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

From the Guidelines

Mineralocorticoid excess and insufficiency have severe consequences on morbidity, mortality, and quality of life, and thus require prompt diagnosis and treatment to prevent complications such as cardiovascular damage, adrenal crisis, and death. The consequences of mineralocorticoid excess, such as primary aldosteronism, include hypertension, hypokalemia, metabolic alkalosis, and increased sodium retention, which can lead to cardiovascular damage and increased mortality 1. In contrast, mineralocorticoid insufficiency, such as Addison's disease, leads to hypotension, hyperkalemia, hyponatremia, and metabolic acidosis, which can cause adrenal crisis and death if left untreated 1.

Key Consequences and Management

• Mineralocorticoid excess:
  • Hypertension
  • Hypokalemia
  • Metabolic alkalosis
  • Increased sodium retention
  • Treatment: mineralocorticoid receptor antagonists like spironolactone (25-100 mg daily) or eplerenone (25-50 mg daily)
• Mineralocorticoid insufficiency:
  • Hypotension
  • Hyperkalemia
  • Hyponatremia
  • Metabolic acidosis
  • Treatment: mineralocorticoid replacement with fludrocortisone (0.05-0.2 mg daily) and often glucocorticoid replacement with hydrocortisone (15-25 mg daily in divided doses)

Perioperative Management

Hydrocortisone 100 mg by intravenous injection should be given at induction of anesthesia in adult patients with adrenal insufficiency, followed by a continuous infusion of hydrocortisone at 200 mg/24 h-1, until the patient can take double their usual oral glucocorticoid dose by mouth 1. This regimen is preferred due to enhanced safety and should be tapered back to the appropriate maintenance dose within 48 hours, although for up to a week if surgery is more major or complicated.

Education and Monitoring

Patients with mineralocorticoid insufficiency must be educated about stress dosing during illness and should carry an emergency steroid card or medical alert identification. Both conditions require regular monitoring of blood pressure, electrolytes, and kidney function to ensure optimal management and prevent complications. Regular monitoring and prompt treatment can significantly improve morbidity, mortality, and quality of life in patients with mineralocorticoid excess and insufficiency.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Corticosteroids are thought to act at least in part, by controlling the rate of synthesis of proteins. Although there are a number of instances in which the synthesis of specific proteins is known to be induced by corticosteroids, the links between the initial actions of the hormones and the final metabolic effects have not been completely elucidated The physiologic action of fludrocortisone acetate is similar to that of hydrocortisone. However, the effects of fludrocortisone acetate, particularly on electrolyte balance, but also on carbohydrate metabolism, are considerably heightened and prolonged 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
• Congregative 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, as seen in apparent mineralocorticoid excess (AME) 3.
• The excess of mineralocorticoids can cause end-organ damage, such as hypertensive retinopathy and left ventricular hypertrophy 3.
• Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, can normalize blood pressure, correct hypokalemia, and reduce hypertensive end-organ damage in patients with mineralocorticoid excess syndromes 3, 4, 5.

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 and potentially other electrolyte imbalances, although this is not directly stated in the provided studies.

Treatment and Management

• Mineralocorticoid receptor antagonists, such as spironolactone and eplerenone, are effective in treating mineralocorticoid excess syndromes, but may have adverse effects such as hyperkalemia and acute deterioration of renal function 4, 6, 7.
• Glucocorticoids can be used to inhibit the ACTH increase that drives mineralocorticoid synthesis, and mineralocorticoid receptor antagonists can be used to manage the abiraterone-induced mineralocorticoid excess syndrome 6.
• The development of novel non-steroidal mineralocorticoid receptor antagonists could substantially widen the use of such agents and reduce the risk of adverse effects 7.