HY lecture notes:
Difference between Cushing syndrome and Cushing disease? –> syndrome = what you look like + can be any cause of Cushingoid appearance; Cushing disease only = anterior pituitary ACTH-secreting tumor; in other words, Cushing disease is a cause of Cushing syndrome.
Most common cause of Cushing syndrome –> exogenous glucocorticoids (e.g., prednisone).
34F + SLE + point tenderness over vertebra; Dx? –> Cushing due to exogenous steroids leading to osteoporotic compression fracture. HY.
Pt not on exogenous steroids + Cushingoid; most common cause? –> Cushing disease most common cause of endogenous Cushing syndrome.
Main causes of Cushing syndrome? –> exogenous steroids (most common overall), Cushing disease (most common endogenous), small cell bronchogenic carcinoma (ectopic ACTH), cortisol-secreting tumor (or diffuse hyperplasia) of zona fasculata of adrenal cortex; CRH tumor rare as fuck.
Patient with chronic disease (i.e., IBD, SLE, RA) + Cushingoid; what are the ACTH + cortisol levels –> need to know this means patient is taking prednisone –> low ACTH + low cortisol (prednisone is NOT the same thing as cortisol) –> prednisone suppresses CRH and ACTH secretion at hypothalamus and anterior pituitary –> decreased endogenous cortisol production.
Patient with Cushing disease; ACTH + cortisol levels? –> high ACTH + high cortisol.
Smoker + Cushingoid –> small cell bronchogenic carcinoma.
Smoker + Cushingoid; ACTH + cortisol levels? –> high ACTH (ectopic) + high cortisol.
When to do dexamethasone suppression test –> Cushingoid patient not on exogenous glucocorticoids and has high serum cortisol.
Low-dose dexamethasone suppression test –> tells us yes or no, patient has pathologic cause of Cushing syndrome (i.e., Cushing disease, or SCC of lung, or cortisol-secreting tumor), but we can’t establish the causation from this; if cortisol doesn’t suppress –> yes, patient has true Cushing syndrome (proceed to high-dose test); if cortisol suppresses à no, patient does not have Cushing syndrome (do not proceed to high-dose test).
High-dose dex –> only cause of Cushing syndrome that will suppress in response is Cushing disease.
Pt has no suppression to low-dose dex + suppresses to high-dose –> Dx = Cushing disease (ACTH secreting tumor of anterior pituitary).
Pt has no suppression to low- or high-dose dex –> ACTH high? –> Yes, answer = SCC of lung; No, answer = cortisol-secreting tumor (or diffuse hyperplasia) of adrenal cortex.
Cushingoid + low ACTH + low cortisol –> exogenous steroids.
Cushingoid + low ACTH + high cortisol –> cortisol-secreting tumor (or diffuse hyperplasia) of adrenal cortex.
Cushingoid + high ACTH + high cortisol –> Cushing disease.
Most accurate test for Dx Cushing syndrome –> 24-hour urine cortisol.
Why dex test not most accurate? –> false-positives in e.g., depression, alcoholism.
Acanthosis nigricans + low K + hyperpigmentation –> Cushing syndrome.
Why acanthosis nigricans –> caused by insulin resistance (unrelated: also can be caused by visceral malignancies).
Why low K in Cushing syndrome –> chronic elevation of glucocorticoid effect at kidney can push out potassium similar to aldosterone.
Why hyperpigmentation –> high ACTH secretion means POMC is high –> high alpha-MSH as well.
Purple striae in obese patient –> Cushing syndrome –> cortisol weakens connective tissue and causes microbleeds.
Why purple striae? –> glucocorticoids weaken collagen –> once again, this causes microbleeding into skin.
Why hypertension in Cushing syndrome –> cortisol upregulates alpha-1 receptors on arterioles, thereby allowing NE and E to do their job.
Graph shows you two scenarios: 1) NE given alone, then BP increases a little; 2) NE + cortisol given together, then BP increases a lot; why the difference? –> cortisol is permissive of the effects of catecholamines (don’t choose synergistic or additive); once again, cortisol merely allows NE and E to do their job; cortisol isn’t directly increasing BP.
Why normally ratio of E to NE in the blood is 80/20? –> NE draining venously out of the adrenal medulla passes through the adrenal cortex –> cortisol upregulates PNMT (converts NE to E).
What does low cortisol cause? –> chronic fatigue syndrome (super important).
