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Urine cortisol levels after burn injury
Burns, 8,333-337
333
Printedin Great Britain
Urine cortisol levels after burn injury E. J. Coombes and G. F. Batstone Department
of Chemical
Pathology,
Salisbury
Summary
The urinary level of cortisol has been assayed in 19 patients with bum injuries of varying severity over a IO-day period. Urine cortisol was increased in all patients over the initial days post burn when compared to normal healthy volunteers. In patients with the more severe burns mean cortisol levels reached a maximum on day 2 post bum when cortisol levels correlated with the percentage body surface area ofthe burn. The overall pattern of cortisol excretion was similar in extent and duration to the changes in the levels of serum cortisol described in a previous study (Batstone et al., 1976). Further, urine cortisol excretion correlated with the levels of urine creatinine, magnesium, potassium and the sodium : potassium ratio lending further evidence to an important role of cortisol in peripheral tissue (particularly muscle). Cortisol output was still significantly raised at the end of the study period emphasizing the duration of the cortisol-induced catabolic drive after bum injury.
Generallnfirmary
Birke et al., 1958). Batstone et al., (1976) showed plasma cortisol to be highest in the first 2 days after burn injury whilst Mortenson et al. (1972) observed that there was no significant rise in cortisol binding capacity implying that free cortisol, the biologically active form, was greatly increased. In this study (Batstone et al., 1976) plasma cortisol correlated with the mobilization of gluconeogenic precursors, with lipid metabolites as well as with plasma urea. It seemed pertinent, in the light of the previous plasma analysis, to study the urine excretion of cortisol as a better indicator of cortisol secretion rate and to assess the possible relationships with the excretion of nitrogenous compounds and ions either associated with muscle protein or whose renal handling is affected by steroids. PATIENTS
INTRODUCTION RECENT work on the relationship
of cortisol to catabolism has been re-evaluated [see review by Alberti and Johnson, (1977)] and contrasts with the earlier ideas of cortisol as a permissive hormone (Ingle et al.. 1951; Exton et al., 1972) especially in the early phase after injury. The primary catabolic effect of cortisol appears to be on peripheral tissues promoting proteolysis in muscle and lipolysis in adipose tissue. Jeejeebhoy et al. (1977) have shown in vitro that cortisol was the important hormone in the stimulation of synthesis of a, acute phase glycoprotein indicating another possible role of cortisol in the catabolic state. Several groups of workers have observed a rise in glucocorticoid secretion in the plasma of thermally-injured patients (Wilson et al., 1955;
AND
METHODS
Patients
Nineteen patients (I 5 male, 4 female) admitted to the Wessex Regional Burns Unit were studied. The treatment of the patients has already been described (Laing and Harvey, 197 1; Batstone et al.. 1976). Patients were divided into two groups, Group I severe and Group II mild burns, based on the predictive Index (D,) ofburn mortality (Moores et al., 1975). Patient group data is described in Table I. Twenty-four-hour collections of urines were made from all patients over the first IO days post burn. No preservative was added to the urines. The urines were volumed and IOO-ml aliquots removed and frozen ( - 20 “C) prior to analysis. Controls
Twenty-four-hour
collections
of urine
were
334
Burns Vol. B/No. 5
Tablel. Patient group data
Sex M F
Group
No.
Severe (1)
9
8
1
10
7
3
Mild (2)
Mean % area of burn (range) 48.7 (20-89) 20.3 (8-39)
made from 43 apparently healthy subjects (age range 18-64 years). The urines were processed in exactly the same manner as the urines from patients with burn injury. In these control subjects mean urine cortisol was observed to be 183 nmo1/24h (s.e. mean 14, range 9-395); mean urine creatinine 13.9 mmo1/24h (s.e. mean 0.53, range 8.3-20-2); mean urea 371 mmo1/24h (s.e. mean 17, range 130-660); mean sodium 163 mmo1/24h (s.e. mean 12, range 46-328); mean potassium 80 mmo1/24h (s.e. 7000’ nmol/24h
Mean predictive index
Mean age
(range) 32.0 (19-64) 32.8 (12-72)
+2.24 +0.65-+6.18) - 1 .Y8 -4.0 44.24)
Deaths 2 0
mean 4, range 50-144); mean calcium 4.9 mmo1/24h (s.e. mean 0.3, range 2-7.9); mean magnesium 4.4 mmo1/24h (s.e. mean 0.2, range 1.7-6.9) and mean urine sodium : potassium ratio 2.1 (s.e. mean 0.14, range 0*7-4.0). Methods
Urine cortisol was measured by a solid phase RIA method (Radiochemical Centre, Amersham). Urines were diluted with distilled water when required. Urine urea was assayed by a diacetyl monoxime method (Marsh et al., 1965) urine creatinine by a picric acid method (Technicon method, No. SF4-0011 FM4). Urine sodium and potassium were measured by flame photometry using a Technicon Mark IV flame photometer and urine calcium and magnesium by atomic absorption on an Instrumentation Laboratories 155 atomic absorption spectrophotometer at 1 422.7 and 285.2 nm respectively Statistical
analysis
Statistical comparisons have been made using the Students t test. Correlations have been performed by standard techniques. RESULTS Urine cortisol
L
,
,
,
1
2
3
,
4 5 6 7 Days post burn
,
8
,
(
910
Urine cortisol levels after bum injury. o--O represents mean (s.e. mean) cortisol levels in patients with severe burns and X-X in patients with mild burns. *Indicates significant differences (see text) in cortisol excretion between the two groups of patients.
Fig, 1.
The results of the measurement of urine cortisol in the two groups of patients with bums are shown in Fig. 1. Results are expressed as mean (ks.e. mean) of all patients in each group on each day. In patients with severe burns urine cortisol on day 1 was greatly elevated compared to the reference range, being 10 times the upper limit of the range for healthy subjects. Mean peak excretion was observed on day 2 post burn falling thereafter. On day 10 post burn, cortisol excretion was still 3 times the upper limit of the reference range. In the group of
18.3(2.7) 12.3(2.6) ns
I 2
:
:
Creatinine (mmob’24h)
Magnesium (mmol/24h)
Calcium (mmoV24h)
766(95) 264(-l 9)
739(132) 225(32! < o,oo I
3.8(1.1) 2.8(0.6) ns
4.6(1.2) 3.7( I .O) ns
??
3.7(0.9) 3,1(0.6) ns
4.4(0,9) 3.4(0.5) ns
17.7t3.6) 13.2f2.5) ns
0.69(0.2 I) 1.27(0.4) ns
0.74(0.16) I .25(0.4) ns
21.7(2.6) 1 O.S(I .4)
55(151 74(21) ns
lOl(14) 57(8) < 0.02
3
77(14) 60(26) ns
12 I(22) 44(6)
2
Figures in brackets represent standard error of the mean. P, Probability; ns, not significant. 1, Severe; 2, mild.
IlS
4.0(1.2) 2.0( 1.6)
4.0( I ,O) 25(09) ns
415(51) 236(42) < 0.02
1 .I 9(0.3) 2.43(0.53) ns
94(223 103(29) ns
I 13(9) 43(8)
I
I 2
??
Urea (mmo1/24h)
ratio
:
:
Sodium (mmoV24h)
Sodium:
1 2
Potassium (mmof/24h)
A nalyte
Patient 91CXJp
Tab/e /I. Results of all analytes measured
45(11) 138(21)
64(I3) 6503) ns
5
2*4(0.5) 3.5(0.9) ns
4.3( I .O) 3.5(0.9) ns
15.5(2.8) 13.2(2.3) ns
656(81) 317(54)
3.0(0,8) 5.6(1.6) ns
4,711 .O) 5.2(0.7) ns
13.2(1.4) 15.6(2,1) ns
622(88) 352(45) < 0.02
0.48iO.I I ) 0.72(0.17) 1.84tO.48) 2.33(0.39) <0.05 < 0.02
37f7f 96(25) <0.05
87(18) 58t9) ns
4
3.3(0.9) 3.4(1.1) ns
5.1 to.51 4.3(0.9) ns
15.6(1.6) 13.9(2.7) ns
690(1 IO) 294(35)
1.22(0.37) 2.07(0.38) ns
49(13) 93(17) ns
65(13) 44(61 ns
6
Time post burn (d)
2.6(0,8) 3.9( 1 .O) ns
3,1(1.0) 3.0(0.7) ns
3,9( 1’2) 2.8(0.3) ns
13.7(2.5) 12.3(2,31 ns
12.9(0.9) 12.2(2.2) ns 4.OtO.6) 3*6(0.7) ns
650(102) 227(36)
657(85) 289(47)
0,53(0.12) 1.9 (0.29)
2.2(0.7 3.4(0.9) ns
4~0(0~7) 3.6(0.7) ns
13.7(1‘3) 10,9(1.71 ns
725(1 16) 261(27)
0.63(0.1 1) 2.35(0.54) < 0.02
41(7) 112(19)
47fl I) 117(18)
4016) 89(15)
0.99(0.31) I ,96(0.2 1) < 0.02
69(8) 67W ns
64t9) 55(10) ns
50(8) ns
51t6)
9
8
7
3.4(0.8) 4.2(1.1) ns
4.3(08) 3*6(0*6) ns
14.5(1.5) 10*3(1,6) ns
646(153) 307(35) eo.05
0.49(O.I 4) 2.67(0.45)
39(12) 131(191
83(1 1) 65(8) ns
10
336
BurnsVol. ~/NO. 5
patients with mild burns, mean peak excretion was demonstrated on day 1 post burn with normal excretion by the end of the study. Signiflcant differences in cortisol excretion were demonstrated in the two groups of patients on days 2 (P
and potassium
The maximal excretion of potassium occurred on day 2 post burn in patients with severe burns. In contrast the excretion of potassium was reasonably constant in patients with mild burns. In both groups of patients urine sodium fell. In the patients with severe burns the fall was drastic and low levels were still recorded at the end of the study period. In patients with mild burns the initial decrease in urine sodium was followed by an upward trend towards normality. The urine Na+: K+ ratio fell within the normal reference range in patients with mild burns but was extremely low in patients with severe burns. All the analytes measured are listed in Table II. Urine calcium
and magnesium
Only small differences were observed between the excretion of calcium and magnesium in the two groups of patients with burns. Urine urea
Urine urea was greatly increased in patients with severe burns when compared to patients with mild burns and to healthy controls. Significant differences were observed between the mean
urea levels of patients with severe and mild burns on all days post burn. Urine creatinine
In the group of patients with severe burns mean peak excretion of creatinine was observed on day 2 post burn, whilst the level of urine creatinine remained reasonably constant in patients with mild burns. Correlations
Correlations (Table III) were sought between cortisol excretion and the different analytes over the first 5 days post burn. Data from all patients, regardless of grouping, were included. Signiflcant positive correlations were demonstrated between urine cortisol and (a) potassium, (b) creatinine and (c) magnesium, whilst a negative correlation was observed between cortisol and the sodium : potassium ratio. DISCUSSION
The measurement of urine cortisol described in this study has clearly established the extent and duration of hypercortisoluria after burn injury. Urine cortisol levels at least ten times the upper limit of the normal reference range have been demonstrated in patients with severe burns with greatly elevated levels still apparent 10 days after the injury. The pattern of urine cortisol excretion paralleled the secretion of cortisol in plasma described in previous work (Batstone et al., 1976). This suggests that increased synthesis/secretion of cortisol, not decreased clearance, is the primary factor responsible for the increased plasma concentration of this hormone after burn injury. Furthermore, urinary cortisol may be a good indicator of the
Table l/1. Correlations between cortisol and selected in urine over the first 5 days post burn r*
1st Variable
2nd Variable
Cortisol
Potassium Magnesium Creatinine Sodium:potassium
0.79 0.62 0.46 -0.46
Sodium Urea Calcium
0.43 0.36 -0.29
?? f, Correlation coefficient t P, Probability of significant difference; ns, not significant.
analytes
Pt
337
Coombes et al.: Urine Cortisol Levels
rate of cortisol synthesis since it is claimed to be a good index (Zilva and Pannall, 1975) of the unbound biologically-active fraction in plasma. Cortisol stimulates proteolysis and increases amino acid release (Ryan et al., 1974) from peripheral tissues, especially muscle. In our study urine cortisol correlated with the excretion of magnesium. found in high concentrations in muscle, (Vernon and Wacher, 1978) and creatinine. an important end product of muscle metabolism as it is derived from muscle creatine phosphate. The fall in sodium excretion paralleled by the increased excretion of potassium after burn injury is well documented (Hinton et al., 1973). The causes of sodium retention are probably multifactional but aldosterone secretion is increased after surgery (Zimmerman et al.. 1955) and may be a contributing factor. An increased secretion of aldosterone would promote potassium excretion and increase the sodium : potassium ratio in urine. Of importance to potassium excretion after injury is the release of this ion from cells as protein is catabolized, particularly in muscle, a process promoted by cortisol. This may account for the strong positive correlation between cortisol and potassium described in this paper. These findings further support the important role of cortisol in the catabolic response to burn injury. Acknowledgements
We would like to thank Mr J. Elsworth Laing for permission to study patients and the nursing staff who collected the urine samples. We are indebted to the Radiochemical Centre, Amersham who kindly provided the kits for the assay ofcortisol.
REFERENCES
Alberti K. G. M. M. and Johnson
D. G. (1977) Cortisol and catabolism: a new perspective. Clin. Sci. Mol. Med. 52,333. Batstone G. F.. Alberti K. G. M. M., Hinks L. et al. (1976) Metabolic studies in subjects following thermal injury. Burns 2,207.
Currr.spondenreshould be addressed to: Dr Fisheries Street. Salisbury, SP2 7SX.
Birke G., Lihjedahl S. 0. and Linderholm H. (1958) Studies on bums. V. Clinical and pathophysiological aspects of circulation and respiration. &a Chir. Scar&. 116,370. Exton J. H.. Friedman N.. Wone. E. H. A. et al. (1972) Interaction of glucocorticoids with glucagon and epinephrine in the control of gluconeogenesis and glycogenolysis in liver and lipolysis in adipose tissue J. Biol. Chem. 247,3579. Hinton P., Allison S. P.. Littlejohn S. et al. (1973) Electrolyte changes after bum injury and effect of treatment. Lancet ii, 2 18. lngle D. J.. Ward S. 0. and Kuizenga M. H. (1951) The relationship of the adrenal glands to changes in urinary non-protein nitrogen following multiple fractures in force-fed rats. .4m. J. Physiol. 149. 5 IO. Jeejeebhoy K. N., Ho J., Mehra J. et al. (1977) Effects of hormones on the synthesis of IX, (acute phase) glycoprotein in isolated rat hepatocytes. Biochem. J. 168,347. Laing J. E. and Harvey J. (I 97 I ) In: The Management and Nursina of‘Burns. 2nd ed. London. English Universities&&s. Marsh W. H., Fingerhut B. and Miller H. (1965) Automated and manual direct methods for the determination of blood urea. Clin. Chem. 11,624. Moores B., Rahman M. M., Browning F. S. C. et al. (1975) Discriminant function analysis of 570 consecutive burns patients admitted to the Yorkshire Regional Bums Centre between 1966-1973. Burnsl, 135. Mortenson R. F.. Johnson A. A. and Eurenius K. (1972) Serum corticosteroid binding following thermal injury. Proc. Sot. Exp. Biol. Med. 139,877. Ryan N. T., George B. C., Odessey R. et al. (1974) Effect of haemorrhagic shock, fasting and corticosterone administration on leucine oxidation and incorporation into protein by skeletal muscle. Metabolism 23,901. Vernon W. B. and Walker W. E. C. (1978) Magnesium metabolism. In: Alberti K. G. M. M. (ed.) Recent Advances in Clinical Biochemistry, p. 50. Wilson H.. Lovelace J. R. and Hardy J. D. (1955) The adrenocortical response to extensive burns in man. Ann. Surg. 141, 175. Zilva J. F. and Pannall P. R. (1975) In: Clinical Chemistry in Diagnosis and Treatment, 2nd ed. P 140. Zimmerman B.. Casey J. H.. Bloch H. S. et al. (1955) Excretion of aldosterone by the postoperative patient. Surg. Forum 6,3. Paper accepted 24 July 198 I.
E. J. Coombes, Department of Chemical Pathology, Salisbury General Infirmary.
333
Printedin Great Britain
Urine cortisol levels after burn injury E. J. Coombes and G. F. Batstone Department
of Chemical
Pathology,
Salisbury
Summary
The urinary level of cortisol has been assayed in 19 patients with bum injuries of varying severity over a IO-day period. Urine cortisol was increased in all patients over the initial days post burn when compared to normal healthy volunteers. In patients with the more severe burns mean cortisol levels reached a maximum on day 2 post bum when cortisol levels correlated with the percentage body surface area ofthe burn. The overall pattern of cortisol excretion was similar in extent and duration to the changes in the levels of serum cortisol described in a previous study (Batstone et al., 1976). Further, urine cortisol excretion correlated with the levels of urine creatinine, magnesium, potassium and the sodium : potassium ratio lending further evidence to an important role of cortisol in peripheral tissue (particularly muscle). Cortisol output was still significantly raised at the end of the study period emphasizing the duration of the cortisol-induced catabolic drive after bum injury.
Generallnfirmary
Birke et al., 1958). Batstone et al., (1976) showed plasma cortisol to be highest in the first 2 days after burn injury whilst Mortenson et al. (1972) observed that there was no significant rise in cortisol binding capacity implying that free cortisol, the biologically active form, was greatly increased. In this study (Batstone et al., 1976) plasma cortisol correlated with the mobilization of gluconeogenic precursors, with lipid metabolites as well as with plasma urea. It seemed pertinent, in the light of the previous plasma analysis, to study the urine excretion of cortisol as a better indicator of cortisol secretion rate and to assess the possible relationships with the excretion of nitrogenous compounds and ions either associated with muscle protein or whose renal handling is affected by steroids. PATIENTS
INTRODUCTION RECENT work on the relationship
of cortisol to catabolism has been re-evaluated [see review by Alberti and Johnson, (1977)] and contrasts with the earlier ideas of cortisol as a permissive hormone (Ingle et al.. 1951; Exton et al., 1972) especially in the early phase after injury. The primary catabolic effect of cortisol appears to be on peripheral tissues promoting proteolysis in muscle and lipolysis in adipose tissue. Jeejeebhoy et al. (1977) have shown in vitro that cortisol was the important hormone in the stimulation of synthesis of a, acute phase glycoprotein indicating another possible role of cortisol in the catabolic state. Several groups of workers have observed a rise in glucocorticoid secretion in the plasma of thermally-injured patients (Wilson et al., 1955;
AND
METHODS
Patients
Nineteen patients (I 5 male, 4 female) admitted to the Wessex Regional Burns Unit were studied. The treatment of the patients has already been described (Laing and Harvey, 197 1; Batstone et al.. 1976). Patients were divided into two groups, Group I severe and Group II mild burns, based on the predictive Index (D,) ofburn mortality (Moores et al., 1975). Patient group data is described in Table I. Twenty-four-hour collections of urines were made from all patients over the first IO days post burn. No preservative was added to the urines. The urines were volumed and IOO-ml aliquots removed and frozen ( - 20 “C) prior to analysis. Controls
Twenty-four-hour
collections
of urine
were
334
Burns Vol. B/No. 5
Tablel. Patient group data
Sex M F
Group
No.
Severe (1)
9
8
1
10
7
3
Mild (2)
Mean % area of burn (range) 48.7 (20-89) 20.3 (8-39)
made from 43 apparently healthy subjects (age range 18-64 years). The urines were processed in exactly the same manner as the urines from patients with burn injury. In these control subjects mean urine cortisol was observed to be 183 nmo1/24h (s.e. mean 14, range 9-395); mean urine creatinine 13.9 mmo1/24h (s.e. mean 0.53, range 8.3-20-2); mean urea 371 mmo1/24h (s.e. mean 17, range 130-660); mean sodium 163 mmo1/24h (s.e. mean 12, range 46-328); mean potassium 80 mmo1/24h (s.e. 7000’ nmol/24h
Mean predictive index
Mean age
(range) 32.0 (19-64) 32.8 (12-72)
+2.24 +0.65-+6.18) - 1 .Y8 -4.0 44.24)
Deaths 2 0
mean 4, range 50-144); mean calcium 4.9 mmo1/24h (s.e. mean 0.3, range 2-7.9); mean magnesium 4.4 mmo1/24h (s.e. mean 0.2, range 1.7-6.9) and mean urine sodium : potassium ratio 2.1 (s.e. mean 0.14, range 0*7-4.0). Methods
Urine cortisol was measured by a solid phase RIA method (Radiochemical Centre, Amersham). Urines were diluted with distilled water when required. Urine urea was assayed by a diacetyl monoxime method (Marsh et al., 1965) urine creatinine by a picric acid method (Technicon method, No. SF4-0011 FM4). Urine sodium and potassium were measured by flame photometry using a Technicon Mark IV flame photometer and urine calcium and magnesium by atomic absorption on an Instrumentation Laboratories 155 atomic absorption spectrophotometer at 1 422.7 and 285.2 nm respectively Statistical
analysis
Statistical comparisons have been made using the Students t test. Correlations have been performed by standard techniques. RESULTS Urine cortisol
L
,
,
,
1
2
3
,
4 5 6 7 Days post burn
,
8
,
(
910
Urine cortisol levels after bum injury. o--O represents mean (s.e. mean) cortisol levels in patients with severe burns and X-X in patients with mild burns. *Indicates significant differences (see text) in cortisol excretion between the two groups of patients.
Fig, 1.
The results of the measurement of urine cortisol in the two groups of patients with bums are shown in Fig. 1. Results are expressed as mean (ks.e. mean) of all patients in each group on each day. In patients with severe burns urine cortisol on day 1 was greatly elevated compared to the reference range, being 10 times the upper limit of the range for healthy subjects. Mean peak excretion was observed on day 2 post burn falling thereafter. On day 10 post burn, cortisol excretion was still 3 times the upper limit of the reference range. In the group of
18.3(2.7) 12.3(2.6) ns
I 2
:
:
Creatinine (mmob’24h)
Magnesium (mmol/24h)
Calcium (mmoV24h)
766(95) 264(-l 9)
739(132) 225(32! < o,oo I
3.8(1.1) 2.8(0.6) ns
4.6(1.2) 3.7( I .O) ns
??
3.7(0.9) 3,1(0.6) ns
4.4(0,9) 3.4(0.5) ns
17.7t3.6) 13.2f2.5) ns
0.69(0.2 I) 1.27(0.4) ns
0.74(0.16) I .25(0.4) ns
21.7(2.6) 1 O.S(I .4)
55(151 74(21) ns
lOl(14) 57(8) < 0.02
3
77(14) 60(26) ns
12 I(22) 44(6)
2
Figures in brackets represent standard error of the mean. P, Probability; ns, not significant. 1, Severe; 2, mild.
IlS
4.0(1.2) 2.0( 1.6)
4.0( I ,O) 25(09) ns
415(51) 236(42) < 0.02
1 .I 9(0.3) 2.43(0.53) ns
94(223 103(29) ns
I 13(9) 43(8)
I
I 2
??
Urea (mmo1/24h)
ratio
:
:
Sodium (mmoV24h)
Sodium:
1 2
Potassium (mmof/24h)
A nalyte
Patient 91CXJp
Tab/e /I. Results of all analytes measured
45(11) 138(21)
64(I3) 6503) ns
5
2*4(0.5) 3.5(0.9) ns
4.3( I .O) 3.5(0.9) ns
15.5(2.8) 13.2(2.3) ns
656(81) 317(54)
3.0(0,8) 5.6(1.6) ns
4,711 .O) 5.2(0.7) ns
13.2(1.4) 15.6(2,1) ns
622(88) 352(45) < 0.02
0.48iO.I I ) 0.72(0.17) 1.84tO.48) 2.33(0.39) <0.05 < 0.02
37f7f 96(25) <0.05
87(18) 58t9) ns
4
3.3(0.9) 3.4(1.1) ns
5.1 to.51 4.3(0.9) ns
15.6(1.6) 13.9(2.7) ns
690(1 IO) 294(35)
1.22(0.37) 2.07(0.38) ns
49(13) 93(17) ns
65(13) 44(61 ns
6
Time post burn (d)
2.6(0,8) 3.9( 1 .O) ns
3,1(1.0) 3.0(0.7) ns
3,9( 1’2) 2.8(0.3) ns
13.7(2.5) 12.3(2,31 ns
12.9(0.9) 12.2(2.2) ns 4.OtO.6) 3*6(0.7) ns
650(102) 227(36)
657(85) 289(47)
0,53(0.12) 1.9 (0.29)
2.2(0.7 3.4(0.9) ns
4~0(0~7) 3.6(0.7) ns
13.7(1‘3) 10,9(1.71 ns
725(1 16) 261(27)
0.63(0.1 1) 2.35(0.54) < 0.02
41(7) 112(19)
47fl I) 117(18)
4016) 89(15)
0.99(0.31) I ,96(0.2 1) < 0.02
69(8) 67W ns
64t9) 55(10) ns
50(8) ns
51t6)
9
8
7
3.4(0.8) 4.2(1.1) ns
4.3(08) 3*6(0*6) ns
14.5(1.5) 10*3(1,6) ns
646(153) 307(35) eo.05
0.49(O.I 4) 2.67(0.45)
39(12) 131(191
83(1 1) 65(8) ns
10
336
BurnsVol. ~/NO. 5
patients with mild burns, mean peak excretion was demonstrated on day 1 post burn with normal excretion by the end of the study. Signiflcant differences in cortisol excretion were demonstrated in the two groups of patients on days 2 (P
and potassium
The maximal excretion of potassium occurred on day 2 post burn in patients with severe burns. In contrast the excretion of potassium was reasonably constant in patients with mild burns. In both groups of patients urine sodium fell. In the patients with severe burns the fall was drastic and low levels were still recorded at the end of the study period. In patients with mild burns the initial decrease in urine sodium was followed by an upward trend towards normality. The urine Na+: K+ ratio fell within the normal reference range in patients with mild burns but was extremely low in patients with severe burns. All the analytes measured are listed in Table II. Urine calcium
and magnesium
Only small differences were observed between the excretion of calcium and magnesium in the two groups of patients with burns. Urine urea
Urine urea was greatly increased in patients with severe burns when compared to patients with mild burns and to healthy controls. Significant differences were observed between the mean
urea levels of patients with severe and mild burns on all days post burn. Urine creatinine
In the group of patients with severe burns mean peak excretion of creatinine was observed on day 2 post burn, whilst the level of urine creatinine remained reasonably constant in patients with mild burns. Correlations
Correlations (Table III) were sought between cortisol excretion and the different analytes over the first 5 days post burn. Data from all patients, regardless of grouping, were included. Signiflcant positive correlations were demonstrated between urine cortisol and (a) potassium, (b) creatinine and (c) magnesium, whilst a negative correlation was observed between cortisol and the sodium : potassium ratio. DISCUSSION
The measurement of urine cortisol described in this study has clearly established the extent and duration of hypercortisoluria after burn injury. Urine cortisol levels at least ten times the upper limit of the normal reference range have been demonstrated in patients with severe burns with greatly elevated levels still apparent 10 days after the injury. The pattern of urine cortisol excretion paralleled the secretion of cortisol in plasma described in previous work (Batstone et al., 1976). This suggests that increased synthesis/secretion of cortisol, not decreased clearance, is the primary factor responsible for the increased plasma concentration of this hormone after burn injury. Furthermore, urinary cortisol may be a good indicator of the
Table l/1. Correlations between cortisol and selected in urine over the first 5 days post burn r*
1st Variable
2nd Variable
Cortisol
Potassium Magnesium Creatinine Sodium:potassium
0.79 0.62 0.46 -0.46
Sodium Urea Calcium
0.43 0.36 -0.29
?? f, Correlation coefficient t P, Probability of significant difference; ns, not significant.
analytes
Pt
337
Coombes et al.: Urine Cortisol Levels
rate of cortisol synthesis since it is claimed to be a good index (Zilva and Pannall, 1975) of the unbound biologically-active fraction in plasma. Cortisol stimulates proteolysis and increases amino acid release (Ryan et al., 1974) from peripheral tissues, especially muscle. In our study urine cortisol correlated with the excretion of magnesium. found in high concentrations in muscle, (Vernon and Wacher, 1978) and creatinine. an important end product of muscle metabolism as it is derived from muscle creatine phosphate. The fall in sodium excretion paralleled by the increased excretion of potassium after burn injury is well documented (Hinton et al., 1973). The causes of sodium retention are probably multifactional but aldosterone secretion is increased after surgery (Zimmerman et al.. 1955) and may be a contributing factor. An increased secretion of aldosterone would promote potassium excretion and increase the sodium : potassium ratio in urine. Of importance to potassium excretion after injury is the release of this ion from cells as protein is catabolized, particularly in muscle, a process promoted by cortisol. This may account for the strong positive correlation between cortisol and potassium described in this paper. These findings further support the important role of cortisol in the catabolic response to burn injury. Acknowledgements
We would like to thank Mr J. Elsworth Laing for permission to study patients and the nursing staff who collected the urine samples. We are indebted to the Radiochemical Centre, Amersham who kindly provided the kits for the assay ofcortisol.
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E. J. Coombes, Department of Chemical Pathology, Salisbury General Infirmary.