The surgical patient taking glucocorticoids
- Amir H Hamrahian, MD
Amir H Hamrahian, MD
- Chief, Endocrinology
- Professor of Medicine
- Cleveland Clinic Abu Dhabi
- Sanziana Roman, MD
Sanziana Roman, MD
- Associate Professor of Surgery (Endocrine Surgery)
- Duke University School of Medicine
- Stacey Milan, MD
Stacey Milan, MD
- Assistant Professor of Surgery (Endocrine Surgery)
- Thomas Jefferson University
- Section Editors
- Lynnette K Nieman, MD
Lynnette K Nieman, MD
- Section Editor — Adrenal Disease
- Senior Investigator
- National Institute of Child Health and Human Development
- Sally E Carty, MD, FACS
Sally E Carty, MD, FACS
- Section Editor — Endocrine Surgery
- Professor, Chief, Division of Endocrine Surgery
- University of Pittsburgh School of Medicine
Chronic glucocorticoid therapy can suppress the hypothalamic-pituitary-adrenal (HPA) axis and, during times of stress such as surgery, the adrenal glands may not respond appropriately. Protocols for "stress dose" steroids followed reports in the 1950s of possible surgery-associated adrenal insufficiency due to sudden preoperative withdrawal of glucocorticoids. However, numerous studies have questioned both the need for and the doses of supplemental perioperative glucocorticoid.
The management of the surgical patient on chronic glucocorticoid therapy is reviewed here. Perioperative glucocorticoid regimens for patients taking replacement glucocorticoid for primary adrenal insufficiency are addressed separately. (See "Treatment of adrenal insufficiency in adults", section on 'Surgery'.)
The use of stress doses of glucocorticoids, such as 300 mg/day of hydrocortisone for several days [1-3], had become a common perioperative practice for patients on glucocorticoid therapy, based upon early case reports of intraoperative adrenal crisis after abrupt withdrawal of glucocorticoids [4,5], and the observation that glucocorticoids have a permissive effect on vascular tone and blood pressure . However, a number of reports, including two randomized studies and a systematic review , have questioned the need for supplemental perioperative stress dose glucocorticoids [1,8-13]. The current approach is to determine perioperative glucocorticoid coverage based upon the patient’s history of glucocorticoid intake, as well as the type and duration of surgery planned [2,14-16].
In addition to suppression of the hypothalamic-pituitary-adrenal (HPA) axis, chronic glucocorticoid therapy may cause a number of other problems in the perioperative period:
●Impaired wound healing 
- Bromberg JS, Alfrey EJ, Barker CF, et al. Adrenal suppression and steroid supplementation in renal transplant recipients. Transplantation 1991; 51:385.
- Salem M, Tainsh RE Jr, Bromberg J, et al. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg 1994; 219:416.
- Shaw M, Mandell BF. Perioperative management of selected problems in patients with rheumatic diseases. Rheum Dis Clin North Am 1999; 25:623.
- FRASER CG, PREUSS FS, BIGFORD WD. Adrenal atrophy and irreversible shock associated with cortisone therapy. J Am Med Assoc 1952; 149:1542.
- LEWIS L, ROBINSON RF, YEE J, et al. Fatal adrenal cortical insufficiency precipitated by surgery during prolonged continuous cortisone treatment. Ann Intern Med 1953; 39:116.
- Axelrod L. Inhibition of prostacyclin production mediates permissive effect of glucocorticoids on vascular tone. Perturbations of this mechanism contribute to pathogenesis of Cushing's syndrome and Addison's disease. Lancet 1983; 1:904.
- Yong SL, Coulthard P, Wrzosek A. Supplemental perioperative steroids for surgical patients with adrenal insufficiency. Cochrane Database Syst Rev 2012; 12:CD005367.
- Mathis AS, Shah NK, Mulgaonkar S. Stress dose steroids in renal transplant patients undergoing lymphocele surgery. Transplant Proc 2004; 36:3042.
- Glowniak JV, Loriaux DL. A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency. Surgery 1997; 121:123.
- Shapiro R, Carroll PB, Tzakis AG, et al. Adrenal reserve in renal transplant recipients with cyclosporine, azathioprine, and prednisone immunosuppression. Transplantation 1990; 49:1011.
- Bromberg JS, Baliga P, Cofer JB, et al. Stress steroids are not required for patients receiving a renal allograft and undergoing operation. J Am Coll Surg 1995; 180:532.
- Friedman RJ, Schiff CF, Bromberg JS. Use of supplemental steroids in patients having orthopaedic operations. J Bone Joint Surg Am 1995; 77:1801.
- Thomason JM, Girdler NM, Kendall-Taylor P, et al. An investigation into the need for supplementary steroids in organ transplant patients undergoing gingival surgery. A double-blind, split-mouth, cross-over study. J Clin Periodontol 1999; 26:577.
- Lamberts SW, Bruining HA, de Jong FH. Corticosteroid therapy in severe illness. N Engl J Med 1997; 337:1285.
- Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA 2002; 287:236.
- de Lange DW, Kars M. Perioperative glucocorticosteroid supplementation is not supported by evidence. Eur J Intern Med 2008; 19:461.
- Anstead GM. Steroids, retinoids, and wound healing. Adv Wound Care 1998; 11:277.
- Stuck AE, Minder CE, Frey FJ. Risk of infectious complications in patients taking glucocorticosteroids. Rev Infect Dis 1989; 11:954.
- BOLLET AJ, BLACK R, BUNIM JJ. Major undesirable side-effects resulting from prednisolone and prednisone. J Am Med Assoc 1955; 158:459.
- Schiff RL, Welsh GA. Perioperative evaluation and management of the patient with endocrine dysfunction. Med Clin North Am 2003; 87:175.
- Wagner RL, White PF, Kan PB, et al. Inhibition of adrenal steroidogenesis by the anesthetic etomidate. N Engl J Med 1984; 310:1415.
- Murray H, Marik PE. Etomidate for endotracheal intubation in sepsis: acknowledging the good while accepting the bad. Chest 2005; 127:707.
- Antoni FA. Hypothalamic control of adrenocorticotropin secretion: advances since the discovery of 41-residue corticotropin-releasing factor. Endocr Rev 1986; 7:351.
- Aguilera G. Regulation of pituitary ACTH secretion during chronic stress. Front Neuroendocrinol 1994; 15:321.
- Chernow B, Alexander HR, Smallridge RC, et al. Hormonal responses to graded surgical stress. Arch Intern Med 1987; 147:1273.
- Jabbour SA. Steroids and the surgical patient. Med Clin North Am 2001; 85:1311.
- Udelsman R, Norton JA, Jelenich SE, et al. Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress. J Clin Endocrinol Metab 1987; 64:986.
- Raff H, Norton AJ, Flemma RJ, Findling JW. Inhibition of the adrenocorticotropin response to surgery in humans: interaction between dexamethasone and fentanyl. J Clin Endocrinol Metab 1987; 65:295.
- REDGATE ES. Spinal cord and ACTH release in adrenalectomized rats following electrical stimulation. Endocrinology 1962; 70:263.
- Brandt M, Kehlet H, Binder C, et al. Effect of epidural analgesia on the glycoregulatory endocrine response to surgery. Clin Endocrinol (Oxf) 1976; 5:107.
- George JM, Reier CE, Lanese RR, Rower M. Morphine anesthesia blocks cortisol and growth hormone response to surgical stress in humans. J Clin Endocrinol Metab 1974; 38:736.
- Yong SL, Marik P, Esposito M, Coulthard P. Supplemental perioperative steroids for surgical patients with adrenal insufficiency. Cochrane Database Syst Rev 2009; :CD005367.
- Axelrod L. Glucocorticoid therapy. Medicine (Baltimore) 1976; 55:39.
- Livanou T, Ferriman D, James VH. Recovery of hypothalamo-pituitary-adrenal function after corticosteroid therapy. Lancet 1967; 2:856.
- GRABER AL, NEY RL, NICHOLSON WE, et al. NATURAL HISTORY OF PITUITARY-ADRENAL RECOVERY FOLLOWING LONG-TERM SUPPRESSION WITH CORTICOSTEROIDS. J Clin Endocrinol Metab 1965; 25:11.
- Westerhof L, Van Ditmars MJ, Der Kinderen PJ, et al. Recovery of adrenocortical function during long-term treatment with corticosteroids. Br Med J 1972; 2:195.
- Cooper MS, Stewart PM. Corticosteroid insufficiency in acutely ill patients. N Engl J Med 2003; 348:727.
- Axelrod L. Perioperative management of patients treated with glucocorticoids. Endocrinol Metab Clin North Am 2003; 32:367.
- LaRochelle GE Jr, LaRochelle AG, Ratner RE, Borenstein DG. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients with rheumatic diseases receiving low-dose prednisone. Am J Med 1993; 95:258.
- HARTER JG, REDDY WJ, THORN GW. STUDIES ON AN INTERMITTENT CORTICOSTEROID DOSAGE REGIMEN. N Engl J Med 1963; 269:591.
- Fauci AS. Alternate-day corticosteroid therapy. Am J Med 1978; 64:729.
- Ackerman GL, Nolsn CM. Adrenocortical responsiveness after alternate-day corticosteroid therapy. N Engl J Med 1968; 278:405.
- Marik PE, Varon J. Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature. Arch Surg 2008; 143:1222.
- Kehlet H, Binder C. Adrenocortical function and clinical course during and after surgery in unsupplemented glucocorticoid-treated patients. Br J Anaesth 1973; 45:1043.
- Kehlet H, Binder C. Value of an ACTH test in assessing hypothalamic-pituitary-adrenocortical function in glucocorticoid-treated patients. Br Med J 1973; 2:147.
- Christy NP. Corticosteroid withdrawal. In: Current Therapy in Endocrinology and Metabolism, 3rd Ed, Bardin CW (Ed), BC Decker, New York 1988. p.113.
- NICHOLS T, NUGENT CA, TYLER FH. DIURNAL VARIATION IN SUPPRESSION OF ADRENAL FUNCTION BY GLUCOCORTICOIDS. J Clin Endocrinol Metab 1965; 25:343.
- Todd GR, Acerini CL, Ross-Russell R, et al. Survey of adrenal crisis associated with inhaled corticosteroids in the United Kingdom. Arch Dis Child 2002; 87:457.
- Lipworth BJ. Systemic adverse effects of inhaled corticosteroid therapy: A systematic review and meta-analysis. Arch Intern Med 1999; 159:941.
- White M, Crisalida T, Li H, et al. Effects of long-term inhaled corticosteroids on adrenal function in patients with asthma. Ann Allergy Asthma Immunol 2006; 96:437.
- Zöllner EW, Lombard C, Galal U, et al. Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids--more common than expected? J Pediatr Endocrinol Metab 2011; 24:529.
- Dahl R. Systemic side effects of inhaled corticosteroids in patients with asthma. Respir Med 2006; 100:1307.
- Walsh P, Aeling JL, Huff L, Weston WL. Hypothalamus-pituitary-adrenal axis suppression by superpotent topical steroids. J Am Acad Dermatol 1993; 29:501.
- Keipert JA, Kelly R. Temporary Cushing's syndrome from percutaneous absorption of betamethasone 17-valerate. Med J Aust 1971; 1:542.
- Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol 2006; 54:1.
- Katz HI, Hien NT, Prawer SE, et al. Superpotent topical steroid treatment of psoriasis vulgaris--clinical efficacy and adrenal function. J Am Acad Dermatol 1987; 16:804.
- de la Fuente-García A, Gómez-Flores M, Mancillas-Adame L, et al. Role of the ACTH test and estimation of a safe dose for high potency steroids in vitiligo: A prospective randomized study. Indian Dermatol Online J 2014; 5:117.
- Tempark T, Phatarakijnirund V, Chatproedprai S, et al. Exogenous Cushing's syndrome due to topical corticosteroid application: case report and review literature. Endocrine 2010; 38:328.
- Reeback JS, Chakraborty J, English J, et al. Plasma steroid levels after intra-articular injection of prednisolone acetate in patients with rheumatoid arthritis. Ann Rheum Dis 1980; 39:22.
- OKA M. Absorption of acetates of hydrocortisone, delta 1-hydrocortisone and cortisone from the joint cavity into the circulation. J Clin Endocrinol Metab 1958; 18:755.
- YOUNG HH, WARD LE, HENDERSON ED. The use of hydrocortisone acetate (compound F acetate) in the treatment of some common orthopaedic conditions. J Bone Joint Surg Am 1954; 36-A:602.
- Lansang MC, Farmer T, Kennedy L. Diagnosing the unrecognized systemic absorption of intra-articular and epidural steroid injections. Endocr Pract 2009; 15:225.
- Duclos M, Guinot M, Colsy M, et al. High risk of adrenal insufficiency after a single articular steroid injection in athletes. Med Sci Sports Exerc 2007; 39:1036.
- Kay J, Findling JW, Raff H. Epidural triamcinolone suppresses the pituitary-adrenal axis in human subjects. Anesth Analg 1994; 79:501.
- Habib G, Khazin F, Jabbour A, et al. Simultaneous bilateral knee injection of methylprednisolone acetate and the hypothalamic-pituitary adrenal axis: a single-blind case-control study. J Investig Med 2014; 62:621.
- Armstrong RD, English J, Gibson T, et al. Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate. Ann Rheum Dis 1981; 40:571.
- Hägg E, Asplund K, Lithner F. Value of basal plasma cortisol assays in the assessment of pituitary-adrenal insufficiency. Clin Endocrinol (Oxf) 1987; 26:221.
- Schmidt IL, Lahner H, Mann K, Petersenn S. Diagnosis of adrenal insufficiency: Evaluation of the corticotropin-releasing hormone test and Basal serum cortisol in comparison to the insulin tolerance test in patients with hypothalamic-pituitary-adrenal disease. J Clin Endocrinol Metab 2003; 88:4193.
- Deutschbein T, Unger N, Mann K, Petersenn S. Diagnosis of secondary adrenal insufficiency: unstimulated early morning cortisol in saliva and serum in comparison with the insulin tolerance test. Horm Metab Res 2009; 41:834.
- Endert E, Ouwehand A, Fliers E, et al. Establishment of reference values for endocrine tests. Part IV: Adrenal insufficiency. Neth J Med 2005; 63:435.
- Dekkers OM, Timmermans JM, Smit JW, et al. Comparison of the cortisol responses to testing with two doses of ACTH in patients with suspected adrenal insufficiency. Eur J Endocrinol 2011; 164:83.
- Dickstein G, Saiegh L. Low-dose and high-dose adrenocorticotropin testing: indications and shortcomings. Curr Opin Endocrinol Diabetes Obes 2008; 15:244.
- Borst GC, Michenfelder HJ, O'Brian JT. Discordant cortisol response to exogenous ACTH and insulin-induced hypoglycemia in patients with pituitary disease. N Engl J Med 1982; 306:1462.
- CORTISOL SECRETION DURING STRESS
- EFFECT OF EXOGENOUS GLUCOCORTICOIDS
- Nonsuppressed HPA axis
- Suppressed HPA axis patients
- Intermediate patients (HPA suppression unknown)
- - Glucocorticoid use in past year
- - Inhaled and topical glucocorticoids
- - Intra-articular and spinal glucocorticoid injections
- EVALUATION OF HPA AXIS SUPPRESSION
- Intermediate patients
- - Morning serum cortisol
- - ACTH stimulation tests
- Urgent or emergency surgery
- SUMMARY AND RECOMMENDATIONS