Conn's syndrome

Consider investigating for other causes of secondary hypertension if indicated, for example with renal ultrasound scan or CT scan of the aorta for coarctation. Also consider investigating for other causes of hypokalaemia for example renal disease, Bartter's or Gitelman's syndromes.  

Angiotensin converting enzyme inhibitors prevent angiotensin production, and angiotensin 2 receptor blockers prevent its action, such that both classes of drug may lead to falsely low ratios (increased renin and decreased aldosterone).

Spironolactone and other aldosterone antagonists prevent its action and so potentially increase the ratio (by increasing aldosterone).

Beta blockers prevent renin release and also lead to unreliably elevated ratios.

Diuretics potentially reduce fluid delivery to renal tubules. This leads to increased renin production and so increased renin and aldosterone. This also makes interpretation of renin:aldosterone ratios difficult.

Patients may well need to start alternative agents to maintain safe blood pressure control. This requires careful involvement of the GP and patient in arranging safe BP and serum potassium monitoring before planning investigations.

Although calcium channel blockers may also interfere with the renin-angiotensin-aldosterone pathway, in practise this is not clinically apparent. Alpha blockers such doxazosin and calcium channel blockers such as amlodipine are thus routinely recommended for blood pressure control during investigation of possible Conn's syndrome.

Severe, uncorrected hypokalaemia may reduce aldosterone secretion.

If patients habitually follow a low salt diet this may also lead to a fall in aldosterone levels.

If clinically suspected, or in the case of borderline results, this can be prevented by giving NaCl 120mmol/24-hours orally for three days prior to further tests, or by suggesting the patient eats a high salt diet for three days, for example eating a shop bought pizza the day before any tests.

The protocol for this test usually requires the patient to lie recumbent and resting for 30 minutes, but can be taken at any time of day.

Historically, renin and aldosterone assessments were repeated at various times of the day, with synchronous cortisol and ACTH measurements, and with or without prior ambulation or rest, to attempt to distinguish degrees of ACTH responsiveness. This was performed in an attempt to determine whether hyperaldosteronism was secondary to unilateral adenoma or bilateral hyperplasia.

However, these are no longer performed in most centres as they are difficult to interpret, non specific and since adrenal imaging and selective venous catheterisation have improved and become more widely available.

International guidelines exist to aid in the diagnosis of Conn's syndrome.

Aldosterone/renin ratio:

Plasma renin: typically <0.3 pmol/ml/hr (normal range 0.5-3.1)

Aldosterone: typically >350 pmol/l (normal range 100-800)

If the ratio is normal, and clinical suspicion is low, the patient may resume their normal medications,  and usually be discharged from endocrine follow up to consider alternative diagnoses.

If results are normal or borderline, but a high degree of clinical suspicion of Conn’s syndrome remains, consider salt loading and repeating the test. Salt loading is usually with 120mmol/day (slow sodium tablets) for 72 hours. Alternatively, ask the patient to eat a high salt diet, for example a shop bought pizza the day before the test.

If the patient is unfit for, or declines surgery, consider starting spironolactone.

Careful BP and serum potassium monitoring is mandatory.

Male patients should be warned that they may experience troublesome gynaecomastia or erectile dysfunction in some cases. In this case, the dose of spironolactone should be reduced to that tolerated, and a potassium sparing diuretic added, for example amiloride.

Alternatively the newer aldosterone antagonist eplerenone can be used. 

If the biochemistry is consistent with Conn's syndrome and the patient potentially suitable for surgery: proceed to CT scan of the adrenals and discuss selective venous sampling.

Spironolactone may be started at this stage, however, this will need to be withdrawn four weeks prior to selective venous sampling if applicable.

A good biochemical and BP response to spironolactone may be predictive of a good surgical outcome. 

Review CT scans at a multidisciplinary meeting. In patients under 50, if a unilateral adenoma is clearly visible with a normal contralateral gland, then unilateral disease is highly likely. Surgical referral can be considered with no further investigations. If imaging is not definitive, proceed to adrenal venous sampling in all patients.

In patients over 50, adrenal venous sampling should be considered in all patients and the results of the CT interpreted with caution since incidental adrenal adenomas are common as is bilateral hyperplasia.  

Selective venous sampling of both adrenal veins is mandatory in patients over 50 and those with ambiguous imaging results. Cannulation of the right adrenal vein can be technically difficult. Interpretation may be improved in such cases by administering synacthen at the time of cannulation. 

Unilateral disease is typified by an aldosterone:cortisol ratio in the affected gland >4:1. The ratio should also be greater than that in the contralateral adrenal gland, and greater than that in the inferior vena cava. All other results should be considered ambiguous and consistent with bilateral disease. These patients should not be considered for surgery.

Usually performed by a laparascopic approach. Prophylactic vaccination may be given in patients requiring left sided surgery in case splenectomy is necessary.

Careful BP and serum potassium monitoring is mandatory.

Male patients should be warned that they may experience troublesome gynaecomastia or erectile dysfunction in some cases. In such cases, the dose of spironolactone should be reduced to that tolerated and a potassium sparing diuretic added, for example amiloride. Alternatively the newer aldosterone antagonist eplerenone can be used. 

Once good control of BP and serum potassium are achieved, consider discharging patient to care of the GP for long term follow up.