Adrenal disorders

13 DOH Abu Dhabi (HAAD) lab licensing practice questions on Adrenal disorders, part of Clinical Chemistry. The first 13 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

1. Question 1 · Hard

   A 52-year-old man has new hypertension of 170/104 mm Hg and muscle weakness. During Ramadan he has been drinking about 1.5 L a day of a traditional licorice-root drink, and he takes no medicines. Results: sodium 144 mmol/L, potassium 2.7 mmol/L (reference 3.5-5.1), bicarbonate 33 mmol/L (reference 22-29), plasma renin activity 0.1 ng/mL/h (reference 0.5-3.3), aldosterone 70 pmol/L (2.5 ng/dL; reference 100-850 pmol/L) and 08:00 cortisol 410 nmol/L (14.9 µg/dL; reference 140-690). A spot urine shows potassium loss that is inappropriately high for the plasma level. The most likely cause is:

   1. ARenovascular hypertension from stenosis
   2. BCushing syndrome from ectopic ACTH
   3. CLicorice inhibiting renal 11β-HSD2
   4. DPrimary aldosteronism (Conn syndrome)

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   Answer: C · Licorice inhibiting renal 11β-HSD2

   Hypertension, hypokalemia with renal potassium loss and metabolic alkalosis show mineralocorticoid excess, but both renin and aldosterone are suppressed, so aldosterone is not the cause. Glycyrrhetinic acid from licorice inhibits 11β-hydroxysteroid dehydrogenase type 2, the kidney enzyme that converts cortisol to inactive cortisone. Cortisol, present at far higher levels than aldosterone, then occupies the mineralocorticoid receptor, a picture called apparent mineralocorticoid excess. Primary aldosteronism has a high aldosterone, renovascular disease raises both renin and aldosterone, and ectopic ACTH gives a very high cortisol. The abnormalities resolve over some weeks after the drink is stopped.

   • A: Renal artery stenosis raises both renin and aldosterone.
   • B: Ectopic ACTH causes hypokalemia through very high cortisol; here cortisol is normal.
   • D: Primary aldosteronism has a high aldosterone with a low renin; here aldosterone is low.

2. Question 2 · Medium

   A 28-year-old woman taking a combined oral contraceptive has an overnight 1 mg dexamethasone suppression test. Her 8 AM serum cortisol is 95 nmol/L (3.4 µg/dL; normal suppression < 50 nmol/L [1.8 µg/dL]). Late-night salivary cortisol is normal. The most likely reason for the failed suppression is:

   1. AEctopic ACTH secretion
   2. BA pituitary corticotroph adenoma
   3. CA cortisol-secreting adrenal adenoma
   4. DRaised cortisol-binding globulin

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   Answer: D · Raised cortisol-binding globulin

   Serum cortisol assays measure total cortisol, most of which is bound to cortisol-binding globulin (CBG). Oral estrogen raises CBG, so total cortisol stays higher after dexamethasone even when free cortisol is suppressed, a common cause of false-positive tests. Salivary cortisol reflects the free hormone and is not affected by CBG, which fits her normal result. Estrogen-containing drugs are stopped for about 6 weeks before serum cortisol testing, or salivary or urine free cortisol is used instead.

   • A: Ectopic ACTH causes marked cortisol excess and a raised salivary cortisol.
   • B: Cushing disease would also raise late-night salivary cortisol.
   • C: An adrenal adenoma would also raise late-night salivary cortisol.

3. Question 3 · Medium

   Which antihypertensive drug most often raises renin and can make a true primary aldosteronism look negative on the aldosterone-to-renin ratio?

   1. ASpironolactone
   2. BDoxazosin
   3. CAtenolol
   4. DVerapamil

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   Answer: A · Spironolactone

   Mineralocorticoid receptor antagonists such as spironolactone block aldosterone's action, and the resulting sodium loss raises renin. A raised renin lowers the ratio and can hide primary aldosteronism, so the drug is often stopped for 4-6 weeks before testing when it is safe, unless renin is already suppressed despite it. Beta-blockers have the opposite effect: they suppress renin and can cause false-positive ratios. Verapamil and alpha-blockers such as doxazosin have little effect and are used to control blood pressure during testing.

   • B: Doxazosin has little effect on the ratio and is often used during testing.
   • C: Beta-blockers suppress renin and tend to cause false-positive ratios.
   • D: Verapamil has little effect on the ratio.

4. Question 4 · Hard

   Screening results in a man with hypertension: potassium 4.1 mmol/L, aldosterone 416 pmol/L, plasma renin activity 0.30 ng/mL/h. The laboratory's cut-off is an aldosterone-to-renin ratio above 30, using aldosterone in ng/dL (pmol/L divided by 27.7) and renin activity in ng/mL/h. What is the ratio and its meaning?

   1. A0.02: a negative screen
   2. B50: a positive screen
   3. C1,387: a positive screen
   4. D4.5: a negative screen

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   Answer: B · 50: a positive screen

   First convert aldosterone to the units of the cut-off: 416 / 27.7 = 15 ng/dL. Then divide by renin activity: 15 / 0.30 = 50, which is above 30, so the screen is positive. A positive ratio is a screening result: it is usually followed by a confirmatory suppression test, such as saline infusion or captopril challenge, and then subtype studies. Multiplying instead of dividing gives 4.5, inverting the ratio gives 0.02, and leaving aldosterone in pmol/L gives 1,387.

   • A: 0.02 is the inverted ratio, renin divided by aldosterone.
   • C: 1,387 uses aldosterone in pmol/L, not the units of the cut-off.
   • D: 4.5 comes from multiplying aldosterone by renin instead of dividing.

5. Question 5 · Hard

   A 45-year-old woman develops a round face, purple striae and easy bruising after months of taking unlabeled herbal capsules for joint pain. At 8 AM, serum cortisol is 25 nmol/L (0.9 µg/dL; reference 140-690 nmol/L) and ACTH < 1.1 pmol/L (< 5 pg/mL; reference 1.6-13.9 pmol/L). The most likely explanation is:

   1. APrimary adrenal insufficiency
   2. BA hidden synthetic glucocorticoid
   3. CEctopic ACTH secretion
   4. DA cortisol-secreting adrenal adenoma

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   Answer: B · A hidden synthetic glucocorticoid

   Cushingoid features with both a low cortisol and a low ACTH mean that something other than cortisol is causing glucocorticoid excess while suppressing the pituitary-adrenal axis. Potent synthetic glucocorticoids such as dexamethasone are not detected by most cortisol immunoassays. Unlabeled herbal products have been found to contain undeclared steroids, and stopping them suddenly can cause adrenal crisis because the adrenals have atrophied. LC-MS/MS steroid screening of serum or urine can identify the drug.

   • A: Primary adrenal insufficiency gives a low cortisol with a high ACTH and no Cushingoid features.
   • C: Ectopic ACTH secretion raises both ACTH and cortisol.
   • D: An adrenal adenoma raises cortisol while it suppresses ACTH.

6. Question 6 · Medium

   For plasma free metanephrines, false-positive results are fewest when blood is collected:

   1. AAfter a standard breakfast with coffee
   2. BImmediately after a brisk walk
   3. CSeated, as soon as the patient arrives
   4. DSupine, after resting for about 30 minutes

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7. Question 7 · Hard

   A hypertensive patient has a tumor beside the aortic bifurcation. Plasma normetanephrine is 6.2 nmol/L (1,136 pg/mL; reference < 0.9 nmol/L) and plasma metanephrine is normal. Why is metanephrine not raised?

   1. AThe tumor lacks COMT, so forms no metanephrine
   2. BMetanephrine is cleared too fast to accumulate
   3. CThe tumor lacks PNMT, so makes no epinephrine
   4. DEpinephrine is stored in the tumor, not released

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8. Question 8 · Hard

   Five days after removal of a large pituitary adenoma, a 250 µg cosyntropin test gives a 30-minute cortisol of 610 nmol/L (22 µg/dL; laboratory cut-off for an adequate response 500 nmol/L [18 µg/dL]). Why may this normal result be falsely reassuring?

   1. AThe adrenals have not yet atrophied
   2. BSurgical stress raises cortisol-binding globulin
   3. CCortisol peaks only after 24 hours of stimulation
   4. DCosyntropin acts directly on the pituitary

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9. Question 9 · Hard

   A 22-year-old woman has hirsutism and irregular periods. An early-morning, follicular-phase 17-hydroxyprogesterone is 18 nmol/L (594 ng/dL; reference < 6 nmol/L). Sixty minutes after cosyntropin it rises to 75 nmol/L (2,475 ng/dL). Which diagnosis fits best?

   1. APolycystic ovary syndrome
   2. BAndrogen-secreting adrenal tumor
   3. CNon-classic 21-hydroxylase deficiency
   4. DClassic salt-wasting CAH

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10. Question 10 · Easy

    Aldosterone secretion by the zona glomerulosa is controlled mainly by:

    1. AADH and plasma osmolality
    2. BACTH and serum cortisol
    3. CNatriuretic peptides and sodium
    4. DAngiotensin II and serum potassium

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11. Question 11 · Medium

    Which drug class most often causes a falsely raised plasma normetanephrine?

    1. AHMG-CoA reductase inhibitors
    2. BProton pump inhibitors
    3. CTricyclic antidepressants
    4. DThyroid hormone replacement

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12. Question 12 · Medium

    Plasma ACTH should be collected and handled as follows:

    1. AHeparin tube left at room temperature overnight
    2. BPlain tube, clotted at room temperature
    3. CEDTA plastic tube on ice, spun cold, frozen
    4. DCitrate tube kept warm at 37 °C

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13. Question 13 · Easy

    Urine homovanillic acid (HVA) and vanillylmandelic acid (VMA) are measured together mainly to detect:

    1. ACarcinoid tumor
    2. BPrimary aldosteronism
    3. CNeuroblastoma
    4. DCushing disease

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