Distinguish between the clinical syndromes caused by ACTH-dependent and -independent Cushing's syndrome.
ACTH-dependent: Patients present with notable weight gain (especially around face and neck), diabetes, osteoporosis, hypertension, and other miscellany.
ACTH-independent: Same symptoms as -dependent. Subtle presentation makes for a difficult diagnosis...
What tests are available to test for hypercortisolism? (not distinguishing between primary/secondary)
Which is (not) preferred?
Urine steroid metabolites (not favored)
Overnight dexamethasone suppression test (cortisol should decrease in normal patients)
Midnight salivary cortisol (nadir is absent in Cushing's)
Name 4 conditions that can cause "physiologic" hypercortisolism
Stressors in general...
Name 3 conditions that are often copresent in Cushing's and should provoke suspicion for the disease.
Osteoporosis (especially in the pre-menopausal)
Adrenal nodules (often an incidental finding)
What should be the first consideration when evaluating for a potential hypercortisolism?
Patient exposure to glucocorticoids, ie are they on steroids.
If hypercortisolism can be established, what can distinguish a primary (ACTH-independent) from a secondary (ACTH-dependent) etiology?
Measure plasma ACTH; primary always presents with diminished ACTH while secondary can have elevated or inappropriately normal ACTH.
Say a patient presents with elevated (>10) cortisol and near-zero ACTH. What is the next step in the workup?
This is a primary hypercortisolism, evaluate the adrenal glands with CT imaging to find nodules, hyperplasia, adenomas or carcinomas.
Say a patient presents with elevated cortisol (>10) and high ACTH. What should the next step in the workup be?
What if this step yields no findings?
This is a secondary hypercortisolism; MRI the pituitary gland to look for adenomas.
If nothing is found, sample the inferior petrosal sinus for ACTH (optionally with a CRH stimulus). This will definitely distinguish a pituitary microadenoma from an ectopic tumor.
Describe the usual surgical interventions for primary and secondary Cushing's.
For primary (adrenal): Laparoscopic removal.
For secondary (pituitary): Transphenoidal removal.
When may bilateral adrenalectomy be considered? What are some possible consequences of this procedure?
What about radiotherapy?
Only as a last resort, eg Inoperable pituitary mass refractory to medical treatment. Decreased quality of life in general. Regrowth of a pituitary tumor due to lost GC negative feedback ("Nelson's syndrome")
Radiotherapy as an adjunctive for pituitary Cushing's after failed surgery.
What are the medical treatments of choice for a pituitary Cushing's?
Include mechanisms of action.
Pasireotide (somatostatin analog; for surgical non-candidates, with many side effects)
Cabergoline (dopamine receptor agonist; off-label)
Describe the two categories of medical treatment used to treat adrenal Cushing's disease.
Adrenal steroid inhibitors
Glucocorticoid receptor antagonists
Describe the mechanism of action and indications for the drugs Metyrapone and Mitotane
In the context of Cushing's disease, these drugs act as steroidogenesis inhibitors.
Metyrapone - 11b-OH inhibitor (off-label)
Mitotane - For adrenal cancer (lytic in high doses)
Name a glucocorticoid receptor antagonist.
What disease can result from the chronic abuse of this drug?
Addison's / Adrenal insufficiency. Makes sense, right?
Name two adrenal steroid inhibitors other than metyrapone and mitotane.
Ketoconazole (normally an anti-fungal) and Etomidate (normally a hypnotic).
Note that treating Cushing's is an off-label use for either.