Adrenal cortical steroids

Introduction

Adrenal cortical steroids, commonly referred to as corticosteroids, are synthetic or naturally occurring hormones derived from the adrenal cortex. They are broadly classified into:

• Glucocorticoids: Primarily influence carbohydrate, protein, and fat metabolism while exerting potent anti-inflammatory and immunosuppressive effects.

• Mineralocorticoids: Regulate electrolyte and water balance by affecting sodium retention and potassium excretion.

• Androgens (adrenal origin): Contribute to secondary sexual characteristics, but less therapeutically relevant compared to glucocorticoids and mineralocorticoids.

Corticosteroids are widely used in endocrinology, rheumatology, pulmonology, oncology, dermatology, nephrology, and critical care medicine. Their pharmacological versatility makes them one of the most prescribed drug classes globally.

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Physiology of Adrenal Cortical Steroids

Glucocorticoids (Cortisol as the prototype)

• Secreted by the zona fasciculata of the adrenal cortex.

• Regulated by the hypothalamic–pituitary–adrenal (HPA) axis through ACTH.

• Functions:

  • Increase gluconeogenesis and maintain blood glucose.

  • Promote protein catabolism and lipolysis.

  • Suppress inflammation and immune responses.

  • Maintain vascular responsiveness to catecholamines.

Mineralocorticoids (Aldosterone as the prototype)

• Produced in the zona glomerulosa.

• Regulated mainly by the renin–angiotensin–aldosterone system (RAAS) and serum potassium.

• Functions:

  • Sodium reabsorption in distal tubules and collecting ducts.

  • Potassium and hydrogen ion excretion.

  • Blood pressure regulation.

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Classification of Adrenal Cortical Steroids

1. Glucocorticoids

Synthetic analogues vary in potency, duration, and mineralocorticoid activity.

Examples and Typical Adult Doses (oral/IV unless stated):

• Hydrocortisone: 20–40 mg/day (short-acting, 8–12 hr).

• Prednisone: 5–60 mg/day (intermediate-acting, 18–36 hr).

• Prednisolone: 5–60 mg/day (active metabolite of prednisone).

• Methylprednisolone: 4–48 mg/day; IV pulse 1 g/day for 3 days in severe autoimmune flare.

• Triamcinolone: 4–16 mg/day (intermediate).

• Dexamethasone: 0.5–10 mg/day (long-acting, 36–54 hr).

• Betamethasone: 0.5–6 mg/day (long-acting).

2. Mineralocorticoids

• Fludrocortisone: 0.05–0.2 mg/day orally; potent sodium-retaining effect.

3. Combined/Other Preparations

• Combination therapies (e.g., glucocorticoid + mineralocorticoid in Addison’s disease).

• Topical, inhaled, intra-articular, ophthalmic, and intranasal formulations exist for local use.

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Therapeutic Uses

Endocrine

• Adrenal insufficiency (Addison’s disease): Hydrocortisone with fludrocortisone.

• Congenital adrenal hyperplasia: Glucocorticoids suppress ACTH and androgen excess.

• Cushing’s syndrome testing: Dexamethasone suppression test.

Non-endocrine (pharmacological use)

• Inflammatory and autoimmune disorders: Rheumatoid arthritis, lupus, vasculitis.

• Respiratory diseases: Asthma (inhaled corticosteroids like budesonide, fluticasone), COPD.

• Allergic conditions: Anaphylaxis adjunct, severe allergic rhinitis, angioedema.

• Oncology: Adjunct in hematologic malignancies (ALL, lymphoma, myeloma).

• Neurology: Cerebral edema (dexamethasone), multiple sclerosis relapse.

• Organ transplantation: Prevent rejection (part of immunosuppressive regimens).

• Dermatology: Psoriasis, eczema, severe dermatitis (topical or systemic).

• Critical care: Septic shock (low-dose hydrocortisone), COVID-19 pneumonia (dexamethasone).

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Adverse Effects

Short-term (days–weeks)

• Mood changes (euphoria, insomnia, psychosis).

• Increased appetite and weight gain.

• Hyperglycemia.

• Hypertension.

• Fluid retention.

Long-term (chronic therapy)

• Cushingoid features: moon face, buffalo hump, central obesity.

• Osteoporosis, fractures.

• Muscle wasting and weakness.

• Skin thinning, striae, poor wound healing.

• Immunosuppression, increased infection risk.

• Peptic ulcers.

• HPA axis suppression → risk of adrenal crisis on withdrawal.

• Cataracts and glaucoma.

• Growth retardation in children.

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Contraindications and Precautions

• Absolute contraindication: Systemic fungal infection (unless treating Addison’s).

• Relative cautions: Peptic ulcer disease, uncontrolled diabetes, hypertension, osteoporosis, psychiatric illness.

• Vaccination: Avoid live vaccines in patients on high-dose systemic corticosteroids.

• Pregnancy: Some agents (e.g., betamethasone) are used to enhance fetal lung maturity, but prolonged use carries maternal/fetal risks.

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Drug Interactions

• CYP3A4 inducers (rifampin, phenytoin): Increase metabolism, reduce efficacy.

• CYP3A4 inhibitors (ketoconazole, ritonavir): Increase steroid exposure.

• NSAIDs: Additive risk of GI bleeding and ulcers.

• Diuretics: Enhanced hypokalemia.

• Warfarin: Variable effects on anticoagulation.

• Vaccines: Reduced immune response.

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Clinical Considerations

• Dosing strategies:

  • Aim for the lowest effective dose.

  • Alternate-day regimens reduce HPA suppression.

  • Tapering is essential after long-term use to allow adrenal recovery.

• Route of administration:

  • Oral for systemic effects.

  • IV for emergencies (status asthmaticus, adrenal crisis).

  • Inhaled for asthma/COPD maintenance.

  • Topical for dermatologic or ocular use.

• Monitoring:

  • Blood pressure, blood glucose, electrolytes.

  • Bone density with long-term use.

  • Signs of infection and HPA axis suppression.