Does glucocorticoid act as cortisol?

From the Guidelines

Glucocorticoids can act similarly to cortisol, but not all glucocorticoids are identical to cortisol in terms of structure and function. When considering the pharmacology of glucocorticoids, it's essential to understand that therapeutic glucocorticoids include hydrocortisone, which is structurally identical to cortisol, as well as prednisolone and dexamethasone, which have different properties 1. The key point is that while hydrocortisone is equivalent to cortisol, other glucocorticoids like prednisolone and dexamethasone have varying immunosuppressive and metabolic effects, with 10 mg of hydrocortisone being roughly equivalent to 2.0 mg of prednisolone and 0.1 mg of dexamethasone 1. Some of the main differences and similarities between glucocorticoids and cortisol include:

• Hydrocortisone is structurally identical to cortisol
• Prednisolone and dexamethasone have different immunosuppressive and metabolic properties compared to cortisol
• Glucocorticoids, including synthetic ones, work by binding to glucocorticoid receptors, influencing gene expression, and producing anti-inflammatory and immunosuppressive effects, similar to cortisol 1. In clinical practice, understanding these differences is crucial for managing patients with adrenal insufficiency, especially during the peri-operative period, as guidelines suggest 1. The primary goal is to ensure that patients receive appropriate glucocorticoid replacement therapy to mimic the natural cortisol production, thereby minimizing morbidity, mortality, and improving quality of life.

From the FDA Drug Label

ACTIONS Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states.

• Glucocorticoids have effects similar to cortisol, a naturally occurring glucocorticoid, as they are used as replacement therapy in adrenocortical deficiency states, implying they act like cortisol in the body.
• The fact that hydrocortisone is used as replacement therapy suggests it has a similar action to cortisol 2.

From the Research

Glucocorticoid and Cortisol Relationship

• Glucocorticoids are used as a replacement therapy for cortisol in patients with adrenal insufficiency, as seen in studies 3, 4, 5, 6.
• The goal of glucocorticoid replacement therapy is to mimic the natural circadian rhythm of cortisol release, but current standard treatment regimens may not adequately achieve this, leading to increased morbidity and decreased life expectancy 3.
• Glucocorticoids can suppress the hypothalamic-pituitary-adrenal axis, leading to adrenal insufficiency, and patients may develop features of Cushing's syndrome and glucocorticoid withdrawal syndrome when treatment is tapered down 4, 5.

Glucocorticoid Replacement Therapy

• The daily glucocorticoid replacement dose recommended by guidelines is 15 to 25 mg of hydrocortisone, but some studies suggest that lower doses may be sufficient and reduce the risk of long-term adverse outcomes 6.
• The choice of glucocorticoid and dosing regimen can affect the risk of adrenal insufficiency and other adverse events, and individualized treatment plans may be necessary to minimize these risks 3, 4, 5.

Mechanism of Action

• Glucocorticoids suppress inflammation by reversing histone acetylation of activated inflammatory genes and recruiting histone deacetylase-2, and they also have post-transcriptional effects and decrease the stability of some proinflammatory mRNAs 7.
• Glucocorticoids can have both trans-repression and trans-activation effects, and the balance between these effects can influence their anti-inflammatory efficacy and side effect profile 7.