- Email: [email protected]
DIFFICULTIES IN CHEMICAL DIAGNOSIS IN PHÆOCHROMOCYTOMA
1014 DIFFICULTIES IN CHEMICAL DIAGNOSIS IN PHÆOCHROMOCYTOMA in the urinary excretion of adrenaline increase SIR,-An
To define the place of dehydroemetine as a fungicide, further trials with oral D.H.E. capsules particularly in the more serious systemic mvcoses are planned. Department of Tropical Medicine, Faculty of Medicine, Alexandria, Egypt, U.A.R.
DEPERSONALISATION view of your remark (Oct. 17) that electroSIR,-In convulsive therapy (E.C.T.) is contraindicated in depersonalisation we should like to report a case in which there was a remarkable response to methylamphetamine and E.C.T. A
noradrenaline1 as well as vanillylmandelic acidhas been used to confirm the diagnosis of phaeochromocytoma. Various tests for these metabolites have been successfully applied in patients with either sustained or paroxysmal hypertension and hypotension. But some patients with phasochromocytoma, even during paroxysms, apparently do not excrete excessive amounts of catecholaminesa
or
HASSAN ABD-RABBO.
had strong evidence of depersonalisa40-year-old tion, derealisation, depression, and phobic anxiety reactions. For eighteen months we treated her with antidepressive drugs, psychotherapy, and two incomplete courses of E.C.T., without any satisfactory result. After reading Davison’s article1 we reassessed her case and gave her 20 mg. of methylamphetamine ’intravenously, to which there was no immediate response; instead, the patient complained of severe headaches. Then a further course of E.C.T. twice a week was begun. After the third E.C.T. the response was striking-in her own words, " as if I am reborn ". After six E.c.T.s her feelings towards herself and the external world were normal. woman
vanillylmandelic acid.4 justified, therefore, in recording a case in which phaeochromocytoma was associated with typical attacks of paroxysmal hypertension and in which the excretion of catecholamines and vanillylmandelic acid (V.M.A.) was only slightly raised, whereas metadrenaline and normetadrenaline levels were distinctly raised.
or
We feel
A man, aged 68 years, was admitted to Medical Department VIII, Ulleval Hospital, Oslo, in August, 1963, with a year’s
history of attacks in which he had a feeling of oppression in his chest and on each side of his neck and became pale and nauseated. This was followed by flushing of his face and headache. At first the attacks happened weekly and lasted for about Our opinion is that this patient responded to intraven10 minutes; in the previous 6 months they had come on several ous methylamphetamine and a course of E.C.T. times a day, without any known precipitating cause. On admission the patient’s physical condition was essentially Shelton Hospital, A. G. KHAN Shrewsbury, 7, normal. His blood-pressure was 160/95 mm. Hg. During J. LITTLEJOHN. Shropshire. attacks, however, his blood-pressure rose to 245/160 mm. Hg, falling to initial values within 1-2 hours. The urinary ENZYME-STRIP ESTIMATION OF excretion of catecholamines and V.M.A. between and during BLOOD-GLUCOSE attacks was only slightly raised (see table). Histamine SIR,-The two articles on enzyme-strip estimations of (0-05 mg. intravenously) raised the blood-pressure to 270/160 blood-glucose (Oct. 24) draw attention to the simple test mm. Hg before phentolamine methanesulphonate (’ Regitine ’) with ’Dextrostix ’ and comment favourably on its use in was given, but the catecholamines and V.M.A. did not increase the context of hospital medicine. significantly. Renal angiography and X-rays after retroperitoneal air My experience of the method (see accompanying table) inflation suggested the presence of a tumour in the left suprain general practice confirms its usefulness as a screening renal region. The clinical findings strongly favoured the RESULTS OF ENZYME-STRIP AND AUTOANALYSER TESTS IN THE SAME diagnosis of phseochromocytoma, and the patient underwent SAMPLE OF BLOOD operation. An adrenal tumour, the size of a plum, was removed from the left suprarenal region. The patient had an attack of hypotension and was given noradrenaline for two days, but recovered completely and has since been free of symptoms. Microscopic examination of the tumour showed typical phaeochromocytoma tissue. Catecholamines in the urine of this patient were first assayed fluorometrically by Prof. 0. Walaas. The 24-hour excretion of noradrenaline was found to be within normal limits, whereas that of adrenaline was slightly raised (see table). Some of the urine samples were also assayed on phenolic acids by means of paper chromatography according to the method of Armstrong et al. Vanillylmandelic acid (V.M.A.) was slightly raised, whereas homovanillic acid (H.V.A.) was normal (see table). H.V.A. levels may rise occasionally in malignant phsochromo-
cytoma.6g
procedure. Besides providing a rapid result, the method saves the patient some anxiety and the family doctor some time. To my mind, the slight sacrifice in accuracy is compensated by the convenience of the method for the general practitioner. I wish to thank Dr. Leslie Duncan, Royal Infirmary, Edinburgh, for the ’Autoanalyser ’ results. Edinburgh. 1.
J. D. E. KNOX. Davison, K. Brit. J. Psychiat. 1964, 110, 505.
After removal of the tumour, metadrenalines were assayed in a preoperative urine sample obtained 4 hours after a positive histamine test according to the method of Kakimoto and Armstrong.’7 This sample was the only one forgotten in the freezer, and it contained four and five times the normal amounts of free metadrenaline and normetadrenaline and eight and seven times the normal amounts of conjugated metadrenaline and normetadrenaline (see table). After operation, the levels of urinary catecholamines, v.M.A., and metadrenaline were normal (see table). von Euler, U. S. Lancet, 1950, ii, 387. Armstrong, M. D., McMillan, A., Shaw, K. N. F. Biochim. biophys. Acta, 1957, 25, 422. 3. Litchfield, J. W., Peart, W. S. Lancet, 1956, ii, 1283. 4. Robinson, R. West-Europ. Symposia, 1963, 2, 63. 5. Armstrong, M. D., Shaw, K. N. F., Wall, P. E. J. biol. Chem. 1956, 218,
1. 2.
Engel, A.,
6. 7.
Robinson, R., Smith, P., Whittaker, S. R. S. Brit. med. J. 1964, i, 1422. Kakimoto, Y., Armstrong, M. D. J. biol. Chem. 1962, 237, 208.
293.
1015 URINARY EXCRETION OF CATECHOLAMINES AND THEIR METABOLITES
2 2 hours after histamine test.
The means
tumour tissue of high-voltage
tography according
t 4 hours after histamine
test.
also tested for catecholamines by electrophoresis combined with chromato the method of Gjessing. The tissue was
contained about 8 mg. of noradrenaline and 4 mg. of adrenaline were per g. wet weight.
It
surprising to find that an adrenal phasochromowith cytoma typical clinical manifestations was secreting such small amounts of catecholamines and V.M.A., even after injection of histamine. But according to Crout et al.9 and Kelleher et al.10 some patients with phaeochromocytoma excrete only normal or slightly raised amounts of V.M.A., and, according to Litchfield and Peart,s normal amounts of catecholamines. Robinson4 emphasises the importance of determining the metadrenalines since these compounds seem more reliable than V.M.A. output as a
was
diagnostic test.
Our values for the free and conjugated metadrenalines before and after operation suggest that they decrease much more than the catecholamines and V.M.A., and that they should be determined in order to diagnose
phasochromocytoma. Biørkely Laboratory, Dikemark Hospital, Asker. Medical Department VIII, Oslo City Hospital, Oslo.
L. R.
GJESSING.
I. HJERMANN.
FERROUS-SULPHATE POISONING TREATED BY EXCHANGE TRANSFUSION SIR,-Ferrous-sulphate poisoning is not uncommon in young children and may be fatal. Acute necrosis of the stomach, duodenum, and jejunum may lead to a rapid death; but initial prostration is sometimes followed by a period of apparent recovery before death supervenes. Animal experiments and necropsy studies 11 have shown that, in such cases, death is probably attributable to true absorptive intoxication, and damage to the mucosa of the gastrointestinal tract is of secondary importance. The serum-iron level and survival-time have been found to be roughly proportional to the dose ingested. For reducing the serum-iron, treatment with a chelating agent, such as desferrioxamine, is the method of choice. I have, however, found exchange transfusion a safe and efficacious alternative. A girl aged 16 months was admitted to Stoke Mandeville Hospital, Aylesbury, 3 hours after swallowing about fifty ferrous-sulphate (’ Fersolate ’) tablets. Thirty unchanged Gjessing, L. R. Scand. J. clin. Lab. Invest. 1963, 15, 479. Crout, J. R., Pisano, J. J., Sjoerdsma. Amer. Heart J. 1961, 61, 375. Kelleher, J., Walters, G., Robinson, R., Smith, P. J. clin. Path. 1964, 17, 399. 11. Reisman, K. R., Coleman, T. J. Blood, 1955, 10, 46. 8. 9. 10.
tablets were brought up in the first vomit, but later only redbrown fluid was returned. Vomiting ceased after 11/2 hours. The stomach was then thought to be empty and no gastric lavage was performed at this stage. The child was drowsy and pale but her clinical condition was satisfactory. Several hours later, vomiting recurred with abdominal pain. The pulse was feeble and the rate 160 per minute. The stomach was washed out and found to contain altered blood and thick mucus but no ferrous-sulphate debris. Hydrocortisone 50 mg. was given intramuscularly to counter incipient shock. Next day the child was restless and semicomatose with a pulse-rate of 200 per minute. The blood-pressure was 100/65 mm. Hg. There were crepitations in both lungs and heart-failure was feared; digoxin, 0-32 mg., was given 8-hourly. The child was now suffering from acute iron intoxication and exchange transfusion was thought worth attempting. Morphine sulphate gr. 1/40 was given and a polyethylene tube inserted into the external saphenous vein and passed four inches up the femoral vein. Over 3 hours, group-0 rhesusnegative blood was exchanged in 20 ml. amounts to a total of 1560 ml.-i.e., about 60 ml. per lb. body-weight. 2 ml. calcium-gluconate solution was given with each 100 ml. blood. Sodium versenate 5 ml. was then given intravenously in 500 ml. dextrose-saline. Intravenous fluids were continued for the next 3 days. During this time the child remained comatose, but she then regained consciousness and made a gradual but complete recovery. The day after the transfusion, the pulserate suddenly dropped from 180 to 70 per minute. An electrocardiogram revealed complete heart-block and very little evidence of digitalisation. The digoxin was withdrawn. The pulse took several hours to become regular. Before the exchange transfusion the serum-iron was 235 mg. per 100 ml.; after the exchange it was 70 mg.
In this case the serum-iron level was not unduly high: levels fifteen to a hundred times the normal have been recorded after accidental poisoning. Nevertheless, there were all the features of acute iron intoxication. When, as here, reduction of the serum-iron is urgent, exchange transfusion is worth bearing in mind as either an adjunct or an alternative to treatment with chelating agents. I wish to thank Dr. Dermod MacCarthy, under whose care this child was admitted, for his help and encouragement, and to Dr. G. Nun for estimating serum-iron and sulphate levels. Hamilton, B. TOMLINSON. ’j’OMLINSON.
New Zealand.. HOSPITAL BOOKINGS
SIR,-Selecting patients for hospital confinement is difficult. Where a hospital supplies midwives for its own district area selection is simpler, provided that facilities for late transfer of district patients exist.l Unfortunately catchment areas and areas served by district midwives do not always correspond, and it would be a great help if closer cooperation could be fostered between district midwives serving an area and the hospital in whose catchment area they work. Until March, 1963, all patients applying to this hospital were interviewed and examined at one of two large clinics of up to 90 patients each, which patients and doctors disliked. Patients were kept waiting for a long time, and there was undesirable pressure on the medical staff because of numbers. Since March, 1963, a card has been sent to patients applying for a bed. The results have been so satisfactory that they are worth reporting. The returned cards, with doctors’ letters and old notes (where applicable) are seen daily-a fifteen-minute task. A firm medical booking or district-clinic booking can often be made, and notes can be printed before the patient attends her routine clinic for the first visit. Where the application is social the card can be referred to the almoner for a report from the health visitor and Dossible social bookins. Patients outside the 1. Tomkinson, J. S. Proc. R. Soc. Med. 1964, 57, 219.
To define the place of dehydroemetine as a fungicide, further trials with oral D.H.E. capsules particularly in the more serious systemic mvcoses are planned. Department of Tropical Medicine, Faculty of Medicine, Alexandria, Egypt, U.A.R.
DEPERSONALISATION view of your remark (Oct. 17) that electroSIR,-In convulsive therapy (E.C.T.) is contraindicated in depersonalisation we should like to report a case in which there was a remarkable response to methylamphetamine and E.C.T. A
noradrenaline1 as well as vanillylmandelic acidhas been used to confirm the diagnosis of phaeochromocytoma. Various tests for these metabolites have been successfully applied in patients with either sustained or paroxysmal hypertension and hypotension. But some patients with phasochromocytoma, even during paroxysms, apparently do not excrete excessive amounts of catecholaminesa
or
HASSAN ABD-RABBO.
had strong evidence of depersonalisa40-year-old tion, derealisation, depression, and phobic anxiety reactions. For eighteen months we treated her with antidepressive drugs, psychotherapy, and two incomplete courses of E.C.T., without any satisfactory result. After reading Davison’s article1 we reassessed her case and gave her 20 mg. of methylamphetamine ’intravenously, to which there was no immediate response; instead, the patient complained of severe headaches. Then a further course of E.C.T. twice a week was begun. After the third E.C.T. the response was striking-in her own words, " as if I am reborn ". After six E.c.T.s her feelings towards herself and the external world were normal. woman
vanillylmandelic acid.4 justified, therefore, in recording a case in which phaeochromocytoma was associated with typical attacks of paroxysmal hypertension and in which the excretion of catecholamines and vanillylmandelic acid (V.M.A.) was only slightly raised, whereas metadrenaline and normetadrenaline levels were distinctly raised.
or
We feel
A man, aged 68 years, was admitted to Medical Department VIII, Ulleval Hospital, Oslo, in August, 1963, with a year’s
history of attacks in which he had a feeling of oppression in his chest and on each side of his neck and became pale and nauseated. This was followed by flushing of his face and headache. At first the attacks happened weekly and lasted for about Our opinion is that this patient responded to intraven10 minutes; in the previous 6 months they had come on several ous methylamphetamine and a course of E.C.T. times a day, without any known precipitating cause. On admission the patient’s physical condition was essentially Shelton Hospital, A. G. KHAN Shrewsbury, 7, normal. His blood-pressure was 160/95 mm. Hg. During J. LITTLEJOHN. Shropshire. attacks, however, his blood-pressure rose to 245/160 mm. Hg, falling to initial values within 1-2 hours. The urinary ENZYME-STRIP ESTIMATION OF excretion of catecholamines and V.M.A. between and during BLOOD-GLUCOSE attacks was only slightly raised (see table). Histamine SIR,-The two articles on enzyme-strip estimations of (0-05 mg. intravenously) raised the blood-pressure to 270/160 blood-glucose (Oct. 24) draw attention to the simple test mm. Hg before phentolamine methanesulphonate (’ Regitine ’) with ’Dextrostix ’ and comment favourably on its use in was given, but the catecholamines and V.M.A. did not increase the context of hospital medicine. significantly. Renal angiography and X-rays after retroperitoneal air My experience of the method (see accompanying table) inflation suggested the presence of a tumour in the left suprain general practice confirms its usefulness as a screening renal region. The clinical findings strongly favoured the RESULTS OF ENZYME-STRIP AND AUTOANALYSER TESTS IN THE SAME diagnosis of phseochromocytoma, and the patient underwent SAMPLE OF BLOOD operation. An adrenal tumour, the size of a plum, was removed from the left suprarenal region. The patient had an attack of hypotension and was given noradrenaline for two days, but recovered completely and has since been free of symptoms. Microscopic examination of the tumour showed typical phaeochromocytoma tissue. Catecholamines in the urine of this patient were first assayed fluorometrically by Prof. 0. Walaas. The 24-hour excretion of noradrenaline was found to be within normal limits, whereas that of adrenaline was slightly raised (see table). Some of the urine samples were also assayed on phenolic acids by means of paper chromatography according to the method of Armstrong et al. Vanillylmandelic acid (V.M.A.) was slightly raised, whereas homovanillic acid (H.V.A.) was normal (see table). H.V.A. levels may rise occasionally in malignant phsochromo-
cytoma.6g
procedure. Besides providing a rapid result, the method saves the patient some anxiety and the family doctor some time. To my mind, the slight sacrifice in accuracy is compensated by the convenience of the method for the general practitioner. I wish to thank Dr. Leslie Duncan, Royal Infirmary, Edinburgh, for the ’Autoanalyser ’ results. Edinburgh. 1.
J. D. E. KNOX. Davison, K. Brit. J. Psychiat. 1964, 110, 505.
After removal of the tumour, metadrenalines were assayed in a preoperative urine sample obtained 4 hours after a positive histamine test according to the method of Kakimoto and Armstrong.’7 This sample was the only one forgotten in the freezer, and it contained four and five times the normal amounts of free metadrenaline and normetadrenaline and eight and seven times the normal amounts of conjugated metadrenaline and normetadrenaline (see table). After operation, the levels of urinary catecholamines, v.M.A., and metadrenaline were normal (see table). von Euler, U. S. Lancet, 1950, ii, 387. Armstrong, M. D., McMillan, A., Shaw, K. N. F. Biochim. biophys. Acta, 1957, 25, 422. 3. Litchfield, J. W., Peart, W. S. Lancet, 1956, ii, 1283. 4. Robinson, R. West-Europ. Symposia, 1963, 2, 63. 5. Armstrong, M. D., Shaw, K. N. F., Wall, P. E. J. biol. Chem. 1956, 218,
1. 2.
Engel, A.,
6. 7.
Robinson, R., Smith, P., Whittaker, S. R. S. Brit. med. J. 1964, i, 1422. Kakimoto, Y., Armstrong, M. D. J. biol. Chem. 1962, 237, 208.
293.
1015 URINARY EXCRETION OF CATECHOLAMINES AND THEIR METABOLITES
2 2 hours after histamine test.
The means
tumour tissue of high-voltage
tography according
t 4 hours after histamine
test.
also tested for catecholamines by electrophoresis combined with chromato the method of Gjessing. The tissue was
contained about 8 mg. of noradrenaline and 4 mg. of adrenaline were per g. wet weight.
It
surprising to find that an adrenal phasochromowith cytoma typical clinical manifestations was secreting such small amounts of catecholamines and V.M.A., even after injection of histamine. But according to Crout et al.9 and Kelleher et al.10 some patients with phaeochromocytoma excrete only normal or slightly raised amounts of V.M.A., and, according to Litchfield and Peart,s normal amounts of catecholamines. Robinson4 emphasises the importance of determining the metadrenalines since these compounds seem more reliable than V.M.A. output as a
was
diagnostic test.
Our values for the free and conjugated metadrenalines before and after operation suggest that they decrease much more than the catecholamines and V.M.A., and that they should be determined in order to diagnose
phasochromocytoma. Biørkely Laboratory, Dikemark Hospital, Asker. Medical Department VIII, Oslo City Hospital, Oslo.
L. R.
GJESSING.
I. HJERMANN.
FERROUS-SULPHATE POISONING TREATED BY EXCHANGE TRANSFUSION SIR,-Ferrous-sulphate poisoning is not uncommon in young children and may be fatal. Acute necrosis of the stomach, duodenum, and jejunum may lead to a rapid death; but initial prostration is sometimes followed by a period of apparent recovery before death supervenes. Animal experiments and necropsy studies 11 have shown that, in such cases, death is probably attributable to true absorptive intoxication, and damage to the mucosa of the gastrointestinal tract is of secondary importance. The serum-iron level and survival-time have been found to be roughly proportional to the dose ingested. For reducing the serum-iron, treatment with a chelating agent, such as desferrioxamine, is the method of choice. I have, however, found exchange transfusion a safe and efficacious alternative. A girl aged 16 months was admitted to Stoke Mandeville Hospital, Aylesbury, 3 hours after swallowing about fifty ferrous-sulphate (’ Fersolate ’) tablets. Thirty unchanged Gjessing, L. R. Scand. J. clin. Lab. Invest. 1963, 15, 479. Crout, J. R., Pisano, J. J., Sjoerdsma. Amer. Heart J. 1961, 61, 375. Kelleher, J., Walters, G., Robinson, R., Smith, P. J. clin. Path. 1964, 17, 399. 11. Reisman, K. R., Coleman, T. J. Blood, 1955, 10, 46. 8. 9. 10.
tablets were brought up in the first vomit, but later only redbrown fluid was returned. Vomiting ceased after 11/2 hours. The stomach was then thought to be empty and no gastric lavage was performed at this stage. The child was drowsy and pale but her clinical condition was satisfactory. Several hours later, vomiting recurred with abdominal pain. The pulse was feeble and the rate 160 per minute. The stomach was washed out and found to contain altered blood and thick mucus but no ferrous-sulphate debris. Hydrocortisone 50 mg. was given intramuscularly to counter incipient shock. Next day the child was restless and semicomatose with a pulse-rate of 200 per minute. The blood-pressure was 100/65 mm. Hg. There were crepitations in both lungs and heart-failure was feared; digoxin, 0-32 mg., was given 8-hourly. The child was now suffering from acute iron intoxication and exchange transfusion was thought worth attempting. Morphine sulphate gr. 1/40 was given and a polyethylene tube inserted into the external saphenous vein and passed four inches up the femoral vein. Over 3 hours, group-0 rhesusnegative blood was exchanged in 20 ml. amounts to a total of 1560 ml.-i.e., about 60 ml. per lb. body-weight. 2 ml. calcium-gluconate solution was given with each 100 ml. blood. Sodium versenate 5 ml. was then given intravenously in 500 ml. dextrose-saline. Intravenous fluids were continued for the next 3 days. During this time the child remained comatose, but she then regained consciousness and made a gradual but complete recovery. The day after the transfusion, the pulserate suddenly dropped from 180 to 70 per minute. An electrocardiogram revealed complete heart-block and very little evidence of digitalisation. The digoxin was withdrawn. The pulse took several hours to become regular. Before the exchange transfusion the serum-iron was 235 mg. per 100 ml.; after the exchange it was 70 mg.
In this case the serum-iron level was not unduly high: levels fifteen to a hundred times the normal have been recorded after accidental poisoning. Nevertheless, there were all the features of acute iron intoxication. When, as here, reduction of the serum-iron is urgent, exchange transfusion is worth bearing in mind as either an adjunct or an alternative to treatment with chelating agents. I wish to thank Dr. Dermod MacCarthy, under whose care this child was admitted, for his help and encouragement, and to Dr. G. Nun for estimating serum-iron and sulphate levels. Hamilton, B. TOMLINSON. ’j’OMLINSON.
New Zealand.. HOSPITAL BOOKINGS
SIR,-Selecting patients for hospital confinement is difficult. Where a hospital supplies midwives for its own district area selection is simpler, provided that facilities for late transfer of district patients exist.l Unfortunately catchment areas and areas served by district midwives do not always correspond, and it would be a great help if closer cooperation could be fostered between district midwives serving an area and the hospital in whose catchment area they work. Until March, 1963, all patients applying to this hospital were interviewed and examined at one of two large clinics of up to 90 patients each, which patients and doctors disliked. Patients were kept waiting for a long time, and there was undesirable pressure on the medical staff because of numbers. Since March, 1963, a card has been sent to patients applying for a bed. The results have been so satisfactory that they are worth reporting. The returned cards, with doctors’ letters and old notes (where applicable) are seen daily-a fifteen-minute task. A firm medical booking or district-clinic booking can often be made, and notes can be printed before the patient attends her routine clinic for the first visit. Where the application is social the card can be referred to the almoner for a report from the health visitor and Dossible social bookins. Patients outside the 1. Tomkinson, J. S. Proc. R. Soc. Med. 1964, 57, 219.