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Hyperaldosteronism Investigations

PLASMA AND URINE ALDOSTERONE, AND PLASMA RENIN ACTIVITY
INDICATIONS

  • Accelerated hypertension.
  • Hypertension with hypokalaemia, spontaneous or easily provoked, i.e. by diuretics or sodium loading - consider if plasma potassium is <3.6mmol/L. As the treatment of hyperaldosteronism is far more effective in correcting hypokalaemia rather than the hypertension extensive investigation in normokalaemic patients is not justified.
  • Assessment of early/impending adrenal cortical failure (Addison's) - see short synacthen test.

CONTRAINDICATIONS

None

SIDE EFFECTS

None

PREPARATION

Remember liquorice ingestion and carbenoxolone may mimic hyperaldosteronism.
Discontinue drugs:
Spironolactone, oestrogens 6 weeks
Diuretics 4 weeks
ACE Inhibitors 2 weeks
NSAIDs 2 weeks
Calcium antagonists 1 week
Sympathomimetics 1 week
Beta-blockers 1 week
If anti-hypertensive therapy needs to be continued then prazosin, doxazosin or bethanidine may be used.
Patient should be on unrestricted sodium intake before admission - in general the salt intake in this part of the world is adequate and patients do not require salt-loading prior to investigation.

FIRST LINE INVESTIGATION:

Random plasma aldosterone/renin ratio
Outpatient procedure
Supply details of all therapy on request form
Ensure adequate salt intake - NOT loading
Correct severe hypokalaemia first

Method

Sit patient quietly for at least 10 minutes
1 X Lithium heparin sample (green top vacutainer)
Send urgently to lab (within half an hour) - NO ice needed

Analysis

Carried out in Dept of Chemical Pathology, St Mary's Hospital
If clinical details and list of medications are provided then St Mary's are very helpful in supplying a full interpretation of results.

Interpretation of results

Aldosterone/renin ratio
>2000 almost certainly Conn's
>1000 Possibly Conn's, investigate further
<800 excludes Conn's

For diagnosis of Conn's: low renin expected
Plasma renin <0.5pmol/ml/hr (ref. 0.5-3.1)
Aldosterone >250pmol/l (ref. 100-800) ie. may be normal or high

POSTURAL STUDIES

It is advisable to discuss the results of first line investigations before proceeding with further investigations.

Syringes.
A 19g cannula.
Saline flushes.
2 EDTA tubes (purple top Vacutainers).
2 Lithium heparin tubes (green top Vacutainers).
Plain 24 hour urine collection bottle for urinary aldosterone.

METHOD

Day 1 Place on liberal sodium intake - 100 mmol/day (e.g. sodium chloride tablets 2g p.o. tds)Take blood for electrolytes - get results on same day.If potassium is low (<3.5 mmol/l) then give oral potassium supplements.Discuss diet with dieticians.
Day 3 Warn patient to remain in bed the next morning.Ask nurses to leave a bedpan or bottle by the bedside for nocturia!
Day 4 0700h Cannulate peripheral vein. Tell patient to remain in bed until told otherwise.
0800h Take blood with patient supine for:ElectrolytesPlasma aldosterone (Lithium heparin)Plasma renin activity (Lithium heparin NOT on ice. Take to lab immediately).Start 24 hour urine collection for aldosterone.Ask patient to get up and mobilise.
1200h Take blood for plasma aldosterone, plasma renin activity.
Day 5 0800h Complete 24 hour urine collection.

INTERPRETATION

Primary hyperaldosteronism Normal ranges
Suppressed upright renin <2.8 pmol/ml/hr 2.8-4.5 pmol/ml/hr upright1.1-2.7 pmol/ml/hr supine
Raised supine aldosterone >450 pmol/l 100-450 pmol/l supinevariable range upright
Raised urinary aldosterone >50 nmol/24 hrs 10-50 nmol/24 hrs

  • If plasma and urine aldosterone are low then consider other causes of hypokalaemia.
  • If aldosterone is raised but plasma renin activity is not suppressed then the diagnosis is likely to be secondary hyperaldosteronism.
  • It is possible to differentiate the two main causes of primary hyperaldosteronism on the basis of the response to posture. In bilateral hyperplasia there is a >33% rise in aldosterone on rising while in an adrenal adenoma there is an anomalous fall in aldosterone.

SENSITIVITY AND SPECIFICITY

The tests have greater than 90% accuracy of correctly diagnosing primary hyperaldosteronism.
The changes with posture may help in the differentiation between adenoma and bilateral hyperplasia but should be interpreted in the light of the results of CT scanning. Interpret results with caution in patients with renal impairment.

REFERENCE

Melby J.C., Clin. Endo. Met. 69,4; 697-703 (1989).