Overview
Primary Hyperaldosteronism (Conn's Syndrome)
1. Clinical Overview
Summary
Primary Hyperaldosteronism (PA), also known as Primary Aldosteronism or Conn Syndrome (When due to an adenoma), is a condition of Autonomous Aldosterone Overproduction by the adrenal glands, Leading to Sodium Retention, Hypertension, Potassium Wasting (Hypokalaemia), and Suppressed Renin. PA is the Most Common Cause of Secondary Hypertension, Estimated to affect 5-15% of all hypertensive patients and up to 20% of those with Resistant Hypertension. The two main subtypes are Bilateral Adrenal Hyperplasia (BAH / Idiopathic Hyperaldosteronism) (~60-65%) and Aldosterone-Producing Adenoma (APA / Conn Syndrome) (~30-35%). Patients with PA have significantly increased Cardiovascular, Cerebrovascular, and Renal Morbidity compared to matched essential hypertensives. Diagnosis involves Screening (Aldosterone-to-Renin Ratio – ARR), Confirmatory Testing (Oral Sodium Loading, Fludrocortisone Suppression), and Subtype Differentiation (CT Adrenals, Adrenal Venous Sampling – AVS). Treatment is Unilateral Adrenalectomy for APA (Potentially curative) or Mineralocorticoid Receptor Antagonists (Spironolactone, Eplerenone) for BAH or non-surgical candidates. [1,2,3]
Clinical Pearls
"Resistant Hypertension = Screen for PA": PA is common in resistant HTN.
"Hypokalaemia is NOT Always Present": Only ~30-50% have low K+. Normokalaemia does not exclude PA.
"ARR for Screening, AVS for Subtyping": Essential for differentiating APA from BAH to guide treatment.
"Surgery for Adenoma, Medical for Hyperplasia": Adrenalectomy cures/Improves APA. Spironolactone for BAH.
2. Epidemiology
Demographics
| Factor | Notes |
|---|---|
| Prevalence in HTN | ~5-15% of all hypertensives. Up to ~20% of resistant HTN. |
| Age | Usually 30-60 years (Adenoma). BAH can be older. |
| Sex | Adenoma: Female = Male (Or slight Female predominance). BAH: Male > Female. |
Subtypes
| Subtype | Proportion | Notes |
|---|---|---|
| Bilateral Adrenal Hyperplasia (BAH) / Idiopathic Hyperaldosteronism (IHA) | ~60-65% | Both adrenals. Medical treatment. |
| Aldosterone-Producing Adenoma (APA) / Conn Syndrome | ~30-35% | Unilateral. Surgical treatment (Adrenalectomy). |
| Familial Hyperaldosteronism (FH) | less than 5% | Types I-IV. Genetic. |
| Unilateral Adrenal Hyperplasia | ~2% | |
| Aldosterone-Producing Carcinoma | less than 1% | Rare. |
3. Pathophysiology
Normal Aldosterone Regulation
- Aldosterone produced by Zona Glomerulosa of adrenal cortex.
- RAAS (Renin-Angiotensin-Aldosterone System): Low BP/Na/Volume → Renin release (Kidney) → Angiotensin II → Aldosterone.
- Aldosterone Actions: Sodium reabsorption, Potassium excretion (Collecting duct of kidney). Leads to volume expansion.
Primary Hyperaldosteronism
- Autonomous Aldosterone Production: From adenoma or hyperplastic adrenals.
- Independent of RAAS: Not suppressed by sodium loading or volume expansion.
- Sodium Retention: Volume expansion → Hypertension.
- Potassium Wasting: Hypokalaemia (Though often normokalaemic due to "escape" mechanisms).
- Renin Suppression: Feedback inhibition due to high aldosterone → Low Renin.
- Metabolic Alkalosis: H+ loss in urine.
- Direct Aldosterone Toxicity: Beyond BP effects – Cardiac fibrosis, Renal damage, Vascular injury.
4. Clinical Presentation
Symptoms (Often Subtle or Absent)
| Symptom | Notes |
|---|---|
| Hypertension | Often severe, Early-onset, Or resistant to treatment. |
| Headache | Related to HTN. |
| Muscle Weakness / Cramps | Hypokalaemia. |
| Polyuria / Nocturia | Hypokalaemia → Nephrogenic DI. |
| Fatigue | |
| Paraesthesia | Hypokalaemia. |
Examination Findings
| Finding | Notes |
|---|---|
| Hypertension | Often >160/100. May be resistant (On ≥3 drugs). |
| Usually Unremarkable Otherwise | |
| No Oedema | "Aldosterone Escape" – Eventually natriuresis limits volume expansion. |
| Target Organ Damage (If Longstanding) | LVH, Retinopathy, Renal impairment. |
Who to Screen (Endocrine Society Guidelines)
| Indication |
|---|
| Sustained BP >150/100 on three occasions. |
| Hypertension Resistant to ≥3 Drugs (Including a diuretic). |
| Controlled BP on ≥4 Drugs. |
| Hypertension + Spontaneous or Diuretic-Induced Hypokalaemia. |
| Hypertension + Adrenal Incidentaloma. |
| Hypertension + Family history of early-onset HTN or CVA (less than 40 years). |
| Hypertensive first-degree relatives of PA patients. |
| Hypertension + Sleep apnoea. |
5. Investigations
Step 1: Screening (Aldosterone-to-Renin Ratio – ARR)
| Test | Notes |
|---|---|
| Plasma Aldosterone Concentration (PAC) | Elevated in PA. |
| Plasma Renin Activity (PRA) or Direct Renin Concentration (DRC) | Suppressed (less than 1 ng/mL/hr PRA or low DRC). |
| ARR (PAC/PRA or PAC/DRC) | Elevated ARR is Screening Positive. Cutoffs vary (e.g., PAC/PRA >30 ng/dL per ng/mL/hr with PAC >15 ng/dL). |
Conditions for Accurate Testing:
- Correct hypokalaemia first (Low K+ suppresses aldosterone).
- Stop interfering medications 2-4 weeks before if safe:
- Interfere Most: Spironolactone, Eplerenone (Stop 4-6 weeks). Beta-blockers. Clonidine. NSAIDs.
- Acceptable to Continue: Verapamil (Non-dihydropyridine CCB). Alpha-blockers (Doxazosin). Hydralazine.
- Liberal sodium diet.
Step 2: Confirmatory Testing (If ARR Positive)
| Test | Notes |
|---|---|
| Oral Sodium Loading Test | High sodium diet x 3 days → Measure 24-hour urinary aldosterone. PA confirmed if Aldosterone >12-14 µg/24h. |
| IV Saline Infusion Test | 2L 0.9% Saline over 4 hours (Sitting). Measure PAC at end. PA confirmed if PAC >10 ng/dL (Some use >6). |
| Fludrocortisone Suppression Test | Gold standard. Complex. 4 days fludrocortisone + KCl + Sodium. Day 4: Measure upright PAC. PA if >6 ng/dL. |
| Captopril Challenge Test | Less commonly used. |
Step 3: Subtype Differentiation (Crucial for Treatment)
| Investigation | Notes |
|---|---|
| CT Adrenals | Identify masses. BUT: Adenoma may be small/Missed. Incidentalomas common (May be non-functioning). CT ALONE cannot reliably distinguish APA from BAH. |
| Adrenal Venous Sampling (AVS) | Gold Standard for Subtyping (If surgery considered). Measures aldosterone/Cortisol from each adrenal vein. Lateralises if APA (One side secreting disproportionately). Essential in patients >35 years or if CT ambiguous. |
6. Management
Management Algorithm
SUSPECTED PRIMARY HYPERALDOSTERONISM
(Screening indications met)
↓
STEP 1: SCREENING (ARR)
- Correct hypokalaemia. Stop interfering drugs.
- Measure PAC, PRA/DRC, Calculate ARR.
┌────────────────┴────────────────┐
ARR NEGATIVE ARR POSITIVE
(PA unlikely) (Proceed to confirm)
↓ ↓
Consider other STEP 2: CONFIRMATORY TEST
causes of 2° HTN (Oral Sodium Load, IV Saline,
or Fludrocortisone Suppression)
↓ ↓
PA CONFIRMED?
┌────────┴────────┐
NO YES
↓ ↓
Repeat/Review STEP 3: SUBTYPE
DIFFERENTIATION
┌──────────────────────────────────────────────────────────┐
│ **CT ADRENALS** │
│ - Identify masses, Exclude carcinoma │
│ │
│ **ADRENAL VENOUS SAMPLING (AVS)** │
│ - Gold standard for lateralisation │
│ - Essential before surgery in most patients │
│ - Exception: Age less than 35 with clear unilateral adenoma │
│ on CT, Contralateral normal → May proceed to surgery │
│ without AVS │
└──────────────────────────────────────────────────────────┘
↓
SUBTYPE AND TREATMENT
┌────────────────┬────────────────┐
UNILATERAL BILATERAL DISEASE
(APA, Unilateral (BAH)
Hyperplasia)
↓ ↓
**SURGICAL** **MEDICAL TREATMENT**
(Preferred)
↓
UNILATERAL ADRENALECTOMY
┌──────────────────────────────────────────────────────────┐
│ - Laparoscopic adrenalectomy preferred │
│ - Pre-op: Correct hypokalaemia, Control BP with MRA │
│ (Spironolactone 6-8 weeks pre-op) │
│ - **Outcomes**: Hypertension cure/Improvement ~50-80%. │
│ Hypokalaemia resolves ~100%. │
└──────────────────────────────────────────────────────────┘
↓
MEDICAL TREATMENT (BAH or Non-Surgical Candidates)
┌──────────────────────────────────────────────────────────┐
│ **MINERALOCORTICOID RECEPTOR ANTAGONISTS (MRA)** │
│ │
│ **Spironolactone (First-Line)** │
│ - Start 12.5-25 mg OD, Titrate up to 100-400 mg/day │
│ - Target: Normalise K+, Control BP │
│ - Side effects: Gynaecomastia, Breast tenderness, │
│ Menstrual irregularities, Erectile dysfunction │
│ (Due to anti-androgen effects) │
│ │
│ **Eplerenone (Alternative)** │
│ - More selective MRA. Fewer anti-androgen side effects. │
│ - Start 25 mg BD, Titrate to 100-200 mg/day │
│ - More expensive. May require higher doses. │
│ │
│ **Add other antihypertensives as needed** │
│ - ACE Inhibitor/ARB, CCB, Thiazide │
│ │
│ **Monitor**: K+, Renal function, BP │
└──────────────────────────────────────────────────────────┘
7. Complications
| Complication | Notes |
|---|---|
| Cardiovascular | LVH, Atrial Fibrillation, Heart Failure, Coronary artery disease. Greater than matched essential HTN. |
| Cerebrovascular | Stroke. |
| Renal | CKD. Albuminuria. |
| Metabolic | Metabolic syndrome. Glucose intolerance. |
| Severe Hypokalaemia | Arrhythmias (If severe). |
8. Prognosis and Outcomes
| Factor | Notes |
|---|---|
| Post-Adrenalectomy (APA) | Hypertension cure in ~30-50%. Improvement in ~40-50%. Hypokalaemia resolves ~100%. |
| Medical Treatment (BAH) | Effective BP and K+ control. Lifelong therapy. |
| Long-Term CV Risk | Higher than essential HTN. Early diagnosis and treatment reduces end-organ damage. |
9. Evidence and Guidelines
Key Guidelines
| Guideline | Organisation | Key Recommendations |
|---|---|---|
| Primary Aldosteronism | Endocrine Society 2016 | Screen high-risk patients (Resistant HTN, Hypokalaemia). ARR for screening. Confirmatory testing. AVS for subtyping. Surgery for APA. MRA for BAH. |
10. Patient and Layperson Explanation
What is Primary Hyperaldosteronism?
Your adrenal glands (Sitting above your kidneys) make a hormone called aldosterone, Which controls salt and potassium balance. In primary hyperaldosteronism, One or both adrenal glands make too much aldosterone without the normal signals.
What does excess aldosterone do?
It causes your body to retain salt and water (Raising blood pressure) and lose potassium (Which can cause muscle weakness and cramps).
How is it diagnosed?
- Blood tests to check aldosterone and renin levels.
- Confirmatory tests to prove aldosterone is not suppressing normally.
- Imaging (CT Scan) and sometimes sampling blood from the adrenal veins to locate the problem.
How is it treated?
- If it's a single nodule (Adenoma): Surgery to remove that adrenal gland. Often cures or significantly improves blood pressure.
- If both adrenal glands are overactive (Hyperplasia): Medication (Spironolactone or Eplerenone) to block aldosterone. This is lifelong.
Why is it important to treat?
Uncontrolled high aldosterone causes more heart, Brain, And kidney damage than regular high blood pressure. Treating PA specifically reduces these risks.
11. References
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;101(5):1889-1916. PMID: 26934393.
- Rossi GP, et al. A prospective study of the prevalence of primary aldosteronism in 1,125 hypertensive patients. J Am Coll Cardiol. 2006;48(11):2293-2300.
- Monticone S, et al. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension. Lancet Diabetes Endocrinol. 2018;6(1):41-50.
12. Examination Focus
Common Exam Questions
- Most Common Cause of Secondary HTN: "What is the most common cause of secondary hypertension?"
- Answer: Primary Hyperaldosteronism (Primary Aldosteronism).
- Screening Test: "What is the screening test for Primary Hyperaldosteronism?"
- Answer: Aldosterone-to-Renin Ratio (ARR).
- Subtyping Gold Standard: "What is the gold standard investigation to differentiate between Aldosterone-Producing Adenoma and Bilateral Hyperplasia?"
- Answer: Adrenal Venous Sampling (AVS).
- Treatment for Bilateral Hyperplasia: "What is the first-line medical treatment for Bilateral Adrenal Hyperplasia causing PA?"
- Answer: Spironolactone (Mineralocorticoid Receptor Antagonist).
Viva Points
- Low Renin, High Aldosterone: Hallmark.
- Normokalaemia Does NOT Exclude PA: Only ~30-50% have hypokalaemia.
- Spironolactone Side Effects: Gynaecomastia, Erectile dysfunction (Anti-androgen). Eplerenone has fewer.
- CV Damage Greater Than Essential HTN: Even at same BP. Direct aldosterone toxicity.
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists.