Resident Editor: Megan Lockwood, M.D.

Faculty Editor: Elisabeth Askin, M.D.

Conversion Table

Oral Glucocorticoid	Approximate Equivalent Dose (mg)
Short Acting (half-life: 8-12 hours)
Cortisone*	25
Hydrocortisone	20
Intermediate Acting (half-life: 12-36 hours)
Prednisone*	5
Prednisolone	5
Triamcinolone	4
Methylprednisolone	4
Fludrocortisone**	-
Long Acting (half-life: 36-72 hours)
Betamethasone	0.6
Dexamethasone	0.75

* Cortisone and prednisone both require hepatic activation. Patients with liver dysfunction and/or hypoalbuminemia may be exposed to higher levels of unbound corticosteroid. However, the clinical significance of these pharmacokinetic and pharmacodynamic effects has not yet been evaluated.

** Mineralocorticoid, not typically used for anti-inflammatory properties

BOTTOM LINE ✔ Associated with several toxicities: use the lowest effective dose for the shortest duration possible ✔ For patients on long-term therapy (>4 weeks), always monitor for complications and adverse events ✔ Know what you are treating with a clear end-goal

Approximate Prednisone Dose Ranges

• Physiologic:                         5mg (usual average adrenal output)
• Supra-physiologic:               10-20mg
• High supra-physiologic:      50-250mg (max adrenal output)

Dosing Instructions

• Frequency: depends on the indication
  • Short-acting steroids (in increased frequency) preferred for patients with primary adrenal insufficiency, to mimic normal physiology of cortisol secretion.
  • For non-compliant patients or patients who have significant side effects, a long-acting formulation may be preferred.
• Single daily dose:
  • Instruct patient to take their dose in the morning (to match the patient’s exogenous cortisol release and circadian rhythm, reduces the likelihood of CNS side effects such as insomnia)
  • Always advise patients to take corticosteroids with food to prevent stomach upset.     
• Obese patients may metabolize steroids more rapidly and need higher doses.
• Look out for drug-drug interactions that may lead to increased hepatic metabolism of steroids (e.g. phenobarbital, phenytoin, rifampin)

Uses

• Physiologic replacement dosing: endocrine disorders such as adrenal insufficiency and congenital adrenal hyperplasia
• Supra-physiologic dosing: inflammatory, allergic, and immunologic disorders

Non-Oral Steroids

• Parenteral: IV methylprednisolone – more often used in emergencies, see Hospitalist Handbook for additional information.
• Intramuscular: IM hydrocortisone, cortisone acetate, triamcinolone, dexamethasone – can work quickly, more variable absorption rate.
• Topical: used often for skin conditions. Can be absorbed and cause HPA axis suppression. Watch for skin side effects below.
• Inhaled: fluticasone has greater systemic absorption and adrenal suppression.

Complications from Chronic Steroid Use

Adrenal suppression:

• May cause suppression of the hypothalamic-pituitary-adrenal axis (HPA), particularly in patients receiving high doses greater than a week.
• Symptoms of adrenal insufficiency include fatigue, weakness, anorexia, nausea, vomiting, hypotension, hypoglycemia, cutaneous pigmentation.
• Particular care is required when patients are transitioned from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Pts receiving >20 mg/day of prednisone (or equivalent) may be most susceptible. Discontinuation of a corticosteroid should be done slowly.

Cardiovascular effects:

• Use with caution in patients with heart failure; long-term corticosteroid use has been associated with fluid retention and hypertension.

Dermatologic:

• Prolonged/excess corticosteroid use has been associated with thin, fragile skin, bruising, striae, acne, alopecia, hirsutism, hypertrichosis, lipodystrophy, and poor wound healing. 

Endocrine/Metabolic effects:

• Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia, particularly post-prandial.
• Excess glucocorticoids has been associated with Cushingoid fat deposition (buffalo hump and moon face) and obesity; also menstrual irregularity and infertility.  

GI effects:

• Use with caution in patients with GI disease (diverticulitis, peptic ulcer, ulcerative colitis) due to perforation risk.

Immunologic effects:

• Acute leukocytosis; prolonged use of corticosteroids may increase the risk of secondary infection (immunosuppression), mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines.  

Musculoskeletal:

• Acute myopathy has been reported with high dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor CK.
• Prolonged use has been associated with osteoporosis and fractures; see below for further discussion of glucocorticoid-induced osteoporosis.

Ocular effects:

• Prolonged use may cause posterior subcapsular cataracts, glaucoma (with possible nerve damage) and may increase risk for ocular infections

Psychiatric disturbances:

• Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, agitation, and personality changes. Pre-existing psychiatric conditions may be exacerbated by corticosteroid use.

Glucocorticoid-induced osteoporosis (GIOP):

• Over 10% of patients on long-term glucocorticoids are diagnosed with a fracture, nearly 40% with radiographic evidence of vertebral fractures
• Osteoporosis is a silent disease until fracture occurs
• The highest rate of bone loss occurs in first 3-6 months of corticosteroids
• Always ensure patients take calcium and vitamin D supplementation
• Steps to evaluate for GIOP
  1. Categorize your patient’s fracture risk
  2. Treat according to risk

Monitoring and Supportive Care

• Stress-dose steroids for patients with HPA axis suppression during illness, surgery, third trimester/labor and delivery during pregnancy
• Consider PCP prophylaxis if using equivalent steroid dose to prednisone 20mg daily >4 weeks
• Monitor for infections (e.g. thrush, yeast) and treat as needed
• Optimize calcium intake (1,000-1,200 mg/day) and vitamin D intake (600-800 IU/day)
• Monitor for glucocorticoid-induced osteoporosis (see above)
• Annual eye exam (monitor and treat glaucoma, cataracts)
• Monitor and manage psychiatric effects
• Monitor and treat HTN or fluid retention
• GI prophylaxis with H2-blocker or PPI
• Monitor and manage hyperglycemia

References

Buckley L, Gordon G, Fink HA, et al. 2017 American College of Rheumatology Guideline for the Prevent and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis and Rheumatology. 2017;69(8):1521-1537.

Cutolo M, Seriolo B, Pizzorni C, et al. Use of glucocorticoids and risk of infections. Autoimmun Rev. 2008;8(2):153-5.

Lexicomp. Lexi-Drugs. “Prednisone.” Accessed online on 3/27/18.

Meikle AW, Tyler FH. Potency and duration of action of glucocorticoids. Am J of Med. 1977;63:200.

Stanbury RM, Graham EM. Systemic corticosteroid therapy-side effects and their management. Br J Ophthalmol. 1998;82(6):704-8.

Uribe, M. Go VL, Kluge D. Prednisone for chronic active hepatitis: pharmacokinetics and serum binding in patients with chronic active hepatitis and steroid major side effects. J Clin Gastroenterol. 1984;6(4):331-335.

Ward MM, Donald F. Pneumocystis carinii pneumonia in patients with connective tissue diseases: the role of hospital experience in diagnosis and mortality. Arthritis Rheum. 1999 Apr;42(4):780-9.