Conn's Syndrome (Primary Hyperaldosteronism)
Summary
Primary Hyperaldosteronism (PA) is the autonomous hypersecretion of aldosterone from the adrenal cortex (Zona Glomerulosa), leading to suppression of renin. It is the most common cause of secondary hypertension (accounting for 5-10% of all hypertension). The classic picture is Hypertension with Hypokalaemia, though up to half of patients are normokalaemic. The two main causes are Unilateral Adrenal Adenoma ("Conn's Syndrome" - 35%) and Bilateral Adrenal Hyperplasia (60%). Distinguishing between them is crucial as the former is surgically curable, while the latter requires lifelong medication. [1,2]
Key Facts
- Mechanism: Aldosterone acts on the Principal Cells of the Collecting Duct. It upregulates the Na+/K+ ATPase pump and ENaC channels, reclaiming Sodium (and Water) constantly, while dumping Potassium and Hydrogen ions into the urine.
- Aldosterone is Toxic: Independent of BP, excess aldosterone causes fibrosis in the heart (LVH), kidneys (Proteinuria), and vessels (Stroke). PA patients have higher cardiovascular morbidity than essential hypertensives matched for BP.
- Screening Gap: It is vastly under-diagnosed. Guidelines recommend screening anyone with "Resistant Hypertension" (on 3+ drugs), hypertension with hypokalaemia, or hypertension less than 40 years.
Clinical Pearls
The Spironolactone Trap: Spironolactone is a Mineralocorticoid Receptor Antagonist. If you measure the Aldosterone/Renin ratio while the patient is on it, the result is invalid (Renin rises). It must be laid off for 4-6 weeks (switch to Doxazosin/CCB) before testing.
Incidentalomas: 5% of healthy adults have a benign lump in the adrenal gland. If you do a CT and see a lump in a PA patient, you cannot assume it is the source. The "lump" might be non-functioning, while the "normal" gland is hyperplastic. Only Adrenal Vein Sampling (AVS) can tell the difference.
Normokalaemic PA: Hypokalaemia is a late sign. Do not wait for low potassium to screen for PA in resistant hypertension.
Demographics
- Prevalence: 5-13% of all hypertensive patients.
- Age: 30-50 years.
- Sex: Female > Male for Adenomas; Male > Female for Hyperplasia.
Causes
- Bilateral Adrenal Hyperplasia (Idiopathic): 60%.
- Aldosterone-Producing Adenoma (APA) (Conn's): 35%.
- Unilateral Hyperplasia: 2%.
- Adrenal Carcinoma: less than 1% (Very rare, very high levels).
- Familial Hyperaldosteronism: Types I, II, III (RARE).
RAAS Failure
- Normal: Low BP -> Renin -> Angiotensin II -> Aldosterone -> Na+ retention -> BP normalises.
- Conn's: Adrenal makes Aldosterone autonomously -> Na+ retention -> High BP -> Renin Suppressed.
- Therefore, the hallmark is High Aldosterone : Low Renin.
Metabolic Consequences
- Hypokalaemia: Muscle weakness, cramps, polyuria (Nephrogenic DI), arrhythmia.
- Metabolic Alkalosis: Due to H+ excretion. Can cause tetany/paraesthesia (low ionised calcium).
Symptoms
- Blood Pressure: Elevated.
- Fundoscopy: Hypertensive retinopathy.
- Fluid Status: Rarely oedematous (thanks to "Aldosterone Escape" phenomenon - ANP rises to cause natriuresis, preventing frank oedema).
Preparation
- Correct hypokalaemia.
- Stop Spironolactone/Eplerenone (4-6w). Stop Beta-blockers, ACEi, ARBs, Diuretics (2w) if possible (use Doxazosin/Verapamil).
Screening
- Aldosterone : Renin Ratio (ARR):
- High Aldosterone (>400-500 pmol/L).
- Low/Suppressed Renin (or DRI).
- A significantly elevated ratio suggests PA.
Confirmatory
- Saline Suppression Test:
- Infuse 2L Saline over 4 hours.
- Normal response: Aldosterone drops (suppressed by volume load).
- PA: Aldosterone remains high (autonomous).
Localization
- CT Adrenals: To look for masses/carcinoma.
- Adrenal Vein Sampling (AVS):
- Gold Standard.
- Catheters placed in both adrenal veins to measure Aldo/Cortisol ratio.
- If one side is >4x the other -> Lateralisation -> Surgery.
- If equal -> Bilateral -> Medical.
Management Algorithm
CONFIRMED HYPERALDOSTERONISM
(High ARR + Failed Suppression)
↓
CT ADRENALS
↓
ADRENAL VEIN SAMPLING (AVS)
(Essential unless young + overt adenoma)
↓
┌────────────┴────────────┐
UNILATERAL BILATERAL
(Conn's Adenoma) (Hyperplasia)
↓ ↓
LAP ADRENALECTOMY MEDICAL THERAPY
(Curative) (MRA Antagonists)
- Spironolactone
- Eplerenone
1. Surgical (Unilateral Disease)
- Laparoscopic Adrenalectomy: Treatment of choice for Adenoma.
- Cure of hypokalaemia: 100%.
- Cure of Hypertension: 50% (long standing HTN causes permanent vessel damage).
- Pre-op: Treat with Spironolactone for 4 weeks to normalise K+.
2. Medical (Bilateral Disease)
- Spironolactone:
- Mechanism: Non-selective mineralocorticoid receptor antagonist.
- Dose: 12.5mg - 50mg OD.
- Side Effects: Gynecomastia, breast pain, erectile dysfunction (blocks testosterone).
- Eplerenone:
- Mechanism: Selective antagonist.
- Pros: No gynecomastia.
- Cons: Less potent, twice daily dosing, expensive. Used if intolerant of Spiro.
- Amiloride: K+ sparing diuretic (blocks ENaC). Third line.
- Cardiovascular: Stroke, MI, Atrial Fibrillation (Aldo excess causes atrial fibrosis).
- Renal: Chronic Kidney Disease.
- Earlier treatment = better CV outcomes.
- Patients with PA have higher risk of stroke/MI than essential hypertensives if left untreated.
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Primary Aldosteronism | Endocrine Society (2016) | Screen all resistant HTN. AVS before surgery. |
| Hypertension | NICE / ESC | Spironolactone is 4th line for resistant HTN (often due to undiagnosed PA). |
Landmark Trials
1. PATHWAY-2 Study (Lancet 2015)
- Findings: Spironolactone was the most effective add-on treatment for resistant hypertension (beating Beta-blockers and Doxazosin), supporting the theory that much "Essential" hypertension is actually salt/aldosterone driven.
What is Conn's Syndrome?
It is a condition where one or both of your adrenal glands produce too much of a hormone called Aldosterone.
What does Aldosterone do?
It tells your kidneys to hold onto salt and water. This increases the volume of fluid in your blood vessels, pushing your blood pressure up. It also tells your kidneys to flush out potassium, which is a vital mineral for your muscles and heart.
How do we fix it?
First, we find out if it's coming from one gland or both.
- If it's one gland (a benign lump): We remove that gland with keyhole surgery. This often cures the problem.
- If it's both glands: We give you a medicine (Spironolactone) that blocks the hormone's effect.
Primary Sources
- Funder JW, et al. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016.
- Mulatero P, et al. Diagnosis and treatment of primary aldosteronism. BMJ. 2013.
- Williams B, et al. Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2). Lancet. 2015.
Common Exam Questions
- Biochemistry: "Blood gas finding in Conn's?"
- Answer: Metabolic Alkalosis (Low H+).
- Pharmacology: "Side effect of Spironolactone?"
- Answer: Gynecomastia.
- Diagnosis: "Interpretation of High Renin + High Aldosterone?"
- Answer: Secondary Hyperaldosteronism (e.g., Renal Artery Stenosis or Heart Failure). In Conn's, Renin is LOW.
- Investigation: "Role of AVS?"
- Answer: To differentiate Unilateral (Surgical) from Bilateral (Medical) disease.
Viva Points
- Aldosterone Escape: Why no oedema? After initial retention, ANP (Atrial Natriuretic Peptide) rises and causes 'pressure natriuresis', so volume stabilizes at a high-normal level, preventing pitting oedema.
- Liddle's Syndrome: A genetic mimic. ENaC channel is permanently 'on'. Low Renin AND Low Aldosterone.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.