Adrenal Pathophys (Fisher) Flashcards
I'm sorry, this isn't very good...His stuff ranges from highly detailed to taught previously
The major action of ACTH on the adrenal gland is:
stimulate conversion of cholesterol
to pregnenolone
What are the major intermediates in the synthesis of cortisol?
cholesterol»_space; pregnenolone»_space; 17alpha-hydroxyprogesterone»_space; 11-deoxycortisol»_space; cortisol
Where does P-450scc catalyze the rate-limiting step in cortisol synthesis?
mitochondria
Defects in the enzymes along the cortisol synthesis pathway will result in:
shunting of substrates in the direction of androgen synthesis
Cortisol acting at both ____ + _____ serves
as a negative feedback on the production of ACTH.
anterior pituitary and hypothalamic
ATCH excess leads to:
hypertrophy and hyperplasia of adrenal cortex
ATCH deficiency leads to:
decreased “steroidogenesis” and adrenal cortex atrophy
3 mechanisms of neuroendocrine control of ATCH release
1) circadian/diurnal rhythm with episodic secretion
2) response to stress
3) feedback inhibition by cortisol; ** can override 1 and 2
Metabolism of androgens is unique in that:
it may result in degradation, inactivation, or (in certain instances) enhancement of potency
How does hypothyroidism affect cortisol?
↓metabolism and ↓excretion
How does hyperthyroidism affect cortisol?
↑metabolism and ↑excretion
How do starvation/anorexia affect cortisol?
↓clearance of cortisol
How does pregnancy affect cortisol?
↓cortisol due to ↑CBG
In the plasma, cortisol is bound mainly to:
corticosteroid-binding globulin
and albumin, to a lesser extent
Androgens are primarily bound to:
albumin
Measurement of a 24-hour urinary free cortisol is a useful indicator of:
total cortisol production by the adrenal (because only free cortisol is filtered by the kidney)
Measuring acute adrenal response to synthetic ACTH is used to diagnose:
both primary and secondary adrenal insufficiency, although it will not distinguish one from the other
The rapid ACTH stimulation test is a stimulus for:
aldosterone + cortisol
What would be the result of a rapid ACTH stimulation test be if the patient had primary adrenal insufficiency due to destruction of the cortex?
neither aldosterone nor cortisol will be responsive to exogenous ACTH
What would be the result of a rapid ACTH stimulation test be if the patient had secondary adrenal insufficiency? (Why?)
aldosterone, but not cortisol, will respond acutely to ACTH
zona glomerulosa is usually intact
Infusion of saline + dexamethasone + cosyntropin is used to:
diagnose adrenal insufficiency, and distinguish between primary and secondary (after 2+ days)
nml = increase in cortisol primary = no increase in cortisol secondary = slight increase in cortisol, which increases with infusion
How does metyrapone test pituitary-adrenal reserve?
- Metyrapone blocks the synthesis of cortisol (inhibits 11ß-hydroxylase)
- ACTH is stimulated when cortisol decreases
- 11-deoxycortisol subsequently increases if hypothalamic-pituitary-adrenal axis is nml
How does insulin-induced hypoglycemia test pituitary-adrenal reserve?
Hypoglycemia induces a CNS stress response, which causes release of ACTH from pituitary and a rise in cortisol in normal pt
What does Corticotropin Releasing Hormone stimulate, and what does this diagnose or rule out?
- -pituitary failure = no response
- -primary adrenal failure = stimulates exaggerated increase in serum ACTH
- -hypothalamic disorder = delayed effect
Primary Adrenocortical Insufficiency:
Etiologies?
o Most common: autoimmune adrenalitis o TB o Amyloidosis o Bilateral adrenalectomy o Adrenal vein thrombosis, adrenal artery embolus o Metastatic carcinoma
Primary Adrenocortical Insufficiency:
Presentation?
o Female o Hyperpigmentation o Hypotension (**May lead to azotemia + mild acidosis) o Weak o Nausea, vomiting
Primary Adrenocortical Insufficiency:
Labs?
o hyponatremia
o hyperkalemia
o elevated ACTH
In Primary Adrenocortical Insufficiency, what may occur following exposure to stress?
“acute adrenal crisis”
- hypovolemic shock (due to anorexia, NV, and volume depletion via increase Na in urine)
- weakness
- Hyponatremia and hyperkalemia
- abdominal pain
- fever (infection or hypoadrenalism)
Bilateral Acute Adrenal hemorrhage:
Presentation?
- pain in abdomen, flank, or back (+ tenderness)
- hypotension → shock
- azotemia 2o to volume depletion
Bilateral Acute Adrenal hemorrhage causes primary adrenocortical insufficiency due to damage to:
both adrenal cortices
Secondary Adrenocortical Insufficiency:
Most common cause?
exogenous glucocorticoid therapy
Congenital Adrenal Hyperplasia leads to:
abnormalities of secondary sexual development and electrolyte imbalance
Congenital Adrenal Hyperplasia is caused by:
Enzymatic defects in the pathway of cortisol synthesis, which shunts substrates into androgen synthesis
What enzyme deficiency is responsible for ambiguous female genitalia?
21-hydrolase deficiency (can be in cortisol pathway or cortisol + aldoseterone pathway)
ACTH dependent causes of Cushing’s?
Ectopic ATCH syndrome (tumors)
Extoptic CRH syndrome
ACTH independent causes of Cushing’s?
- Adrenal adenoma
- Adrenal carcinoma
- Micronodular and macronodular hyperplasia
Pseudo-cushing’s syndrome is related to what conditions?
major depressive disorder and alcoholism
To diagnose Cushing’s dz, you need what 3 tests?
(1) 24 hr urine free cortisol: shows excess ATCH
(2) measurement of plasma cortisol and ATCH (↑ATCH and cortisol): shows dependence of cortisol on secretion of ATCH
(3) high-dose dex suppression test: show pituitary source of ATCH
Loss of circadian rhythm of plasma cortisol is symptomatic of:
Cushing’s
Dexamethasone suppression test:
Low dose will determine if the patient has…
High dose will distinguish…
Cushing’s (cortisol will increase, no resp to GC)
Cushing’s from ectopic ATCH syndrome
