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Potassium supplements in patients treated with corticosteroids
Brit. J. Dis. Chest (1975) 69, 171
POTASSIUM TREATED GILLIAN Asthma
SUPPLEMENTS IN PATIENTS WITH CORTICOSTEROIDS
M. SHENFIELD, Research Council Cardiothoracic
G. K. KNOWLES,
N. THOMAS
AND J. W. PATERSON
Clinical Pharmacology Unit, Department of Medicine, Institute, and Brompton Hospital, London
hypokalaemic alkalosis often seen in Cushing’s syndrome is due to hypersecretion of cortisol (Christy & Laragh 1961). Hypokalaemia and sodium retention were considerable problems in the early days of corticosteroid therapy when cortisone and cortisol (hydrocortisone) were the only substances available (Sprague et al. I 950). These authors showed that patients treated with 200 mg of cortisone daily (equivalent to 40 mg of prednisone) went into negative nitrogen and potassium balance, whereas patients on IOO mg of cortisone did not. It was routine to give corticosteroid-treated patients a low sodium diet with potassium supplements to minimize the electrolyte imbalance (Kinsell et al. 1952; Liddle et al. 1953; Liddle 1959). When prednisone and prednisolone were first introduced it was quickly recognized that, although they were more potent than cortisol as anti-inflammatory agents, they had less effect on fluid and electrolyte balance (Barach et al. 1955; Bunim et al. rg55a, b; Demartini et al. 1955; Pechet 1955; Pechet & Bartter 1955). The difference between the two groups of compounds was so considerable that the use of special diets and supplements was discontinued and the problem of potassium loss largely forgotten. Lindholm (1967) found no loss of total exchangeable potassium in asthmatic patients treated with cortisone or prednisone but they were on doses of only 25-75 mg of cortisone (5-15 mg of prednisone). Nevertheless with prednisone in doses of 30-40 mg daily there is an initial urinary loss of potassium of the order of 30 mEq/day followed by a smaller sustained loss (Nabarro et al. 1955; Thorn et al. 1955; Liddle 1959; Harter et al. 1963). A recent survey of deaths from asthma showed that several of the patients had low serum potassium levels (Cochrane 1973). As a result patients on high doses of corticosteroids have been routinely given potassium supplements. It is, however, not known whether such patients are potassium deficient or whether they retain their supplements. There is good evidence that normal subjects do not retain potassium supplements (Tarail & Elkington 1g4g), but that if they are made artificially potassium deficient their kidneys will conserve potassium (Fourman 1952 ; Lowe 1953). There is conflicting evidence about the retention of potassium supplements in the presence of potassium deficiency in various disease states. Potassium supplements are to some extent retained in cardiac failure (White 1970) and in patients with hypertension (Edmonds & Jasani
THE
(Received
for publication
December
1974)
SHENFIELD
172
ET
AL.
1972). Other studies have shown no evidence of retention of potassium supplements in hypertension (Anderson et al. 197 I), ascites (Read et al. 1958) and in diuretic therapy for chronic heart failure (Down et al. 1972). It would therefore seem that, in the absence of renal disease, if there is retention of potassium supplements then there is definite potassium deficiency whereas failure to retain potassium supplements may mean either that body potassium is normal or that homeostasis has failed and a chronic disease is present. With this in mind we have attempted to see whether potassium supplements are required in patients taking high doses of corticosteroids for various lung diseases. Patients
and Methods
Eight patients were studied and Table I gives details of their age, diagnosis and dose of prednisone. Those patients who had been taking prednisone for several TABLE
Patient
A.H.
I.
CLINICAL
z* AS.. H.G. G.W. R.G. M.L.
56, 65, 48, 69,
F F M F
ON INDIVIDUAL Length of time on corticosteroids
Age and sex
64, M 4% M 29, 19, M
DATA
Fibrosing alveolitis Late onset asthma Aspergillosis Eosinophilic granuloma Extrinsic asthma Intrinsic asthma Asthma, bronchitis Intrinsic asthma
3 weeks years week 4 months 3 years 5 years 33 years 13 years 2 I
PATIENTS PreviotLs estimated average daib dose of prednisone b-4
Daily dose of prednisone during study bd
60 20
;:
30 25 7’5 7’5
30
20
5
f: 40 30 30
years used high doses for exacerbations and the figure given is an estimated average daily dose for the period. During the study the dose of prednisone was left unchanged at the level shown in the last column. All patients were free from renal diseases as judged by a normal blood urea and urine analysis and were not on any other treatment likely to alter electrolyte balance. The first 5 patients were studied for 4 days and the other 3 for 8 days (only 7 days’ results are available for G.W.). On alternate days of the 4-day studies patients were given 2 tablets 3 times a day of Slow K containing 600 mg of potassium chloride each (8 mEq potassium) making a total of 48 mEq of potassium a day. On the other days they had no potassium supplements. For the 8-day studies, 2 patients had 2 periods of 2 days on and off supplements and the third had 4 days off and 4 days on supplements. Blood was taken on the morning of each day and plasma potassium measured. Full n4-hour urine collections were made and potassium excretion measured. The measurements were made in triplicate with an EEL flame (emission) photometer. The patients were all on a standard hospital diet (estimated to contain 50-100 mEq of potassium daily), and it was not possible to put them on a fixed potassium intake.
POTASSIUM
SUPPLEMENTS
AND
CORTICOSTEROIDS
‘73
Results Fig. I shows the results for all 8 patients. In no patient was there a consistent change in plasma potassium and in all patients more potassium was excreted on the days when supplement was given. Table 2 gives the mean a4-hour urinary excretion of potassium with and without potassium supplements. It can be seen that there is a wide range in the mean difference between these results (g-2 to 38. I mEq) . The mean retained potassium refers to the part of the 48 mEq supplement retained and the calculation assumes that the dietary intake remains Number 12
of Days
34
M
Plasma
30mg
Gs)
Urinary
1 20mg
q
.::: :::::: ., ;::. ,.;_._ _~_~.~...~.~_~_ ,.,._._ ..: ::. .::_ _._.:, .;;;. ::::._ ..__.......,.... : ::._. ..~_~_~.~.~,~.~,~. ;;~~~~~;~;~;~A~~~
bh)
Plasma
n
Prednisone Slow K 48mEq/day
q
Urinary excretion
d&)
Urinary b&)
Number FE.
I.
Plasma
TABLE
and
&Y: ci% G%. R.G. M.L.
potassium
with and without patient data
potassium
supplements:
individual
~.POTASSIUMEXCRETIONWITHANDWITHOUTSUPPLEMENTS: INDIVIDUALDATA
Patient
A.H.
urinary
of Days
Mean q-hour urinary potassium with supplements bW 74 :: 57 103 z”s 68
Mean q-hour urinary potassium leithoutt~$ements
96 I37 89 80
Mean $@i:f
26 ;i
IO
9 23
39 25 28
;: 38 33
I2 IO
122
126 124 101
Mean retained potassium Wq)
‘5
SHENFIELD
‘74
ET
AL.
constant. The presumed retained potassium ranges from 9.9 to 38.8 mEq/ 24 hours. There is a relationship between the quantity of potassium excreted without supplements and the dose of prednisone, the larger doses are related to greater potassium excretion (r = 0.77; P= 0.01). There is also a relationship between the dose retained and the duration of previous therapy: the longer the previous treatment the smaller the dose retained (r = 0.64; P = 0.05). Discussion
Normal subjects do not retain potassium supplements (Tarail & Elkington 1949) but if they are made artificially potassium-deficient they will conserve potassium (Fourman 1952; Lowe 1953). Slow K is completely absorbed from the gastrointestinal tract (Wynn 1965). It is unlikely that our patients varied their diet consistently in phase with the supplements. We did not measure total exchangeable potassium or whole body potassium but the fact that some patients retained over half of their supplements suggests that they were potassium deficient. Those patients retaining less of their supplements were, by analogy, either not potassium depleted or else had altered their adaptive mechanisms (Down et al. 1972). Loss of potassium in patients taking prednisone is well documented and seems to be due to at least four processes (Liddle 1959). When first starting the drugs there is an immediate loss of potassium due to a release of potassium from cells (Bartter & Fourman 1957). This accounts for the initial large kaliuresis which, for a dose of 30-40 mg of prednisone seems to be of the order of 25-30 mEq/24 hours (Nabarro et al. 1955 ; Thorn et al. 1955; Harter et al. 1963). Further sustained losses are of the order of 10-15 mEq a day and are due to increased glomerular filtration rate, and an effect on renal tubular exchange of cations (Liddle 1959). In addition the corticosteroids are catabolic, and for every gram of nitrogen-containing tissue broken down 2.7 mEq of potassium are lost (Black 1960). In patients with chest diseases there is the added problem that any disturbance of acid-base balance interferes with potassium homeostasis. Stanbury and Thomson (1952) have shown that in respiratory alkalosis due to hyperventilation plasma potassium falls and urinary potassium excretion rises. Acidosis has the reverse effect. In our laboratory the upper limit of normal for urinary potassium excretion is of 70 mEq/24 hours with a normal ward diet. All but 2 of our 8 patients taking prednisone exceeded that level of excretion whilst off supplements which suggests that they were in negative potassium balance. The positive correlation between the dose of prednisone and potassium excretion suggests that higher doses of prednisone cause greater losses of potassium. Those patients who had been taking prednisone for only a short period retained more than half of their supplement which suggests that they were potassium deficiency despite normal plasma potassium levels. Plasma potassium does not correlate well with intracellular or total body potassium (Black 1960). Those patients who had been taking corticosteroids for several years did not retain so much of the supplement, which suggests either that they were not potassium deficient or that they were
POTASSIUM
SUPPLEMENTS
AND
‘75
CORTICOSTEROIDS
unable to retain the potassium supplements as is the case in diuretic treated cardiac failure (Down et al. ~gp), ascites (Read et al. 1958) and hypertension (Anderson et al. 1971) : the latter seems much the most likely explanation. It would be important to know the extent of their deficiency and at what stage in their treatment they lose the capacity to retain supplements. We have found a definite correlation between this ability to retain potassium supplements and duration of corticosteroid administrations. It is possible that if patients taking corticosteroids for long periods were given potassium supplements from the start of treatment with corticosteroids then the development of long-term potassium depletion might be avoided. Summary I. Preliminary studies are reported on 8 patients with lung disease given prednisone both with and without potassium supplements. 2. There were no abnormalities of plasma potassium but there was a relationship between the dose of prednisone and the urinary excretion of potassium whilst off supplements: higher doses were associated with increased potassium excretion. 3. Patients who had been on treatment for a short period retained more of their supplements than did those who had been on treatment for several years. 4. It is suggested that with prolonged treatment control of potassium homeostasis may be altered, and that more detailed metabolic studies should be carried out.
ACKNOWLEDGEMENTS
We thank the Physicians at the Brompton care. G.M.S. was supported by a grant Reprint requests to J.W.P.
from
Hospital for allowing us to study the Medical Research Council.
patients
under
their
REFERENCES
ANDERSON, J., GODFREY, B. E., HILL, D. M., MUNRO-FAURE, A. D. & SHELDON, J. (1971) A comparison of the effects of hydrochlorothiazide and of frusemide in the treatment of hypertensive patients. Q.31 Med., 40, 541. BARACH, A. L., BICKERMAN, H. A. & BECK, G. J. (1955) Clinical and physiological studies on the use of metacortandracin in respiratory disease. I Bronchial asthma. Dis. Chest, 27, 5 I 5. BARTTER, F. C. & FOURMAN, P. (1957) A non-renal effect of adrenal cortical steroids upon potassium metabolism. clin. Invest., 36, 872. BLACK, D. A. K. (1960) Essentials Fluid Balance, 2nd ed. Oxford: Blackwell Scientific. BUNIM, J. J., BLACK, R. L., BOLLET, A. J. & PECHET, M. M. (I g55a) Metabolic effects of metacortandralone and metacortandracin Ann. Jv.T. Acad. Sci., 61, 358. BUNIM, J. J., PECHET, M. M. & BOLLET, A. J. (195513) Studies on metacortandralone and metacortandracin in rheumatoid arthritis; anti-asthmatic potency, metabolic effects, and hormonal properties. Am. med. Ass., 157, 31 I. CHRISTY, N. P. & LARAGH, J. H. (rg6r) Pathogenesis of hypokalaemic alkalosis in Cushing’s syndrome. NeNew Engl. Med., 265, 1083. COCHRANE, G. McL. (1973) Personal communication.
3.
3.
3.
of
176
SHENFIELD
ET
AL.
DEMARTINI, F., BOOTS, R. H., SNYDER, A. I., SANDSON, J. & RAGAN, C. (1955) Comparative effects of prednisone and cortisone. J. Am. med. Ass., 158, 1505. DOWN, P. F., POLAK, A., RAO, R. & MEAD, J. A. (1971) Diuretics and potassium supplements. Lancet, 2, 72 I. EDMONDS, C. J. & JASANI, B. (1972) Total-body potassium in hypertensive patients during prolonged diuretic therapy. Lancet, 2, 8. FOURMAN, P. (1952) The ability of the normal kidney to conserve potassium. Lancet, I, 1042. HARTER, J. G., REDDY, W. J. & THORN, G. W. (1968) Studies on an intermittent corticosteroid dosage regimen. New Engl. J. Med., 269, 591. KINSELL, L. W., PARTRIDGE, J. W., BOLING, L. & MARGEN, S. (1952) Dietary modification of the metabolic and clinical effects of ACTH and cortisone. Ann. intern. Med., 37, 92 I. LIDDLE, G. W. (1959) Effects of anti-inflammatory steroids on electrolyte metabolism. Ann. N. Y. Acad. Sci., 82,854. LIDDLE, G. W., BENNETT, L. L. & FORSHAM, P. H. (1958) The prevention of ACTH-induced sodium retention by the use of potassium salts: a quantitative study. 3. clin. Invest., 32, ‘197. LINDHOLM, B. (1967) Body cell mass during long-term cortisone treatment in asthmatic subjects. Acta endocr., 55, 202. Lowe, K. G. (1958) Metabolic studies with protein-free, electrolyte-free diet in man. Clin. Sci., 12957. NABARRO, J. D. N., STEWART, J. S. & WALKER, G. (1955) Clinical and metabolic effects of prednisone. Lancet, 2,993. PECHET, M. M. (I 955) The metabolic effects of metacortandracin and metacortandralone in man: a new series of A194diene steroids. J. clin. Invest., 34, 913. PECHET, M. M. & BARTTER, F. C. (1955) Studies with a new series of steroids: metacortandracin and metacortandralone. J. clin. Endocr., 15, 85 I. READ, A. E., HASLAM, R. M., LAIDLAW, J. & SHERLOCK, S. (1958) Chlorothiazide in control of ascites in hepatic cirrhosis. Br. med. J., I, 963. SPRAGUE, R. G., POWER, M. H., MASON, H. L., ALBERT, A., MATHIESON, D. R., HENCH, P. S., KENDALL, E. C., SLOCUMB, C. H. & POLLEY, H. F. (1950) Observations on physiologic effects of cortisone and ACTH in man. Arch intern. Med., 85, 199. STANBURY, S. W. & THOMSON, A. E. (1952) The renal response to respiratory alkalosis. Clin. Sci., II, 357. TARAIL, R. & ELKINGTON, J. R. (1949) Potassium deficiency and role of kidney in its production. J. clin. Invest., 28, gg. THORN, G. W., RENOLD, A. F., MORSE, W. I., GOLDFIEN, A. & REDDY, W. J. (1955) Highly potent adrenal cortical steroids: structure and biologic activity. Ann. intern. Med., 43,979. WHITE, R. J. (1970) Effect of potassium supplements on the exchangeable potassium in chronic heart disease. Br. med. J., 3, I 4 I, WYNN, V. (I 965) Potassium chloride and intestinal ulceration. Lancet, 2, I 241.
POTASSIUM TREATED GILLIAN Asthma
SUPPLEMENTS IN PATIENTS WITH CORTICOSTEROIDS
M. SHENFIELD, Research Council Cardiothoracic
G. K. KNOWLES,
N. THOMAS
AND J. W. PATERSON
Clinical Pharmacology Unit, Department of Medicine, Institute, and Brompton Hospital, London
hypokalaemic alkalosis often seen in Cushing’s syndrome is due to hypersecretion of cortisol (Christy & Laragh 1961). Hypokalaemia and sodium retention were considerable problems in the early days of corticosteroid therapy when cortisone and cortisol (hydrocortisone) were the only substances available (Sprague et al. I 950). These authors showed that patients treated with 200 mg of cortisone daily (equivalent to 40 mg of prednisone) went into negative nitrogen and potassium balance, whereas patients on IOO mg of cortisone did not. It was routine to give corticosteroid-treated patients a low sodium diet with potassium supplements to minimize the electrolyte imbalance (Kinsell et al. 1952; Liddle et al. 1953; Liddle 1959). When prednisone and prednisolone were first introduced it was quickly recognized that, although they were more potent than cortisol as anti-inflammatory agents, they had less effect on fluid and electrolyte balance (Barach et al. 1955; Bunim et al. rg55a, b; Demartini et al. 1955; Pechet 1955; Pechet & Bartter 1955). The difference between the two groups of compounds was so considerable that the use of special diets and supplements was discontinued and the problem of potassium loss largely forgotten. Lindholm (1967) found no loss of total exchangeable potassium in asthmatic patients treated with cortisone or prednisone but they were on doses of only 25-75 mg of cortisone (5-15 mg of prednisone). Nevertheless with prednisone in doses of 30-40 mg daily there is an initial urinary loss of potassium of the order of 30 mEq/day followed by a smaller sustained loss (Nabarro et al. 1955; Thorn et al. 1955; Liddle 1959; Harter et al. 1963). A recent survey of deaths from asthma showed that several of the patients had low serum potassium levels (Cochrane 1973). As a result patients on high doses of corticosteroids have been routinely given potassium supplements. It is, however, not known whether such patients are potassium deficient or whether they retain their supplements. There is good evidence that normal subjects do not retain potassium supplements (Tarail & Elkington 1g4g), but that if they are made artificially potassium deficient their kidneys will conserve potassium (Fourman 1952 ; Lowe 1953). There is conflicting evidence about the retention of potassium supplements in the presence of potassium deficiency in various disease states. Potassium supplements are to some extent retained in cardiac failure (White 1970) and in patients with hypertension (Edmonds & Jasani
THE
(Received
for publication
December
1974)
SHENFIELD
172
ET
AL.
1972). Other studies have shown no evidence of retention of potassium supplements in hypertension (Anderson et al. 197 I), ascites (Read et al. 1958) and in diuretic therapy for chronic heart failure (Down et al. 1972). It would therefore seem that, in the absence of renal disease, if there is retention of potassium supplements then there is definite potassium deficiency whereas failure to retain potassium supplements may mean either that body potassium is normal or that homeostasis has failed and a chronic disease is present. With this in mind we have attempted to see whether potassium supplements are required in patients taking high doses of corticosteroids for various lung diseases. Patients
and Methods
Eight patients were studied and Table I gives details of their age, diagnosis and dose of prednisone. Those patients who had been taking prednisone for several TABLE
Patient
A.H.
I.
CLINICAL
z* AS.. H.G. G.W. R.G. M.L.
56, 65, 48, 69,
F F M F
ON INDIVIDUAL Length of time on corticosteroids
Age and sex
64, M 4% M 29, 19, M
DATA
Fibrosing alveolitis Late onset asthma Aspergillosis Eosinophilic granuloma Extrinsic asthma Intrinsic asthma Asthma, bronchitis Intrinsic asthma
3 weeks years week 4 months 3 years 5 years 33 years 13 years 2 I
PATIENTS PreviotLs estimated average daib dose of prednisone b-4
Daily dose of prednisone during study bd
60 20
;:
30 25 7’5 7’5
30
20
5
f: 40 30 30
years used high doses for exacerbations and the figure given is an estimated average daily dose for the period. During the study the dose of prednisone was left unchanged at the level shown in the last column. All patients were free from renal diseases as judged by a normal blood urea and urine analysis and were not on any other treatment likely to alter electrolyte balance. The first 5 patients were studied for 4 days and the other 3 for 8 days (only 7 days’ results are available for G.W.). On alternate days of the 4-day studies patients were given 2 tablets 3 times a day of Slow K containing 600 mg of potassium chloride each (8 mEq potassium) making a total of 48 mEq of potassium a day. On the other days they had no potassium supplements. For the 8-day studies, 2 patients had 2 periods of 2 days on and off supplements and the third had 4 days off and 4 days on supplements. Blood was taken on the morning of each day and plasma potassium measured. Full n4-hour urine collections were made and potassium excretion measured. The measurements were made in triplicate with an EEL flame (emission) photometer. The patients were all on a standard hospital diet (estimated to contain 50-100 mEq of potassium daily), and it was not possible to put them on a fixed potassium intake.
POTASSIUM
SUPPLEMENTS
AND
CORTICOSTEROIDS
‘73
Results Fig. I shows the results for all 8 patients. In no patient was there a consistent change in plasma potassium and in all patients more potassium was excreted on the days when supplement was given. Table 2 gives the mean a4-hour urinary excretion of potassium with and without potassium supplements. It can be seen that there is a wide range in the mean difference between these results (g-2 to 38. I mEq) . The mean retained potassium refers to the part of the 48 mEq supplement retained and the calculation assumes that the dietary intake remains Number 12
of Days
34
M
Plasma
30mg
Gs)
Urinary
1 20mg
q
.::: :::::: ., ;::. ,.;_._ _~_~.~...~.~_~_ ,.,._._ ..: ::. .::_ _._.:, .;;;. ::::._ ..__.......,.... : ::._. ..~_~_~.~.~,~.~,~. ;;~~~~~;~;~;~A~~~
bh)
Plasma
n
Prednisone Slow K 48mEq/day
q
Urinary excretion
d&)
Urinary b&)
Number FE.
I.
Plasma
TABLE
and
&Y: ci% G%. R.G. M.L.
potassium
with and without patient data
potassium
supplements:
individual
~.POTASSIUMEXCRETIONWITHANDWITHOUTSUPPLEMENTS: INDIVIDUALDATA
Patient
A.H.
urinary
of Days
Mean q-hour urinary potassium with supplements bW 74 :: 57 103 z”s 68
Mean q-hour urinary potassium leithoutt~$ements
96 I37 89 80
Mean $@i:f
26 ;i
IO
9 23
39 25 28
;: 38 33
I2 IO
122
126 124 101
Mean retained potassium Wq)
‘5
SHENFIELD
‘74
ET
AL.
constant. The presumed retained potassium ranges from 9.9 to 38.8 mEq/ 24 hours. There is a relationship between the quantity of potassium excreted without supplements and the dose of prednisone, the larger doses are related to greater potassium excretion (r = 0.77; P= 0.01). There is also a relationship between the dose retained and the duration of previous therapy: the longer the previous treatment the smaller the dose retained (r = 0.64; P = 0.05). Discussion
Normal subjects do not retain potassium supplements (Tarail & Elkington 1949) but if they are made artificially potassium-deficient they will conserve potassium (Fourman 1952; Lowe 1953). Slow K is completely absorbed from the gastrointestinal tract (Wynn 1965). It is unlikely that our patients varied their diet consistently in phase with the supplements. We did not measure total exchangeable potassium or whole body potassium but the fact that some patients retained over half of their supplements suggests that they were potassium deficient. Those patients retaining less of their supplements were, by analogy, either not potassium depleted or else had altered their adaptive mechanisms (Down et al. 1972). Loss of potassium in patients taking prednisone is well documented and seems to be due to at least four processes (Liddle 1959). When first starting the drugs there is an immediate loss of potassium due to a release of potassium from cells (Bartter & Fourman 1957). This accounts for the initial large kaliuresis which, for a dose of 30-40 mg of prednisone seems to be of the order of 25-30 mEq/24 hours (Nabarro et al. 1955 ; Thorn et al. 1955; Harter et al. 1963). Further sustained losses are of the order of 10-15 mEq a day and are due to increased glomerular filtration rate, and an effect on renal tubular exchange of cations (Liddle 1959). In addition the corticosteroids are catabolic, and for every gram of nitrogen-containing tissue broken down 2.7 mEq of potassium are lost (Black 1960). In patients with chest diseases there is the added problem that any disturbance of acid-base balance interferes with potassium homeostasis. Stanbury and Thomson (1952) have shown that in respiratory alkalosis due to hyperventilation plasma potassium falls and urinary potassium excretion rises. Acidosis has the reverse effect. In our laboratory the upper limit of normal for urinary potassium excretion is of 70 mEq/24 hours with a normal ward diet. All but 2 of our 8 patients taking prednisone exceeded that level of excretion whilst off supplements which suggests that they were in negative potassium balance. The positive correlation between the dose of prednisone and potassium excretion suggests that higher doses of prednisone cause greater losses of potassium. Those patients who had been taking prednisone for only a short period retained more than half of their supplement which suggests that they were potassium deficiency despite normal plasma potassium levels. Plasma potassium does not correlate well with intracellular or total body potassium (Black 1960). Those patients who had been taking corticosteroids for several years did not retain so much of the supplement, which suggests either that they were not potassium deficient or that they were
POTASSIUM
SUPPLEMENTS
AND
‘75
CORTICOSTEROIDS
unable to retain the potassium supplements as is the case in diuretic treated cardiac failure (Down et al. ~gp), ascites (Read et al. 1958) and hypertension (Anderson et al. 1971) : the latter seems much the most likely explanation. It would be important to know the extent of their deficiency and at what stage in their treatment they lose the capacity to retain supplements. We have found a definite correlation between this ability to retain potassium supplements and duration of corticosteroid administrations. It is possible that if patients taking corticosteroids for long periods were given potassium supplements from the start of treatment with corticosteroids then the development of long-term potassium depletion might be avoided. Summary I. Preliminary studies are reported on 8 patients with lung disease given prednisone both with and without potassium supplements. 2. There were no abnormalities of plasma potassium but there was a relationship between the dose of prednisone and the urinary excretion of potassium whilst off supplements: higher doses were associated with increased potassium excretion. 3. Patients who had been on treatment for a short period retained more of their supplements than did those who had been on treatment for several years. 4. It is suggested that with prolonged treatment control of potassium homeostasis may be altered, and that more detailed metabolic studies should be carried out.
ACKNOWLEDGEMENTS
We thank the Physicians at the Brompton care. G.M.S. was supported by a grant Reprint requests to J.W.P.
from
Hospital for allowing us to study the Medical Research Council.
patients
under
their
REFERENCES
ANDERSON, J., GODFREY, B. E., HILL, D. M., MUNRO-FAURE, A. D. & SHELDON, J. (1971) A comparison of the effects of hydrochlorothiazide and of frusemide in the treatment of hypertensive patients. Q.31 Med., 40, 541. BARACH, A. L., BICKERMAN, H. A. & BECK, G. J. (1955) Clinical and physiological studies on the use of metacortandracin in respiratory disease. I Bronchial asthma. Dis. Chest, 27, 5 I 5. BARTTER, F. C. & FOURMAN, P. (1957) A non-renal effect of adrenal cortical steroids upon potassium metabolism. clin. Invest., 36, 872. BLACK, D. A. K. (1960) Essentials Fluid Balance, 2nd ed. Oxford: Blackwell Scientific. BUNIM, J. J., BLACK, R. L., BOLLET, A. J. & PECHET, M. M. (I g55a) Metabolic effects of metacortandralone and metacortandracin Ann. Jv.T. Acad. Sci., 61, 358. BUNIM, J. J., PECHET, M. M. & BOLLET, A. J. (195513) Studies on metacortandralone and metacortandracin in rheumatoid arthritis; anti-asthmatic potency, metabolic effects, and hormonal properties. Am. med. Ass., 157, 31 I. CHRISTY, N. P. & LARAGH, J. H. (rg6r) Pathogenesis of hypokalaemic alkalosis in Cushing’s syndrome. NeNew Engl. Med., 265, 1083. COCHRANE, G. McL. (1973) Personal communication.
3.
3.
3.
of
176
SHENFIELD
ET
AL.
DEMARTINI, F., BOOTS, R. H., SNYDER, A. I., SANDSON, J. & RAGAN, C. (1955) Comparative effects of prednisone and cortisone. J. Am. med. Ass., 158, 1505. DOWN, P. F., POLAK, A., RAO, R. & MEAD, J. A. (1971) Diuretics and potassium supplements. Lancet, 2, 72 I. EDMONDS, C. J. & JASANI, B. (1972) Total-body potassium in hypertensive patients during prolonged diuretic therapy. Lancet, 2, 8. FOURMAN, P. (1952) The ability of the normal kidney to conserve potassium. Lancet, I, 1042. HARTER, J. G., REDDY, W. J. & THORN, G. W. (1968) Studies on an intermittent corticosteroid dosage regimen. New Engl. J. Med., 269, 591. KINSELL, L. W., PARTRIDGE, J. W., BOLING, L. & MARGEN, S. (1952) Dietary modification of the metabolic and clinical effects of ACTH and cortisone. Ann. intern. Med., 37, 92 I. LIDDLE, G. W. (1959) Effects of anti-inflammatory steroids on electrolyte metabolism. Ann. N. Y. Acad. Sci., 82,854. LIDDLE, G. W., BENNETT, L. L. & FORSHAM, P. H. (1958) The prevention of ACTH-induced sodium retention by the use of potassium salts: a quantitative study. 3. clin. Invest., 32, ‘197. LINDHOLM, B. (1967) Body cell mass during long-term cortisone treatment in asthmatic subjects. Acta endocr., 55, 202. Lowe, K. G. (1958) Metabolic studies with protein-free, electrolyte-free diet in man. Clin. Sci., 12957. NABARRO, J. D. N., STEWART, J. S. & WALKER, G. (1955) Clinical and metabolic effects of prednisone. Lancet, 2,993. PECHET, M. M. (I 955) The metabolic effects of metacortandracin and metacortandralone in man: a new series of A194diene steroids. J. clin. Invest., 34, 913. PECHET, M. M. & BARTTER, F. C. (1955) Studies with a new series of steroids: metacortandracin and metacortandralone. J. clin. Endocr., 15, 85 I. READ, A. E., HASLAM, R. M., LAIDLAW, J. & SHERLOCK, S. (1958) Chlorothiazide in control of ascites in hepatic cirrhosis. Br. med. J., I, 963. SPRAGUE, R. G., POWER, M. H., MASON, H. L., ALBERT, A., MATHIESON, D. R., HENCH, P. S., KENDALL, E. C., SLOCUMB, C. H. & POLLEY, H. F. (1950) Observations on physiologic effects of cortisone and ACTH in man. Arch intern. Med., 85, 199. STANBURY, S. W. & THOMSON, A. E. (1952) The renal response to respiratory alkalosis. Clin. Sci., II, 357. TARAIL, R. & ELKINGTON, J. R. (1949) Potassium deficiency and role of kidney in its production. J. clin. Invest., 28, gg. THORN, G. W., RENOLD, A. F., MORSE, W. I., GOLDFIEN, A. & REDDY, W. J. (1955) Highly potent adrenal cortical steroids: structure and biologic activity. Ann. intern. Med., 43,979. WHITE, R. J. (1970) Effect of potassium supplements on the exchangeable potassium in chronic heart disease. Br. med. J., 3, I 4 I, WYNN, V. (I 965) Potassium chloride and intestinal ulceration. Lancet, 2, I 241.