STEPTRACKERPHARMACOLOGY + ENDOCRINOLOGY | ENDOCRINE | HIGH-YIELD REVIEW

Adrenal Drugs & Glucocorticoids

Glucocorticoids are the most-used anti-inflammatory drugs — powerful, broad and predictably toxic with long use. Other drugs replace or block adrenal hormones.

FOCUS ON

Glucocorticoids (hydrocortisone, prednisone, methylprednisolone, dexamethasone, budesonide): bind cytosolic receptor → gene changes; ↓ NF-κB and phospholipase A₂ (via annexin/lipocortin) → ↓ prostaglandins, leukotrienes, cytokines; ↓ eosinophils and lymphocytes, ↑ neutrophils (demargination). Adverse (Cushingoid): hyperglycemia, osteoporosis, avascular necrosis, myopathy, cataracts, glaucoma, infection, peptic ulcer (with NSAIDs), psychosis, insomnia, hypertension, skin thinning, poor wound healing, growth suppression; adrenal suppression → taper, stress dosing. Potency: hydrocortisone (mineralocorticoid too) < prednisone < dexamethasone (no mineralocorticoid). Fludrocortisone: Addison mineralocorticoid replacement, orthostatic hypotension. Blockers: ketoconazole, metyrapone (11β-hydroxylase), osilodrostat, mifepristone (receptor) for Cushing; spironolactone/eplerenone for hyperaldosteronism.

DRUG

PROFILE

USE

NOTES

Hydrocortisone

Short-acting; glucocorticoid + mineralocorticoid

Adrenal insufficiency, adrenal crisis (IV), CAH

Stress dosing for surgery, illness

Prednisone · prednisolone · methylprednisolone

Intermediate; prednisone is a prodrug (liver)

Autoimmune disease, asthma/COPD flares, transplant, IV pulse (methylpred)

Prednisolone in liver disease

Dexamethasone · betamethasone

Long-acting, potent, no mineralocorticoid effect

Cerebral edema (tumor), fetal lung maturity, croup, bacterial meningitis, suppression test

Strong HPA suppression

Budesonide · fluticasone

High first-pass or topical inhaled/nasal

Asthma, allergic rhinitis, Crohn (budesonide), eosinophilic esophagitis

Oral thrush (rinse mouth), dysphonia

Fludrocortisone

Strong mineralocorticoid

Primary adrenal insufficiency, orthostatic hypotension, CAH (salt-wasting)

Edema, hypertension, ↓ K⁺

Ketoconazole · osilodrostat · metyrapone

Block steroidogenic enzymes (11β-hydroxylase etc.)

Cushing syndrome

Ketoconazole hepatotoxic, antiandrogen

Mifepristone

Glucocorticoid and progesterone receptor antagonist

Cushing hyperglycemia; medical abortion (with misoprostol)

Hypokalemia

Spironolactone · eplerenone

Mineralocorticoid receptor antagonists

Primary hyperaldosteronism (bilateral hyperplasia)

↑ K⁺

Phenoxybenzamine → β-blocker

α then β blockade

Pheochromocytoma

Metyrosine adjunct

Steroid effects on blood counts

↑ Neutrophils (demargination), ↓ eosinophils, lymphocytes, basophils, monocytes

—

Leukocytosis without infection

Long-term steroid adverse effects

Bone, eyes, glucose, BP, mood, infection, skin, muscle, growth

—

Calcium + vitamin D ± bisphosphonate; PJP prophylaxis at high doses

Withdrawal / adrenal crisis

HPA axis suppressed after ~3 weeks of supraphysiologic doses

Hypotension, hyponatremia, hypoglycemia, shock

Taper; IV hydrocortisone in crisis

Mechanism — anti-inflammatory action

Steroid enters cellBinds cytosolic receptor

→

Complex moves to nucleus

→

↑ Annexin A1, ↓ NF-κB, ↓ COX-2

→

Fewer eicosanoids and cytokinesIL-1, IL-2, TNF

Potency comparison

DRUG

ANTI-INFLAMMATORY

SALT-RETAINING

Hydrocortisone

Prednisone

0.8

Dexamethasone

25–30

Fludrocortisone

125+

How it's tested

COMMON CONFUSIONPrimary adrenal insufficiency needs both glucocorticoid and mineralocorticoid (fludrocortisone); secondary needs only glucocorticoid — aldosterone is controlled by RAAS.

THE TRAPA patient on long-term prednisone who becomes hypotensive after surgery may be in adrenal crisis — give stress-dose hydrocortisone.

YOUR APPROACHRoute (inhaled, topical, oral, IV) → duration → mineralocorticoid need → plan for toxicity and tapering.

If you see… think…

Hip pain on long-term steroids → avascular necrosis of femoral head

Oral thrush on an inhaler → inhaled corticosteroid

Leukocytosis with eosinopenia after starting a drug → glucocorticoid

Cerebral edema around a tumor → dexamethasone

Preterm labor before 34 weeks → betamethasone (fetal lung)

Addison disease with hyperkalemia → hydrocortisone + fludrocortisone

Hypotension after surgery in a steroid user → adrenal crisis

Glucocorticoid receptor blocker → mifepristone

Steroid enzyme inhibitor for Cushing → ketoconazole, metyrapone, osilodrostat

Phospholipase A₂ inhibition (indirect) → glucocorticoids