- Email: [email protected]
CREATINE KINASE ISOENZYMES IN ASPIRIN INTOXICATION
864 We treated a depressed woman with tyrosine, 100 mg/kg/day, in three daily doses. Tyrosine was administered as 500 mg tablets. The patient’s plasma tyrosine 2 h after a tyrosine dose had approximately doubled, and a double-blind, placebo-controlled cross-over trial suggested that her depression responded favourably to tyrosine
therapy.9
We believe that
orally administered tyrosine can raise plasma concentrations and the plasma tyrosine: LNAA ratio. tyrosine There is also reason to believe that this may lead to increased cerebral catecholamine synthesis, which might benefit patients with certain disease states, such as depression. We are conducting trials to evaluate these questions further.
nervosa we found low T3, low-normal T4, and normal TSH values before and after TRH stimulation. Thus we find that TRH dose of 1 J.lg/kg intravenously is the ideal dose in children, inducing a significant increase of TSH secretion in all euthyroid children (i.e., an increase of at least 2-55 IJU/ml). Higher doses do not give any more clinical information. In evaluating TRH-induced TSH secretion age-related variations in children up to 2 years of age must be considered.
University Children’s Clinic, 6650 Homburg-Saar, West Germany
SIEGFRIED ZABRANSKY
CREATINE KINASE ISOENZYMES IN ASPIRIN
Department of Psychiatry, Harvard Medical School, and Massachusetts General Hospital, Boston, Massachusetts 02114, U.S.A.
INTOXICATION
ALAN J. GELENBERG RICHARD J. WURTMAN
SIR,-The value of creatine kinase (CK) isoenzyme assay for the of myocardial damage has been often discussed in your
diagnosis columns,
TRH TEST DOSE IN CHILDREN
SIR,-The TRH
test
dose for children has
not
been determined
by dose-related studies; the doses used in published work range from2 4 to 10 !.tg/kg, from 50 to 200 g/child, and from 100 to 120 g/m2 and seem to have been chosen arbitrarily. In this centre we draw blood before and 30 min after the rapid intravenous injection of only 1 g/kg TRH/kg. The preparation we use (’Relefact-TRH’; Hoechst) comes in vials containing 200 g TRH in 1 ml solution. We add 1 ml 0 - 9% saline to obtain a concentration of 100 g/ml. With a syringe graduated in 100 sections the same number of graduations as the child weighs in kilograms is drawn up. Why do we use such a low dose? 2 years ago we studied several TRH doses in 67 children aged 2 weeks to 2 years. With the agreement of the parents 0’ 5 jug, 1 !.tg, 1 jug/kg, 2 g/kg, and 200 !.tg were injected. The smallest doses (0.5 5 pg and 1 !.tg per child) induced a TSH increase of 250%. After 1 !.tg/kg the increase was 750%, and larger doses did not improve on this. Thus the ideal i.v. dosage is 1 lag TRH/kg. In the past 2 years we have done TRH tests on children of all agegroups, using 1 µg/kg. Of 70 euthyroid children older than 2 years (up to 16 years) all responded. The table shows the results of TRH tests done with 1 g/kg or 200 pg per child. The TRH-induced TSH secretion 30 min after stimulation is not significantly different. The smaller dose proved as discriminating as the larger dose for both diagnosis and control of children with hypothyroidism or goitre. It is possible to distinguish hyperthyroidism also. Details of these studies will be published elsewhere. Children up to 2 years were more sensitive to TRH than older children: for children aged 2 weeks to 2 years the increase in TSH above baseline was, 30 min after 1 g/kg TRH, 14 -6±6 - 7 pU/ml; for older children it was 8 - 7±4 - 5 U/ml. Values for newborns are in other ranges. They are not reported here. Body-weight and body-surface do not correlate with serum levels of thyroid hormones and TSH. This applies equally to children with a body weight more or less than 20% of their ideal weight. TRH-induced TSH secretion in fat and in thin children is the same as that of children of normal weight. In girls with anorexia
euthyroid
9.
Gelenberg AJ, Wojcik JD, Growdon JH, Sved AF, Wurtman RJ. Tyrosine for the treatment of depression. Am J Psychiat 1980; 137: 622-23.
and measurement of the MB isoenzyme (CK-MB) has been used to estimate the size of myocardial injury. 1,2 Drugs can affect the measurement of enzyme activity3by altering serum concentrations of activators or inhibitors or the rate of removal of cellular enzymes from the interstitial fluid. While the presence of CK-MB in the serum usually signifies myocardial damage,4 less is known about the presence of CK-BB, found mainly in the central nervous system. We have detected all the three major CK isoenzymes in the serum of a patient who had taken an overdose of aspirin who had no evidence of myocardial damage. A 53-year-old woman had epigastric pain which later radiated to her chest. For many years she had been taking 30 tablets (10’5g) of aspirin daily without medical reasons. For her pain she took another 30 tablets of aspirin. Tinnitus developed and she went to hospital. She had tachypnoea (22/min) but no other physical abnormalities were noted. Her blood gases, while she was receiving oxygen (2 1/min), were: p02 116 mm Hg, pC02 24 mm Hg, bicarbonate 16 mmol/1. Her serum chloride was 112 mmol/1, urate 0-07 mmol/1, CK activity 162 U/l (normal, up to 160 U/1), lactate dehydrogenase (LD) activity 264 U/1 (normal, up to 250 U/1). The serum salicylate 510 mg/1 (toxic level above 300 mg/1). Agarose-gel was electrophoretic fractionation of CK revealed CK-BB 9-8%, CK-MB 9 -3%, and CK-MM 73 - 9% of the total CK activity. The chest pain disappeared by the next day when CK activity in serum was 130 U/l and CK isoenzymes assay revealed CK-MM only. Several electrocardiograms during the first 3 days in hospital were normal. The LD isoenzyme fractionation on agarose-gel on day 2 and 3 revealed a normal pattern (LD 1:LD2 ratio 0 ° 54). The patient was discharged 3 days after admission. This patient had a metabolic acidosis, which is common after aspirin overdose; this was compensated for by tachypnoea. It is likely that the acidosis contributed to the release of CK isoenzymes from various organs, including the brain, and could have enhanced the permeability of the blood-brain barrier. Perhaps metabolic acidosis is a common denominator for various conditions associated with the presence in serum ofCK-BB. 5,6 This case illustrates how laboratory findings can be misinterpreted-i.e., the finding of CK-MB could have been attributed to myocardial infarction. This is also an example of another mechanism.whereby drugs can affect the enzymes. Studies of CK isoenzymes in metabolic acidosis due to other causes should be of interest.
ADRIAN O. VLADUTIU MARY REITZ
Buffalo General Hospital, Buffalo, N.Y. 14203, U.S.A. DOSE-RELATED STUDIES: CHILDREN OLDER THAN 2 YEARS 1.
2. 3.
der Laarse A, Davids HS, Hollaar L, van der Volk EJM, Witteveen SAGJ, Hermens WT. Recognition and quantification of myocardial injury by means of plasma enzyme and isoenzyme activities after cardiac surgery. Br Hearl 1979; 41: 660-67. Roe CR. Validity of estimating myocardial infarct size from serial measurements of enzyme activity in the serum. Clin Chem 1977; 23: 1807-12 Editorial. Serum enzymes and myocardial mfarct size: the effect of drugs. Lancet 1978; ii: 1082-83. Lott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clzn Chem 1980; 26: 1241-50. Itano M. The detection ofCPK-1 (BB) m serum. Am] Clrn Parhol 1976; 65: 351-55 Mercer DW. Frequent appearance ofcreatine kinase isoenzyme BB in sera of cnncalcare patients. Clm Chem 1977; 23: 611-12. van
,
The normal values measured in our laboratory (’Immo Phase’ kits) are: upper limit of basal TSH secretion in children aged 2 weeks up to 16 years 7 - 5 U/ml. The upper limit ofTSH-serum level 30 min after stimulation with 1 pg/kg is 36 pU/ml in children aged 2 weeks to 2 years and 20 pulml in older children.
4. 5. 6.
therapy.9
We believe that
orally administered tyrosine can raise plasma concentrations and the plasma tyrosine: LNAA ratio. tyrosine There is also reason to believe that this may lead to increased cerebral catecholamine synthesis, which might benefit patients with certain disease states, such as depression. We are conducting trials to evaluate these questions further.
nervosa we found low T3, low-normal T4, and normal TSH values before and after TRH stimulation. Thus we find that TRH dose of 1 J.lg/kg intravenously is the ideal dose in children, inducing a significant increase of TSH secretion in all euthyroid children (i.e., an increase of at least 2-55 IJU/ml). Higher doses do not give any more clinical information. In evaluating TRH-induced TSH secretion age-related variations in children up to 2 years of age must be considered.
University Children’s Clinic, 6650 Homburg-Saar, West Germany
SIEGFRIED ZABRANSKY
CREATINE KINASE ISOENZYMES IN ASPIRIN
Department of Psychiatry, Harvard Medical School, and Massachusetts General Hospital, Boston, Massachusetts 02114, U.S.A.
INTOXICATION
ALAN J. GELENBERG RICHARD J. WURTMAN
SIR,-The value of creatine kinase (CK) isoenzyme assay for the of myocardial damage has been often discussed in your
diagnosis columns,
TRH TEST DOSE IN CHILDREN
SIR,-The TRH
test
dose for children has
not
been determined
by dose-related studies; the doses used in published work range from2 4 to 10 !.tg/kg, from 50 to 200 g/child, and from 100 to 120 g/m2 and seem to have been chosen arbitrarily. In this centre we draw blood before and 30 min after the rapid intravenous injection of only 1 g/kg TRH/kg. The preparation we use (’Relefact-TRH’; Hoechst) comes in vials containing 200 g TRH in 1 ml solution. We add 1 ml 0 - 9% saline to obtain a concentration of 100 g/ml. With a syringe graduated in 100 sections the same number of graduations as the child weighs in kilograms is drawn up. Why do we use such a low dose? 2 years ago we studied several TRH doses in 67 children aged 2 weeks to 2 years. With the agreement of the parents 0’ 5 jug, 1 !.tg, 1 jug/kg, 2 g/kg, and 200 !.tg were injected. The smallest doses (0.5 5 pg and 1 !.tg per child) induced a TSH increase of 250%. After 1 !.tg/kg the increase was 750%, and larger doses did not improve on this. Thus the ideal i.v. dosage is 1 lag TRH/kg. In the past 2 years we have done TRH tests on children of all agegroups, using 1 µg/kg. Of 70 euthyroid children older than 2 years (up to 16 years) all responded. The table shows the results of TRH tests done with 1 g/kg or 200 pg per child. The TRH-induced TSH secretion 30 min after stimulation is not significantly different. The smaller dose proved as discriminating as the larger dose for both diagnosis and control of children with hypothyroidism or goitre. It is possible to distinguish hyperthyroidism also. Details of these studies will be published elsewhere. Children up to 2 years were more sensitive to TRH than older children: for children aged 2 weeks to 2 years the increase in TSH above baseline was, 30 min after 1 g/kg TRH, 14 -6±6 - 7 pU/ml; for older children it was 8 - 7±4 - 5 U/ml. Values for newborns are in other ranges. They are not reported here. Body-weight and body-surface do not correlate with serum levels of thyroid hormones and TSH. This applies equally to children with a body weight more or less than 20% of their ideal weight. TRH-induced TSH secretion in fat and in thin children is the same as that of children of normal weight. In girls with anorexia
euthyroid
9.
Gelenberg AJ, Wojcik JD, Growdon JH, Sved AF, Wurtman RJ. Tyrosine for the treatment of depression. Am J Psychiat 1980; 137: 622-23.
and measurement of the MB isoenzyme (CK-MB) has been used to estimate the size of myocardial injury. 1,2 Drugs can affect the measurement of enzyme activity3by altering serum concentrations of activators or inhibitors or the rate of removal of cellular enzymes from the interstitial fluid. While the presence of CK-MB in the serum usually signifies myocardial damage,4 less is known about the presence of CK-BB, found mainly in the central nervous system. We have detected all the three major CK isoenzymes in the serum of a patient who had taken an overdose of aspirin who had no evidence of myocardial damage. A 53-year-old woman had epigastric pain which later radiated to her chest. For many years she had been taking 30 tablets (10’5g) of aspirin daily without medical reasons. For her pain she took another 30 tablets of aspirin. Tinnitus developed and she went to hospital. She had tachypnoea (22/min) but no other physical abnormalities were noted. Her blood gases, while she was receiving oxygen (2 1/min), were: p02 116 mm Hg, pC02 24 mm Hg, bicarbonate 16 mmol/1. Her serum chloride was 112 mmol/1, urate 0-07 mmol/1, CK activity 162 U/l (normal, up to 160 U/1), lactate dehydrogenase (LD) activity 264 U/1 (normal, up to 250 U/1). The serum salicylate 510 mg/1 (toxic level above 300 mg/1). Agarose-gel was electrophoretic fractionation of CK revealed CK-BB 9-8%, CK-MB 9 -3%, and CK-MM 73 - 9% of the total CK activity. The chest pain disappeared by the next day when CK activity in serum was 130 U/l and CK isoenzymes assay revealed CK-MM only. Several electrocardiograms during the first 3 days in hospital were normal. The LD isoenzyme fractionation on agarose-gel on day 2 and 3 revealed a normal pattern (LD 1:LD2 ratio 0 ° 54). The patient was discharged 3 days after admission. This patient had a metabolic acidosis, which is common after aspirin overdose; this was compensated for by tachypnoea. It is likely that the acidosis contributed to the release of CK isoenzymes from various organs, including the brain, and could have enhanced the permeability of the blood-brain barrier. Perhaps metabolic acidosis is a common denominator for various conditions associated with the presence in serum ofCK-BB. 5,6 This case illustrates how laboratory findings can be misinterpreted-i.e., the finding of CK-MB could have been attributed to myocardial infarction. This is also an example of another mechanism.whereby drugs can affect the enzymes. Studies of CK isoenzymes in metabolic acidosis due to other causes should be of interest.
ADRIAN O. VLADUTIU MARY REITZ
Buffalo General Hospital, Buffalo, N.Y. 14203, U.S.A. DOSE-RELATED STUDIES: CHILDREN OLDER THAN 2 YEARS 1.
2. 3.
der Laarse A, Davids HS, Hollaar L, van der Volk EJM, Witteveen SAGJ, Hermens WT. Recognition and quantification of myocardial injury by means of plasma enzyme and isoenzyme activities after cardiac surgery. Br Hearl 1979; 41: 660-67. Roe CR. Validity of estimating myocardial infarct size from serial measurements of enzyme activity in the serum. Clin Chem 1977; 23: 1807-12 Editorial. Serum enzymes and myocardial mfarct size: the effect of drugs. Lancet 1978; ii: 1082-83. Lott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clzn Chem 1980; 26: 1241-50. Itano M. The detection ofCPK-1 (BB) m serum. Am] Clrn Parhol 1976; 65: 351-55 Mercer DW. Frequent appearance ofcreatine kinase isoenzyme BB in sera of cnncalcare patients. Clm Chem 1977; 23: 611-12. van
,
The normal values measured in our laboratory (’Immo Phase’ kits) are: upper limit of basal TSH secretion in children aged 2 weeks up to 16 years 7 - 5 U/ml. The upper limit ofTSH-serum level 30 min after stimulation with 1 pg/kg is 36 pU/ml in children aged 2 weeks to 2 years and 20 pulml in older children.
4. 5. 6.