The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 85, Issue 11

Scientific Articles | November 01, 2003

Endogenous Cortisol Production in Response to Knee Arthroscopy and Total Knee Arthroplasty

Seth S. Leopold, MD¹; Michael T. Casnellie, MD²; Winston J. Warme²; Paul J. Dougherty²; Susan T. Wingo²; Susan Shott, P³

¹ Department of Orthopaedic Surgery and Sports Medicine, University of Washington Medical Center, 1959 N.E. Pacific Street, Box 356500, Seattle, WA 98195. E-mail address: leopold@u.washington.edu
² Orthopaedic Surgery Service (M.T.C., W.J.W., and P.J.D.) and Endocrinology Service (S.T.W.), William Beaumont Army Medical Center, 5005 North Piedras Street, El Paso, TX 79920
³ Biostatistics Unit, Rush-Presbyterian-St. Luke's Medical Center, 1725 West Harrison Street, Chicago, IL 60612

View Disclosures and Other Information

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from William Beaumont Army Medical Center, Department of Clinical Investigation (Grant WBAMC 01/20). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

The views expressed in this manuscript are those of the authors and do not reflect the official policy of the Department of Defense or the United States Government.

Investigation performed at the William Beaumont Army Medical Center, El Paso, Texas, and the University of Washington Medical Center, Seattle, Washington

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J Bone Joint Surg Am, 2003 Nov 01;85(11):2163-2167

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Abstract

Background: There is controversy about whether patients who take exogenous glucocorticoids, such as prednisone, require supplemental (exogenous) glucocorticoids in order to meet the physiological demands of surgery. In this study, we sought to define the magnitude of the surgical stress response in normal patients undergoing major and minor elective orthopaedic surgery.

Methods: A prospective, observational study of thirty patients who had not taken exogenous glucocorticoids and who underwent either elective knee arthroscopy or elective unilateral total knee arthroplasty was performed. Regional anesthesia was used for all patients, and all patients treated with total knee arthroplasty had continuous epidural anesthesia for forty-eight hours after the surgery. The stress response was assessed on the basis of serum and twenty-four-hour urine cortisol levels; comparisons of the urine values were made after correcting for renal function by calculating the cortisol-to-creatinine clearance ratio.

Results: Preoperatively, patients undergoing arthroscopy and total knee arthroplasty had similar cortisol-to-creatinine clearance ratios. Patients treated with total knee arthroplasty had a significant (p < 0.001) surgical stress response on the day of the surgery, compared with baseline, whereas patients treated with arthroscopy did not. The mean cortisol-to-creatinine clearance ratio in patients treated with total knee arthroplasty was highest on the day of the surgery and decreased on the third postoperative day. However, on the third postoperative day, the cortisol-to-creatinine clearance ratio still was significantly higher than the baseline value (p < 0.001). Significant differences in the serum cortisol levels also were detected between the patients treated with arthroscopy and those treated with total knee replacement.

Conclusions: Patients undergoing total knee arthroplasty had a significant surgical stress response (a seventeenfold increase in the cortisol-to-creatinine clearance ratio); patients treated with arthroscopy did not. Additional studies, including a prospective trial of patients taking exogenous glucocorticoids, are warranted. Until they are performed, the significantly increased cortisol production observed in non-steroid-dependent patients following total knee arthroplasty leaves open the possibility that steroid-dependent patients undergoing this procedure could benefit from perioperative glucocorticoid supplementation. Since the non-steroid-dependent patients in the present series did not mount a substantial stress response to knee arthroscopy, our results do not support the use of supplemental steroids for that less-invasive procedure.

Level of Evidence: Therapeutic study, Level II-1 (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence.

Figures in this Article

There is debate about whether patients taking exogenous glucocorticoids, such as prednisone, require supplemental (exogenous) glucocorticoids (so-called stress steroids) in order to meet the physiological demands of surgery^1-8. The rationale for perioperative steroid supplementation is based on the suppression of the hypothalamic-pituitary-adrenal axis that occurs with the chronic use of exogenous glucocorticoids. This can result in refractory hypotension, shock, and even death when the adrenal cortex fails to produce enough glucocorticoids in response to the stress of surgery^1,9,10. The frequency of this complication, called acute adrenal crisis, is unknown.

Two small observational studies were performed to determine whether patients who had taken exogenous (oral) glucocorticoids chronically had a substantial surgical stress response^2,3. No significant increase in endogenous cortisol production following surgery was found in those small series. However, the patients may have been experiencing secondary adrenal cortical insufficiency as a result of the exogenous steroid use. To our knowledge, the normal adrenal stress response to major and minor orthopaedic surgery, if there is one, has not been established in a population of patients with similar preoperative diagnoses and surgical procedures. Until that is done, perioperative data on patients who may be adrenally suppressed^2,3 should not be presumed to represent normal physiology, and interpretation of perioperative data on steroid-dependent patients in the absence of similar data on normal patients is difficult.

In this study, we tested the hypothesis that there is no significant increase in endogenous cortisol production, compared with baseline values, in normal (non-adrenally suppressed) patients undergoing total knee replacement or knee arthroscopy.

Materials and Methods

Materials and Methods | Results | Discussion | Appendix | References

Patients

This comparative observational study was approved by the medical center institutional review board, and all patients gave informed consent. Two groups of patients were enrolled. Group I included adult patients undergoing elective, unilateral total knee arthroplasty under continuous epidural anesthesia for the treatment of osteoarthritis or posttraumatic arthritis. Group II included adult patients undergoing elective, unilateral knee arthroscopy without concomitant ligament reconstruction, open meniscal repair, or arthrotomy. These procedures also were performed under regional anesthesia. Patients were excluded if they had taken prednisone or other oral or intravenous glucocorticoids in the last year, were immunocompromised (for example, had active malignant disease or clinically evident malnutrition), or were pregnant at the time of enrollment or the surgery.

Demographic data, including preoperative diagnosis, age, gender, weight, and body-mass index, were gathered prospectively for all patients. Surgical data, including total operative time and intraoperative and postoperative complications, were recorded as well.

Evaluation of Adrenal Cortical Function (Cortisol Assays)

Cortisol production was measured in urine and serum specimens as follows.

Group I (total knee arthroplasty): Twenty-four-hour urine specimens for measurement of free cortisol and creatinine were obtained at three time-points: five or more days before the surgery; on the day of the surgery, beginning when the incision was made; and beginning forty-eight hours after the surgery. Serum cortisol levels were measured at seven time-points: five or more days before the surgery (at approximately the same time of day as the surgery was planned); on the day of the surgery, when the first intravenous line was placed; intraoperatively, thirty minutes after the incision was made; and one hour, six hours, twenty-four hours, and approximately seventy-two hours postoperatively.

Group II (knee arthroscopy): Twenty-four-hour urine specimens for measurement of free cortisol and creatinine were obtained at two time-points: five or more days before the surgery and on the day of the surgery, beginning when the incision was made. Serum cortisol levels were measured at six time-points: five or more days before the surgery (at approximately the same time of day as the surgery was planned); on the day of the surgery, when the first intravenous line was placed; intraoperatively, thirty minutes after the incision was made; and one hour, six hours, and twenty-four hours postoperatively.

Serum cortisol assays were performed with use of the ADVIA Centaur Cortisol Assay (Bayer, East Walpole, Massachusetts) in accordance with the manufacturer's guidelines¹¹. Measurements of free cortisol and creatinine levels in the twenty-four-hour urine specimens were performed by Quest Diagnostics (Dallas, Texas) in compliance with that laboratory's standards for specimen storage, handling, and transportation. In order to allow comparisons among patients who may have had differences in renal function, the measurements of cortisol in the twenty-four-hour urine specimens were adjusted by calculating the cortisol-to-creatinine clearance ratio. This value is the standard for data comparison in studies of this type and was used in the only other orthopaedic study of this type of which we are aware³.

Statistical Methods

SPSS for Windows (version 10; SPSS, Chicago, Illinois) was used for data management and statistical analysis. Because histograms of the data indicated that the variables had non-normal distributions, nonparametric statistical methods were used to analyze the data. The Friedman test was done separately for analysis of each study group to test for changes over time with respect to non-nominal variables. The Mann-Whitney test was used to compare the study groups at each time-point with respect to non-nominal variables. The chi-square test of association was used to compare the study groups with respect to gender. A 0.05 significance level was used for all statistical tests. No one-sided statistical tests were done.

Results

Materials and Methods | Results | Discussion | Appendix | References

Group I (Total Knee Arthroplasty; Fifteen Patients)

The median cortisol-to-creatinine clearance ratio for the twenty-four-hour urine specimens collected five days or more before the surgery was 0.15 µg-min/24 hr-mL (range, 0.05 to 0.53 µg-min/24 hr-mL). It increased significantly to 2.52 µg-min/24 hr-mL (range, 0.21 to 13.77 µg-min/24 hr-mL) for the specimens collected starting at the time of the incision (p < 0.001), suggesting a pronounced response to the stress of total knee arthroplasty (see Appendix). There was a trend (although it did not achieve significance; p = 0.071) toward a decrease in the cortisol-to-creatinine clearance ratio between the data obtained on the day of the surgery and those obtained on the third postoperative day, when the median clearance ratio was 1.62 µg-min/24 hr-mL (range, 0.42 to 5.00 µg-min/24 hr-mL). However, the median cortisol-to-creatinine clearance ratio on the third postoperative day was still significantly elevated compared with the preoperative value (p < 0.001), despite continuous epidural analgesia over the first forty-eight hours following the surgery.

With the numbers available, the median serum cortisol value obtained on the day of the surgery (12.62 µg/dL [348.19 nmol/L]) was not significantly different from the median value obtained five days or more prior to the surgery (11.75 µg/dL [324.18 nmol/L]) (p = 0.796). However, the serum cortisol level increased significantly between the preoperative time-point and the test done twenty-four hours after the surgery (19.46 µg/dL [536.90 nmol/L], p = 0.001; Table I).

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TABLE I Serum Cortisol Values

	Serum Cortisol Value*(µg/dL [nmol/L])
Time of Sample	Patients Treated with Arthroscopy	Patients Treated with Total Knee Arthroplasty	P Value†
Baseline (drawn =5 days preop.)	9.9 (273.1) ± 3.9 (107.6)	11.8 (325.6) ± 4.0 (110.4)	0.80
Day of surgery (preop.)	12.9 (355.9) ± 5.2 (143.5)	12.6 (347.6) ± 6.2 (171.1)	0.37
Intraop., 30 min after incision	6.3 (173.8) ± 5.7 (157.3)‡	7.8 (215.2) ± 10.1 (278.7)	0.28
1 hr postop.	6.0 (165.5) ± 8.2 (226.2)	13.9 (383.5) ± 7.0 (193.1)	0.01
6 hr postop.	5.2 (143.5) ± 7.9 (218.0)	21.3 (587.7) ± 8.8 (242.8)	<0.001
24 hr postop.	4.8 (132.4) ± 2.6 (71.7)	19.5 (538.0) ± 11.9 (328.3)‡	<0.001
72 hr postop.	N/A	18.2 (502.1) ± 8.7 (240.0)	N/A

The values are given as the mean and standard deviation. N/A = not available. †According to the Mann-Whitney test comparing data between the arthroscopy and total knee arthroplasty groups at each time-point. ‡According to the Friedman test, there was a significant change compared with the baseline value within the group (p < 0.05).

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TABLE I Serum Cortisol Values

	Serum Cortisol Value*(µg/dL [nmol/L])
Time of Sample	Patients Treated with Arthroscopy	Patients Treated with Total Knee Arthroplasty	P Value†
Baseline (drawn =5 days preop.)	9.9 (273.1) ± 3.9 (107.6)	11.8 (325.6) ± 4.0 (110.4)	0.80
Day of surgery (preop.)	12.9 (355.9) ± 5.2 (143.5)	12.6 (347.6) ± 6.2 (171.1)	0.37
Intraop., 30 min after incision	6.3 (173.8) ± 5.7 (157.3)‡	7.8 (215.2) ± 10.1 (278.7)	0.28
1 hr postop.	6.0 (165.5) ± 8.2 (226.2)	13.9 (383.5) ± 7.0 (193.1)	0.01
6 hr postop.	5.2 (143.5) ± 7.9 (218.0)	21.3 (587.7) ± 8.8 (242.8)	<0.001
24 hr postop.	4.8 (132.4) ± 2.6 (71.7)	19.5 (538.0) ± 11.9 (328.3)‡	<0.001
72 hr postop.	N/A	18.2 (502.1) ± 8.7 (240.0)	N/A

Group II (Knee Arthroscopy; Fifteen Patients)

The median cortisol-to-creatinine clearance ratio for the twenty-four-hour urine specimens was 0.20 µg-min/24 hr-mL (range, 0.09 to 0.48 µg-min/24 hr-mL) five or more days before the surgery and 0.25 µg-min/24 hr-mL (range, 0.08 to 1.27 µg-min/24 hr-mL) in the specimens collected starting at the time of the incision. With the numbers available, this difference was not significant (p = 0.44) (see Appendix). The median serum cortisol value obtained on the day of the surgery (12.88 µg/dL [355.36 nmol/L]) was not significantly different from the median value obtained five days or more prior to the surgery (9.9 µg/dL [273.14 nmol/L]) (p = 0.285). With the numbers available, neither the intraoperative nor the postoperative serum cortisol levels were found to be significantly increased compared with the preoperative value; in fact, the serum cortisol levels following arthroscopy were somewhat decreased compared with the baseline values (Table I).

Comparisons Between Groups

There were several significant differences between the two study groups in terms of demographic and surgical parameters, including age, gender, and duration of surgery. Patients treated with total knee arthroplasty were older and were more likely to be female (eight of the patients treated with total knee arthroplasty and only one of those treated with arthroscopy were female, p = 0.005). Also, the arthroplasty procedures were of longer duration than the arthroscopy procedures. With the numbers available, no significant differences in weight or body-mass index were detected between the groups (see Appendix).

Despite the demographic differences (age and gender) between the study groups, the median preoperative cortisol-to-creatinine clearance ratio in the knee arthroscopy group (0.20 µg-min/24 hr-mL; range, 0.09 to 0.48 µg-min/24 hr-mL) was not significantly different (p = 0.22) from that in the total knee arthroplasty group (0.15 µg-min/24 hr-mL; range, 0.05 to 0.53 µg-min/24 hr-mL). However, the increase in the cortisol-to-creatinine clearance ratio between the preoperative specimens and the specimens collected beginning at the time of the incision was significantly greater (p < 0.001) in the total knee arthroplasty group (median increase, 2.37 µg-min/24 hr-mL) than in the arthroscopy group (median increase, 0.05 µg-min/24 hr-mL), suggesting that the stress response in patients treated with total knee arthroplasty was significantly greater than that in patients treated with arthroscopy.

At all postoperative time-points, the patients treated with total knee arthroplasty demonstrated significantly higher median serum cortisol levels than did those treated with arthroscopy (p = 0.01 for one hour postoperatively, p < 0.001 for six hours postoperatively, and p < 0.001 for twenty-four hours postoperatively; Table I).

Discussion

Materials and Methods | Results | Discussion | Appendix | References

In this prospective, comparative observational study, we sought to define the normal stress response to major and minor elective knee surgery. Patients who underwent knee arthroscopy were not found to have a significant increase in cortisol production following surgery, with the numbers available. In contrast, patients treated with total knee arthroplasty had a very large increase in endogenous cortisol production following surgery, and the cortisol-to-creatinine clearance ratios remained elevated for at least seventy-two hours despite good postoperative analgesia with continuous epidural anesthesia.

These results may contribute to an evolving consensus about the perioperative management of patients who routinely take exogenous corticosteroids, such as prednisone, for any of a number of chronic illnesses. Since the publication, in the 1950s, of several case reports on patients who were taking exogenous corticosteroids before being operated on and then died following the surgery^9,10, a variety of sources¹² have recommended steroid supplementation in such patients in order to minimize the likelihood of such a catastrophic outcome.

In contrast, an observational study of nineteen glucocorticoid-dependent patients with various diagnoses³ demonstrated no significant increase in cortisol-to-creatinine clearance ratio or twenty-four-hour urinary cortisol excretion after orthopaedic surgery. On the basis of that finding and the fact that no patient had symptoms or signs of acute adrenal crisis, the authors suggested that perioperative "stress steroid" regimens may not be necessary. This is an appealing conclusion, since stress steroid regimens are cumbersome and use of corticosteroids may predispose patients to infection^13-17 as well as to other orthopaedic complications^18-20.

However, several issues arise when one interprets the data generated in a few small (mostly non-orthopaedic) studies of patients taking exogenous glucocorticoids before surgery^2,3,21-23. Most importantly, the absence of a perioperative increase in cortisol production in patients in whom the hypothalamic-pituitary-adrenal axis is probably suppressed does not mean that such an increase would not be appropriate or beneficial. Although no life-threatening complications were observed in those small series, many of the patients underwent minor procedures, and their steroid and medical histories varied widely. In view of those issues, there remains a real possibility that an uncommon—but potentially fatal—complication would occur if the recommendation to stop using postoperative glucocorticoid supplementation^2,3 were to be adopted widely. The results of the present study, which defined the normal adrenal stress response following major and minor knee surgery in non-steroid-dependent patients, indicate that the absence of a perioperative stress response observed in the orthopaedic report on patients who took exogenous glucocorticoids³ is in fact an abnormal finding. The present study also included more patients and a more homogeneous population than did the prior report³.

In the present study, patients undergoing knee arthroscopy did not have an increase in the cortisol-to-creatinine clearance ratio whereas those treated with total knee arthroplasty had a seventeenfold increase. Non-orthopaedic studies have also demonstrated relationships between the extent of the procedure and the hormonal stress response^4,24. However, there were important differences in baseline characteristics, including age and gender, between the two study groups in the present report. It is also conceivable that medical comorbidities within each study group contributed to different responses among patients. (The small size of the study cohort precludes subanalysis on the basis of comorbid conditions.) However, stringent inclusion and exclusion criteria resulted in fairly homogeneous study populations, and surgical factors, including operative and anesthetic techniques, were tightly controlled. It is interesting to note that perhaps the most obvious difference between the total knee arthroplasty and arthroscopy groups—that the patients treated with total knee arthroplasty were significantly older— would be expected to cause a blunting, and not an accentuation, of the stress cortisol response^25-28.

The decision regarding whether to use any of a variety of glucocorticoid supplementation protocols^1,12, or none at all^2,3, requires weighing of the risks of potentially fatal postoperative adrenal insufficiency^9,10 against the risks associated with steroid treatment itself ^14,15,18,20. Additional studies, including a large randomized, controlled trial of patients taking exogenous glucocorticoids, are warranted. Until they are performed, the significantly increased cortisol production observed in non-steroid-dependent patients treated with total knee arthroplasty suggests that it is possible that steroid-dependent patients undergoing total knee arthroplasty could benefit from perioperative glucocorticoid supplementation. A randomized, controlled study of such a population would be needed to resolve that issue more definitively. Since the non-steroid-dependent patients in the present series did not mount a substantial stress response to knee arthroscopy, our results do not support the use of stress steroids for that less-invasive procedure.

Appendix

Materials and Methods | Results | Discussion | Appendix | References

Tables showing the cortisol-to-creatinine clearance ratios and the demographic and surgical parameters are available with the electronic versions of this article, on our web site at (go to the article citation and click on "Supplementary Material") and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).

References

Materials and Methods | Results | Discussion | Appendix | References

Williams GH, Dluhy RG. Disorders of the adrenal cortex. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 15th ed. New York: McGraw-Hill; 2001. p 2084-104.2084 2001

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: 532-6.180532 1995

Friedman RJ, Schiff CF, Bromberg JS. Use of supplemental steroids in patients having orthopaedic operations. J Bone Joint Surg Am.1995;77: 1801-6.771801 1995 [PubMed]

Friedrich M, Rixecker D, Friedrich G. Evaluation of stress-related hormones after surgery. Clin Exp Obstet Gynecol.1999;26: 71-5.2671 1999

Glowniak JV, Loriaux DL. A double-blind study of perioperative steroid requirements in secondary adrenal insufficiency. Surgery.1997;121: 123-9.121123 1997 [PubMed][CrossRef]

Kilickan L, Toker K. The effects of preemptive intravenous versus preemptive epidural morphine on postoperative analgesia and surgical stress response after orthopaedic procedures. Minerva Anestesiol.2000;66: 649-55.66649 2000 [PubMed]

Lacoumenta S, Yeo TH, Burrin JM, Paterson JL, Hall GM. The effects of cortisol supplementation on the metabolic and hormonal response to surgery. Clin Physiol.1987;7: 455-64.7455 1987 [CrossRef]

Symreng T, Karlberg BE, Kagedal B, Schildt B. Physiological cortisol substitution of long-term steroid-treated patients undergoing major surgery. Br J Anaesth.1981;53: 949-54.53949 1981 [CrossRef]

Fraser CG, Preuss FS, Bigford WD. Adrenal atrophy and irreversible shock associated with cortisone therapy. JAMA.1952;149: 1542-3.1491542 1952

Lewis L, Robinson RF, Yee J, Hacker LA, Eisen G. Fatal adrenal cortical insufficiency precipitated by surgery during prolonged continuous cortisone treatment. Ann Intern Med.1953;39: 116-26.39116 1953

Bayer I. Cortisol assay. In: ADVIA centaur assay manual. East Walpole, MA: Bayer; 2000. p 1-12.1 2000

Lloyd EL. A rational regimen for perioperative steroid supplements and a clinical assessment of the requirement. Ann R Coll Surg Engl.1981;63: 54-7.6354 1981 [PubMed]

Bohnen JM, Mustard RA, Schouten BD. Steroids, APACHE II score, and the outcome of abdominal infection. Arch Surg.1994;129: 33-8.12933 1994 [PubMed]

Peersman G, Laskin R, Davis J, Peterson M. Infection in total knee replacement: a retrospective review of 6489 total knee replacements. Clin Orthop.2001;392: 15-23.39215 2001 [PubMed][CrossRef]

Espehaug B, Havelin LI, Engesaeter LB, Langeland N, Vollset SE. Patient-related risk factors for early revision of total hip replacements. A population register-based case-control study of 674 revised hips. Acta Orthop Scand.1997;68: 207-15.68207 1997 [PubMed][CrossRef]

Dhillon N, Ries MD, Jacobs R.Poor outcomes of MRSA infected joint replacements. Read at the Annual Meeting of the American Academy of Orthopaedic Surgeons; 2002 Feb 13-17; Dallas, TX. 2002

Wilson MJ, Kelley K, Thornhill TS. Infection as a complication of total knee-replacement arthroplasty. Risk factors and treatment in sixty-seven cases. J Bone Joint Surg Am.1990;72: 878-83.72878 1990

Fast A, Alon M, Weiss S, Zer-Aviv FR. Avascular necrosis of bone following short-term dexamethasone therapy for brain edema. Case report. J Neurosurg.1984;61: 983-5.61983 1984 [PubMed][CrossRef]

Nasser SM, Ewan PW. Lesson of the week: depot corticosteroid treatment for hay fever causing avascular necrosis of both hips. BMJ.2001;322: 1589-91.3221589 2001 [PubMed][CrossRef]

O'Brien TJ, Mack GR. Multifocal osteonecrosis after short-term high-dose corticosteroid therapy. A case report. Clin Orthop.1992;279: 176-9.279176 1992 [PubMed]

Jasani MK, Freeman PA, Boyle JA, Reid AM, Diver MJ, Buchanan WW. Studies of the rise in plasma 11 hydroxycorticosteroids (11-OCHS) in corticosteroid-treated patients with rheumatoid arthritis during surgery: correlations with the functional integrity of the hypothalamo-pituitary-adrenal axis. Q J Med.1968;37: 407-21.37407 1968

Kehlet H, Binder C. Adrenocortical function and clinical course during and after surgery in unsupplemented glucocorticoid-treated patients. Br J Anaesth.1973;45: 1043-8.451043 1973 [CrossRef]

Shapiro R, Carroll PB, Tzakis AG, Cemaj S, Lopatin WB, Nakazato P. Adrenal reserve in renal transplant recipients with cyclosporine, azathioprine, and prednisone immunosuppression. Transplantation.1990;49: 1011-3.491011 1990 [PubMed][CrossRef]

Chernow B, Alexander HR, Smallridge RC, Thompson WR, Cook D, Beardsley D, Fink MP, Lake CR, Fletcher JR. Hormonal responses to graded surgical stress. Arch Intern Med.1987;147: 1273-8.1471273 1987 [CrossRef]

Zietz B, Hrach S, Scholmerich J, Straub RH. Differential age-related changes of hypothalamus-pituitary-adrenal axis hormones in healthy women and men—role of interleukin 6. Exp Clin Endocrinol Diabetes.2001;109: 93-101.10993 2001 [CrossRef]

Katayama M, Nomura K, Ujihara M, Obara T, Demura H. Age-dependent decline in cortisol levels and clinical manifestations in patients with ACTH-independent Cushing's syndrome. Clin Endocrinol (Oxf).1998;49: 311-6.49311 1998 [PubMed][CrossRef]

Noth RH, Mazzaferri EL. Age and the endocrine system. Clin Geriatr Med.1985;1: 223-50.1223 1985 [PubMed]

Boscaro M, Paoletta A, Scarpa E, Barzon L, Fusaro P, Fallo F, Sonino N. Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man. J Clin Endocrinol Metab.1998;83: 1380-3.831380 1998 [PubMed][CrossRef]

Topics

hydrocortisone ; arthroscopy ; creatinine ; glucocorticoids ; steroids ; hydrocortisone measurement ; knee replacement arthroplasty ; knee arthroscopy

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Seth S. Leopold, Michael T. Casnellie, Winston J. Warme, Paul J. Dougherty, Susan T. Wingo, Susan Shott; Endogenous Cortisol Production in Response to Knee Arthroscopy and Total Knee Arthroplasty. The Journal of Bone & Joint Surgery. 2003 Nov;85(11):2163-2167.

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