Effect of Precdnisolone on Urate and Oxypurine Excretion I. Hisatome1 , R. Ishiko1 , N. Sasaki , H. Kotake1 , M. Kobayashi1, K. Ogino1 , J. Hasegawa1 , A. Yoshida1 , C.Shigemasa1, H. Mashiba1 and S. Endo2 1FirstDepartment of Internal Medicine, Tottori University School of Medicine, Yonago, Japan Department of Internal Medicine, San-in Rosai Hospital, Yonago, Japan
(Cur), urate-creatinine clearance ratio (Cur/Ccr), urinary urate excretion (Uur), urinary hypoxanthine excretion (UHX), and urinary xanthine excretion (Ux) were calculated during a 24-h period. Urinary Hypouricemia in the psychological stress group {Francis 1981) and hyperuricemia after adrenalectomy (Itskovits and oxypurine (UOXY) excretion were expressed as the sum of urinary hypoxanthine and xanthine excretion. Data were expressed as Sellers 1963) had been reported, indicating the relationship between serum urate level and steroid hormone. Recently, Frocht, Leek and mean ± S. D. and Mann-Whitney test or paired t-test were used to determine the statistical significance. Difference between means were Robbins (1987) reported that the prevalence of gout with systemic considered significant at p < 0.05. lupus erythematosus may be modified or suppressed by steroid hormone therapy and may be misinterpreted as SLE arthritis. Actually, it is well known that serum urate level in patients with rheumatic arthritis Results {Wallace, Klinenberg, Morhaim, Berlanstein, Callis and Biren 1979), SLE, or Crohn's disease(Derus,Levinson, Bowman, Bengoa and Sitrin Table la shows the comparison of urate metabolism 1987) were lower and prevalence of gout or hyperuricemia with these between control and patients treated with prednisolone. Sur in the disease thought to be uncommon. Hypouricemia may be induced by cases treated with prednisolone were significantly lower than control the disease itself. However, these patients have regularly received group, accompanied by elevation of Cur and Cur/Ccr. Seven days steroid hormone therapy. Therefore, we studied the urate and oxyafter administration of prednisolone, Sur significantly decreased in all purine, i. e., hypoxanthine and xanthine, excretion in admitted patients and both Cur and Cur/Ccr increased, comparing before adpatients treated with oral administration of prednisolone and deministration, however, urine volume did not significantly change scribed that prednisolone could directly induce hypouricemia asbefore and after administration of prednisolone (mean value: 1200 vs sociated with hyperuricosuria and hypooxypurinuria. 1500 ml/day) and there ws no evidence of hyperglycemia or hyperglycosuria. Table lb shows the comparison of oxypurine excretion between patients with prednisolone and normal subjects. UHX, UX and Material and Method UOXY in the cases treated with prednisolone were significantly lower than control group. The patients and control subjects were on a regular diet and did not receive any medications known to affect the urate metabolism and alcohol during admission. The patients with either renal Discussion failure, liver in sufficiency, hypertension, or diabetes mellitus were excluded. First, we compared the urate metabolism between 14 patients In the present study, serum urate level in the patients with steroid hormone (6 males and 8 females, mean age = 47 and treated with prednisolone were significantly lower than control group, mean body weight = 56 kg) and 10 normal subjects who were matched and urate clearance also had been increased. This difference may be age, sex and body weight. The patients treated with prednisolone from due to either disease difference or the effect of prednisolone. Oral ad10 to 60 mg/day were composed of hyperthyroidism (1: number), ministration of prednisolone could decrease serum urate level aschronic hepatitis (2), rheumatic arthritis (1), Crohn's disease (1), sociated with hyperuricosuria, which suggested that prednisolone neuritis (3), tonsillitis (1), multiple sclerosis (1), encephalitis (1), directly could decrease serum urate level. The possible mechanisms of asthma (1), CML (1), and brain tumor (1). Second, in order to estimate prednisolone-induced hyperuricosuria may be the direct effect of the direct effect of prednisolone on urate metabolism, we measured prednisolone on urate transport in renal tubulues or the secondary efthe urate metabolism in 8 patients (3 males and 5 females, mean age = fect of steroid via volume expansion or hyperglycemia. As previously 49 and mean body weight = 57 kg), who needed steroid therapy, i. e., reported {Beck 1979), in human, an increase or a decrease in effective Crohn's disease (3), neuritis (1), asthma (3), multiple sclerosis (1), intravascular volume is known to be associated with an increase or a before and seven days during oral prednisolone administration of 30 decrease in the clearance of urate. Although we did not find either hymg/day. Third, we compared the serum and urinary oxypurine beperglycemia, hyperglycosuria, or increase in urine volume, we could tween 7 patients (3 males and 4 females, mean age = 48 and mean not deny the possibility of volume expansion, because it would not be body weight = 54 kg), who needed oral prednisolone administrtion of reflected in the urine volume. Miller (1980) reported that intravenous 30 mg/day, i. e., allergic pneumonitis (2), asthma (1), autoimmune heinjection of hydrocortisone sodium inhibited the reabsorption of urate patitis (1), dermatomyositis (2), malignant exophthalmus (1), and 5 in the kidney, which led to hyperuricosuria. Additionally, predninormal subjects (3 males and 2 females, mean age = 49 and mean solone might modify the de novo synthesis of urate, because in the prebody weight = 56 kg). Serum urate (Sur) and urinary urate were sent study, the urinary oxypurine excretion in the patients with prednimeasured by uricase method (Kageyama 1971). Serum and urinary solone were lower than that in normal subjects. Bishop, Garner and creatinine were measured enzymatically. Serum and urinary hypoxanTalbott (1951) previously reported that using labeled urate, cortisone thine and xanthine were measured by high-performance liquid chroincreased the turn-over rate of urate but decreased the pool size of matography (Hisatome, Ishiko, Miyakoda, Saito, Kitamura, Kinugawa, Kobayashi, Kotake, Mashiba and Sato 1990). Urate clearance urate, and therefore, the latter effect might reflect the decrease in de novo synthesis of urate, which is in favour of our findings. However, as
Horm.metab.Res. 23(1991)513-514 © Georg Thieme Verlag Stuttgart.NewYork
Received: 8 Dec. 1989
Accepted: 23 June 1991 after revision
Downloaded by: NYU. Copyrighted material.
Introduction
514 Horm. metab. Res. 23 (1991)
I. Hisatome, R. Ishiko, N. Sasaki, H. Kotake M. Kobayashi et al.
Table 1a Urate metabolism in patients treated with prednisolone. n
Sur (mg/dl)
Uur (mg/day)
Cur (ml/min)
Cur/Ccr
Control group
10
5.5 ±0.9
361 ± 146
4.30 ±1.95
8.5 ±2.9
Prednisolone treated group
14
3.8 ±0.9**
391 ±139
7.49 ±2.67**
Before administration
8
5.2 ±0.9
405 ±139
5.78 ±2.4
8.0 ±2.0
During administration
8
3.6 ±0.9*
384 ±132
7.93 ±2.70
13.5 ±3.1**
(%)
12.7 ±4.8*
Table 1b Oxypurine excretion in patients treated with prednisolone. (p,g/ml)
Sx (u.g/ml)
SHX
Control group
5
0.23 ±0.11
0.11 ±0.04
Prednisolone treated group
7
0.20 ±0.04
0.11 ±0.04
(mg/day)
Ux (mg/day)
18.4±3.7
20.8 ±4.8
39.3 ±6.3
12.6 ±6.4*
22.5 ±11.4*
UHX
9.9 ±5.2*
UOXY
(mg/day)
Abbreviations: Sur = serum urate level, Uur = urinary urate excretion, Cur = urate clearance, Cur/Ccr = urate-creatinine clearance ratio. SHX = serum hypoxanthine concentration, Sx = serum xanthine concentration, UHX = urinary hypoxanthine excretion, Ux = urinary xanthine excretion, UOXY = the sum of urinary hypoxanthine and xanthine excretion. Values represent the mean±SD. * and **, significant difference (p < 0.05, p
(Cur), urate-creatinine clearance ratio (Cur/Ccr), urinary urate excretion (Uur), urinary hypoxanthine excretion (UHX), and urinary xanthine excretion (Ux) were calculated during a 24-h period. Urinary Hypouricemia in the psychological stress group {Francis 1981) and hyperuricemia after adrenalectomy (Itskovits and oxypurine (UOXY) excretion were expressed as the sum of urinary hypoxanthine and xanthine excretion. Data were expressed as Sellers 1963) had been reported, indicating the relationship between serum urate level and steroid hormone. Recently, Frocht, Leek and mean ± S. D. and Mann-Whitney test or paired t-test were used to determine the statistical significance. Difference between means were Robbins (1987) reported that the prevalence of gout with systemic considered significant at p < 0.05. lupus erythematosus may be modified or suppressed by steroid hormone therapy and may be misinterpreted as SLE arthritis. Actually, it is well known that serum urate level in patients with rheumatic arthritis Results {Wallace, Klinenberg, Morhaim, Berlanstein, Callis and Biren 1979), SLE, or Crohn's disease(Derus,Levinson, Bowman, Bengoa and Sitrin Table la shows the comparison of urate metabolism 1987) were lower and prevalence of gout or hyperuricemia with these between control and patients treated with prednisolone. Sur in the disease thought to be uncommon. Hypouricemia may be induced by cases treated with prednisolone were significantly lower than control the disease itself. However, these patients have regularly received group, accompanied by elevation of Cur and Cur/Ccr. Seven days steroid hormone therapy. Therefore, we studied the urate and oxyafter administration of prednisolone, Sur significantly decreased in all purine, i. e., hypoxanthine and xanthine, excretion in admitted patients and both Cur and Cur/Ccr increased, comparing before adpatients treated with oral administration of prednisolone and deministration, however, urine volume did not significantly change scribed that prednisolone could directly induce hypouricemia asbefore and after administration of prednisolone (mean value: 1200 vs sociated with hyperuricosuria and hypooxypurinuria. 1500 ml/day) and there ws no evidence of hyperglycemia or hyperglycosuria. Table lb shows the comparison of oxypurine excretion between patients with prednisolone and normal subjects. UHX, UX and Material and Method UOXY in the cases treated with prednisolone were significantly lower than control group. The patients and control subjects were on a regular diet and did not receive any medications known to affect the urate metabolism and alcohol during admission. The patients with either renal Discussion failure, liver in sufficiency, hypertension, or diabetes mellitus were excluded. First, we compared the urate metabolism between 14 patients In the present study, serum urate level in the patients with steroid hormone (6 males and 8 females, mean age = 47 and treated with prednisolone were significantly lower than control group, mean body weight = 56 kg) and 10 normal subjects who were matched and urate clearance also had been increased. This difference may be age, sex and body weight. The patients treated with prednisolone from due to either disease difference or the effect of prednisolone. Oral ad10 to 60 mg/day were composed of hyperthyroidism (1: number), ministration of prednisolone could decrease serum urate level aschronic hepatitis (2), rheumatic arthritis (1), Crohn's disease (1), sociated with hyperuricosuria, which suggested that prednisolone neuritis (3), tonsillitis (1), multiple sclerosis (1), encephalitis (1), directly could decrease serum urate level. The possible mechanisms of asthma (1), CML (1), and brain tumor (1). Second, in order to estimate prednisolone-induced hyperuricosuria may be the direct effect of the direct effect of prednisolone on urate metabolism, we measured prednisolone on urate transport in renal tubulues or the secondary efthe urate metabolism in 8 patients (3 males and 5 females, mean age = fect of steroid via volume expansion or hyperglycemia. As previously 49 and mean body weight = 57 kg), who needed steroid therapy, i. e., reported {Beck 1979), in human, an increase or a decrease in effective Crohn's disease (3), neuritis (1), asthma (3), multiple sclerosis (1), intravascular volume is known to be associated with an increase or a before and seven days during oral prednisolone administration of 30 decrease in the clearance of urate. Although we did not find either hymg/day. Third, we compared the serum and urinary oxypurine beperglycemia, hyperglycosuria, or increase in urine volume, we could tween 7 patients (3 males and 4 females, mean age = 48 and mean not deny the possibility of volume expansion, because it would not be body weight = 54 kg), who needed oral prednisolone administrtion of reflected in the urine volume. Miller (1980) reported that intravenous 30 mg/day, i. e., allergic pneumonitis (2), asthma (1), autoimmune heinjection of hydrocortisone sodium inhibited the reabsorption of urate patitis (1), dermatomyositis (2), malignant exophthalmus (1), and 5 in the kidney, which led to hyperuricosuria. Additionally, predninormal subjects (3 males and 2 females, mean age = 49 and mean solone might modify the de novo synthesis of urate, because in the prebody weight = 56 kg). Serum urate (Sur) and urinary urate were sent study, the urinary oxypurine excretion in the patients with prednimeasured by uricase method (Kageyama 1971). Serum and urinary solone were lower than that in normal subjects. Bishop, Garner and creatinine were measured enzymatically. Serum and urinary hypoxanTalbott (1951) previously reported that using labeled urate, cortisone thine and xanthine were measured by high-performance liquid chroincreased the turn-over rate of urate but decreased the pool size of matography (Hisatome, Ishiko, Miyakoda, Saito, Kitamura, Kinugawa, Kobayashi, Kotake, Mashiba and Sato 1990). Urate clearance urate, and therefore, the latter effect might reflect the decrease in de novo synthesis of urate, which is in favour of our findings. However, as
Horm.metab.Res. 23(1991)513-514 © Georg Thieme Verlag Stuttgart.NewYork
Received: 8 Dec. 1989
Accepted: 23 June 1991 after revision
Downloaded by: NYU. Copyrighted material.
Introduction
514 Horm. metab. Res. 23 (1991)
I. Hisatome, R. Ishiko, N. Sasaki, H. Kotake M. Kobayashi et al.
Table 1a Urate metabolism in patients treated with prednisolone. n
Sur (mg/dl)
Uur (mg/day)
Cur (ml/min)
Cur/Ccr
Control group
10
5.5 ±0.9
361 ± 146
4.30 ±1.95
8.5 ±2.9
Prednisolone treated group
14
3.8 ±0.9**
391 ±139
7.49 ±2.67**
Before administration
8
5.2 ±0.9
405 ±139
5.78 ±2.4
8.0 ±2.0
During administration
8
3.6 ±0.9*
384 ±132
7.93 ±2.70
13.5 ±3.1**
(%)
12.7 ±4.8*
Table 1b Oxypurine excretion in patients treated with prednisolone. (p,g/ml)
Sx (u.g/ml)
SHX
Control group
5
0.23 ±0.11
0.11 ±0.04
Prednisolone treated group
7
0.20 ±0.04
0.11 ±0.04
(mg/day)
Ux (mg/day)
18.4±3.7
20.8 ±4.8
39.3 ±6.3
12.6 ±6.4*
22.5 ±11.4*
UHX
9.9 ±5.2*
UOXY
(mg/day)
Abbreviations: Sur = serum urate level, Uur = urinary urate excretion, Cur = urate clearance, Cur/Ccr = urate-creatinine clearance ratio. SHX = serum hypoxanthine concentration, Sx = serum xanthine concentration, UHX = urinary hypoxanthine excretion, Ux = urinary xanthine excretion, UOXY = the sum of urinary hypoxanthine and xanthine excretion. Values represent the mean±SD. * and **, significant difference (p < 0.05, p
