Primary Hyperaldosteronism (Conn's Syndrome)

📋 Key Information Summary

📋

Primary hyperaldosteronism (PHA) is the most common cause of secondary hypertension, affecting 5–13% of all hypertensive patients and up to 20% with resistant hypertension.
PHA results from autonomous aldosterone secretion from an aldosterone-producing adenoma (APA) or bilateral idiopathic adrenal hyperplasia (IHA), with excess aldosterone causing sodium retention, potassium wasting, and renin suppression.
Screening is indicated in all patients with resistant hypertension (≥3 antihypertensives), hypertension with spontaneous or diuretic-induced hypokalaemia, adrenal incidentaloma with hypertension, onset of hypertension before age 20, or hypertension with a family history of early-onset cerebrovascular events.
The screening test of choice is the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio, performed in the morning after the patient has been ambulant for at least 2 hours, off interfering medications where possible for ≥4 weeks.
A screening ARR ≥750 pmol/L per ng/mL/h (with PAC ≥415 pmol/L) is considered positive; confirmatory salt-loading or fludrocortisone suppression testing is then required.
Confirmatory testing mandates a 4-day oral salt-loading protocol (slow-release NaCl 300 mmol/day with KCl supplementation) followed by 24-hour urine aldosterone collection — values >33 nmol/24 h confirm autonomous secretion.
Adrenal CT is the initial localisation study but has poor sensitivity for micro-adenomas; adrenal vein sampling (AVS) by an experienced interventional radiologist is the gold standard for distinguishing unilateral APA from bilateral IHA.
Unilateral APA is treated with laparoscopic adrenalectomy, which can cure or significantly improve hypertension in 50–80% of cases and resolve hypokalaemia in >90%.
Bilateral IHA and patients unsuitable for surgery are managed medically with mineralocorticoid receptor antagonists — spironolactone (first-line) or eplerenone (fewer anti-androgenic side effects), titrated to blood pressure and potassium targets.
Peri-operative management requires spironolactone pre-operatively for ≥4 weeks to normalise potassium and reduce operative risk; post-operative monitoring for hypoaldosteronism and hypotension is essential.
PHA confers excess cardiovascular risk independent of blood pressure, including left ventricular hypertrophy, atrial fibrillation, albuminuria, and metabolic syndrome — early identification and treatment reduces long-term morbidity.
Aboriginal and Torres Strait Islander peoples experience higher rates of resistant hypertension and cardiovascular disease; screening for PHA should have a lower threshold in this population.

🎧 Audio Brief

Why stubborn blood pressure hides Conn's Syndrome

A short clinical audio briefing generated from this article — perfect for the commute or ward round.

Introduction & Australian Epidemiology

Primary hyperaldosteronism (PHA), historically termed Conn's syndrome, is characterised by autonomous overproduction of aldosterone from the adrenal cortex, independent of the renin–angiotensin–aldosterone system (RAAS). The resultant aldosterone excess drives sodium and water retention, potassium excretion, and renin suppression, producing a clinical phenotype of hypertension (often resistant), hypokalaemia, and metabolic alkalosis.

Previously considered rare, PHA is now recognised as the most common specific cause of secondary hypertension. Prevalence estimates vary by population studied: 5–13% in general hypertension clinics, up to 20% in resistant hypertension, and 25–30% in patients with spontaneous hypokalaemia and hypertension. In Australia, with approximately 6 million adults affected by hypertension, the estimated burden of undiagnosed PHA is substantial — potentially 300,000–780,000 individuals.

The two principal subtypes are aldosterone-producing adenoma (APA, 30–40% of PHA) and bilateral idiopathic adrenal hyperplasia (IHA, 60–70%). Rare causes include familial hyperaldosteronism (FH types I–III), unilateral adrenal hyperplasia, and aldosterone-producing adrenocortical carcinoma. PHA affects all age groups, peaks in the 3rd–5th decades for APA and 5th–6th decades for IHA, and is more common in females for APA.

Undiagnosed PHA carries significant morbidity. Compared with patients who have essential hypertension at equivalent blood pressure levels, PHA patients have a 4-fold higher risk of atrial fibrillation, 6-fold higher risk of heart failure, and increased rates of left ventricular hypertrophy, stroke, coronary artery disease, metabolic syndrome, and albuminuria. Early detection and appropriate management are therefore critical to reducing long-term cardiovascular outcomes.

⚠️

Under-diagnosis: PHA remains vastly under-diagnosed in Australian clinical practice. Studies suggest fewer than 2% of eligible patients undergo appropriate screening. The condition should be actively considered in any patient with resistant or early-onset hypertension.

Pathophysiology & Causes

Normal Aldosterone Physiology

Aldosterone is synthesised in the zona glomerulosa of the adrenal cortex under the primary control of angiotensin II, serum potassium, and, to a lesser extent, ACTH. Angiotensin II acts via AT1 receptors on zona glomerulosa cells to stimulate aldosterone synthase (CYP11B2) and aldosterone production. Aldosterone then acts on the mineralocorticoid receptor (MR) in the distal nephron and collecting duct, upregulating epithelial sodium channels (ENaC) and Na⁺/K⁺-ATPase, promoting sodium reabsorption and potassium secretion.

Mechanisms of Autonomous Aldosterone Secretion

In PHA, aldosterone production escapes normal physiological regulation. The principal pathological mechanisms are:

Subtype	Proportion	Mechanism	Key Features
Aldosterone-producing adenoma (APA)	30–40%	Somatic mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, or CTNNB1 genes; autonomous aldosterone secretion from a single adenoma	Younger patients, higher aldosterone levels, more likely hypokalaemic, curable by adrenalectomy
Bilateral idiopathic adrenal hyperplasia (IHA)	60–70%	Diffuse or nodular hyperplasia of both adrenal glands; enhanced sensitivity to angiotensin II and other secretagogues	Older patients, milder biochemical phenotype, typically normokalaemic, medical management
Primary unilateral adrenal hyperplasia (UAH)	<2%	Nodular hyperplasia confined to one adrenal gland; functionally equivalent to APA	May be missed on CT; diagnosed by AVS
Familial hyperaldosteronism type I (FH-I / GRA)	<1%	Chimeric CYP11B1/CYP11B2 gene duplication; aldosterone regulated by ACTH instead of angiotensin II	Autosomal dominant, onset typically <20 years, suppressible with low-dose dexamethasone
Familial hyperaldosteronism type II	<5%	Linked to chromosome 7p22; can present as APA or IHA	Not dexamethasone-suppressible; familial clustering without chimeric gene
Familial hyperaldosteronism type III	Rare	Germline KCNJ5 mutations; severe bilateral adrenal hyperplasia with massive aldosterone excess	Childhood onset, may require bilateral adrenalectomy
Aldosterone-producing adrenocortical carcinoma	<1%	Malignant adrenal tumour with autonomous aldosterone and often cortisol or androgen co-secretion	Rapid onset, very high aldosterone, large (>4 cm) adrenal mass

Downstream Pathological Effects

Excess aldosterone exerts deleterious effects through both genomic and non-genomic pathways:

Mineralocorticoid receptor activation: Upregulation of ENaC and Na⁺/K⁺-ATPase in the distal nephron → sodium retention, volume expansion, hypertension, and hypokalaemia.
Cardiac fibrosis: Direct MR activation in cardiomyocytes and fibroblasts promotes collagen deposition, left ventricular hypertrophy (LVH), and diastolic dysfunction independent of blood pressure.
Vascular inflammation and endothelial dysfunction: Aldosterone increases reactive oxygen species (ROS) generation via NADPH oxidase, promoting vascular inflammation and impaired nitric oxide (NO) bioavailability.
Metabolic effects: Aldosterone impairs insulin signalling through MR-mediated oxidative stress in adipose tissue and skeletal muscle, contributing to insulin resistance and metabolic syndrome.
Renal injury: Glomerular hyperfiltration, podocyte injury, and tubulointerstitial fibrosis contribute to albuminuria and progressive renal impairment.
Atrial fibrillation: Aldosterone-driven atrial fibrosis, electrical remodelling, and inflammation significantly increase AF risk — approximately 4-fold compared with essential hypertension.

Medication-Related Aldosterone Excess

Certain medications can exacerbate or unmask PHA. Liddle syndrome (gain-of-function ENaC mutation) and apparent mineralocorticoid excess (AME, 11β-HSD2 deficiency) are important differential diagnoses. Liquorice, carbenoxolone, and glycyrrhizic acid inhibit 11β-HSD2, causing pseudo-hyperaldosteronism with suppressed renin and aldosterone.

Clinical Features & Screening

Clinical Presentation

PHA most commonly presents with hypertension detected incidentally or during investigation for resistant or early-onset hypertension. The classic triad of hypertension, hypokalaemia, and metabolic alkalosis is present in fewer than 50% of patients — the majority are normokalaemic, making clinical suspicion paramount.

Symptoms and Signs

Feature	Frequency	Mechanism
Hypertension	~100%	Sodium retention, volume expansion
Spontaneous hypokalaemia (K⁺ <3.5 mmol/L)	~37% (higher in APA)	Renal potassium wasting
Muscle weakness / cramps	Common with hypokalaemia	Altered muscle membrane potential
Polyuria / polydipsia	Moderate	Nephrogenic diabetes insipidus from hypokalaemia
Nocturia	Moderate	Polyuria, diuretic effects
Headaches	Common	Hypertension
Palpitations / arrhythmias	Moderate	Hypokalaemia, cardiac fibrosis, AF
Fatigue	Common	Hypokalaemia, metabolic derangement
Paraesthesiae	With severe hypokalaemia	Electrolyte disturbance
Metabolic alkalosis	With hypokalaemia	H⁺ secretion in distal nephron

Cardiovascular Complications

PHA produces target organ damage disproportionate to the degree of hypertension:

Left ventricular hypertrophy (LVH) — concentric, present in 40–50% at diagnosis
Diastolic dysfunction — prevalence 45–65%
Atrial fibrillation — 4-fold increased risk vs essential hypertension
Heart failure — 6-fold increased risk
Stroke — 2-fold increased risk
Coronary artery disease — 2.5-fold increased risk
Albuminuria / chronic kidney disease

Screening Indications

The Endocrine Society (2016) and Australian consensus guidelines recommend screening for PHA in the following groups:

Standard

All resistant hypertension

BP above target on ≥3 optimally dosed antihypertensives, including a diuretic

Primary care / specialist referral

Moderate suspicion

Hypertension + hypokalaemia

Spontaneous or diuretic-induced K⁺ <3.5 mmol/L

Primary care screening

High suspicion

Additional risk factors

Adrenal incidentaloma with HTN, HTN onset <20 yrs, family history early CVA, severe HTN (≥160/100) with poor control

Endocrinologist referral

Screening Test: Aldosterone–Renin Ratio (ARR)

The plasma aldosterone concentration to plasma renin activity (PAC/PRA) ratio, or aldosterone–renin ratio (ARR), is the recommended screening test. Accuracy depends on careful preparation:

Pre-test Preparation

Timing: Blood drawn mid-morning, after the patient has been ambulant for ≥2 hours, seated for 5–15 minutes.
Sodium intake: Patient should follow their usual (liberal) sodium diet — salt restriction can suppress aldosterone and cause false negatives.
Potassium: Hypokalaemia should be corrected before testing (low K⁺ can suppress aldosterone secretion, causing false negatives).
Medication adjustments: If clinically safe, withhold for ≥4 weeks:
- Spironolactone, eplerenone, amiloride, triamterene (potassium-sparing diuretics)
- High-dose liquorice
Less interfering medications (hold ≥2 weeks if possible): β-blockers, clonidine, methyldopa, NSAIDs, ACE inhibitors, ARBs — these affect renin but may still allow ARR interpretation.
Acceptable medications during screening: Verapamil (slow-release), hydralazine, prazosin, doxazosin — these have minimal effect on ARR.

Interpretation

Parameter	Positive Screening	Notes
ARR (pmol/L per ng/mL/h)	≥750	Using PAC in pmol/L and PRA in ng/mL/h
PAC threshold	≥415 pmol/L (~15 ng/dL)	Both ARR and PAC must be elevated for positive screen
PRA threshold	<0.6 ng/mL/h (suppressed)	Confirms renin suppression

⚠️

False positives/negatives: β-blockers may cause false-positive ARR (suppress renin disproportionately). ACE inhibitors, ARBs, and diuretics may cause false-negative ARR (stimulate renin). Always consider medication effects when interpreting results.

If the initial ARR is positive, repeat testing at least once to confirm. Persistent elevation warrants confirmatory testing.

Confirmatory Tests & Adrenal Vein Sampling

Confirmatory Salt-Loading Test

A positive screening ARR must be confirmed by demonstrating non-suppressible aldosterone secretion. The Endocrine Society recommends one of four confirmatory tests; the most widely used in Australia is the oral salt-loading test:

1

Preparation

Patient follows a high-sodium diet (≥6 g NaCl/day or 6–12 salt tablets daily) for 3 days. Ensure serum K⁺ is corrected to ≥3.5 mmol/L before starting.

2

Salt supplementation

Slow-release NaCl tablets (1 g = 17 mmol Na⁺) — target 300 mmol Na⁺/day for 3 days. Simultaneous KCl supplementation to maintain K⁺ ≥3.5 mmol/L.

3

24-hour urine collection

Commence on day 3 morning. Collect 24-hour urine for aldosterone, sodium, and creatinine (to confirm adequate sodium intake ≥200 mmol/24 h).

4

Interpretation

24-hour urine aldosterone >33 nmol/24 h (or >12 μg/24 h) with adequate sodium excretion confirms autonomous aldosterone secretion.

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Contraindications to salt loading: Do NOT perform salt-loading in patients with uncontrolled hypertension (BP >170/110 mmHg), heart failure (NYHA III–IV), severe hypokalaemia (K⁺ <3.0 mmol/L), renal impairment (eGFR <60 mL/min/1.73 m²), or significant oedema. Monitor blood pressure, serum potassium, and eGFR daily during testing.

Alternative Confirmatory Tests

Test	Protocol	Positive Result	Availability
Fludrocortisone suppression test	Fludrocortisone 0.1 mg QID × 4 days + NaCl supplementation; upright PAC on day 4	Upright PAC >277 pmol/L at 10:00 am	Limited — specialist centres only
Captopril challenge test	Captopril 25–50 mg PO; measure PAC and PRA at baseline, 1 h, and 2 h	Post-captopril ARR remains elevated; PAC not suppressed by >30%	Widely available; less sensitive
IV saline infusion test	2 L 0.9% NaCl IV over 4 hours; measure PAC pre- and post-infusion	Post-infusion PAC >139 pmol/L	Requires inpatient setting; haemodynamic monitoring

Adrenal Imaging

Once PHA is biochemically confirmed, adrenal imaging is performed for localisation. However, imaging alone is insufficient for surgical decision-making — adrenal vein sampling is essential:

Adrenal CT (thin-cut, contrast-enhanced): First-line imaging. Detects adenomas ≥1 cm, but has limited sensitivity for micro-adenomas and may show non-functioning incidental nodules. CT discordance with AVS occurs in 37–50% of cases.
MRI adrenal: Alternative if CT contraindicated (contrast allergy, pregnancy). Similar sensitivity to CT.
NP-59 scintigraphy: Largely superseded by AVS; limited availability in Australia.

Adrenal Vein Sampling (AVS)

AVS is the gold standard for distinguishing unilateral APA from bilateral IHA and is mandatory before adrenalectomy in patients aged <35 years with clear unilateral adenoma on CT. In patients aged <35 with a solitary adenoma >1 cm, normal contralateral adrenal, and florid biochemical phenotype, CT alone may suffice — but this is uncommon and expert review is recommended.

1

Operator experience

Must be performed by an experienced interventional radiologist. Success rates improve significantly at centres performing >20 AVS procedures per year.

2

Cosyntropin stimulation

Continuous IV tetracosactide (cosyntropin) infusion (50 μg/h) improves selectivity and reduces stress-related variability. Non-stimulated AVS is an alternative.

3

Bilateral sampling

Simultaneous catheterisation of both adrenal veins and an iliac or IVC sample. Cortisol and aldosterone measured from all sites.

4

Selectivity index (SI)

Adrenal vein cortisol / peripheral cortisol. With cosyntropin: SI ≥3 confirms adequate cannulation. Without cosyntropin: SI ≥2.

5

Lateralisation index (LI)

Higher side aldosterone/cortisol ÷ lower side aldosterone/cortisol. LI ≥4 (with cosyntropin) or ≥2 (without) indicates unilateral disease.

AVS Result	Interpretation	Management
Both SI adequate, LI ≥4	Unilateral aldosterone production (APA or UAH)	Laparoscopic adrenalectomy of the dominant side
Both SI adequate, LI <4	Bilateral aldosterone production (IHA)	Medical therapy with MR antagonist
One or both SI inadequate	Technical failure — repeat AVS recommended	Repeat procedure or experienced centre referral

ℹ️

Australian AVS availability: AVS is available at major tertiary centres (Royal Adelaide, Royal Melbourne, Westmead, Prince of Wales, Royal Brisbane, Fiona Stanley) and requires endocrinologist and interventional radiologist coordination. Telehealth referral for AVS planning is appropriate for regional patients.

Management (Medical & Surgical)

Management Algorithm

Treatment depends on subtype determination (unilateral vs bilateral) and patient operability:

1

Confirm PHA

Positive ARR (×2) → confirmatory salt-loading test with 24-hour urine aldosterone >33 nmol/24 h.

2

Localise with CT + AVS

Thin-cut adrenal CT → AVS (gold standard) to distinguish unilateral from bilateral disease.

3

Determine subtype

Unilateral (APA/UAH) → surgery. Bilateral (IHA) → medical therapy. Consider surgery only if refractory.

4

Treat & monitor

Peri-operative optimisation or MRA titration. Lifelong monitoring of BP, K⁺, renal function, and cardiovascular risk.

Surgical Management: Laparoscopic Adrenalectomy

Laparoscopic (keyhole) adrenalectomy is the treatment of choice for confirmed unilateral APA or UAH. It is well-established at all major Australian surgical centres and is performed by urologists or endocrine surgeons.

Pre-operative Optimisation

Spironolactone 25–100 mg daily for ≥4 weeks pre-operatively to: normalise serum potassium, reduce blood pressure, correct volume expansion, and reduce peri-operative cardiovascular risk.
Target serum K⁺ ≥4.0 mmol/L and BP <140/90 mmHg before surgery.
If spironolactone is not tolerated (gynaecomastia, breast tenderness), substitute amiloride 5–20 mg daily.
Additional antihypertensives as needed: calcium channel blockers (amlodipine) preferred.
Stop spironolactone on the day of surgery.

Post-operative Care

Hypoaldosteronism risk: The contralateral suppressed adrenal may not immediately resume aldosterone production. Monitor for hypotension, hyperkalaemia, and hyponatraemia for 1–3 months post-operatively.
Fludrocortisone 50–100 μg daily may be required temporarily if hyperkalaemia or hypotension develops post-operatively. Taper over weeks as contralateral adrenal recovers.
Monitor serum electrolytes (Na⁺, K⁺) at 1 week, 1 month, 3 months, and 6 months post-operatively.
BP reassessment at 1 month — taper or cease antihypertensives as BP normalises. 50–80% of patients achieve significant BP improvement or cure.
Biochemical cure confirmed by normalised aldosterone, potassium without supplementation, and renin recovery.

✅

Surgical outcomes: Laparoscopic adrenalectomy for APA provides complete resolution of hypertension in 30–60%, significant improvement in 20–30%, and hypokalaemia cure in >90%. Factors predicting complete cure: younger age, shorter duration of hypertension, fewer pre-operative antihypertensives, female sex, lower BMI.

Medical Management: Mineralocorticoid Receptor Antagonists

Medical therapy is indicated for bilateral IHA, patients declining or unfit for surgery, and as adjunctive pre-operative optimisation.

💊

Spironolactone

Aldactone® · Spiractin® · Aldactone® · Potassium-sparing diuretic / MRA

Adult dose Start 12.5–25 mg PO daily; titrate to 25–100 mg daily (max 400 mg for resistant cases)

Dose in PHA Typical maintenance 25–50 mg daily for bilateral IHA; 50–100 mg daily pre-operatively for APA

Paediatric dose 1–3 mg/kg/day in divided doses (FH-III); specialist supervision required

Route Oral

Renal adjustment Use with caution if eGFR <30 — increased hyperkalaemia risk. Monitor K⁺ closely. Dose ≤25 mg daily.

Hepatic adjustment Half-life prolonged in hepatic impairment. Start low (12.5 mg), titrate cautiously.

Key side effects Gynaecomastia (up to 10% at 50 mg/day), breast tenderness, menstrual irregularity, sexual dysfunction, hyperkalaemia

PBS status ✔ PBS General Benefit

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Eplerenone

Inspra® · Selective MRA — fewer anti-androgenic effects

Adult dose Start 25 mg PO BD; titrate to 50 mg BD (max 100 mg BD)

Route Oral

Renal adjustment eGFR 30–50: max 25 mg BD. eGFR <30: avoid or use with extreme caution.

Hepatic adjustment Severe hepatic impairment (Child-Pugh C): avoid.

Key side effects Hyperkalaemia (less gynaecomastia vs spironolactone), dizziness, fatigue

PBS status ⚠ PBS Authority Required

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Amiloride

Midamor® · Kaluril® · ENaC blocker / potassium-sparing diuretic

Adult dose 5–10 mg PO daily; titrate to max 20 mg daily

Route Oral

Role in PHA Alternative to spironolactone if intolerant (no gynaecomastia). Often used in combination with spironolactone for additive potassium-sparing effect.

Renal adjustment Avoid if eGFR <30 or K⁺ ≥5.0 mmol/L

PBS status ✔ PBS General Benefit

MRA Monitoring Protocol

Serum potassium and creatinine at baseline, 1 week, 4 weeks, then every 3–6 months.
Hold spironolactone/eplerenone if K⁺ >5.5 mmol/L; reduce dose if K⁺ 5.0–5.5 mmol/L.
Target K⁺ 4.0–5.0 mmol/L. BP target <130/80 mmHg (or <140/90 if elderly/frail).
Avoid concurrent use with ACE inhibitors, ARBs, or potassium supplements without careful K⁺ monitoring.
Gynaecomastia management: switch from spironolactone to eplerenone or amiloride.

Additional Antihypertensives in PHA

If MRA monotherapy is insufficient for blood pressure control, add:

Calcium channel blockers (amlodipine 5–10 mg daily): effective, no potassium effects, PBS general benefit.
Thiazide diuretics (hydrochlorothiazide 12.5–25 mg daily): synergistic with MRA but increase hypokalaemia risk — monitor K⁺ closely.
ACE inhibitors / ARBs: Can be used with MRAs but increase hyperkalaemia risk. May provide some benefit in suppressing residual angiotensin II–mediated aldosterone.
β-blockers: Less useful as renin is already suppressed; may further reduce renin and cause false-negative ARR if re-testing.

Novel and Emerging Therapies

Baxdrostat and lorundrostat are selective aldosterone synthase (CYP11B2) inhibitors currently in Phase III trials. These agents reduce aldosterone production at the enzymatic level, independent of MR, and may offer improved efficacy for resistant PHA. They are not yet available on the PBS or TGA-listed in Australia.

Monitoring and Long-Term Follow-Up

Post-surgical: Electrolytes (Na⁺, K⁺, creatinine) at 1 week, 1 month, 3 months, 6 months, then annually. ARR at 3 months to confirm biochemical cure. BP medication review — taper/cease as appropriate.
Medical therapy: BP, K⁺, creatinine/eGFR at 1 week after any dose change, then every 3–6 months. Annual echocardiogram if LVH present at baseline.
Cardiovascular risk reduction: Lipid management (statins as indicated), glycaemic monitoring, smoking cessation, weight management, exercise prescription.
Atrial fibrillation screening: Annual ECG or ambulatory monitoring if symptomatic. Consider anticoagulation per CHA₂DS₂-VASc score.
Renal monitoring: Annual urine ACR and eGFR.

Special Populations

🤰 Pregnancy

Diagnosis

PHA is rare in pregnancy but can cause severe pre-eclampsia-like syndromes. ARR interpretation is complicated by normal pregnancy physiology (expanded plasma volume, elevated aldosterone). Postpone confirmatory testing and AVS to post-partum if possible.

Spironolactone

Category B3. Anti-androgenic effects — avoid in first trimester if possible. Use lowest effective dose for shortest duration. Amiloride (Category B1) is preferred if potassium-sparing agent needed.

Eplerenone

Limited pregnancy data. Avoid unless benefit clearly outweighs risk.

Management

Methyldopa, labetalol, or nifedipine for blood pressure control (pregnancy-safe agents). MRA therapy for confirmed PHA — specialist endocrine and obstetric co-management essential. Adrenalectomy in second trimester if refractory.

👶 Paediatrics

Consider PHA

In any child with hypertension, particularly if age <10 years, family history, or severe/resistant HTN. Always consider familial hyperaldosteronism (FH-I, FH-III).

Screening

ARR using age-appropriate reference ranges (paediatric ranges differ from adults). Low-threshold for genetic testing (FH-I: dexamethasone suppression; FH-III: KCNJ5 mutation).

Treatment

Spironolactone 1–3 mg/kg/day. FH-I responds to low-dose dexamethasone (0.125–0.25 mg/day). FH-III may require bilateral adrenalectomy. Paediatric endocrinologist involvement mandatory.

👴 Elderly

Diagnosis

PHA prevalence increases with age; IHA predominates. ARR may be less reliable due to age-related renin decline. Higher false-positive rates — confirmatory testing essential.

Management

Medical therapy (MRA) preferred. Start low-dose spironolactone (12.5 mg) due to increased hyperkalaemia risk from reduced GFR and concurrent ACE inhibitor/ARB use. BP target <140/90 (or <150/90 if frail). Avoid surgery if comorbidities preclude safe anaesthesia.

🫘 Renal Impairment

eGFR 30–59

MRA use with caution. Monitor K⁺ frequently (weekly initially). Spironolactone ≤25 mg daily. Avoid salt-loading confirmatory test — use captopril challenge or fludrocortisone suppression.

eGFR <30

MRA generally contraindicated due to hyperkalaemia risk. Specialist nephrology-endocrine co-management. Consider amiloride if MRA essential. AVS may still be technically feasible.

🫁 Hepatic Impairment

Spironolactone

Extensively used in hepatic ascites (different indication). In PHA with cirrhosis, start low, titrate cautiously. Monitor for hepatic encephalopathy (diuretic-induced hypokalaemia).

Eplerenone

Avoid in severe hepatic impairment (Child-Pugh C).

🛡️ Immunocompromised

Considerations

PHA does not cause immunosuppression per se, but patients on immunosuppressants (e.g., calcineurin inhibitors — cyclosporin, tacrolimus) may have concurrent hyperkalaemia and hypertension that complicates diagnosis. MRA dose adjustment if concurrent nephrotoxic drug use.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health

Disease burden

Aboriginal and Torres Strait Islander peoples experience hypertension at 1.5–2× the rate of non-Indigenous Australians, with earlier onset and greater severity. Resistant hypertension is more prevalent, increasing the likelihood of undiagnosed PHA. Cardiovascular disease — the leading cause of mortality in this population — may be partly attributable to unrecognised secondary causes such as PHA.

Screening barriers

ARR screening requires access to pathology services that can process aldosterone and renin samples (which are temperature-sensitive and require rapid transport). In remote and very remote communities, specimen transport delays may compromise sample integrity. Point-of-care testing for aldosterone/renin is not currently available.

Specialist access

Confirmatory testing (salt-loading), adrenal CT, and AVS require tertiary centre access. Aboriginal and Torres Strait Islander peoples in remote Northern Territory, Western Australia, and Queensland face significant travel burdens. Telehealth endocrinology consultation and Fly-In Fly-Out (FIFO) specialist services should be leveraged. Patient-assisted travel schemes (PATS) apply.

Medication considerations

Spironolactone is PBS general benefit and widely available. However, ongoing monitoring (K⁺, creatinine) requires accessible pathology. Remote area nurses and Aboriginal Health Workers should be empowered to perform MRA monitoring under GP supervision. DAA (Dose Administration Aids) and Webster-pak dispensing improve adherence.

Cultural safety

Discuss diagnosis and management in culturally appropriate settings. Involve Aboriginal Health Workers/Practitioners and, where relevant, family and community elders in care planning. Respect for traditional healing practices alongside Western medical management. Use of Aboriginal interpreter services where English is not the first language.

Holistic approach

Address social determinants of health — housing, nutrition (low sodium intake advocacy must be culturally sensitive to bush tucker practices), access to fresh food, and health literacy. Integrate PHA management into chronic disease care plans (715 health checks, GPMP/TCA). Link with Aboriginal Community Controlled Health Organisations (ACCHOs) for continuity of care.

⚠️

Key recommendation: In Aboriginal and Torres Strait Islander patients with resistant hypertension or early-onset hypertension, actively consider and screen for PHA with a low threshold. Advocate for telehealth-enabled confirmatory pathways to reduce barriers to definitive diagnosis and surgical cure.

📚 References

1. Funder JW, Carey RM, Mantero F, 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. doi:10.1210/jc.2015-4061
2. 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
3. Rossi GP, Bernini G, Caliumi C, 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. doi:10.1016/j.jacc.2006.07.059
4. Mulatero P, Monticone S, Bertello C, et al. Long-term cardio- and cerebrovascular events in patients with primary aldosteronism. J Clin Endocrinol Metab. 2013;98(12):4826–4833. doi:10.1210/jc.2013-2805
5. Milliez P, Girerd X, Plouin PF, et al. Evidence for an increased rate of cardiovascular events in patients with primary aldosteronism. J Am Coll Cardiol. 2005;45(8):1243–1248. doi:10.1016/j.jacc.2005.01.015
6. Rossi GP, Sacchetto A, Visentin P, et al. Changes in left ventricular anatomy and function in hypertension and primary aldosteronism. Hypertension. 1996;28(5):789–795. doi:10.1161/01.HYP.28.5.789
7. Stowasser M, Gordon RD. Primary aldosteronism: changing definitions and new concepts of physiology and pathophysiology both inside and outside the kidney. Physiol Rev. 2016;96(4):1327–1384. doi:10.1152/physrev.00026.2015
8. Vaidya A, Carey RM. Evolution of the primary aldosteronism syndrome: updating the approach. J Clin Endocrinol Metab. 2020;105(12):3771–3783. doi:10.1210/clinem/dgaa604
9. Australian Institute of Health and Welfare (AIHW). Cardiovascular disease in Aboriginal and Torres Strait Islander people. AIHW Cardiovascular Disease Series. Canberra: AIHW; 2023.
10. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J. 2018;39(33):3021–3104. doi:10.1093/eurheartj/ehy339
11. The Royal Australian College of General Practitioners (RACGP). Guidelines for preventive activities in general practice. 10th edition. East Melbourne: RACGP; 2018.
12. National Aboriginal Community Controlled Health Organisation (NACCHO). National guide to a preventive health assessment for Aboriginal and Torres Strait Islander people. 3rd edition. South Melbourne: RACGP; 2018.
13. Lenders JWM, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2014;99(6):1915–1942. doi:10.1210/jc.2014-1498
14. Freel EM, Stowasser M, Gordon RD. Mineralocorticoid receptor antagonists in primary aldosteronism. Clin Endocrinol (Oxf). 2015;82(6):747–754. doi:10.1111/cen.12735
15. Freeman MW, Halvorsen Y-D, Marshall W, et al. Phase 2 trial of baxdrostat for treatment-resistant hypertension. N Engl J Med. 2023;388(5):395–405. doi:10.1056/NEJMoa2213169