Are Stress-Dose Steroids Indicated in Patients with Adrenal Insufficiency Hospitalized with Noncritical, Nonsurgical Illness?

Case

A 46-year-old woman with Addison’s disease and type II diabetes presents with one day of right leg pain, swelling, and redness. She has had mild nausea and vomiting over the past week, with an episode of diarrhea three days prior. She takes hydrocortisone 30mg in the morning and 10mg at bedtime, as well as fludrocortisone 0.2mg in the morning. She is afebrile with a pulse of 108 beats per minute. Her initial blood pressure was 74/49 mmHg, which improved to 84/45 mmHg following one liter of normal saline. She is mentating appropriately. The physical exam is significant for a large, tender area of erythema and warmth from the right ankle to mid-calf. She is admitted for cellulitis and intravenous antibiotics are initiated.

Does she require an increase in her glucocorticoid dose during her acute illness?

Overview

Adrenal insufficiency occurs in approximately 5 out of every 10,000 people and results from primary failure of the adrenal gland, or secondary impairment of the hypothalamic-pituitary-adrenal (HPA) axis, which regulates cortisol secretion.1 In developed countries, 90% of primary adrenal insufficiency (Addison’s disease) cases are due to autoimmune adrenalitis, which might occur in isolation or as part of an autoimmune polyglandular syndrome.1,2 Secondary adrenal insufficiency is most commonly the result of chronic glucocorticoid therapy, though lesions involving the hypothalamus or pituitary gland might be implicated.2,3

In a healthy individual, cortisol is secreted in a diurnal pattern from the adrenal glands under the control of corticotropin (ACTH) produced by the pituitary gland and corticotropin-releasing hormone (CRH) produced by the hypothalamus (see Figure 1, p. 19). In the normal state, during periods of such systemic stress as illness, trauma, burns, or surgery, cortisol production increases to a degree roughly proportional to the degree of illness (as much as sixfold).4,5 Patients with adrenal insufficiency are unable to mount an appropriate cortisol response and, therefore, are at risk for adrenal crisis—a life-threatening condition characterized by hypotension and hypovolemic shock.

Although recommendations for high-dose intravenous steroids in adrenally insufficient patients who are critically ill or undergoing surgery have been extensively discussed in the literature, there are relatively few data regarding the appropriate management of adrenal insufficiency in patients hospitalized for noncritical illness.

Several recent studies have investigated the patient characteristics, situations, and conditions most likely to provoke adrenal crisis in order to establish guidelines dictating the use of supra-physiologic steroid dosing.

KEY Points

  • Doubling or tripling a patient’s normal dose of glucocorticoid is recommended for most mild to moderate illness. The appropriate length of therapy is not clearly defined and should be based on clinical judgment.
  • In gastrointestinal illnesses, absorption across the gastrointestinal mucosa is likely to be compromised. Steroids should be given intravenously to avoid adrenal crisis.
  • All patients should be monitored carefully for signs of increasing adrenal insufficiency, including hypotension, nausea and vomiting, and weakness; those with primary insufficiency, long-term steroid use, or co-morbid conditions (e.g., hyperthyroidism, asthma, or diabetes) might be at higher risk of progressing to adrenal crisis.

Additional Reading

  • Jung C, Inder WJ. Management of adrenal insufficiency during the stress of medical illness and surgery. Med J Aust. 2008;188:409-413.
  • Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med. 2003;348:727-734.
  • Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287:236-240.
  • Arlt W, Allolio B. Adrenal insufficiency. Lancet. 2003;361:1881-1893.

Review of the Data

Studies have estimated the prevalence of adrenal crisis in patients with underlying insufficiency at 3.3 to 6.3 events per 100 patient years, with 42% of patients reporting at least one crisis.2,5,6 A recent survey of 982 patients with Addison’s disease in the United Kingdom reported an 8% annual frequency.7

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