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Bone Wizardry · Endocrine

Adrenal Adenomas

Conn vs Cushing vs Pheo · the triad that keeps coming back on boards.

Clinical Vignette
A 32-year-old woman presents with hypertension resistant to three antihypertensives. Labs show K+ 2.9 mEq/L, bicarb 33 mEq/L, normal glucose. No other symptoms. No medications before the antihypertensives. Which additional lab finding is most expected?

The Board Trap

45% of students pick the wrong answer on this one.

Why They Get It Wrong

The question gave you a young, healthy woman with hypertension, hypokalemia, and metabolic alkalosis. No other symptoms. No meds. Normal glucose.

45% of students picked "increased angiotensin II" · because they know aldosterone is high and assumed the whole RAAS chain must be up. That's the trap.

The Truth

In primary hyperaldosteronism, the tumor makes aldosterone on its own · it doesn't need renin or angiotensin II. The high aldosterone actually suppresses renin via negative feedback. Renin is LOW. Angiotensin II is LOW.

The correct answer is low plasma renin levels. The tumor bypasses the whole RAAS cascade.

Conn Syndrome

Primary Hyperaldosteronism

An aldosterone-secreting adenomaA benign tumor in the adrenal cortex (zona glomerulosa) that pumps out aldosterone independently of the RAAS system. It doesn't care what renin is doing · it just keeps making aldosterone. in the adrenal cortex. It makes aldosterone all by itself, ignoring the normal RAAS signals. 🔑Conn = Can't stop making aldosterone. The Connection to renin is Cut.

The Classic Triad

1. Hypertension · often resistant (won't respond to 3 drugs)

2. Hypokalemia · K+ < 3.5

3. Metabolic alkalosis · bicarb > 29

WHY Each Part of the Triad Happens

Hypertension

Aldosterone tells the collecting duct to reabsorb Na+. More Na+ retained = more water follows = blood volume up = BP up. Simple plumbing.

Hypokalemia

Aldosterone reabsorbs Na+ by exchanging it for K+ and H+. More aldosterone = more K+ dumped into urine = blood K+ drops.

Metabolic Alkalosis

Same exchange: Na+ in, H+ out. Dumping H+ into urine makes the blood more basic. Plus, hypokalemia itself causes alkalosis (H+ shifts into cells to replace K+).

The RAAS in Conn · see what's suppressed:

Kidney senses low BP → Renin
Angiotensinogen → Angiotensin I
ACE → Angiotensin II
bypassed
TUMOR → Aldosterone (unregulated)
Na+ retained, K+ & H+ dumped

Everything above the tumor is suppressed by negative feedback. The tumor doesn't need the RAAS cascade · it's autonomous.

Diagnosis

Aldosterone:Renin ratio · aldosterone is HIGH, renin is LOW. The ratio is elevated. This is the screening test. If the ratio is high, confirm with salt loading test (aldosterone stays high even when you flood the body with salt · because the tumor doesn't respond to feedback).

Quick Check
In Conn syndrome, renin levels are LOW because...

Primary vs Secondary

Both have high aldosterone. The difference is WHY.

Feature Primary (Conn) Secondary
Source of aldosterone Adrenal tumor (autonomous) Normal adrenals responding to high renin
Renin LOW (suppressed by feedback) HIGH (driving the aldosterone)
Angiotensin II LOW HIGH
Aldosterone:Renin ratio Very HIGH Normal or low
Cause Adrenal adenoma Low renal perfusion (CHF, cirrhosis, renal artery stenosis)
The kidney is... Fine · just suppressed by volume Sensing low flow → cranking out renin
Board Question Shortcut

Hypertension + hypokalemia + metabolic alkalosis? Check renin. Low renin = primary (Conn). High renin = secondary. That's it. 🔑Primary = the price of renin drops (low). Secondary = the kidney secretes renin (high).

The Adrenal Trio

Conn vs Cushing vs Pheo · three tumors, three hormones, three presentations.

If you can tell them apart, you get easy points.

Feature Conn (Aldo) Cushing (Cortisol) Pheo (Catecholamines)
Tumor location Cortex (zona glomerulosa) Cortex (zona fasciculata) Medulla
Hormone Aldosterone Cortisol Epi/NE/Dopamine
Presentation Usually asymptomatic, found on labs Moon facies, buffalo hump, striae, truncal obesity Episodic headache, sweating, palpitations
HTN pattern Resistant (won't budge on 3 drugs) Sustained Episodic (paroxysmal spikes)
BMP clue Hypokalemia + met alkalosis Hyperglycemia Normal
Diagnosis Aldosterone:renin ratio Late-night salivary cortisol, dex suppression Serum/urine metanephrines
Key fact #1 cause of resistant HTN Can be subclinical (still causes osteoporosis, DM) 10% malignant; alpha-block before surgery
Board Trap · Pheo Surgery

Pheo needs an alpha blocker BEFORE surgery. If you cut out a pheo without blocking alpha receptors first, the catecholamine surge during manipulation can cause a fatal hypertensive crisis. Phenoxybenzamine first, then surgery.

Board Trap · Incidentalomas

All adrenal incidentalomasAn adrenal mass found accidentally on imaging done for something else (CT for kidney stones, etc.). Even if the patient has no symptoms, you must screen for all three functional tumors. must be screened for all three · Conn, Cushing, AND Pheo · regardless of symptoms. Subclinical Cushing is real and dangerous long-term.

Board Traps

Don't fall for these.

Trap 1 · "Increased Angiotensin II" in Conn

45% of students picked this. In PRIMARY hyperaldosteronism, the RAAS cascade is suppressed. Renin LOW, Ang II LOW, aldosterone HIGH (from tumor). Only in SECONDARY would Ang II be high.

Trap 2 · Conn vs Type 4 RTA

Both involve aldosterone and potassium. But they're opposites. Conn = TOO MUCH aldosterone (hypokalemia, alkalosis). Type 4 RTA = TOO LITTLE aldosterone (hyperkalemia, acidosis).

Trap 3 · Normal Glucose Rules Out Cushing

This patient has normal glucose, which helps point away from Cushing (which causes hyperglycemia). But remember · subclinical Cushing exists with normal-looking labs. Always screen incidentalomas.

Trap 4 · "Decreased Renal Blood Flow" as Conn's Mechanism

Decreased renal blood flow causes SECONDARY hyperaldosteronism (high renin). Conn syndrome is PRIMARY · the tumor acts independently of renal perfusion.

Test Day Algorithm

Step-by-step decision tree for the exam.

1

Young patient + hypertension + hypokalemia + metabolic alkalosis? → Think Conn syndrome

2

Check renin.
Low renin = primary (tumor makes its own aldosterone)
High renin = secondary (kidney is responding to low perfusion)

3

If the question asks "what additional finding" · low renin is the answer. Not high Ang II (that's suppressed too).

4

If HTN is episodic with sweating/headache/palpitations → Pheo (check metanephrines).
If moon facies + striae + hyperglycemia → Cushing (check cortisol).

Decision Tree: Adrenal Incidentaloma Workup

Adrenal mass found on imaging. Follow the branch points.

Adrenal mass found incidentally on imaging. Where do you go first?

Quiz

4 Adrenal Tumors Walk Into a Clinic · let's see if you can tell them apart.