Which synthetic steroids exhibit mineralocorticoid activity?

From the Guidelines

Fludrocortisone is the most clinically significant synthetic steroid that exhibits mineralocorticoid activity, used primarily to treat adrenal insufficiency and orthostatic hypotension at doses of 0.05-0.2 mg daily. Several synthetic steroids possess mineralocorticoid activity, including 9α-fluorocortisol, deoxycorticosterone acetate (DOCA), and to varying lesser degrees, prednisone, prednisolone, and methylprednisolone [ 1 ].

Key Points

• The mineralocorticoid effects of these medications result from their ability to bind to mineralocorticoid receptors in the distal tubules and collecting ducts of the kidney, promoting sodium reabsorption and potassium excretion.
• Some synthetic steroids like dexamethasone and betamethasone have minimal mineralocorticoid activity [ 1 ].
• When using these medications, particularly fludrocortisone, monitoring for hypertension, edema, and hypokalemia is essential, as these are common side effects of excessive mineralocorticoid activity.
• Fludrocortisone has approximately 125 times the sodium-retaining potency of hydrocortisone.

Mineralocorticoid Replacement

Mineralocorticoids are vital for maintaining blood pressure, and water and electrolyte homeostasis [ 1 ].

Synthetic Steroids with Mineralocorticoid Activity

Other synthetic steroids with mineralocorticoid effects include:

• 9α-fluorocortisol
• Deoxycorticosterone acetate (DOCA)
• Prednisone
• Prednisolone
• Methylprednisolone Note that the evidence from [ 1 ] does not directly relate to the question of which synthetic steroids exhibit mineralocorticoid activity, but rather discusses the management of glucocorticoids during the peri-operative period for patients with adrenal insufficiency.

From the FDA Drug Label

Fludrocortisone acetate tablets USP, 0.1 mg contain fludrocortisone acetate, a synthetic adrenocortical steroid possessing very potent mineralocorticoid properties and high glucocorticoid activity; 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 synthetic steroid that exhibits mineralocorticoid activity is fludrocortisone acetate 2 2.

• Key effects of fludrocortisone acetate include:
  • Marked sodium retention
  • Increased urinary potassium excretion
  • Rise in blood pressure due to effects on electrolyte levels

From the Research

Synthetic Steroids with Mineralocorticoid Activity

• Fludrocortisone is a synthetic steroid that exhibits mineralocorticoid activity, as evidenced by its use in replacing mineralocorticoids in patients with primary adrenal insufficiency 3, 4, 5, 6.
• The mineralocorticoid activity of fludrocortisone is dose-dependent, with higher doses resulting in increased sodium levels and decreased potassium and renin levels 3.
• Other synthetic glucocorticoids, such as those used in replacement therapy for congenital adrenal hyperplasia, do not appear to increase mineralocorticoid needs in adult patients with salt wasting congenital adrenal hyperplasia 7.

Factors Affecting Mineralocorticoid Activity

• The metabolism of fludrocortisone can be affected by certain drugs, such as phenytoin, which can increase hepatic 6-beta-hydroxylation and alter mineralocorticoid requirements in patients with primary adrenal insufficiency 5.
• Plasma renin activity can be used to evaluate the adequacy of mineralocorticoid replacement in primary adrenal insufficiency, but its usefulness is limited by variability in renin levels during treatment 6.
• Clinical evaluation and measurement of urea and electrolyte levels in blood may be more useful in assessing patients with primary adrenal insufficiency than monitoring plasma renin activity 6.