How is the diagnosis of primary hyperaldosteronism confirmed?
The important points here are:
- to diagnose hyperaldosteronism biochemically
- to establish the cause to enable treatment decisions to be made.
Establishing primary hyperaldosteronism biochemically.
The important diagnostic indicators are:
- low serum (blood) potassium concentration (<3 mmols/l)
- high 24 hour urine potassium amount (>30 mmols)
Useful indicators are also a mild metabolic alkalosis (bicarbonate >30 mmols/l) and a mildly elevated serum glucose level due to the low potassium interfering with insulin secretion and glucose regulation. All tests should be made with the patient not taking any normal anti-hypertensive medication, such as diuretics and spironolactone, as this can invalidate the results.
Confirmatory findings are from blood tests showing:
- decreased renin activity in the plasma
- increased plasma aldosterone concentrations
Establishing the cause of the hyperaldosteronism.
Tests must be performed to indicate what the cause of the diagnosed primary hyperaldosteronism is as this determines the treatment.
Imaging
CT or MRI scans of the adrenal glands will demonstrate any obvious tumours and indicate whether one or both glands are involved. They are sensitive enough to pick out more than 90% of APAs larger than 1 cm. If the mass is larger than 3 cm it is either an incidental finding unrelated to the hyperaldosteronism (an 'incidentaloma') or rarely a cancer secreting aldosterone. Imaging is less sensitive and specific for the remaining causes and any equivocal scan warrants further tests.
Posture studies
The principle here is that the adrenal adenomas producing aldosterone are sensitive to ACTH whereas bilateral idiopathic adrenal hyperplasia is sensitive to angiotensin II. Patients have blood tests at 08:00 for aldosterone, cortisol and renin after sleeping all night. After four hours of being upright and walking around (which stimulates angiotensin II production due to blood pressure changes, not affecting ACTH) the blood tests are repeated. Adrenal adenomas will show very little change in aldosterone levels whereas the benign adrenal hyperplasia cases will show increased aldosterone (due to stimulation by the increased angiotensin II.)
Diagram to illustrate posture studies - click to enlarge
Captopril™ test
This is an Angiotensin Converting-Enzyme (ACE) inhibitor (see physiology section) blocking angiotensin II production from angiotensin I. When given to patients with APA, plasma aldosterone levels remain unchanged due to the tumour being responsive only to ACTH. When given to patients with IHA, plasma aldosterone levels will fall as the hyperplastic glands are responsive to angiotensin II.
18-hydroxycorticosterone (18-OHB) and -cortisol (18-OHF) tests
18-OHB is an intermediate compound produced in the synthesis of aldosterone from cholesterol in the adrenal cortex (see physiology section and section on Congenital Adrenal Hyperplasia). 18-OHF is formed from circulating cortisol in the adrenal cortex. Plasma and urine concentrations are elevated in most causes of primary hyperaldosteronism but are highest in glucocorticoid-suppressible aldosteronism (GSA), less high in APA and least high in IHA. This pattern can provide some useful information when used in conjunction with other tests.
Invasive tests - more uncomfortable for the patient but often more accurate, these include:
- Radiolabelling tests
A mildly radioactive compound (131I-6-beta-iodomethyl-19-norcholesterol) is injected into the patient and taken up by the adrenal glands. On scanning it allows a more accurate view of the adrenals allowing differentiation of APA from IHA in 72% cases. - Adrenal venous sampling
Catheters are passed through the femoral veins in the leg into the adrenal veins on both sides and blood samples taken after the administration of ACTH. Aldosterone and cortisol levels are measured. The aldosterone:cortisol ratio level indicates the following:
Aldosterone:cortisol ratio Significance Greater than 4:1 likely to be APA Less than 4:1 likely to be IHA
This is 95% accurate and vital prior to adrenalectomy to determine if the tumour seen on a CT scan is actually the source of the excess aldosterone. Although it is technically difficult to do and there is a small risk of adrenal infarction, it will eliminate the risk of unnecessary surgery in the patient with bilateral adrenal hyperplasia.The Hammersmith Hospital experience from 2000 to 2009 of 41 cases presented to the BAETS in 2010 of venous sampling of which 28 were operated on confirmed that when well selected no patient following surgery needed potassium supplements and the antihypertensive drug burden fell by over 50%.This imaging is very specialised, the tumours are frequently very small and great expertise is needed to get good results.