Medicolegal Issues

Steroid Stress Dosing


Adrenal response to stress can vary broadly from patient to patient. For hospitalists, the challenge is predicting patients’ cortisol needs.

The variability exists whether one is dealing with a healthy patient or a patient with adrenal insufficiency (AI).1 Glucocorticoid use is even more complicated in patients with chronic autoimmune or inflammatory disorders who have been treated with high doses of glucocorticoids, or with those who are hypothalamic-pituitary-adrenal (HPA) axis suppressed.


Exforge, a single-tablet combination of amlodipine and valsartan, has been FDA approved for treatment of hypertension in patients who have not achieved good control with either a calcium channel blocker or an angiotensin-receptor blocker, or for patients who have experienced dose-limiting side effects on either agent.

Tamiflu, (oseltamivir phosphate, Roche) has been FDA-approved as 30- and 45-mg capsules to provide an alternative for the treatment and prevention of influenza types A and B in patients 1 year old or older. The capsules also have a longer shelf-life than the liquid suspension (five years compared with two). The new capsules will be available for the 2007-2008 influenza season.


  • Florinef (fludrocortisone acetate, King Pharmaceuti-cals) tablets due to generic availability and other pharmacologic options for management of Addison’s disease;
  • Permax (pergolide, Valeant Pharmaceuticals) tablets due to their risk of causing serious heart valve damage; and
  • Prosom (estazolam, Abbott) tablets due to generic availability and many other alternate therapies for insomnia.

Additionally, glucocorticoid ad­min­istration is the most common cause of AI. Guidelines for adrenal supplementation therapy published in JAMA in 2002 note the difficulty in determining exact patient needs. JAMA’s review of guidelines for adrenal supplementation therapy is based on expert opinion, extrapolation from research literature, and clinical experience rather than clinical trials and should be consulted for more specific patient recommendations.2

Around the same time, similar guidelines on the management of rheumatoid arthritis (RA) patients on chronic glucocorticoids were published in the Bulletin on the Rheumatic Diseases.3 The guidelines suggest lower doses and shorter therapy than many textbooks advocate to counter problems associated with excessive steroid dosing. Problems such as immunosuppression, hyperglycemia, hypertension, acute psychosis, and accelerated protein catabolism lead to poor wound healing.

Additionally, the guidelines recommend that all patients receiving chronic glucocorticoids with an illness or while undergoing any procedure continue their normal daily glucocorticoid therapy. The authors caution that in patients with rheumatic disease, discontinuation of even low glucocorticoid doses may lead to a significant disease flare. Patients who receive 5 mg or less of prednisone daily do not require additional supplementation—regardless of whether they are undergoing a procedure or have an intercurrent illness. Patients undergoing superficial surgical procedures while less than an hour under local anesthesia (e.g., routine dental work, skin biopsy, minor orthopedic surgery) require their normal daily glucocorticoid dose without additional supplementation.

Patients with primary AI should receive individualized supplemental homeostatic glucocorticoid replacement therapy—usually with 20 to 30 mg of hydrocortisone two to three times daily in divided doses. Adjust based on patient factors and use of concomitant medications. Also consider that mineralocorticoid replacement may be necessary in these patients.

When considering patients for potential use of corticosteroids in the hospital, identify those who may be HPA-axis suppressed versus those who are not. The time to achieve HPA-axis suppression varies among patients. Patients can be considered not suppressed if:

  • They have received any glucocorticoid doses for less than weeks; and
  • They have received alternate-day glucocorticoid therapy. 4-6
  • On the contrary, patients should be assumed to have HPA-axis suppression if they:
  • Have received less than 20 mg of prednisone or its equivalent daily for more than three weeks (e.g., 16 mg/day methylprednisolone, 2 mg/ day dexamethasone, 80 mg/ day hydrocortisone); and/or
  • Have clinical Cushing’s syndrome (e.g., centripetal obesity, glucose intolerance, proximal myopathy, hypertension, psychological chan-ges, and easy bruisability).

Intermediate patient categories may require HPA axis function testing with cosyntropin to determine if AI is present. TH

Michele Kaufman is a clinical/managed care consultant and medical writer based in New York City.


  1. Lamberts SWJ, Bruining HA, de Jong FK. Cortico­steroid therapy in severe illness. N Engl J Med. 1997 Oct 30;337(18):1285-1292.
  2. Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002 Jan 9;287(2):236-240.
  3. Kelley JT, Conn DL. Perioperative management of the rheumatic disease patient. Bull Rheum Dis. 2002;51(6).
  4. Nieman LK, Kovacs WJ. Pharmacologic use of glucocorticoids. UpToDate. Waltham, Mass. 2007. Available at: www.pharmacologic use of glucocorticoids
  5. Nieman LK. Clinical manifestations of Cushing’s syndrome. UpToDate. Waltham, Mass. 2007.
  6. Welsh GA, Manzullo EF, Nieman LK. The surgical patient taking glucocorticoids. UpToDate. Waltham, Mass. 2007. Available at:


Actos tablets (pioglitazone, Eli Lilly) and Avandia tablets (rosiglitazone, GlaxoSmithKline)

  • These are oral thiazolidinediones (glitazones).
  • They have an increased risk of heart failure. They cause fluid retention, which may lead to or exacerbate congestive heart failure. Their warnings have been updated to reflect this because these agents are sometimes prescribed to patients with heart failure. Monitor patients carefully for the development of adverse cardiac effects.
  • Don’t start or continue glitazones in patients with heart failure.

Avandia tablets (rosiglitazone, GlaxoSmithKline)

  • These are oral thiazolidinediones (glitazones).
  • Rosiglitazone has been associated with different rates of ischemic cardiovascular events (fatal and non-fatal). However, diabetic patients have an increased risk of cardiovascular disease.
  • Analysis of rosiglitazone safety is ongoing. The Endocrinologic and Metabolic Drugs and the Drug Safety and Risk Management Advisory Committees meet jointly to discuss the cardiovascular ischemic and thrombotic risks of thiazolidinediones, especially focusing on rosiglitazone.

Additional information

Injectable Magnetic Resonance Imaging Contrast Agents: Magnevist (gadopentetate dimeglumine), MultiHance (gadobenate dimeglumine), Omniscan (gadodiamide), OptiMARK (gadoversetamide), and ProHance (gadoteridol)

  • These are gadolinium-based contrast agents (GBCA).
  • Patients with severe kidney insufficiency (a glomerular filtration rate [GLR] <30 mL/min/1.73m2) who receive GBCA are at risk for developing nephrogenic systemic fibrosis (NSF), a debilitating and potentially fatal disease. NSF may result in fatal or debilitating systemic fibrosis.
  • Patients who are pre- or post-liver transplantation or have chronic liver disease with renal insufficiency also risk developing NSF.
  • Screen patients for kidney problems prior to prescribing one of these GBCA. Do not exceed the recommended dose. Ensure that the recommended time has lapsed between doses of GBCA if it is to be used again.
  • Boxed warning includes avoiding use of GBCAs unless the diagnostic information is essential and unavailable with non-contrast enhanced magnetic resonance imaging. Screen all patients for renal dysfunction. For patients receiving hemodialysis (HD), consider prompt HD following use of a GBCA. Published data indicate that GBCA elimination may be enhanced with HD. It has been reported that from the first to third HD sessions that average GBCA clearance rates were 78%, 96%, and 99%, respectively. It is not known whether HD prevents NSF.
  • Report possible cases of NSF to the FDA through the FDA’s MedWatch program at

New Indication

  • Apidra (insulin glulisine), Sanofi-Aventis’ rapid-acting insulin, has been FDA approved for intravenous (IV) administration in a clinical setting under medical supervision for glycemic control in adults with Type 1 or Type 2 diabetes mellitus. This approval provides another hospital-based option for diabetic patients, who may benefit from IV therapy in a clinical setting. Apidra is already approved for use subcutaneously from the vial, via external insulin infusion pump, or via the OptiClick reusable insulin pen.

Recommended Reading

Surgical Steroid Replacement
The Hospitalist
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