Correspondence
Adrenal Insufficiency
N Engl J Med 1997; 336:1105-1107April 10, 1997
- Article
To the Editor:
The concise review of adrenal insufficiency by Dr. Oelkers (Oct. 17 issue)1 was excellent, but the corticotropin stimulation test is even less valuable than he suggests, and the incidence of clinically significant secondary adrenal insufficiency due to long-term glucocorticoid therapy is much lower than generally believed.2-5 What does Dr. Oelkers recommend for patients receiving exogenous glucocorticoids? My data suggest that the adrenal function of such patients need not be tested except when there are clear-cut clinical indications, since in such patients the physiologic value of the biochemical tests is poor and clinical adrenal insufficiency is rare.
5 ReferencesJonathan S. Bromberg, M.D., Ph.D.
University of Michigan, Ann Arbor, MI 48109-03311
Oelkers W . Adrenal insufficiency. N Engl J Med 1996;335:1206-1212
Full Text | Web of Science | Medline2
Bromberg JS ,Alfrey EJ ,Barker CF , et al. Adrenal suppression and steroid supplementation in renal transplant recipients. Transplantation 1991;51:385-390
CrossRef | Web of Science | Medline3
Roberts CS ,LaFond J ,Fitts CT , et al. New patterns of transplant nephrectomy in the cyclosporine era. J Am Coll Surg 1994;178:59-64
Web of Science | Medline4
Salem M ,Tainsh RE Jr ,Bromberg J ,Loriaux DL ,Chernow B . Perioperative glucocorticoid coverage: a reassessment 42 years after emergence of a problem. Ann Surg 1994;219:416-425
CrossRef | Web of Science | Medline5
Friedman RJ ,Schiff CF ,Bromberg JS . Use of supplemental steroids in patients having orthopaedic operations. J Bone Joint Surg Am 1995;77:1801-1806
Web of Science | Medline
To the Editor:
Dr. Oelkers's recommendation to double or triple the maintenance dose of hydrocortisone during any febrile illness or injury in patients receiving replacement therapy should not be extended to apply to the much larger group of patients receiving steroids for therapeutic purposes (for example, transplant recipients and patients with autoimmune diseases). Despite the long-term use of steroids for maintenance therapy, these patients usually have adequate endogenous adrenocortical function and do not require so-called stress steroids even during major surgical procedures.
Several studies have reported on more than 100 transplant recipients1,2 and other patients3 receiving an average of 5 to 10 mg of prednisone per day as maintenance therapy, who underwent a variety of surgical procedures without receiving additional steroids. None had signs of adrenal insufficiency. In addition, biochemical tests of the hypothalamic–pituitary–adrenal axis appeared to be too sensitive and not predictive of outcome. At our institution, we do not recommend the use of stress steroids to treat transplant recipients who are undergoing elective or emergency surgical procedures or who are admitted with sepsis.
The practice of administering supraphysiologic doses of steroids to such patients during periods of “stress” is unnecessary and may in fact be deleterious. We recommend that patients receiving more than 5 mg of prednisone per day continue that dose during the period of stress (for example, surgery or sepsis) and be monitored closely for evidence of adrenal insufficiency. Patients receiving less than 5 mg of prednisone per day should be given the drug in a short course of 5 to 10 mg per day if biochemical testing suggests adrenal insufficiency (or if testing was not performed). Tapering the steroids over a period of 24 to 48 hours after the stressful event is unnecessary.4
4 ReferencesAlfredo J. Fabrega, M.D.
Claudia Corwin, M.D.
Maureen Martin, M.D.
University of Iowa Hospitals and Clinics, Iowa City, IA 52242-10861
Bromberg JS ,Alfrey EJ ,Barker CF , et al. Adrenal suppression and steroid supplementation in renal transplant recipients. Transplantation 1991;51:385-390
CrossRef | Web of Science | Medline2
Bromberg JS ,Baliga P ,Cofer JB ,Rajagopalan PR ,Friedman RJ . Stress steroids are not required for patients receiving a renal allograft and undergoing operation. J Am Coll Surg 1995;180:532-536
Web of Science | Medline3
Friedman RJ ,Schiff CF ,Bromberg JS . Use of supplemental steroids in patients having orthopaedic operations. J Bone Joint Surg Am 1995;77:1801-1806
Web of Science | Medline4
Salem M ,Tainsh RE Jr ,Bromberg J ,Loriaux DL ,Chernow B . Perioperative glucocorticoid coverage: a reassessment 42 years after emergence of a problem. Ann Surg 1994;219:416-425
CrossRef | Web of Science | Medline
To the Editor:
Septic shock is also a cause of adrenal insufficiency, as numerous groups of investigators have reported.1-3 The failure of glucocorticoid treatment to decrease mortality 4 among patients with septic shock may account for the confusion surrounding this association and the omission of septic shock from lists of causes of adrenal insufficiency. The cause of adrenal dysfunction in septic shock may be cytokine-mediated inhibition of the release of corticotropin,3 which would place the disorder in the category of secondary hypoadrenalism.
4 ReferencesGary M. Pepper, M.D.
1411 N. Flagler Dr., West Palm Beach, FL 334011
Sibbald WJ ,Short A ,Cohen MP ,Wilson RF . Variation in adrenocortical responsiveness during severe bacterial infections: unrecognized adrenocortical insufficiency in severe bacterial infections. Ann Surg 1977;186:29-33
CrossRef | Web of Science | Medline2
Cook DJ ,Guyatt GH ,McIlroy M , et al. Serum cortisol: a predictor of mortality in sepsis? J Intensive Care Med 1992;6:84-893
Soni A ,Pepper GM ,Wyrwinski PM , et al. Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels. Am J Med 1995;98:266-271
CrossRef | Web of Science | Medline4
Bone RC ,Fisher CJ Jr ,Clemmer TP , et al. A controlled clinical trial of high-dose methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 1987;317:653-658
Full Text | Web of Science | Medline
Author/Editor Response
Dr. Oelkers replies:
To the Editor: Dr. Pepper maintains that septic shock can lead to spontaneous adrenocortical insufficiency in the absence of major anatomical lesions of the adrenals, such as those due to hemorrhage or infarction. Among the patients his group studied who had low cortisol levels, two who died despite steroid supplementation had anatomically normal adrenals. In that study,1 the authors assumed that in patients with septic shock and low plasma cortisol levels, as compared with those with high plasma cortisol levels, slightly lower levels of interleukin-6 could be one cause of insufficient adrenocorticotropic hormone (and cortisol) stimulation.
That study1 seemed to show that in patients with septic shock, base-line plasma cortisol measurements identify two non-overlapping groups of patients with cortisol levels that are either low (around 10 μg per deciliter [276 nmol per liter]) or high (around 27 μg per deciliter [745 nmol per liter]). Patients with low cortisol levels (“adrenal insufficiency”) and refractory hypotension were treated with corticosteroids, but 4 of 5 such patients died, whereas only 7 of 16 patients with high plasma cortisol levels died. Another recent report suggests that there is reversible functional adrenocortical failure,2 but adrenal function was, unfortunately, not tested after recovery in the surviving patients. In my view, it remains uncertain whether reversible adrenocortical failure is an important clinical problem in patients with septic shock.
I agree with Dr. Bromberg and Fabrega et al. that there is a tendency to overestimate the incidence of adrenal insufficiency in patients receiving long-term glucocorticoid therapy. Patients receiving 5 mg or less of prednisolone daily in the morning almost always have normal cortisol levels before their morning steroid dose. The likelihood of secondary adrenal insufficiency increases with higher doses of steroids. A consensus paper3 makes reasonable and clear recommendations for the dose and duration of steroid supplementation according to both the preoperative dose and the severity of the surgical stress (minor, moderate, or major). The dosages recommended are derived from published studies on rates of cortisol secretion in healthy subjects undergoing minor or major surgery. The guidelines in this consensus paper can help avert unnecessary, excessive, and overly extended treatment with steroids, while adequate corticosteroids are given to patients at risk for acute adrenal crisis due to surgical stress or postoperative complications.
3 ReferencesWolfgang Oelkers, M.D.
Klinikum Benjamin Franklin, 12200 Berlin, Germany1
Soni A ,Pepper GM ,Wyrwinski PM , et al. Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels. Am J Med 1995;98:266-271
CrossRef | Web of Science | Medline2
Baldwin WA ,Allo M . Occult hypoadrenalism in critically ill patients. Arch Surg 1993;128:673-676
Web of Science | Medline3
Salem M ,Tainsh RE Jr ,Bromberg J ,Loriaux DL ,Chernow B . Perioperative glucocorticoid coverage: a reassessment 42 years after emergence of a problem. Ann Surg 1994;219:416-425
CrossRef | Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Herschel S. Zackheim. (2003) Treatment of patch-stage mycosis fungoides with topical corticosteroids. Dermatologic Therapy 16:4, 283-287
CrossRef2
Herschel S. Zackheim. (2003) Treatment of mycosis fungoides/Sezary syndrome: the University of California, San Francisco (UCSF) approach. International Journal of Dermatology 42:1, 53-56
CrossRef
