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Flashcards in Adrenal Pathophysiology Deck (44)
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What is Cushing's syndrome?

It's an umbrella term for the syndrome produced by having too much cortisol. Has lots of etiologies.


Important: What's the most common etiology of Cushing's syndrome?

Iatrogenic - from excessive corticosteroid use.


What's the most common non-iatrogenic cause of Cushing's syndrome?

Cushing's disease, i.e. pituitary (corticotroph) adenoma.


4 metabolic derangements caused by excess glucocorticoids?

1) Increased gluconeogenesis --> hyperglycemia.
2) Increased lipogenesis.
3) Insulin resistance.
4) Increased skeletal muscle catabolism.


There's no pathognomic sign of Cushing's syndrome, but what's the most common feature?



What are 3 main areas of fat deposition in Cushing's syndrome?

"Centripetal" fat deposition
1) Dewlap (double chin)
2) Supraclavicular fat pads
3) Buffalo hump.
(accompanied by muscle atrophy)


What's the term used to describe how people's face looks in Cushing's syndrome?

"Moon faced" - cheeks sort of form a circle with neck fat.


Immune, hematopoietic, opthalmic, and musculoskeletal effects of glucocorticoid excess?

Immune: immune supression.
Hematopoetic: Increased clotting factors
Eyes: Cataract formation
Musculoskeletal: muscle-wasting, osteoporosis, fat-redistribution


CV effects of too much cortisol? (3 things)

1) Cardiomyopathy
2) Hypertension
3) Thromboembolic events


Effects of excess cortisol on skin?

Thin skin -> stretch marks where you can see red capillaries of dermis through skin.
Easy bruising.
Hyperpigmentation (if ACTH is high).


Psychiatric effects of high cortisol?

Can cause a lot of things. Most commonly causes insomnia. Can cause mania, psychosis, depression, etc.


In what disease will you see bilateral adrenal hyperplasia?

Cushing's disease - pituitary (corticotroph) adenoma producing ACTH -> drives adrenal cortical hyperplasia.


How can you get signs of hyperaldosteronism from too much cortisol?

Conversion to cortisone can be overwhelmed -> hypertension and hypokalemia.


Do you usually see "marked virilization" in women with Cushing's disease?

No. Menses can be irregular, increased testosterone.
But marked virilization is more suggestive of a malignant adrenal carcinoma.


What's the first thing to rule out when trying to figure out the cause of Cushing's syndrome?

Exogenous cortisol, prescribed or otherwise.


3 tests done in Cushing's syndrome workup? What does each test?

1) Late night salivary cortisol - tests for loss of diurnal regulation.
2) Dexamethasone suppression test - tests for independence from ACTH.
3) 24 hr urine collection for cortisol - texts for excess.


When would a late night salivary cortisol test yield confusing results?

When the patient has a circadian rhythm disorder and/or works night shifts.


What will happen in a normal dexamethasone suppression test?

Both ACTH and cortisol levels will decrease.
- Exogenous dex will suppress pituitary (prevent ACTH secretion-- prevent adrenal production of cortisol)


Patient has suspected Cushing's. High urine cortisol and high cortisol are found after dexamethasone suppression test. ACTH is measured at 55 pg/ml (normal 9-57 pg/ml). What's the cause of the Cushing's syndrome?

Cushing's disese - pituitary adenoma. The ACTH is aberrantly normal - should be suppressed if the cortisol is high.


If cortisol is being produced by an adrenal tumor, what will ACTH levels be like?

They'll be low.


Main treatment for most causes of Cushing's syndrome?



Does Cushing's syndrome resolve immediately when the cause is removed?

No. Signs can last a long time (up to 12mo) - and psych symptoms can persist.
(Also, one should taper the patient with exogenous glucocorticoids down from the high levels they'll be used to.)


Primary vs. secondary adrenal failure? What are ACTH levels like in each?

Primary: adrenal itself fails - ACTH will be high.
Secondary: loss of ACTH - ACTH will be low.


What is it called when you don't have enough cortisol?

Addison's disease.


In primary adrenal failure, is it just the zona fasiculata (cortisol) that's affected?

No, often the production of all cortical hormones is lost - can cause hypoaldosteronism (hyponatremia, hyperkalemia, hypotension)


6 clinical characteristics of primary adrenal failure?

Hyperpigmentation (due to high ACTH -> MSH).
Weight loss.
Muscle and joint pains.
Nausea, abdominal pain.
(some of these are the opposite of Cushing's syndrome)


Most common etiology of primary adrenal insufficiency? What was most common in Addison's day? Other important common?

Today most common: Auto-immune.
In Addison's day: TB.
Other causes: infections, metastatic cancer (lung and breast), hemorrhage/infarct, trauma, various drugs.


What do you do right away if you patient is hypotensive and you expect Addison's?

Give dexamethasone right away, test cortisol levels later. (won't interfere with assay... somehow)


4 etiologies of adrenal crises?

1) New primary adrenal failure.
2) Under treatment of existing adrenal insufficiency.
3) Acute withdrawal of high dose glucocorticoids.
4) Pituitary apoplexy.


What's pituitary apoplexy?

Pituitary adenoma gets too large -> hemorrhage and infarct -> sudden loss of pituitary function.


Short term treatment of Addisonian crisis?

Saline (they'll be dehydrated)
Monitor electrolytes and BP.


What "syndromes" are associated with auto-immune Addison's?

Polyglandular syndromes - stuff like T1D, thyroiditis... don't worry about the details.


5 signs of hyperaldosteronism? Why does each one happen?

1) Hypertension - water retention (following Na+).
2) Hypokalemia - aldosterone increases K+ excretion.
3) Mild hypernatremia - aldosterone increases Na+ resorption.
4) Metabolic alkylosis - adolesterone increases H+ excretion.
5) Muscle weakness - (electrolyte/pH imbalance?)


2 etiologies of hyperaldosteronism?

1) Benign aldosterone-producing adenoma.
2) Bilateral adrenal hyperplasia.


If blood pressure is high, what should renin levels be like? Test for this.

Renin should be low - and thus so should be aldosterone.
Can measure aldosterone:renin ratio after salt load.


Treatment for hyperaldosteronism caused by bilateral adrenal hyperplasia?

Mineralocorticocoid receptor antagonist.


Are adrenal adenomas secreting androgens common? Presentation in men vs. women?

No, they're not common.
Women - verilization.
Men - more subtle: impaired libido, fertility, etc. etc.


What do you call a catecholamine-secreting tumor?



Classic presentation of a pheo?

Spells of hypertension (headaches), feelings of doom, etc. due to epinephrine being dumped into system.


3 endocrine causes of hypertension?

1) Cushing's syndrome
2) Hyperaldosteronism
3) Pheochromocytoma


Is biopsy-ing a suspected pheo helpful?

No!!! That can cause a massive release of catecholamines that could kill the patient.
Surgical removal requires alpha blocking and beta blocking the patient first.


What are the 3 "Derangements" of the HPA Axis seen in Cushing's? (IE. What is the pathogenesis)

1) Loss of diurnal variation of cortisol secretion (normal= highest upon waking, lowest at bed time)
- Cortisol peaks are LONGER and HIGHER
2) Autonomy from "central" ACTH--> Loss of response to feedback inhibition
3) Excess cortisol secretion


If you suspect Cushing's--> get abnormal DST--> and get low ACTH- what is the cause? What is ATCH is normal or high?

If ACTH is low--> consider adrenal source

If ACTH is normal/high--> consider pituitary/ectopic source


How do you DX adrenal insufficiency?

1) Early AM cortisol levels/ ACTH concentration
2) Cosyntropin stimulation test
- Inject synthetic ACTH--> measure cortisol response at intervals
- If cortisol still low--> DX of adrenal failure