What are the consequences of mineralocorticoid (corticosteroid hormone) excess and insufficiency?

From the Guidelines

Mineralocorticoid excess and insufficiency both cause significant disruptions to electrolyte balance and blood pressure regulation, and their management requires careful consideration of the underlying cause and individual patient needs, as outlined in recent guidelines 1.

Mineralocorticoid Excess

In mineralocorticoid excess (hyperaldosteronism), patients experience hypertension, hypokalemia, metabolic alkalosis, and increased sodium retention. This occurs because excess aldosterone enhances sodium reabsorption and potassium excretion in the distal tubules of the kidneys. Patients may present with muscle weakness, headaches, polyuria, and polydipsia.

• Treatment typically involves mineralocorticoid receptor antagonists like spironolactone (starting at 25-100 mg daily) or eplerenone (25-50 mg daily), along with addressing the underlying cause, which may be adrenal adenoma (requiring surgical removal) or bilateral adrenal hyperplasia (managed medically) 1.
• The optimal antihypertensive regimen in patients with Cushing syndrome, which can also cause mineralocorticoid excess, remains to be adequately described, but adequate diuretic therapy will likely prove to be a cornerstone of successful therapy 1.

Mineralocorticoid Insufficiency

Conversely, mineralocorticoid insufficiency (as in Addison's disease) leads to hyponatremia, hyperkalemia, metabolic acidosis, and hypotension due to inadequate aldosterone production. Patients experience fatigue, weakness, salt craving, orthostatic hypotension, and may develop an Addisonian crisis with severe hypotension and shock if untreated.

• Management requires mineralocorticoid replacement with fludrocortisone (typically 0.05-0.2 mg daily), along with glucocorticoid replacement (usually hydrocortisone 15-25 mg daily in divided doses) 1.
• Patients need regular monitoring of blood pressure, electrolytes, and plasma renin activity to ensure appropriate dosing and prevent complications from either under or over-replacement.
• The annual consultation should include questions regarding family relationships and professional duties, self-esteem and possible complaints due to primary adrenal insufficiency (PAI), as well as questions about the quality of the daily replacement therapy, self-medication during intercurrent illness and previous adrenal crises 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY ... Mineralocorticoids act on the distal tubules of the kidney to enhance the reabsorption of sodium ions from the tubular fluid into the plasma; they increase the urinary excretion of both potassium and hydrogen ions The consequence of these three primary effects together with similar actions on cation transport in other tissues appear to account for the entire spectrum of physiological activities that are characteristic of mineralocorticoids. ADVERSE REACTIONS Most adverse reactions are caused by the drug’s mineralocorticoid activity (retention of sodium and water) and include hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis

The consequences of mineralocorticoid excess include:

• Hypertension
• Edema
• Cardiac enlargement
• Congestive heart failure
• Potassium loss
• Hypokalemic alkalosis The consequences of mineralocorticoid insufficiency are not directly stated in the provided drug labels. 2 2

From the Research

Consequences of Mineralocorticoid Excess

• Mineralocorticoid excess can lead to severe hypertension, hypokalemia, and hyporeninemic hypoaldosteronism 3, 4, 5
• Apparent mineralocorticoid excess syndrome is a genetic disorder that causes severe hypertension, hypokalemia, and left ventricular hypertrophy 3, 4, 5
• Mineralocorticoid excess can also lead to end-organ damage, such as hypertensive retinopathy and renal failure 4
• Abiraterone-induced mineralocorticoid excess syndrome can cause mineralocorticoid excess symptoms, including hypertension, hypokalemia, and fluid retention 6

Consequences of Mineralocorticoid Insufficiency

• There is limited information available on the consequences of mineralocorticoid insufficiency in the provided studies
• However, it can be inferred that mineralocorticoid insufficiency may lead to decreased blood pressure, hyperkalemia, and decreased fluid retention

Treatment of Mineralocorticoid Excess and Insufficiency

• Treatment of mineralocorticoid excess includes the use of mineralocorticoid receptor antagonists, such as spironolactone and eplerenone 3, 6, 4, 7
• Glucocorticoids can also be used to inhibit the ACTH increase that drives mineralocorticoid synthesis 6
• Salt deprivation and potassium supplements may also be used to manage mineralocorticoid excess 6, 7, 5
• Treatment of apparent mineralocorticoid excess syndrome includes the use of spironolactone, amiloride, and potassium citrate 3, 4, 5