Diagnosis of Conn's Syndrome

As with most endocrine surgical problems the important steps are:

• to establish the diagnosis of hyperaldosteronism
• to localise the tumour if present, or determine another cause to enable the appropriate treatment decisions to be made.

1. Confirmation of the biochemical diagnosis of hyperaldosteronism

The important indicators to perform primary testing for hyperaldosteronism are:

Other possible clues to the diagnosis include the finding of a mild metabolic alkalosis (bicarbonate >30 mmol/l) and a mildly elevated serum glucose level due to the low potassium interfering with insulin secretion and glucose regulation.

a) Plasma aldosterone/renin ratio

The most important confirmatory test is the calculation of the plasma aldosterone/renin ratio, which in Conn’s syndrome is elevated >1700, because of suppressed renin activity and elevated aldosterone levels in plasma. Aldosterone should be greater than 250pmol/l (normal 100-800 pmol/l), so can be normal or high, while renin activity (highly sensitive) should be low - less than 0.5pmol/ml/hour (normal 0.5-3.1 pmol/ml/hr). Patients with ratios <700 are unlikely to have Conn's syndrome, while intermediate levels require further confirmation.

Note that care needs to be taken that certain medications are stopped prior to the tests as they can interfere with the results. Spironolactone, beta blockers, oestrogens, diuretics, ACE inhibitors and vasodilators all should be stopped, but hypertension can be controlled with alpha blockers like doxazosin, or calcium channel blockers.

b) Saline Infusion Test 

If further confirmation is required due to an equivocal aldo/renin ratio, the second-line investigation is a saline infusion test. This involves measuring aldosterone levels before and after an intravenous infusion of 2 litres of normal saline, given over 4 hours. What should normally happen is that the intravascular expansion should suppress the excretion of aldosterone, but a lack of suppression indicates primary hyperaldosteronism. 

An aldosterone level of <120 pmol/l indicates a probably normal response, while an aldosterone level >240 pmol/l suggests Conn's syndrome is more likely.

2. Establishing the pathological cause

It is vital to determine the cause of the primary hyperaldosteronism, particularly whether the patient has unilateral (single gland) or bilateral (both adrenals) disease, as this will determine the appropriate treatment. This is done by a combination of imaging studies and adrenal venous sampling.

Imaging

CT or MRI of the adrenal glands

Fig.1: CT scan of typical small left adrenal Conn's tumourThis will demonstrate any obvious tumours and indicate whether one or both glands are involved. They are sensitive enough to pick out more than 85% of aldosterone secreting tumours larger than 1 cm (Fig. 1).

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.

Adrenal venous sampling (AVS)

This needs to be done in most cases when a biochemical diagnosis of hyperaldosteronism has been made, in order to determine if the patient has unilateral or bilateral disease.

One group of patients that probably do not require venous sampling are those aged < 40 years, with marked primary hyperaldosteronism, and with a clear unilateral adrenal adenoma and a normal contralateral adrenal gland on imaging.

Those with bilateral disease generally need medical treatment, not surgery, and this can only be established by AVS.

Just because CT picks up a lesion in one adrenal, it does not automatically mean that this is the source of the excess aldosterone. More than 25% of patients with single gland disease on CT scan can in fact have bilateral disease, making surgery inappropriate. Some patients can even have a lesion in one adrenal, with AVS finding the disease is actually in the other adrenal, raising the possibility of the surgeon taking out the wrong adrenal gland.  

AVS is performed by passing catheters through the femoral veins in the leg into the adrenal veins on both sides, where blood samples are taken after the administration of ACTH. Aldosterone and cortisol levels are measured to determine the aldosterone/cortisol (A/C) ratio (Fig. 2).

Fig.2: Venous sampling report showing Conn's tumour in the left adrenal glandThe A/C ratio will indicate the most likely cause of the excess aldosterone production:

• A/C ratio > 4 is likely to be due to aldosterone secreting tumour in the affected side

• A/C ratio < 4 is likely to be due to bilateral adrenal hyperplasia

Venous sampling is 90% accurate, but needs an experienced interventional radiologist to perform it, and there is a small risk of adrenal infarction. It is not used as an initial diagnostic tool, but to confirm the side of the problem.

Next page: Conn's Syndrome treatment