Primary hyperaldosteronism (Conn's syndrome)

Aldosterone induces sodium and water retention but this is followed within a few days by a spontaneous diuresis (called aldosterone escape) that returns excretion to the level of intake and partially lowers the extracellular fluid volume toward normal thus avoiding any clinically significant oedema

About

• Excess production of Aldosterone may cause 5% of cases of HTN

Aetiology

• High Aldosterone suppresses Renin with Na retention and K and H ion excretion
• Hypertension and hypokalaemia and alkalosis is the main clue

Causes

• Aldosterone secreting adrenal adenoma - 75%
• Bilateral Adrenal Hyperplasia 25%
• Adrenal carcinoma - rare
• Glucocorticoid remedial aldosteronism - rare

Clinical

• Hypertension, headaches, weakness
• Muscle weakness, myopathy, cramps due to hypokalaemia
• HTN often refractory to usual treatment

Indications for screening

• Hypertension and hypokalaemia (not diuretic-induced)
• Resistant hypertension
• Adrenal incidentaloma and hypertension
• Severe hypertension (SBP >160, DBP >100)

Investigations (test off diuretics, ACEIs and ARB)

Aldosterone (pmol/L) to renin (mIU/L) ratio of greater than 30 where the aldosterone is greater than 300 pmol/L suggests primary aldosteronism(99% sensitivity, 79% specificity).

• U&E: Mild High Na, Low K, Low Mg, Mild Metabolic alkalosis. More than 50% are normokalaemic.
• Seated resting mid-morning plasma renin and aldosterone. Correct K before testing with supplements. Use Doxazosin to control BP. High aldosterone (normal up to 630pmol/L) along with Low or undetectable plasma renin. Note that ACE inhibitors, ARBs and diuretics may falsely elevate plasma renin activity. Diagnosis likely with Aldosterone / Renin ratio > 20-30
• Confirm inability to suppress aldosterone with Saline Suppression Test 2000 ml IV normal saline infused over 4 hours. Aldosterone checked at the start and finish. Normal response is for aldosterone to fall < 200pmol/l
• 131-Iodocholesterol scanning
• Echo : Left ventricular hypertrophy
• Localise with CT/MRI of the adrenals
• Adrenal venous sampling to confirm
• Consider genetics tests for Glucocorticoid Remediable Hyperaldosteronism

Differential

• Glucocorticoid remedial aldosteronism
• Apparent Mineralocorticoid Excess e.g. Licorice or Glycyrrhizic Acid a sweeteneer
• Liddle's syndrome - BP, Hypokalaemia, Metabolic alkalosis but Low aldosterone
• Congenital adrenal hyperplasia
• Gordon's Syndrome (PHA 2)

Management

• Laparoscopic adrenalectomy of adenoma or unilateral if possible. Hypertension is cured in about 70% of patients. The response to spironolactone can be used to predict the response to surgery of patients with adenomas.
• Hyperplasia or non-surgical candidate: Aldosterone antagonists e.g. spironolactone 25-100 mg/day for hyperplasia or Eplerenone (50–100 mg/day) is a mineralocorticoid antagonist without antiandrogen effects and greater selectivity than that of spironolactone. Amiloride can also be used.
• Glucocorticoid Remediable Hyperaldosteronism. Suspect in patients with early-onset familial hypertension. Biochemically indistinguishable from other causes of Primary Aldosteronism Adrenals normal or diffuse hyperplasia on CT. Diagnosis PCR for the chimeric gene. Treat with Low dose dexamethasone. Also responds to aldosterone antagonists and amiloride
• Adrenal carcinoma: consider surgery and postoperative adrenolytic therapy with mitotane is usually required. Prognosis is usually poor.

References

• Screening for Conn's Syndrome (Primary Aldosteronism)