Hydrocortisone (Cortisol) - Mechanism, Uses & Doses

Drug Overview

Hydrocortisone is the pharmaceutical form of cortisol, the naturally occurring glucocorticoid secreted by the adrenal cortex. It has both glucocorticoid and mild mineralocorticoid activity.

Brand names: Solu-Cortef (IV), Cortef (oral), Alkindi Sprinkle (pediatric oral granules), Cortenema (rectal)

Mechanism of Action

Genomic (Primary) Mechanism

Hydrocortisone diffuses across cell membranes and binds intracellular glucocorticoid receptors (GR). The hormone-receptor complex translocates to the nucleus, where it binds glucocorticoid response elements (GREs) on DNA, directly regulating gene transcription - inducing anti-inflammatory proteins and suppressing pro-inflammatory genes (including cytokines via NF-kB inhibition).

Non-Genomic (Rapid) Effects

Rapid effects (e.g., initial ACTH suppression within minutes) occur too fast for gene transcription and are mediated via:

Direct effects on cell membrane receptors
G-protein-coupled membrane receptors
Palmitoylated steroid receptors near the plasma membrane interacting with cytoplasmic proteins

Circadian Interaction

Tissue sensitivity to glucocorticoids is inversely related to circulating cortisol levels - sensitivity is highest in the evening/early night (explaining why evening dosing has greater effect). CLOCK acetyltransferase acetylates the GR hinge region, reducing transcriptional activity in the morning.

Physiologic & Pharmacologic Effects

System	Effect
Carbohydrate	Stimulates gluconeogenesis, inhibits peripheral glucose uptake → hyperglycemia
Protein	Promotes muscle catabolism, releases amino acids for gluconeogenesis
Fat	Stimulates lipolysis, promotes fat redistribution (central adiposity)
Immune	Suppresses cytokine production (NF-kB inhibition), inhibits phospholipase A2 → reduces prostaglandins/leukotrienes
Vascular	Permissive effect on catecholamine-mediated vasoconstriction
Mineralocorticoid	Mild sodium retention, potassium excretion (less than fludrocortisone)

Pharmacokinetics

Half-life: ~60-90 minutes (may be prolonged in stress, hypothyroidism, liver disease, or with large doses)
Protein binding: ~90% bound to corticosteroid-binding globulin (CBG), ~5% to albumin, ~5% free
CBG is saturated at plasma cortisol >20-30 mcg/dL; above this, free cortisol rises sharply
Metabolism: Primarily hepatic; ~20% converted to cortisone by 11-hydroxysteroid dehydrogenase in kidney
Excretion: ~1% unchanged in urine; metabolites excreted as 17-hydroxysteroids

Dosing

Status Asthmaticus

Population	Dose
Child (load, optional)	4-8 mg/kg/dose IV; max 250 mg
Child (maintenance)	8 mg/kg/24 hr divided Q6h IV
Adult	100-500 mg/dose Q6h IV

Anti-inflammatory / Immunosuppressive

Population	Route	Dose
Child	PO	2.5-10 mg/kg/24 hr divided Q6-8h
Child	IM/IV	1-5 mg/kg/24 hr divided Q12-24h
Adolescent/Adult	PO/IM/IV	15-240 mg/dose Q12h

Acute Adrenal Insufficiency

Follow protocol from physiologic replacement guidelines (weight-based, typically stress dosing: 50-100 mg IV bolus in adults, then continuous infusion or Q6-8h dosing)

Ulcerative Colitis (mild-moderate, induction)

Rectal enema: 100 mg once daily to BID x 2-3 weeks (child, adolescent, adult)

Hemorrhoids (adult)

Rectal cream (1% or 2.5%): apply sparingly BID
Suppository: 25 or 30 mg PR BID x 2 weeks

Topical (all ages)

Apply to affected areas BID-QID depending on severity

Key Safety Points

Avoid in immunocompromised patients with exposure risk to chickenpox or measles
Hypertrophic cardiomyopathy reported in premature infants
Alkindi Sprinkle granules: sprinkle directly on tongue or in soft food - do NOT swallow capsule
Bioavailability differs between Alkindi Sprinkle and compounded/split-tab formulations

Sources:

Katzung's Basic and Clinical Pharmacology, 16th Ed, pp. 1101-1103 (mechanism, pharmacokinetics, metabolic effects)
The Harriet Lane Handbook, 23rd Ed, pp. 1173-1174 (dosing by indication and age group)

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