Secondary Adrenal Insufficiency Related to Exogenous Steroid Usage

Overall, the most common adrenal insufficiency is the secondary adrenal insufficiency resulting from exogenous steroid usage. Numerous and diverse conditions are treated with corticosteroids: inflammatory bowel disease, asthma, arthritis, and dermatologie conditions, to name a few. Inhaled steroids are a mainstay of therapy for asthma and can produce the potential for adrenal insufficiency in both children and adults.12 Corticosteroids are part of the therapeutic regimen of transplantation immunosuppression and cancer chemotherapy. Short courses of high-dose corticosteroids are used in numerous inflammatory conditions. Corticosteroid use is so common that an inquiry regarding corticosteroid use should be made of every patient preoperatively. The trauma patient unable to give a history should be suspected of having used steroids. Exogenous corticosteroid therapy even for only a few days may produce some inability of the pituitary-adrenal axis to respond to stress. The generally accepted rule is to provide stress-dose steroids to any patient undergoing surgical stress who has received steroids for more than 1 week within the previous year.

Adrenal suppression has been identified in patients using high-dose steroids for very short periods of time, and the longer the steroid use, the longer the impairment may last. No study has definitively answered how short an exposure to how much steroid is the minimum amount to suppress adrenal function. Graber and colleagues studied 14 patients: 8 after resection of a functioning cortical adenoma and 6 after supraphysiologic doses of steroids for 1 to 10 years. During the first month without therapy, corticotropin failed to increase in these patients, despite low Cortisol levels. During the second to fifth months, plasma corticotropin rose to normal or supernormal values but the plasma corticosteroid response to corticotropin remained subnormal. During the sixth to ninth months, the plasma and urinary corticoid levels were normal, but adrenal responsiveness could be demonstrated only with supernormal levels of corticotropin. After 9 months, pituitary-adrenal responses returned to normal.13 Even though the series is small, this study demonstrates the fallacy of using baseline steroid levels to determine the adequacy of adrenal function and the length of time necessary for return to normal.

Stress-Induced Adrenal Insufficiency

Merry and colleagues, in 1994, reported on a small group of patients who had transient corticotropin deficiency, which caused postoperative acute adrenal failure.14 These patients presented with unexplained postoperative hypotension. Schlaghecke and coworkers, in a series of 279 patients, demonstrated that corticosteroid reserve cannot be reliably determined on the basis of dose and duration of therapy.15 Plasma baseline Cortisol levels were similarly unreliable. Because there is no simple, reliable method of determining the adrenal response to stress and definitive testing is time consuming and costly, empirical steroid administration to cover the period of stress is conventional.

The magnitude and duration of stress requiring increased corticosteroid production have been studied in numerous circumstances. In particular, the methods of assessing adequacy of adrenal function and the routine use of corticosteroids in the critically ill, septic, intensive care unit patient have been the subject of extensive controversy. Manglik and associates, in a prospective clinical trial involving 100 patients, found that 9% of septic patients failed the ACTH stimulation test and 4% of septic patients had occult pituitary disease or secondary adrenal insufficiency.16 Jurney and colleagues demonstrated no advantage of routine evaluation of baseline Cortisol or corticotropin stimulation studies in the intensive care unit.17 Baseline Cortisol levels were not useful in predicting adrenal insufficiency. Patients with low baseline Cortisol levels did not necessarily have impaired corticotropin stimulation. Although baseline Cortisol levels did correlate with survival, patients with the highest levels had the worst prognosis. Barton and coworkers demonstrated a positive correlation of plasma Cortisol with injury severity score (ISS) in patients with minor or moderate injuries but a negative correlation with high ISS scores, no difference between head-injured and non-head-injured patients, and no difference with age or time of day when samples were taken.18

A study of intensive care unit patients performed by Rivers and coworkers again raises the question of critical illness increasing the probability of adrenal insufficiency. They studied 104 patients with severe sepsis or septic shock. They described a group with functional hypoadrenalism, who exhibited any hypoadrenal laboratory values. They found an improvement in vasopressor-dependent refractory hypotension, even in the group with normal adrenal function. This study suggests that we need to reconsider our assessment of adrenal insufficiency and our use of corticosteroids in the severely ill. They recommended considering hydrocortisone treatment in patients older than 55 years in the presence of continued need for vasopressors after adequate volume resuscitation.19

Corticotropin stimulation studies remain reliable at determining adrenal response in the trauma victim. The cosyn-tropin stimulation test is used to determine whether the adrenal cortex is able to respond normally to this corticotropin analog by increasing the production of corticosteroids. Serum Cortisol level is measured at 0, 30, and 60 minutes after intravenous or intramuscular injection of 250 pg of cosyntropin. Patients with a normal adrenal response should increase the serum Cortisol level by at least 7 (ig/dL or have a peak level of at least 20 pg/dL. Harris and colleagues performed urinary and plasma Cortisol and cosyntropin (synthetic corticotropin) stimulation studies on 30 patients after traumatic injury and 125 after extensive elective abdominal or thoracic operation. Levels were similar in both groups. With an uncomplicated clinical course, the levels returned to normal in 1 to 2 days.20 They found a mean stimulated serum Cortisol level of 44.5 ± 12.0 pg/dL and concluded that a stimulated mean Cortisol level of greater than 20.5 pg/dL would include 97.5% of normal subjects. Any value less than 20.5 pg/dL should be considered indicative of adrenal insufficiency. Stress levels of steroids should, therefore, be maintained at high doses for at least 48 hours and raised again if complications ensue.

Current recommendations for steroid coverage of patients anticipated to have adrenal insufficiency as a result of previous steroid therapy are empirical. For major surgical procedures, 100 mg of hydrocortisone hemisuccinate is administered intravenously the evening before surgery, the morning of surgery, and every 8 hours for 24 hours until the major stress of the operation is resolved. Usually, 48 hours is required for major operations with continued high-dose steroids if complications arise. If high-dose steroids are required for fewer than 72 hours, rapid tapering over 5 to 7 days can safely prevent adrenal insufficiency. For minor outpatient procedures, 100 mg of hydrocortisone at the induction of anesthesia followed by the usual oral doses postoperatively is sufficient. Numerous other steroid regimens exist, but advantages of one over the other are unproved. Rarely is the addition of mineralocorticoid necessary in this acute setting.21

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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