You’re cruising through a hypertension question in a Q-bank, and suddenly the vignette hits you with hypokalemia and metabolic alkalosis. This is one of those moments where Step writers are basically waving a flag that says: “Don’t just pick the right diagnosis—prove you can rule out the close cousins.” Let’s break down a classic Conn syndrome (primary hyperaldosteronism) vignette and then walk through why every answer choice matters.
Tag: Cardiovascular > Hypertension & Vascular Disease
The Clinical Vignette (Classic Q-bank Style)
A 38-year-old woman has persistent hypertension despite lifestyle changes. She reports intermittent muscle weakness and cramps. She takes no medications. BP is 168/96 mm Hg. Labs show:
- Na⁺: 145 mEq/L
- K⁺: 2.9 mEq/L
- HCO₃⁻: 32 mEq/L
- Plasma renin activity: low
- Plasma aldosterone: high
CT shows a small unilateral adrenal nodule.
Question: What is the most likely cause of her hypertension?
Correct Answer: Conn Syndrome (Primary Hyperaldosteronism)
What it is
Conn syndrome = autonomous aldosterone secretion, most commonly from:
- Aldosterone-producing adrenal adenoma (unilateral)
- Bilateral adrenal hyperplasia (more common than adenoma in some populations, but adenoma is the “classic” board vignette)
Why it causes HTN
Aldosterone increases:
- Na⁺ reabsorption (via principal cells in collecting duct) → intravascular volume expansion → HTN
- K⁺ secretion → hypokalemia
- H⁺ secretion (via alpha-intercalated cells) → metabolic alkalosis
The diagnostic “pattern”
The Step-friendly triad is:
- HTN
- Hypokalemia
- Metabolic alkalosis
- plus low renin due to volume expansion (negative feedback)
Best initial screening test
- Aldosterone-to-renin ratio (ARR): elevated in primary hyperaldosteronism
- High aldosterone + suppressed renin = big ratio
Confirmatory testing (often asked Step 2-style)
- Saline infusion test: aldosterone should suppress in normal physiology
- In Conn: fails to suppress
Next step: differentiate unilateral vs bilateral
- CT can show nodules, but adrenal vein sampling is often the best way to lateralize if surgery is planned (because incidentalomas exist).
Treatment
- Unilateral adenoma: laparoscopic adrenalectomy
- Bilateral hyperplasia: mineralocorticoid receptor antagonists
- Spironolactone (anti-androgen side effects: gynecomastia, impotence)
- Eplerenone (fewer anti-androgen effects)
Why Each Distractor Matters (And How to Kill It Fast)
Below are the most common answer choices writers use to test whether you understand the renin–aldosterone axis and how to interpret K⁺ and acid–base clues.
Quick Comparison Table (High-Yield)
| Condition | Renin | Aldosterone | K⁺ | Acid–base | Key clue |
|---|---|---|---|---|---|
| Conn (primary hyperaldo) | Low | High | Low | Metabolic alkalosis | Adrenal adenoma/hyperplasia |
| Renal artery stenosis (secondary hyperaldo) | High | High | Low (often) | Metabolic alkalosis | Abdominal bruit, flash pulm edema |
| Liddle syndrome | Low | Low | Low | Metabolic alkalosis | ENaC activation; responds to amiloride |
| Apparent mineralocorticoid excess / licorice | Low | Low | Low | Metabolic alkalosis | 11β-HSD2 inhibited; cortisol acts like aldosterone |
| Pheochromocytoma | Variable | Variable | Usually normal | — | Episodic HA, sweating, palpitations |
| Cushing syndrome | Low-ish | Low-ish | Sometimes low | Metabolic alkalosis possible | Cortisol excess; striae, proximal weakness |
| Addison disease | High | Low | High | Non-anion gap metabolic acidosis | Hypotension, hyperpigmentation |
Distractor 1: Renal Artery Stenosis (Secondary Hyperaldosteronism)
Why it tempts you
It can also cause:
- HTN
- hypokalemia
- metabolic alkalosis
How to rule it out
Secondary hyperaldosteronism has:
- High renin
- High aldosterone
So if the stem gives low renin, renal artery stenosis is out.
Clues pointing to RAS instead of Conn:
- Abdominal bruit
- Sudden-onset severe HTN
- Rise in creatinine after ACE inhibitor
- Recurrent “flash” pulmonary edema (especially with bilateral RAS)
Distractor 2: Liddle Syndrome
What it is
Gain-of-function mutation in ENaC (collecting duct) → increased Na⁺ reabsorption independent of aldosterone.
Similarities to Conn
- HTN
- Hypokalemia
- Metabolic alkalosis
Key distinguishing labs
- Low renin
- Low aldosterone
So if aldosterone is high, it’s not Liddle.
Treatment (classic Step fact)
- Amiloride or triamterene (ENaC blockers)
- Spironolactone doesn’t help much because aldosterone is already low.
Distractor 3: Apparent Mineralocorticoid Excess (AME) / Licorice Ingestion
What it is
Problem with 11β-HSD2, which normally converts cortisol → cortisone in mineralocorticoid-sensitive tissues.
- If 11β-HSD2 is inhibited (e.g., licorice/glycyrrhetinic acid) or genetically deficient, cortisol activates mineralocorticoid receptors.
Looks like hyperaldosteronism clinically
- HTN
- Hypokalemia
- Metabolic alkalosis
But labs show
- Low renin
- Low aldosterone (because the body senses volume expansion)
If the question stem includes “licorice,” “chewing tobacco,” or an “herbal supplement,” this should jump to mind.
Distractor 4: Pheochromocytoma
Why it shows up in HTN blocks
Because it’s a board-favorite cause of secondary hypertension.
How to rule it out fast
Pheo causes catecholamine surges:
- Episodic headaches
- Sweating
- Palpitations
- Tremor
- Anxiety
- Orthostatic hypotension can occur
Electrolytes usually aren’t the clue—you don’t typically get the Conn-style hypokalemic metabolic alkalosis pattern.
Best test: plasma free metanephrines (screening) or 24-hour urine metanephrines/catecholamines.
Distractor 5: Cushing Syndrome (Glucocorticoid Excess)
Why it’s tricky
At high levels, cortisol can have mineralocorticoid effects (especially if 11β-HSD2 is overwhelmed), leading to:
- HTN
- sometimes hypokalemia
- sometimes metabolic alkalosis
How to differentiate
Look for Cushing features:
- Central obesity
- Purple striae
- Proximal muscle weakness
- Easy bruising
- Glucose intolerance
- Osteoporosis
Labs won’t show the clean “high aldosterone, low renin” pattern of Conn.
Distractor 6: Addison Disease (Primary Adrenal Insufficiency)
Why writers include it
It tests whether you understand that aldosterone deficiency does the opposite of Conn syndrome.
What you’d expect instead
- Hypotension
- Hyperkalemia
- Non-anion gap metabolic acidosis (type 4 RTA physiology—low aldosterone → reduced H⁺ and K⁺ excretion)
- Hyperpigmentation (high ACTH)
So Addison is a polarity check: if the stem screams “low K and alkalosis,” Addison is not your answer.
Step-Smart Takeaways (High-Yield)
- Primary hyperaldosteronism (Conn) = high aldosterone, low renin, plus hypokalemic metabolic alkalosis.
- Secondary hyperaldosteronism (renal artery stenosis, renin-secreting tumor) = high renin, high aldosterone.
- Liddle + AME/licorice mimic hyperaldosteronism clinically but have low aldosterone.
- When the question mentions resistant HTN, think secondary causes; when it adds hypokalemia, think aldosterone/ENaC axis.
- Don’t be fooled by adrenal nodules alone—incidentalomas exist; ARR is your screening anchor.
Rapid-Fire Practice: One-Liners You Should Be Able to Say
- “Low renin + high aldosterone = primary hyperaldosteronism.”
- “High renin + high aldosterone = secondary hyperaldosteronism.”
- “Low renin + low aldosterone + alkalosis = Liddle or AME.”
- “Hypokalemia + metabolic alkalosis narrows it to mineralocorticoid effect or diuretics.”