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), represents autonomous aldosterone overproduction by the adrenal glands, independent of the renin-angiotensin-aldosterone system (RAAS). This results in sodium retention, hypertension, potassium wasting (hypokalaemia), and suppressed renin. PA is the most common cause of secondary hypertension, affecting 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension. [1,2]

The two principal subtypes are:

• Bilateral Adrenal Hyperplasia (BAH) or Idiopathic Hyperaldosteronism (IHA): ~60-65% of cases
• Aldosterone-Producing Adenoma (APA): ~30-35% of cases (Conn Syndrome proper)

PA carries significantly greater cardiovascular, cerebrovascular, and renal morbidity compared to matched essential hypertension, independent of blood pressure levels. This excess risk is attributable to direct aldosterone-mediated organ damage including cardiac fibrosis, vascular inflammation, and renal injury. [3,4]

Diagnosis follows a structured pathway:

1. Case detection screening using Aldosterone-to-Renin Ratio (ARR)
2. Confirmatory testing (saline suppression, oral sodium loading, or fludrocortisone suppression)
3. Subtype differentiation via CT adrenals and Adrenal Venous Sampling (AVS)

Treatment is unilateral laparoscopic adrenalectomy for APA (potentially curative) or mineralocorticoid receptor antagonists (MRA) – spironolactone or eplerenone – for BAH or non-surgical candidates. Early diagnosis and targeted treatment reduce cardiovascular and renal complications. [5,6]

Clinical Pearls

"Resistant Hypertension = Screen for PA": PA prevalence reaches 15-20% in resistant hypertension populations. [2]

"Hypokalaemia is NOT Always Present": Only 9-37% of PA patients have spontaneous hypokalaemia. Normokalaemic PA is the norm. [7]

"ARR for Screening, AVS for Subtyping": ARR identifies PA; AVS lateralises aldosterone excess to guide surgical candidacy. [5]

"Surgery for Adenoma, Medical for Hyperplasia": Adrenalectomy achieves biochemical cure in ~95% of APA; hypertension cure/improvement in 50-60%. Spironolactone/eplerenone for BAH. [8,9]

"PA Causes Excess CV Damage Independent of BP": Direct aldosterone toxicity drives LVH, fibrosis, and vascular injury beyond hypertensive effects. [3]

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2. Epidemiology

Prevalence

Demographics

Subtypes

Exam Detail: ### Molecular Pathogenesis of APA

Somatic mutations driving autonomous aldosterone production in APA have been characterised in > 90% of cases: [13,14]

Clinical Implication: Genotype-phenotype correlation emerging, but routine genotyping not yet standard of care. May guide future targeted therapies.

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3. Pathophysiology

Normal Aldosterone Regulation

Aldosterone is synthesised in the zona glomerulosa of the adrenal cortex. Physiological regulation:

1. Renin-Angiotensin-Aldosterone System (RAAS):

   • Low BP / Volume / Na⁺ → Juxtaglomerular apparatus releases Renin
   • Renin cleaves Angiotensinogen → Angiotensin I
   • ACE converts Angiotensin I → Angiotensin II
   • Angiotensin II stimulates Aldosterone synthesis (via AT1 receptors in zona glomerulosa)

2. Potassium: Hyperkalaemia directly stimulates aldosterone synthesis.

3. ACTH: Minor role (diurnal variation).

Aldosterone Actions (Mineralocorticoid Receptor – MR – activation in distal nephron):

• Sodium reabsorption (principal cells, collecting duct)
• Potassium excretion (principal cells)
• Hydrogen ion excretion (intercalated cells)
• Volume expansion and BP elevation

Negative Feedback: Volume expansion → Suppressed renin release → Reduced angiotensin II → Reduced aldosterone.

Primary Hyperaldosteronism – Pathophysiological Cascade

In PA, aldosterone production becomes autonomous (independent of renin-angiotensin):

1. Autonomous Aldosterone Secretion

• APA: Somatic mutations (KCNJ5, ATP1A1, etc.) drive constitutive aldosterone synthesis. [13]
• BAH: Mechanism less clear; likely polyclonal proliferation and dysregulation of zona glomerulosa.

2. Renal Effects

• Sodium Retention: MR activation in distal nephron → ENaC upregulation → Na⁺ reabsorption → Volume expansion.
• Potassium Wasting: Na⁺ reabsorption creates lumen-negative potential → K⁺ secretion → Hypokalaemia (though often masked by "aldosterone escape" – see below).
• Hydrogen Ion Excretion: Metabolic alkalosis (↑ HCO₃⁻).
• Magnesium Wasting: Hypomagnesaemia (exacerbates hypokalaemia).

3. Cardiovascular Effects

• Hypertension: Volume expansion + increased peripheral vascular resistance (aldosterone-mediated vascular effects).
• Direct Cardiac Toxicity: MR activation in cardiomyocytes → Myocardial fibrosis, collagen deposition, diastolic dysfunction, left ventricular hypertrophy (LVH). [3,15]
• Vascular Injury: Endothelial dysfunction, inflammation, oxidative stress, arterial stiffness. [4]
• Arrhythmogenesis: Hypokalaemia (when present) + atrial fibrosis → Atrial fibrillation (AF). [16]

4. Renal Parenchymal Damage

• Glomerular Hyperfiltration: Early phase.
• Podocyte Injury and Proteinuria: Aldosterone directly injures podocytes. [17]
• Tubulointerstitial Fibrosis: MR activation drives renal fibrosis → Chronic Kidney Disease (CKD). [17]
• Albuminuria: Marker of renal and CV risk.

5. Renin Suppression

• Negative Feedback: Volume expansion → Suppressed renin release from juxtaglomerular apparatus.
• Diagnostic Hallmark: Low renin + High aldosterone = Elevated ARR.

6. "Aldosterone Escape" Phenomenon

• Despite continued sodium retention, patients do not develop oedema.
• Mechanism: Volume expansion triggers:
  • Atrial Natriuretic Peptide (ANP) release
  • Pressure natriuresis (renal)
  • Downregulation of proximal Na⁺ reabsorption
• Result: New steady state with volume expansion, hypertension, but no oedema.
• Clinical Implication: Normokalaemia in ~60-90% of PA cases; absence of oedema does NOT exclude PA. [7]

Exam Detail: ### Why PA Causes More Damage Than Essential Hypertension

Multiple studies demonstrate PA patients have greater target organ damage than essential hypertensives matched for age, sex, and BP: [3,4]

Key Evidence: The PAPY study showed PA patients had 4-fold higher odds of stroke and 6-fold higher odds of AF vs essential hypertensives at similar BP levels. [3]

Clinical Implication: PA is not "just hypertension" – it's a multisystem disease requiring specific diagnosis and MR-targeted therapy.

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4. Clinical Presentation

Symptoms

PA is often asymptomatic or presents with non-specific symptoms. Classic triad (hypertension, hypokalaemia, metabolic alkalosis) is now minority presentation. [7]

Key Point: Normokalaemia is common (~60-90% of PA cases). Absence of hypokalaemia does NOT exclude PA. [7]

Examination Findings

Physical examination is typically unremarkable apart from hypertension.

Clinical Clues Suggesting PA

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5. Diagnosis

Diagnosis of PA follows a three-step pathway: [5]

1. Case Detection (Screening): Aldosterone-to-Renin Ratio (ARR)
2. Confirmatory Testing: Demonstrate autonomous aldosterone secretion
3. Subtype Differentiation: Distinguish APA from BAH

Who to Screen? (Endocrine Society 2016 Guidelines) [5]

Step 1: Case Detection – Aldosterone-to-Renin Ratio (ARR)

Rationale

PA is characterised by high aldosterone and suppressed renin. ARR is the most sensitive screening test. [5,19]

Test Components

ARR Interpretation (Example Cutoffs – Vary by Lab)

Important: Cutoffs vary by assay, units, and laboratory. Use local reference ranges.

Conditions for Accurate ARR Testing

ARR is affected by medications, posture, potassium, and sodium intake. Optimise testing conditions: [5]

Medication Effects on ARR

Practical Approach: If stopping medications is unsafe (e.g., severe hypertension), continue with verapamil SR (slow-release), alpha-blockers (doxazosin), and/or hydralazine for BP control during washout. Interpret ARR with caution.

ARR Result Interpretation

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Step 2: Confirmatory Testing

ARR has high sensitivity but moderate specificity. Confirmatory testing is required to prove autonomous aldosterone secretion (failure to suppress aldosterone with sodium/volume loading). [5]

Available Confirmatory Tests

Choice of Test: Oral sodium loading and IV saline are most widely used. Fludrocortisone suppression reserved for equivocal cases.

Interpretation:

• Positive confirmatory test → PA confirmed → Proceed to Step 3 (Subtype Differentiation).
• Negative confirmatory test → PA unlikely; consider repeat testing if clinical suspicion high or alternative diagnosis.

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Step 3: Subtype Differentiation (APA vs BAH)

Distinguishing unilateral disease (APA, unilateral hyperplasia – surgical candidates) from bilateral disease (BAH – medical management) is crucial for treatment planning. [5,9]

CT Adrenals (Initial Imaging)

Protocol: Thin-slice (≤3 mm) non-contrast CT or contrast-enhanced adrenal CT.

Findings:

Limitations of CT Alone: [5,9]

• APA may be too small to visualise (less than 1 cm microadenomas).
• Non-functioning adrenal incidentalomas are common (prevalence ~5-10% in general population > 50 years) → May coexist with contralateral PA.
• Bilateral micronodular hyperplasia may mimic normal adrenals.
• CT CANNOT reliably distinguish functional APA from non-functional incidentaloma.

Conclusion: CT alone is INSUFFICIENT for subtype diagnosis in most cases. CT is used to:

1. Exclude large masses (> 4 cm) concerning for carcinoma.
2. Identify obvious unilateral macroadenoma in young patients (less than 35 years) – may proceed to surgery without AVS (see below).

Adrenal Venous Sampling (AVS) – Gold Standard for Lateralisation

Indications for AVS: [5,9]

• All patients being considered for surgery (to confirm unilateral aldosterone excess).
• Exception: Patients less than 35 years with spontaneous hypokalaemia, markedly elevated aldosterone, and unequivocal unilateral adenoma > 1 cm on CT with normal contralateral adrenal may proceed to surgery without AVS (lower risk of incidentaloma; higher pretest probability of APA).

Rationale: AVS directly measures aldosterone secretion from each adrenal gland, distinguishing lateralised (surgical) from bilateral (medical) disease.

Procedure:

1. Venous catheterisation: Interventional radiologist cannulates both adrenal veins (right often difficult due to anatomy) and IVC (peripheral sample).
2. Sampling: Measure aldosterone and cortisol from:
   • Right adrenal vein
   • Left adrenal vein
   • IVC (peripheral)
3. ACTH stimulation (optional): Some centres give ACTH (Cosyntropin) 250 µg bolus 15 minutes before sampling to maximise cortisol gradient (aids confirmation of successful adrenal vein cannulation). [9]

AVS Interpretation:

Step 1: Confirm Successful Cannulation (Selectivity Index – SI)

If SI inadequate on one side → Repeat AVS (non-diagnostic).

Step 2: Determine Lateralisation (Lateralisation Index – LI)

Step 3: Assess Contralateral Suppression (Contralateral Suppression Index – CSI)

AVS Result Summary:

Practical Considerations:

• AVS is technically challenging (right adrenal vein cannulation success ~70-90%).
• Complication rate ~2.5% (adrenal haemorrhage, vein rupture, dissection).
• Requires experienced interventional radiologist.
• Some centres advocate sequential sampling (bilateral simultaneous sampling difficult).

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6. Differential Diagnosis

Causes of Hypertension + Low Renin

Causes of Hypertension + Hypokalaemia + HIGH Renin

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7. Management

Management is subtype-dependent: [5,8,9]

• Unilateral disease (APA, unilateral hyperplasia) → Surgical (laparoscopic adrenalectomy)
• Bilateral disease (BAH) or non-surgical candidates → Medical (mineralocorticoid receptor antagonist – MRA)

Management Algorithm

CONFIRMED PRIMARY HYPERALDOSTERONISM
(Positive ARR + Confirmatory test)
              ↓
SUBTYPE DIFFERENTIATION
(CT Adrenals + AVS)
              ↓
    ┌─────────┴─────────┐
UNILATERAL             BILATERAL
(APA, Unilateral       (BAH)
 Hyperplasia)
    ↓                      ↓
SURGICAL CANDIDATE?    MEDICAL MANAGEMENT
┌───┴────┐              (MRA)
YES      NO
↓        ↓
SURGERY  MEDICAL

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Surgical Management – Laparoscopic Adrenalectomy

Indications

• Unilateral aldosterone excess confirmed by AVS (or young patient less than 35 years with clear unilateral adenoma). [9]
• Patient willing and fit for surgery.
• No contraindications to surgery.

Pre-Operative Preparation

1. Correct hypokalaemia: Target K⁺ > 4.0 mmol/L (supplement oral KCl).
2. Control BP: Start spironolactone 25-50 mg daily, titrate to 100-400 mg/day for 4-6 weeks pre-op to normalise BP and K⁺. Reduces surgical risk. [8]
3. Additional antihypertensives as needed (CCB, ACE inhibitor/ARB).
4. Anaesthetic assessment: Higher perioperative risk due to hypertension, LVH, hypokalaemia.

Surgical Technique

• Laparoscopic transperitoneal or retroperitoneal adrenalectomy (preferred).
• Open adrenalectomy if large mass (> 6 cm) or suspicion of carcinoma.
• Unilateral adrenalectomy (remove affected adrenal; preserve contralateral).

Post-Operative Management

• Immediate post-op: Risk of hyperkalaemia (sudden loss of aldosterone excess; continue spironolactone cautiously or stop). Monitor K⁺ closely.
• Hypotension: May occur (loss of volume expansion). Reduce/stop antihypertensives as needed.
• Gradual taper of MRA: Stop spironolactone over 2-4 weeks post-op (monitor K⁺, BP).
• Long-term follow-up: Reassess BP, K⁺, ARR at 1-3 months post-op.

Outcomes After Adrenalectomy [8,9,20]

Predictors of Hypertension Cure: [20]

• Younger age (less than 45 years)
• Shorter duration of hypertension (less than 5 years)
• Fewer antihypertensive drugs pre-op (≤2)
• No family history of hypertension
• Female sex (in some studies)

Important: Even if hypertension not cured, surgery removes aldosterone excess → Reduces CV and renal damage independent of BP.

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Medical Management – Mineralocorticoid Receptor Antagonists (MRA)

Indications

• Bilateral disease (BAH) [5,8]
• Unilateral disease in patients who:
  • Decline surgery
  • Have contraindications to surgery (comorbidities, high operative risk)
• Pre-operative BP and K⁺ control before adrenalectomy.

Mineralocorticoid Receptor Antagonists (MRA)

Spironolactone (First-Line)

Practical Tip: Anti-androgen side effects are dose-dependent and common at higher doses (> 100 mg/day). Explain to patients before starting. If intolerable → Switch to eplerenone.

Eplerenone (Alternative)

Indications for Eplerenone over Spironolactone:

• Intolerable anti-androgen side effects (gynaecomastia, sexual dysfunction).
• Patient preference.
• Availability and cost permitting.

Add-On Antihypertensives

Many PA patients require additional antihypertensives alongside MRA to achieve BP control: [8]

Avoid:

• Potassium supplements (unless hypokalaemia persists despite MRA – rare).
• Potassium-sparing diuretics (amiloride, triamterene) in combination with MRA (additive hyperkalaemia risk).

Monitoring on MRA

Outcomes of Medical Therapy

• Biochemical control (normalised K⁺): Achieved in > 90% of patients on adequate MRA dose. [8]
• BP control: ~70-80% achieve target BP on MRA ± add-on drugs. Some require multiple agents.
• Cardiovascular protection: MRA therapy reduces LV mass, improves diastolic function, and reduces CV events compared to untreated PA. [15]
• Lifelong therapy: BAH requires indefinite MRA treatment.

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Special Scenarios

Familial Hyperaldosteronism Type I (FH-I / Glucocorticoid-Remediable Aldosteronism – GRA)

• Pathophysiology: Chimeric gene (CYP11B1-CYP11B2 fusion) → Aldosterone synthesis driven by ACTH (instead of angiotensin II).
• Clinical Features: Early-onset hypertension, family history (autosomal dominant), often severe hypertension and cerebrovascular events less than 40 years.
• Diagnosis: Elevated 18-hydroxycortisol and 18-oxocortisol in urine. Genetic testing (CYP11B1-CYP11B2 fusion).
• Treatment: Dexamethasone 0.25-0.5 mg PO once daily (suppresses ACTH → suppresses aldosterone synthesis). Alternative: Spironolactone/eplerenone. [5]

Pregnancy and PA

• Screening in pregnancy: Difficult (physiological increase in renin and aldosterone in pregnancy). ARR unreliable.
• Management: Avoid MRA (spironolactone/eplerenone are teratogenic – anti-androgen effects).
• Safe antihypertensives: Methyldopa, labetalol, nifedipine.
• Surgery: Defer adrenalectomy until post-partum (unless adrenal carcinoma suspected).

PA in CKD

• Prevalence: PA is a cause AND consequence of CKD.
• Diagnosis: ARR may be altered by CKD (renin often low). DRC preferred over PRA in CKD.
• MRA use in CKD: Exercise caution (hyperkalaemia risk). Start low dose (spironolactone 12.5-25 mg/day). Close K⁺ monitoring. May need dietary K⁺ restriction or K⁺ binders (patiromer, sodium zirconium cyclosilicate) to allow MRA use.
• Benefit: MRA has renoprotective and cardioprotective effects in CKD; consider even in advanced CKD with careful monitoring. [17]

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8. Complications and Cardiovascular Risk

PA is associated with greater cardiovascular, cerebrovascular, and renal morbidity than essential hypertension at similar BP levels. [3,4]

Cardiovascular Complications

Cerebrovascular Complications

Renal Complications

Metabolic Complications

Other Complications

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9. Prognosis and Outcomes

Prognosis by Subtype and Treatment

Factors Predicting Hypertension Cure After Adrenalectomy [20]

Long-Term Cardiovascular Outcomes

Before Treatment: PA patients have significantly higher CV event rates than essential hypertension (even when BP matched). [3]

After Treatment (Surgery or MRA):

• LVH regression: Significant reduction in LV mass index within 6-12 months of adrenalectomy or MRA therapy. [15]
• Improved diastolic function: Echocardiographic parameters improve.
• Reduced AF incidence: AF risk decreases post-treatment (though remains elevated if pre-existing AF).
• Stroke risk reduction: Treatment reduces stroke risk toward baseline (though some residual excess may persist if longstanding PA).
• Renal function stabilisation: Albuminuria improves; eGFR decline slows after MRA or surgery. [17]

Key Point: Early diagnosis and treatment of PA reduces target organ damage and improves long-term CV outcomes. Delayed diagnosis results in irreversible LVH, fibrosis, and CKD.

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10. Evidence and Guidelines

Key Guidelines

Landmark Studies

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11. Examination Focus

High-Yield Exam Facts

Common MRCP / FRACP SBA Stems

1. "48-year-old man, BP 165/102 mmHg on 3 drugs, K⁺ 3.0 mmol/L. What is the most appropriate next investigation?"

   • Answer: Plasma aldosterone and renin (ARR).

2. "ARR elevated, PAC 25 ng/dL. Confirmatory saline suppression test: PAC 12 ng/dL at 4 hours. Diagnosis?"

   • Answer: Primary Aldosteronism confirmed (PAC > 10 ng/dL post-saline = positive).

3. "CT shows 1.5 cm left adrenal adenoma. What is the next step before surgery?"

   • Answer: Adrenal Venous Sampling (AVS) (to confirm lateralised aldosterone secretion; CT alone insufficient unless less than 35 years with clear phenotype).

4. "Patient with bilateral adrenal hyperplasia on AVS. Best treatment?"

   • Answer: Spironolactone or Eplerenone (MRA for bilateral disease).

5. "Post-adrenalectomy for APA: K⁺ normalised, but BP remains 145/90 on 2 drugs. Outcome?"

   • Answer: Biochemical cure but not hypertension cure (occurs in ~50%; still significant improvement and CV benefit).

6. "Which medication must be stopped longest before ARR testing?"

   • Answer: Spironolactone / Eplerenone (4-6 weeks; markedly affect ARR).

Viva Voce Scenarios

Examiner: "Tell me about Primary Aldosteronism."

Model Answer: "Primary Aldosteronism is autonomous aldosterone secretion by the adrenal glands, independent of the renin-angiotensin system. It's the most common cause of secondary hypertension, affecting 5-10% of all hypertensives and up to 20% of those with resistant hypertension. The two main subtypes are bilateral adrenal hyperplasia (~60%) and aldosterone-producing adenoma (~30%). PA causes hypertension, hypokalaemia in about one-third of cases, and importantly, greater cardiovascular damage than essential hypertension due to direct aldosterone-mediated organ injury including cardiac fibrosis and renal damage. Diagnosis involves screening with the aldosterone-to-renin ratio, confirmatory testing with saline suppression or oral sodium loading, and subtype differentiation using adrenal CT and adrenal venous sampling. Treatment is surgical adrenalectomy for unilateral disease, which is curative in most cases, or medical therapy with mineralocorticoid receptor antagonists like spironolactone for bilateral disease."

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Examiner: "Why is adrenal venous sampling necessary if CT shows a unilateral adenoma?"

Model Answer: "Adrenal incidentalomas are very common, occurring in about 5-10% of people over 50. In a patient with primary aldosteronism, a nodule on CT could be a non-functioning incidentaloma coinciding with bilateral hyperplasia, or the contralateral adrenal could be the source of excess aldosterone. CT cannot determine which adrenal is functionally responsible. Adrenal venous sampling directly measures aldosterone secretion from each gland, calculating a lateralisation index. Studies show CT alone misclassifies about 25-37% of cases. AVS is therefore the gold standard before surgery to avoid unnecessary adrenalectomy of the wrong gland or operating on bilateral disease. The exception is young patients under 35 with spontaneous hypokalaemia and a clear unilateral adenoma, where the pretest probability of APA is very high and incidentaloma risk is lower."

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Examiner: "A patient has resistant hypertension and you suspect PA. Which medications should you stop before testing?"

Model Answer: "Ideally, we should stop interfering medications 2-4 weeks before ARR testing if safe to do so. The most important to stop are mineralocorticoid receptor antagonists like spironolactone and eplerenone – these need 4-6 weeks washout as they markedly increase both renin and aldosterone, potentially causing a false-negative ARR. Beta-blockers should be stopped as they suppress renin and can cause a false-positive ARR. ACE inhibitors, ARBs, and diuretics increase renin and should also be stopped if possible as they can cause false-negative results. NSAIDs suppress renin and can cause false-positives. For blood pressure control during the washout period, we can use agents with minimal effect on the renin-aldosterone axis: verapamil or diltiazem, alpha-blockers like doxazosin, or hydralazine. However, if stopping these medications poses a significant risk due to severe hypertension, we proceed with testing while on medication and interpret the results cautiously, potentially repeating the test after safer withdrawal."

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Examiner: "What are the side effects of spironolactone and how would you manage them?"

Model Answer: "Spironolactone is a non-selective mineralocorticoid receptor antagonist that also has anti-androgen effects. The most common side effects relate to this anti-androgen activity: gynaecomastia and breast tenderness in men, occurring in 10-50% depending on dose, menstrual irregularities in women, decreased libido, and erectile dysfunction. These are dose-dependent and more common at doses above 100 mg daily. Other side effects include hyperkalaemia, particularly in patients with CKD or those on ACE inhibitors or ARBs, and GI upset. If anti-androgen side effects are troublesome, I would switch to eplerenone, which is a selective MR antagonist with minimal anti-androgen effects. Eplerenone is generally better tolerated but more expensive and may require higher doses for equivalent efficacy. For hyperkalaemia, I'd review renal function, reduce or stop concomitant RAAS inhibitors if safe, consider dietary potassium restriction, and potentially use potassium binders if we need to continue the MRA for its cardiovascular benefits."

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12. Patient and Layperson Explanation

What is Primary Hyperaldosteronism?

Your body has two small glands called adrenal glands that sit on top of your kidneys. These glands produce many hormones, including one called aldosterone. Aldosterone helps control the balance of salt and water in your body, which affects your blood pressure and potassium levels.

In Primary Hyperaldosteronism (also called PA or Conn's Syndrome), one or both of your adrenal glands make too much aldosterone without the normal signals from your body telling them to do so.

What Does Excess Aldosterone Do?

When your body has too much aldosterone:

• Your kidneys retain too much salt and water → This raises your blood pressure.
• Your kidneys lose too much potassium → This can cause low potassium levels (though many people with PA still have normal potassium).
• The excess aldosterone directly damages your heart, blood vessels, and kidneys over time, leading to heart muscle thickening, irregular heart rhythms, and kidney disease.

How Common is This?

Primary Hyperaldosteronism is more common than we used to think:

• About 5-10 out of every 100 people with high blood pressure have PA.
• If your blood pressure is hard to control even with multiple medications, the chance of PA is even higher (15-20 out of 100).

What Are the Symptoms?

Many people with PA don't notice specific symptoms – they just have high blood pressure that may be difficult to control. Some people experience:

• Headaches (from high blood pressure)
• Muscle weakness or cramps (if potassium is low)
• Frequent urination, especially at night
• Fatigue

How is Primary Hyperaldosteronism Diagnosed?

Your doctor will do a series of tests:

1. Blood Test (Screening): Measure aldosterone and renin levels in your blood. In PA, aldosterone is high and renin is low. We calculate a ratio (called ARR) to screen for PA.

2. Confirmatory Test: If the screening test is positive, we do another test to confirm. This might involve giving you extra salt (either as a high-salt diet or through a drip) and checking if your aldosterone level drops. In PA, it doesn't drop normally.

3. Imaging (CT Scan): A CT scan of your adrenal glands looks for any lumps or abnormalities.

4. Adrenal Vein Sampling (AVS): This is a specialised test where a radiologist takes blood samples directly from the veins draining each adrenal gland. This tells us whether one gland or both are making too much aldosterone. This is important for deciding on treatment.

What Are the Types of Primary Hyperaldosteronism?

There are two main types:

1. Aldosterone-Producing Adenoma (APA) – About 30-35% of cases:

   • A small benign tumour (adenoma) in one adrenal gland is making excess aldosterone.
   • This type can often be cured with surgery.

2. Bilateral Adrenal Hyperplasia (BAH) – About 60-65% of cases:

   • Both adrenal glands are overactive (enlarged).
   • This type is treated with long-term medication, not surgery.

How is Primary Hyperaldosteronism Treated?

Treatment depends on which type you have:

If You Have an Aldosterone-Producing Adenoma (One Gland Affected):

• Surgery (Adrenalectomy): We remove the affected adrenal gland using keyhole (laparoscopic) surgery. This is often curative.
• Outcomes After Surgery:
  • Your potassium level almost always returns to normal (> 95% of cases).
  • "Your blood pressure improves or is cured in most people:"
    • About 30-50% are completely cured (off all blood pressure medications).
    • About 40-50% have significant improvement (need fewer medications, easier to control).
  • Your heart and kidneys benefit even if blood pressure isn't completely cured.

If You Have Bilateral Adrenal Hyperplasia (Both Glands Affected) or Can't Have Surgery:

• Medication (Spironolactone or Eplerenone): These are tablets called mineralocorticoid receptor antagonists (MRAs). They block the action of aldosterone.
• How It Works: The medication counteracts the excess aldosterone, lowering your blood pressure and normalising potassium levels.
• Duration: This is usually lifelong treatment.
• Side Effects:
  • Spironolactone can cause breast enlargement and tenderness in men, menstrual changes in women, and sexual side effects (because it also blocks male hormones).
  • Eplerenone is a newer, more selective medication with fewer sexual side effects, but it may be more expensive.
  • Both can cause high potassium (the opposite problem), so we monitor your blood tests regularly.

You may also need other blood pressure medications alongside the MRA to fully control your blood pressure.

Why is Treatment Important?

Primary Hyperaldosteronism isn't just "high blood pressure." The excess aldosterone causes extra damage to your heart, blood vessels, brain, and kidneys beyond what high blood pressure alone would cause. People with untreated PA have:

• 4 times higher risk of stroke
• 6 times higher risk of irregular heart rhythm (atrial fibrillation)
• Thickening of the heart muscle
• Faster loss of kidney function
• Higher risk of heart attacks

Treating PA specifically (with surgery or the right medication) reduces these risks and protects your organs better than just treating high blood pressure with standard medications.

What Can I Expect Long-Term?

• If you have surgery: Most people see significant improvement. Your heart muscle can shrink back toward normal size, and your kidneys stabilise. You may still need some blood pressure medication if you have other risk factors, but your overall cardiovascular risk is much lower.

• If you take medication (MRA): With good adherence, your potassium normalises, blood pressure is controlled, and your heart and kidneys are protected. Regular blood tests (every few months) monitor potassium and kidney function.

• Early diagnosis and treatment make a big difference: The sooner PA is diagnosed and treated, the less permanent damage occurs to your heart and kidneys.

Key Takeaways

• Primary Hyperaldosteronism is a common cause of high blood pressure caused by excess aldosterone from your adrenal glands.
• It causes more damage to your heart, brain, and kidneys than regular high blood pressure.
• Diagnosis involves blood tests, confirmatory tests, and imaging.
• Treatment is either surgery (if one gland is affected – potentially curative) or lifelong medication (if both glands are affected).
• Treatment significantly reduces your risk of heart attacks, strokes, and kidney disease.

If you have any questions about your diagnosis or treatment, please discuss them with your doctor.

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13. References

Primary Sources

1. Monticone S, Burrello J, Tizzani D, et al. Prevalence and Clinical Manifestations of Primary Aldosteronism Encountered in Primary Care Practice. J Am Coll Cardiol. 2017;69(14):1811-1820. doi:10.1016/j.jacc.2017.01.052. PMID: 28385310.

2. Käyser SC, Dekkers T, Groenewoud HJ, et al. Study Heterogeneity and Estimation of Prevalence of Primary Aldosteronism: A Systematic Review and Meta-Regression Analysis. J Clin Endocrinol Metab. 2016;101(7):2826-2835. doi:10.1210/jc.2016-1472. PMID: 27186859.

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