Everything You Need to Know About Primary hyperaldosteronism (Conn syndrome) for Step 1

Primary hyperaldosteronism (Conn syndrome) is one of those adrenal topics that shows up everywhere on Step 1: hypertension workups, acid–base questions, renin/aldosterone arrows, and those “metabolic alkalosis + hypokalemia” vignettes. If you can recognize the physiology pattern quickly, you’ll pick up easy points.

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Big Picture: What Is Primary Hyperaldosteronism?

Primary hyperaldosteronism = autonomous aldosterone production from the adrenal cortex (zona glomerulosa), leading to:

• Sodium (Na⁺) retention → hypertension
• Potassium (K⁺) wasting → hypokalemia
• Hydrogen (H⁺) wasting → metabolic alkalosis
• Suppressed renin due to volume expansion → low plasma renin activity

Most common causes

• Bilateral idiopathic adrenal hyperplasia (most common overall)
• Aldosterone-producing adenoma (classic “Conn syndrome” in many resources)
• Less common: aldosterone-producing adrenal carcinoma, familial hyperaldosteronism

First Aid cross-reference: Endocrine → Adrenal disorders → Hyperaldosteronism (look for the aldosterone/renin patterns and HTN + hypokalemic alkalosis).

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Pathophysiology (Step 1 Level Deep Dive)

Aldosterone acts on principal cells and $\alpha$-intercalated cells in the collecting duct:

Principal cells: Na⁺ reabsorption, K⁺ secretion

Aldosterone upregulates:

• ENaC (epithelial sodium channel) on the luminal side
• Na⁺/K⁺ ATPase on the basolateral side
• ROMK activity (promotes K⁺ secretion)

Net effect:

• ↑ Na⁺ reabsorption → ↑ ECF volume → hypertension
• ↑ K⁺ secretion → hypokalemia

$\alpha$-intercalated cells: H⁺ secretion

Aldosterone increases:

• H⁺ ATPase activity → ↑ H⁺ secretion

Net effect:

• Metabolic alkalosis

Why edema usually doesn’t happen (“aldosterone escape”)

Despite Na⁺ retention, most patients don’t have dramatic edema because:

• Volume expansion triggers ANP/BNP
• Increased GFR + pressure natriuresis promotes Na⁺ excretion
• You still get hypertension, but not typically massive edema

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Clinical Presentation: What Shows Up in Vignettes?

Classic findings

• Hypertension (often resistant)
• Hypokalemia (may be mild or absent early)
• Metabolic alkalosis
• Low renin

Symptoms (often from low K⁺)

• Weakness, fatigue
• Muscle cramps
• Polyuria/polydipsia (hypokalemia can impair urinary concentrating ability)
• Paresthesias
• Palpitations (arrhythmias)

High-yield nuance: hypokalemia is not guaranteed

Many patients—especially with milder disease or high sodium intake—can have normal K⁺. Don’t rule it out just because potassium is normal.

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Key Labs and Patterns (Memorize the Arrow Logic)

Primary hyperaldosteronism lab pattern

• ↑ Aldosterone
• ↓ Renin
• ↑ Na⁺ (often normal or slightly high due to water following sodium)
• ↓ K⁺
• ↑ HCO₃⁻ (metabolic alkalosis)

Compare to look-alikes (extremely testable)

First Aid cross-reference: Endocrine → Adrenal pharmacology & pathology; Renal → Collecting duct physiology; Cardio/Renal → Secondary hypertension differentials.

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Diagnosis: Step-by-Step (How It’s Actually Tested)

1) Screening test: Aldosterone-to-renin ratio (ARR)

• ARR = plasma aldosterone concentration / plasma renin activity
• In primary hyperaldosteronism: aldosterone high + renin low → ARR high

High-yield screening clue: HTN + hypokalemic metabolic alkalosis → check ARR.

2) Confirmatory testing (prove autonomous aldosterone)

After a positive ARR, confirm with suppression testing:

• Saline infusion test (common): normal physiology suppresses aldosterone with volume expansion
  • In primary hyperaldosteronism: aldosterone fails to suppress
• Other options (less Step 1 detailed): oral sodium loading, fludrocortisone suppression, captopril challenge

3) Determine laterality: adenoma vs bilateral hyperplasia

This guides treatment.

• CT adrenal can identify a mass, but incidentalomas exist
• Adrenal venous sampling is the gold standard for lateralization (more Step 2/clinical)

Classic board-style fork:

• Unilateral aldosterone-producing adenoma → surgery helps
• Bilateral hyperplasia → medical therapy

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Treatment (What to Pick in Questions)

If unilateral aldosterone-producing adenoma

• Laparoscopic adrenalectomy
• Often improves BP and corrects hypokalemia

If bilateral adrenal hyperplasia (or not surgical candidate)

• Mineralocorticoid receptor antagonists:
  • Spironolactone (also blocks androgen receptor → side effects)
  • Eplerenone (more selective; fewer endocrine side effects)

High-yield adverse effects (Step 1 favorite)

• Spironolactone → antiandrogen effects:
  • Gynecomastia
  • Decreased libido, impotence
  • Menstrual irregularities
• Eplerenone → less gynecomastia (more selective MR blockade)

First Aid cross-reference: Pharm → Diuretics → K⁺-sparing diuretics (spironolactone/eplerenone).

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HY Associations & Rapid-Fire Testable Facts

“Primary hyperaldo” = low renin hypertension

If you see:

• HTN + low renin Think about:
• Primary hyperaldosteronism (aldosterone ↑)
• Liddle (aldosterone ↓)
• Apparent mineralocorticoid excess (aldosterone ↓)

Aldosterone biology: where it’s made + what regulates it

• Made in zona glomerulosa
• Regulated by:
  • Angiotensin II (RAAS)
  • Hyperkalemia
• ACTH has only a minor effect (test writers may bait you)

First Aid cross-reference: Adrenal cortex zonation: GFR → “Salt, Sugar, Sex”.

Why metabolic alkalosis happens (be able to explain it)

Aldosterone increases H⁺ secretion by $\alpha$-intercalated cells → ↑ HCO₃⁻ in blood.

ECG changes from hypokalemia (vignette spice)

• U waves, flattened T waves, arrhythmias (esp. with weakness/cramps)

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Common Step-Style Vignettes (What They’re Really Asking)

Vignette 1

Resistant HTN + muscle weakness + low K⁺ + metabolic alkalosis
Answer path: primary hyperaldo → ARR elevated → renin low

Vignette 2

HTN + hypokalemia + low renin + low aldosterone
Answer path: not Conn → think Liddle or licorice/AME

• Liddle: treat with amiloride/triamterene
• AME: treat by removing licorice, +/- MR antagonists

Vignette 3

HTN + hypokalemia + high renin
Answer path: secondary hyperaldo (renal artery stenosis, renin tumor)

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Quick Summary Table (One-Glance Memory)