Conn's syndrome

From Ganfyd

Introduction

Primary hyperaldosteronism is a condition characterized by excess aldosterone production leading to sodium retention, potassium loss and the combination of hypertension and hypokalaemia with alkalosis. It is actually the most common form of secondary hypertension so a low index of clinical suspicion is justified with case finding studies resulting in prevalence estimates of 5-13% of all patients with hypertension^[1].

Historical

First described in 1953 by Michal Litynski^[2] the description by Jerome Conn in 1955 got him an eponym.

screen if: Hypertension and hypokalaemia (regardless of presumed cause) Treatment-resistant hypertension (3 antihypertensive drugs fail) Severe hypertension (≥ 160 mmHg systolic or ≥ 100 mmHg diastolic) Hypertension and incidental adrenal mass Onset of hypertension at a young age Suspicion for secondary hypertension from other cause

Aetiology

Primary aldosterone excess due to:

1. Unilateral adrenal adenoma
2. Bilateral adrenal hyperplasia
3. Glucocorticoid-remediable aldosteronism (GRA, familial hyperaldosteronism type I)
4. Familial hyperaldosteronism type II
5. Carcinomas

Clinical

• Hypertension
• Muscle weakness - from hypokalaemia
• Nocturia - hypokalaemia renders the collecting duct insensitive to the action of anti-diuretic hormone thus nephrogenic diabetes insipidus can occur
• Tetany

Biochemical

• Hypokalaemia (<3.5mmol/l though some may have normal serum K⁺)
• Alkalosis - as potassium is predominantly an intracellular cation body stores can be severely depleted while the serum potassium remains normal. The acid base status of the patient reflects the total body potassium state much more reliably

The hypertension may be severe and associated with renal, cardiac and retinal damage

Have a low threshold for testing in

• Young patients
• Poor response to treatment
• Requiring many antihypertensives, good response to amiloride or spironolactone
• Hypokalaemic alkalosis - even if on diuretics

Catches: Calcium channel blockers can mask hypokalaemia as they suppress aldosterone secretion[3] Significant hypokalaemia on a low dose thiazide is suggestive of the diagnosis - don't be reassured

Investigations

Biochemistry

• U&E - hypokalaemic alkalosis
• Screen by morning (preferably between 08:00 and 10:00) ambulatory paired random
  • Plasma renin activity (PRA) - (or plasma renin mass)
    • Classically to consider Conn's renin should be undetectable and, as such, it is a necessary hallmark of primary aldosteronism
    • However cases of Conn's with low normal renin activity and normal aldosterone early in the tumour course have been described
  • Serum aldosterone (PAC) - usually high but can be normal. Where there is another mineralocorticoid in the circulation it can be suppressed
• Increased PAC:PRA ratio is not diagnostic by itself
• Confirm by showing inappropriate aldosterone secretion with an aldosterone suppression test eg:
  • Oral sodium chloride load and urinary aldosterone or
  • Intravenous sodium chloride load and PAC

Radiology

• CT - should be evaluated after biochemistry. Beware "Incidentalomas"
• MRI
• Venous sampling from both adrenal veins

Treatment

Medical

Medical therapy is the treatment of choice in bilateral adrenal hyperplasia. In aldosterone producing adenoma medical therapy with an aldosterone antagonist can help predict the likely response to surgery and thus, in some way, the suitability of surgery.

• Spironolactone is an effective aldosterone antagonist and will reverse whatever component of the hypertension is due to aldosterone. The usual dose is 50 - 400 mg in two divided doses. It is also a weak anti-androgen so gynaecomastia and impotence are rare side effects in males limiting its use. In women dysmennorrhoea and intermenstrual bleeding can occur.
• Eplerenone is a new weak aldosterone antagonist with no antiandrogen activity
• Amiloride or triamterine are often used where side effects prevent spironolactone being used.

• Lifestyle advice - stopping smoking, regular exercise, maintainance of ideal body weight and dietary restriction of sodium to <100 mmol per day will augment the success of any pharmacological regime.

Surgical

Surgical removal, usually by a laparoscopic^[4] or 'lap and glove' approach is the treatment of choice for a unilateral aldosterone producing adenoma.

• Surgery is more likely to correct the hypokalaemia than the hypertension if the patient has a long undiagnosed history.

References