Cushing's & adrenal insufficiency flashcards
23 high-yield MRCP Part 1 cards from the Intellect Medicos Endocrinology & Diabetes course. Try to answer each question before you open it — then study them properly with spaced repetition, which brings each card back just before you would forget it.
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What is the most common cause of Cushing's syndrome?
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Iatrogenic — exogenous glucocorticoid therapy.
Why? Among endogenous causes, Cushing's disease (an ACTH-secreting pituitary adenoma) is the commonest.
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Cushing's DISEASE is hypercortisolism caused by an ______.
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ACTH-secreting pituitary adenoma
Why? Cushing's SYNDROME is the clinical state of cortisol excess from any cause.
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Which cause of Cushing's syndrome most often produces marked pigmentation and severe hypokalaemia?
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Ectopic ACTH secretion (e.g. small cell lung cancer).
Why? Very high ACTH levels stimulate melanocytes, and very high cortisol overwhelms 11β-HSD2 so cortisol acts on mineralocorticoid receptors.
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What is the first-line screening test for suspected Cushing's syndrome?
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1 mg overnight dexamethasone suppression test.
Why? In health, 1 mg dexamethasone at night suppresses 9am cortisol; failure to suppress suggests hypercortisolism.
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Once hypercortisolism is confirmed, which blood test separates adrenal from ACTH-dependent Cushing's?
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Plasma ACTH — low (suppressed) ACTH points to an adrenal cause.
Why? An adrenal tumour makes cortisol autonomously and suppresses pituitary ACTH; pituitary and ectopic causes have normal or high ACTH.
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On a high-dose dexamethasone suppression test, which cause of Cushing's shows cortisol suppression?
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A pituitary ACTH adenoma (Cushing's disease).
Why? Pituitary adenomas keep some feedback sensitivity at high doses; ectopic ACTH and adrenal tumours do not suppress.
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Which test best distinguishes pituitary from ectopic ACTH secretion when pituitary MRI is inconclusive?
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Inferior petrosal sinus sampling (IPSS).
Why? A central-to-peripheral ACTH gradient (especially after CRH) shows the ACTH is coming from the pituitary.
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What is the treatment of choice for Cushing's disease?
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Trans-sphenoidal removal of the pituitary adenoma.
Why? External pituitary irradiation is used after failed surgery; bilateral adrenalectomy is a last resort.
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What is the mechanism of action of metyrapone in Cushing's syndrome?
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It inhibits 11β-hydroxylase, blocking the final step of cortisol synthesis.
Why? It is used to control cortisol before surgery or radiotherapy. Osilodrostat works the same way and is more potent.
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When metyrapone is used to control Cushing's, what mean serum cortisol is targeted on a day curve?
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About 150–300 nmol/L.
Why? This range removes the harm of cortisol excess without causing adrenal insufficiency.
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Which important adverse effect must be monitored when ketoconazole is used to treat Cushing's syndrome?
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Hepatotoxicity — monitor liver function tests.
Why? Ketoconazole blocks several steroid-synthesis enzymes; liver injury is its main serious risk.
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Which intravenous drug can be used to lower cortisol rapidly in severe, life-threatening hypercortisolism?
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Etomidate infusion.
Why? At low (non-anaesthetic) doses etomidate inhibits 11β-hydroxylase and acts within hours.
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After bilateral adrenalectomy for Cushing's disease, a patient develops increasing skin pigmentation and an enlarging pituitary mass. What is the syndrome?
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Nelson syndrome.
Why? Loss of cortisol negative feedback lets the ACTH-secreting adenoma grow; very high ACTH causes pigmentation. Treat with trans-sphenoidal surgery and/or radiotherapy.
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What is the most common cause of pseudo-Cushing's syndrome?
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Alcohol excess (often with a raised MCV).
Why? Alcohol raises CRH and impairs hepatic cortisol metabolism. It resolves with abstinence. Obesity, depression and chronic stress are other causes.
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What is the most common cause of Addison's disease in the UK?
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Autoimmune adrenalitis.
Why? Tuberculosis is a common cause where TB and HIV are prevalent.
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Which adrenal autoantibodies are most commonly found in autoimmune Addison's disease?
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21-hydroxylase antibodies.
Why? Adrenal antibodies are positive in about 90% of autoimmune adrenalitis.
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Why are hyperkalaemia and hyperpigmentation seen in primary but not secondary adrenal insufficiency?
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Primary disease destroys aldosterone production (hyperkalaemia) and raises ACTH (pigmentation); secondary disease has low ACTH and intact aldosterone.
Why? Aldosterone is controlled mainly by the renin–angiotensin system, so it is preserved when only ACTH is lacking.
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What test confirms adrenal insufficiency?
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Short Synacthen (ACTH stimulation) test — an absent or impaired cortisol rise.
Why? A random daytime cortisol <100 nmol/L strongly suggests the diagnosis and >550 nmol/L makes it unlikely, but the Synacthen test confirms it.
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Low cortisol with a high 9am plasma ACTH indicates which type of adrenal insufficiency?
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Primary adrenal insufficiency (Addison's disease).
Why? Low or inappropriately normal ACTH with low cortisol indicates secondary (pituitary) adrenal insufficiency.
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What is the immediate drug treatment of an adrenal (Addisonian) crisis?
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Hydrocortisone 100 mg IV (or IM) immediately, with IV 0.9% saline.
Why? Then give 200 mg/24 h by continuous IV infusion (or 50 mg IV/IM 6-hourly) with rapid IV 0.9% saline (about 1 L in the first hour). Correct hypoglycaemia, and do not delay treatment to wait for cortisol results.
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Why is fludrocortisone not needed in the acute management of adrenal crisis?
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High-dose hydrocortisone has enough mineralocorticoid activity on its own.
Why? Fludrocortisone is introduced once the hydrocortisone dose is reduced, before discharge.
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What is the standard long-term drug replacement in Addison's disease?
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Hydrocortisone (glucocorticoid) plus fludrocortisone (mineralocorticoid).
Why? Both cortisol and aldosterone are lost in primary adrenal failure.
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What is the steroid "sick day rule" for a patient on replacement hydrocortisone with a febrile illness?
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Double the glucocorticoid dose during the intercurrent illness.
Why? The body normally raises cortisol under stress; replacement doses must mimic this to prevent crisis. Patients should also carry a steroid card and have emergency IM hydrocortisone at home.
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