How to Diagnose Secondary Hyperaldosteronism
Secondary hyperaldosteronism is diagnosed by demonstrating elevated aldosterone levels with elevated (not suppressed) renin levels, distinguishing it from primary aldosteronism where renin is suppressed. 1
Understanding the Key Distinction
The fundamental difference between primary and secondary hyperaldosteronism lies in the renin-aldosterone relationship:
- Primary hyperaldosteronism: Autonomous aldosterone production from the adrenal glands with suppressed renin 1, 2
- Secondary hyperaldosteronism: Both aldosterone AND renin are elevated, indicating the aldosterone excess is driven by renin-angiotensin system activation 1
This distinction is critical because it completely changes your diagnostic approach and treatment strategy.
Initial Laboratory Testing
Measure Both Aldosterone and Renin
The cornerstone of diagnosis is measuring plasma aldosterone concentration and plasma renin activity simultaneously. 1
- In secondary hyperaldosteronism, you will find both elevated 1
- The aldosterone-to-renin ratio (ARR) will typically be normal or low (unlike primary aldosteronism where ARR >20-30) 3, 2, 4
- Plasma aldosterone should be measured in ng/dL and plasma renin activity in ng/mL/hour 4
Check Serum Electrolytes
- Assess for hypokalemia, though it may be absent in many cases 1
- Measure serum creatinine, sodium, and potassium 3
Patient Preparation Before Testing
Ensure the patient is potassium-replete before testing, as hypokalemia can suppress aldosterone production and cause false-negative results. 2, 4
Key preparation steps:
- Correct any hypokalemia first 2, 4
- Patient should have unrestricted salt intake 3, 4
- Blood should be drawn in the morning, with patient seated for 5-15 minutes 4
- Patient should be out of bed for 2 hours prior to collection 4
Medication Considerations
Several medications can interfere with aldosterone and renin measurements 3:
Medications that lower renin (can cause false-positive ARR in primary aldosteronism screening, but less relevant for secondary):
Medications that raise renin (can cause false-negative ARR):
When feasible, substitute with long-acting calcium channel blockers or alpha-receptor antagonists, which minimally interfere with testing 4. If medications cannot be stopped, interpret results in the context of current medications 2.
Identifying the Underlying Cause
Once secondary hyperaldosteronism is confirmed (elevated aldosterone with elevated renin), investigate the underlying cause:
Common Causes to Screen For:
Renovascular hypertension 3:
- Renal doppler ultrasound 3
- Abdominal CT angiogram or MRI 3
- Check eGFR, albuminuria 3
- Consider in patients <40 years (fibromuscular dysplasia) or >60 years with acute BP change or flash pulmonary edema (atherosclerosis) 3
Renal parenchymal disease 3:
- Plasma creatinine, sodium, potassium 3
- eGFR 3
- Urine dipstick for blood and protein 3
- Urinary albumin-to-creatinine ratio 3
- Renal ultrasound 3
Other causes: Heart failure, cirrhosis, nephrotic syndrome, or diuretic use can all activate the renin-angiotensin-aldosterone system and cause secondary hyperaldosteronism.
Critical Pitfalls to Avoid
Do not confuse secondary hyperaldosteronism with primary aldosteronism - this is the most important distinction:
- Primary aldosteronism has suppressed renin with elevated aldosterone (high ARR) 1, 2
- Secondary hyperaldosteronism has elevated renin with elevated aldosterone (normal/low ARR) 1
Do not rely on hypokalemia alone - it is absent in approximately 50% of hyperaldosteronism cases 4
Do not proceed with confirmatory testing for primary aldosteronism (saline suppression, oral salt loading) if renin is elevated - these tests are only for primary aldosteronism where autonomous aldosterone production is suspected 3, 2, 4
When to Refer
If the diagnosis remains unclear or if you identify a complex underlying cause (such as renovascular hypertension requiring intervention), refer to a hypertension specialist, nephrologist, or endocrinologist for further evaluation 3, 2.