa, or hydrocortisone- high dose at night, reduce ACTH)-optimise with clinical+17Oh progest lvls (but can lead to cushings again)

Question 10

How do you diagnose 21 hydroxylase deficiency? How do you

Answer 10

Measure the precursor-17a hydroxyprgesterone, would be sky high and it cant be used
High ACTH-drive cause adrenal to grow, and causes more and more sex hormones to be produce
Use the 17ahydroxypogesterone to measure therapy as well

Question 11

What is the average production of cortisol a day? and with stress? Why does it matter with replacement cortisol?

Answer 11

around 20mg/day-made with stress - x10 (200mg)
And it helps recover from disease which means trouble if addison’s-tipping point for crisis
BUT in replacement, cant increase the production in stress-so must increase dose with illness-2x in small illness, in surgery, even more/IV)-if forget can die