Correspondence
Predisposing Factors for Adrenal Insufficiency
N Engl J Med 2009; 361:824-825August 20, 2009
- Article
To the Editor:
The review of predisposing factors for adrenal insufficiency by Bornstein (May 28 issue)1 includes a welcome discussion of the limitations of current tests that measure plasma cortisol levels in critically ill patients. However, in the review, stimulation with 1 μg of corticotropin is recommended to identify patients with relative adrenal insufficiency, and I believe the current evidence does not support this.
At least two studies2,3 have questioned the reproducibility of corticotropin stimulation testing in critically ill patients. A substantial number of patients appear to have different responses to 250 μg of corticotropin when they are tested on two consecutive days, with results of one test showing adequate adrenal function and results of the other showing inadequate function. Venkatesh et al.4 found that hour-to-hour changes in plasma cortisol levels in the same patient are substantial and that spontaneous hourly increases are often greater than the increase of 9 μg per deciliter (250 nmol per liter) that is commonly used to define adequate adrenocortical response.
These issues of reproducibility and signal detection against a noisy background should be resolved before corticotropin stimulation testing can be recommended to identify relative adrenal insufficiency.
4 ReferencesDavid A. Kaufman, M.D.
Bridgeport Hospital, Bridgeport, CT
pdkauf@bpthosp.org 1
Bornstein SR . Predisposing factors for adrenal insufficiency. N Engl J Med 2009;360:2328-2339
Full Text | Web of Science | Medline2
Bouachour G ,Roy PM ,Guiraud MP . The repetitive short corticotropin stimulation test in patients with septic shock. Ann Intern Med 1995;123:962-963
Web of Science | Medline3
Loisa P ,Uusaro A ,Ruokonen E . A single adrenocorticotropic hormone stimulation test does not reveal adrenal insufficiency in septic shock. Anesth Analg 2005;101:1792-1798
CrossRef | Web of Science | Medline4
Venkatesh B ,Mortimer RH ,Couchman B ,Hall J . Evaluation of random plasma cortisol and the low dose corticotropin test as indicators of adrenal secretory capacity in critically ill patients: a prospective study. Anaesth Intensive Care 2005;33:201-209
Web of Science | Medline
To the Editor:
According to a recent consensus conference, adrenal insufficiency in critical illness is best diagnosed by an increase in cortisol (in response to the injection of 250 μg of corticotropin) of less than 9 μg per deciliter or a random total cortisol level of less than 10 μg per deciliter (276 nmol per liter).1 This conflicts with Bornstein's statement that the best test for establishing the diagnosis of glucocorticoid insufficiency related to critical illness is the 1-μg corticotropin stimulation test, in which cortisol levels are measured 30 minutes after stimulation, with a level of less than 25 μg per deciliter (690 nmol per liter) or an increment over baseline of less than 9 μg per deciliter representing an inadequate adrenal response.
1 ReferencesLaurent Seravalli, M.D.
Hôpital Neuchâtelois, La Chaux-de-Fonds, Switzerland
laurent.seravalli@ne. ch 1
Marik PE ,Pastores SM ,Annane D , et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008;36:1937-1949
CrossRef | Web of Science | Medline
To the Editor:
In the review article by Bornstein, a reference to bilateral massive adrenal hemorrhage is lacking. This clinical entity represents a rare but potentially life-threatening situation.1
The most common factors associated with the development of a bilateral adrenal hemorrhage are anticoagulant therapy, postoperative state and trauma-related shock, sepsis (meningococcal is the classic type), primary antiphospholipid syndrome, steroid use, metastases, thrombocytopenia and renal-vein thrombosis, and hypercoagulability.2,3
Moreover, a spontaneous bilateral adrenal hemorrhage, without any recognized predisposing factor, is an uncommon but possible clinical presentation. Its frequency is unknown since it is rarely reported and is usually overlooked.4
4 ReferencesEnrique Anton, M.D., Ph.D.
Hospital of Zumarraga, Zumarraga, Spain
ejaaranda@hotmail.com 1
Rao RH . Bilateral massive adrenal hemorrhage. Med Clin North Am 1995;79:107-129
Web of Science | Medline2
Xarli VP ,Steele AA ,Davis PJ ,Buescher ES ,Rios CN ,Garcia-Bunuel R . Adrenal hemorrhage in the adult. Medicine (Baltimore) 1978;57:211-221
Web of Science | Medline3
Kovacs KA ,Lam YM ,Pater JL . Bilateral massive adrenal hemorrhage: assessment of putative risk factors by the case-control method. Medicine (Baltimore) 2001;80:45-53
CrossRef | Web of Science | Medline4
Tan PL ,Moore NR . Spontaneous idiopathic bilateral adrenal hemorrhage in adults. Clin Radiol 2003;58:890-892
CrossRef | Web of Science | Medline
Author/Editor Response
Kaufman and Seravalli address the difficulties encountered in defining glucocorticoid insufficiency related to critical illness with the use of endocrine testing. Seravalli suggests that according to the recommendations of a recent consensus conference on adrenal insufficiency in critical illness, the 250-μg corticotropin test1 may be more appropriate than the 1-μg corticotropin test as recommended by other groups.2 This panel of experts points out that whereas the 1-μg corticotropin stimulation test may be more physiological and have a greater sensitivity, there is more evidence available for the use of the 250-μg stimulation test in the case of critically ill patients. However, the panel clearly admits that this recommendation classifies as weak with only a moderate grade of evidence. Therefore, as pointed out by Kaufman and discussed in my review, endocrine-function testing during critical illness remains a challenge.
Currently, there is agreement that corticosteroid insufficiency related to critical illness should be suspected and treated with glucocorticoids only in patients with hypotension that does not respond appropriately to fluids and vasopressors. There is, however, a clear need to improve endocrine testing for severely ill patients, including trauma patients,3 and to identify early on patients with adrenal dysfunction. Clinicians should be aware of the long list of causes that may confer a predisposition for adrenal insufficiency. Such an example includes bilateral massive adrenal hemorrhage, as pointed out by Anton. His statement that spontaneous bilateral adrenal hemorrhage may occur without any obvious predisposing factor further corroborates the notion that because the adrenal gland is hypervascular, it may be particularly susceptible to vascular injury during stress.
3 ReferencesStefan R. Bornstein, M.D.
Technical University of Dresden, Dresden, Germany
stefan.bornstein@uniklinikum-dresden. de 1
Marik PE ,Pastores SM ,Annane D , et al. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med 2008;36:1937-1949
CrossRef | Web of Science | Medline2
Kazlauskaite R ,Evans AT ,Villabona CV , et al. Corticotropin tests for hypothalamic-pituitary-adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008;93:4245-4253
CrossRef | Web of Science | Medline3
Guillamondegui OD ,Gunter OL ,Patel S ,Fleming S ,Cotton BA ,Morris JA Jr . Acute adrenal insufficiency may affect outcome in the trauma patient. Am Surg 2009;75:287-290
Web of Science | Medline
- Citing Articles (2)
Citing Articles
1
Hye-Suk Han, Young Kwang Shim, Jeong Eun Kim, Hyun-Jung Jeon, Sung-nam Lim, Tae-Keun Oh, Ki Hyeong Lee, Seung Taik Kim. (2011) A pilot study of adrenal suppression after dexamethasone therapy as an antiemetic in cancer patients. Supportive Care in Cancer
CrossRef2
David A. Kaufman. (2010) Re: Induction Agents for Intubation of the Trauma Patient. The Journal of Trauma: Injury, Infection, and Critical Care 68:3, 748
CrossRef
