Investigation of primary hyperaldosteronism (Secondary Care, HHSCP only) (Guidelines)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

Measurement of random aldosterone / renin ratio (ARR)

Principal/Indication

The first line screening test to investigate patients with hypertension (and hypokalaemia) for primary hyperaldosteronsim (Conn’s Syndrome) is a random aldosterone/renin ratio (ARR). This is less affected by drug therapy, diurnal variation and patient position than aldosterone and renin alone. The initial screening test can usually be done on treatment.

Preparation and procedure
  1. Whilst optimal to perform this test on no interfering anti-hypertensive drug therapy, this is often impractical and may result in significant risk to the patient. Therefore, with the exception of the mandatory medication withdrawals listed in Table 1, this initial screening test can be performed on anti-hypertensive therapy provided these medications are noted and the requesting clinician is aware of their potential effects on aldosterone and/or renin.
    It is the responsibility of the physician co-ordinating the investigations to oversee the withdrawal of the medication and to ensure that the patient has a clear plan for when to restart previous medications.
  2. Correct hypokalaemia and do not restrict salt intake prior to the test.
  3. Patient should be adequately hydrated.
  4. Ideally perform at 9-10 am, unless undertaking ad hoc testing in clinic.
  5. Ensure patient has been ambulant during a 2 hours period prior to the test.
  6. Patient should then sit upright for 15 minutes.
  7. Inform lab of test.
  8. Complete laboratory request forms for renin & aldosterone & U&Es
  9. Take blood for U&Es (brown gel tube), renin and aldosterone (2 x red ETDA tubes) and send to lab immediately, not on ice.
  10. End test.
Interpretation
  • The aldosterone reference range is 130-800pmol/l. Plasma renin is reported as Plasma Renin Concentration (PRC) therefore the Aldo/PRC should be used to guide further investigation for hyperaldosteronism.
  • An aldosterone to renin ratio (ARR) of < 35 is normal
  • An aldosterone to renin ratio (ARR) of ≥ 35 cannot exclude primary hyperaldosteronism (especially if plasma aldosterone level >410 pmol/l)
  • If the initial random ARR is abnormal and the patient was still on drugs which are known to interfere with the ARR then the test should be repeated off the offending drugs, as per Table 1, substituting with doxazosin and/or twice daily verapamil MR if required. Double check liquorice and chewing tobacco intake. If the second test off interfering drugs is abnormal proceed to the saline infusion test.
  • If the patient has spontaneous hypokalaemia, and significant biochemical aldosterone excess (>550 pmol/L) and undetectable PRC then confirmatory testing (saline infusion) is not required.

Saline Infusion Test for Diagnosis of Primary Hyperaldosteronism

Indication/Principle

This is a second line test for the confirmation of primary hyperaldosteronism. Patients will already have been screened and found to have an elevated aldosterone/renin ratio and a raised aldosterone concentration. This should be done with the patient off all ACE inhibitors, ARBs, diuretics, β blockers, dihydropyridine CCBs and methyldopa. Change to a drug which does not affect the renin-angiotensin-aldosterone axis eg doxazosin, verapamil MR, and hydralazine (starting the verapamil before the hydralazine to reduce reflex tachycardia). The principle of the test is that control of aldosterone is lost and is not suppressed in response to an excessive salt and water load.

Contraindication

The test is contraindicated in patients with cardiac failure, renal impairment, severe uncontrolled hypertension and hypokalaemia.

Preparation and procedure
  1. Stop all interfering drugs as per Table 1. Change to non-interfering drug.
    It is the responsibility of the physician co-ordinating the investigations to oversee the withdrawal of the medication and to ensure that the patient has a clear plan for when to restart previous medications.
  2. Ideally start test at 08.30-09.00am
  3. Insert an IV cannula into each arm- one for saline infusion and one for blood tests
  4. The patient should be seated 1 hr prior to test) and should remain seated throughout.
  5. Check and record pulse and BP
  6. Take blood sample for U&Es, aldosterone (red EDTA) and renin (red EDTA), send to lab immediately, not on ice.
  7. Commence infusion of 2L of 0.9% normal saline over 4 hours i.e. infusion pump rate of 500ml/hour.
  8. Measure pulse and BP hourly throughout test
  9. At completion of infusion immediately take blood for aldosterone (red EDTA) and renin (red EDTA) still in seated position. Send to lab immediately, not on ice.
  10. Remove cannulae
  11. Repeat pulse and BP
  12. End test.
Interpretation
  • Serum aldosterone > 270 picomol/L at the end of the study confirms a diagnosis of primary hyperaldosteronism.
  • Serum aldosterone <170 picomol/L excludes primary aldosteronism.
  • Aldosterone values 170-270 picomol/L are equivocal and should be discussed in detail with the referring clinician. If the test is positive the patient requires adrenal imaging.

Adapted from GG&C guidance courtesy of Dr Marie Freel

Table 1: Medication withdrawal for investigation of primary hyperaldosteronism

Table 1: Medication withdrawal for investigation of primary hyperaldosteronism
Mandatory medication withdrawl 
Medications Washout period 
Beta blockers 2 weeks 
NSAIDs 2 weeks 
Spironolactone, eplerenone, amiloride 6 weeks 
Medications to discontinue prior to saline suppression test.  Can be continued for initial ARR, interpreting in line with Table 2 
ACE inhibitors/ARBs 2 weeks 
DHP calcium channel blockers 2 weeks 
Diuretics 4 weeks 
Oestrogen eg HRT, COCP 6 weeks 

Table 2: Factors influencing aldosterone and renin levels.

Table 2: Factors influencing aldosterone and renin levels.   From the Endocrine Society Clinical Practice Guideline 2008. 

False positive (FP), False negative (FN) 

Abbreviations

Abbreviation  Meaning 
BP  blood pressure 
CCBs calcium channel blocker 
EDTA   ethylenediamine tetraacetic acid
pmol/L  Picomoles per litre
U&E  urea and electrolytes 

Editorial Information

Last reviewed: 01/09/2022

Next review date: 30/09/2025

Version: 1

Reviewer name(s): Dr D MacFarlane, Consultant Endocrinologist .

Document Id: TAM529