1082 We have found that most clinicians will accept that the panis normal after a normal ultrasound examination and investigate the pancreas no further. Only a small number of patients are left in whom there is a strong suggestion of pancreatic disease, and in these an isotope scan is performed. If the pancreas is normal there is a more than 50% chance that the isotope scan will also be normal and no further investigation of the pancreas will be required for the moment. Those with a positive isotope scan will probably be investigated more invasively, but this would have happened anyway. We therefore suggest that the use of ultrasound followed by isotope scanning will significantly decrease the number of patients who require these more expensive and time-consuming
creas
tests.
Department of Radiology, Royal Free Hospital, London NW3
2QG
L. A. BERGER
REGRESSION OF PITUITARY PROLACTINOMA AFTER TREATMENT WITH BROMOCRIPTINE
A
Nov. 3, 1976, showed no change in the adensize (see figure) and revealed a moderate internal hydrocephalus. On Nov. 6, 1976, bromocriptine treatment was started at 2-5 mg, increasing to 10 mg daily within 4 weeks. Higher doses caused nausea and unsteadiness. After 6 weeks the serum-prolactin was normal (9 ng/ml), and the patient noted an improvement in his headaches after 2 months of treatment. This improvement has now lasted 21years. The headaches have not disappeared but the continuous pain is diminished, and severe attacks are rare. A third c.T. scan showed a considerable decrease in the tumour size on Sept. 27, 1977 (figure)-i.e., 11 months after starting bromocriptine treatment. The serum-prolactin has fallen below 2 ng/ml. A fourth c.T. scan demonstrated an unchanged picture on Oct. 30, 1978. In this case we have direct radiographic evidence of a reduction in a pituitary prolactinoma during bromocriptine treatment. With one exception previous evidence has been indirect. The reduction in size may have been due to spontaneous necrosis, a late effect of radiotherapy, bromocriptine treatment, or a combination of the effects of bromocripc.T. scan on
oma
SiR,—The beneficial endocrine effects of bromocriptine in the treatment of pituitary adenomas are well known, but evidence for changes in tumour size is less clear-cut. Improvement in visual-field defects has been reported in some cases;I-4 temporary regression of an incomplete cavernous sinus syndrome has been reported in a man with invasive prolactinoma;5 there has been one brief report of "radiographic improvement";2 and Sobrinho et a1.6 observed a reduction of an infrasellar softtissue mass in the sphenoid sinus in a patient with a prolactinoma. We have seen a case of tumour regression demonstrated by computerised axial tomography (c.T.). A 56-year-old man with congenital amaurosis of the right eye presented at the age of 49 with progressive visual loss in the left eye of 6 years’ duration, worsening headaches, impotence, and apathy. He had a small atrophic optic disc on the right and a concentric narrowing of the left visual field. Endocrinological examination revealed hypogonadism, adrenal insufficiency, and myxredema. Radiographic studies revealed an enlarged pituitary fossa with suprasellar extension. In March, 1973, a chromophobe adenoma was removed. Postoperatively the patient had transitory diabetes insipidus. Cortisone and levothyroxine were prescribed. His clinical condition improved considerably, though the headaches did not disappear completely. 2 years later the headaches became much
worse. A c.T. scan Oct. 28, 1975, demonstrated tumour recurrence (see figure). Endocrine evaluation revealed continuing hypopituitarism and hyperprolactinaemia (620 ng/ml, normal 6-14 ng/ml). Prolactin had not been measured previously. X-rays showed that the adenoma had extended again into the suprasellar space and broken into the sphenoid sinus and upper clivus. A subtotal removal of the adenoma was done via the transsphenoidal route. The headaches immediately got better. In March, 1976, 1 month after radiotherapy (4000 rad in 22 fractions), the serum-prolactin was 400 ng/ml. The headaches soon returned, and increasingly severe attacks required injections of 20 mg scopolamine butylbromide and 2.5 g dipyrone once or twice a week. Treatment of his labile arterial hypertension failed to improve his condition.
on
Carenblum, B., Webster, B. R., Mortimer, C. B., Ezrin, C. Clin. Res. 1975, 23, 614A. 2. Linquette, M. in La bromocriptine (edited by H. Bricaire); p. 173. Sandoz, Rueil Malmaison, 1977. 3. Vaidya, R., Aloorkar, S., Shet, A. Fertil. Steril. 1977, 28, 363. 4. Werder, K., Fahlbusch, R., Landgraf, R., Pickardt, C. R., Rjosk, H. K., Scriba, P. C. J. Endocr. Invest. 1978, 1, 47. 5. Landolt, A. M. in Advances and Technical Standards in Neurosurgery (edited by H. Krayen buhl); vol. v, p. 3. Vienna, 1978. 6. Sobrinho, L. G., Nunes, M. C. P., Santos, M. A., Mauricio, J. C. Lancet, 1978, ii, 257.
1.
Basal and
higher C.T.
sections.
(a) Oct. 28, 1975: before second operation. (b) Nov. 3, 1976: 1 year after operation. (c) Sept. 28, 1977: 11 months after bromocriptine therapy size diminution of adenoma visible in last
examination.
Note
1083
radiotherapy. However, spontaneous necrosis due to infarction of the adenoma is often accompanied by hoemorrhage into the tumour, and in this case neither the clinical course nor the c.T. scans suggest that this happened. Reporting results of radiotherapy in pituitary adenoma Svien and Colby7 state that vision improved within 6 months, though in many cases 6-9 months was required; most radiotherapy failures became evident within a year of treatment. 9 months after a course of radiotherapy our patient still had his headaches and the c.T. showed no reduction in adenoma size. Bromocriptine does not usually seem to affect the size of prolactinomas. Morphological studies of human prolactinomas treated with bromocriptine have shown that the drug blocks the release of prolactin granules from the tumour cel1,5 but there has been no evidence for drug-induced tumour-cell reduction. Furthermore hyperprolactinxmia promptly reappears when bromocriptine tine and
is discontinued.8 This leaves the possibility of synergism between bromocriptine and radiotherapy. Our patient’s serum-prolactin fell to normal within 6 weeks on bromocriptine but after 1½years prolactin values were below normal. Bromocriptine does not usually lower prolactin concentrations below the normal
additional therapeutic effect after the first prolactin determination during bromocriptine treatment. We believe that a synergistic action of radiotherapy (which is notoriously inefficient if applied as the only treatment of hyperprolactinæmia2,7,10) and bromocriptine caused the necrosis of this adenoma. We now give combined radiotherapy and bromocriptine treatment in patients with invasive prolactinomas which cannot be extirpated radically.
range,9 suggesting some
We thank Dr E. del
Pozo, Sandoz Ltd., Basle for his help.
Department of Neurosurgery, University Hospital, 8091 Zurich, Switzerland
Department of Neurology, University of Basle
A. M. LANDOLT
R. WÜTHRICH H. FELLMANN
Lucerne
ANTIBODIES IN HOSPITAL STAFF EXPOSED TO LEGIONNAIRES’ DISEASE
SIR,-The publicity engendered by the first recognised outbreak of legionnaires’ diseasel,2 and subsequent reports suggesting the ubiquity of this disease have raised questions about the safety of those caring for affected patients or handling biological samples in hospital laboratories. Two patients returning from holiday in Spain were admitted 2 days apart as emergencies to a medical ward of this teaching hospital. Legionnaires’ disease was diagnosed 48 h after the admission of one patient with pneumonia who was then nursed under strict isolation facilities. The second patient was admitted in hepatic coma and pneumonia subsequently developed. A serological diagnosis of legionnaires’ disease was made post mortem after the patient had received 11 days of standard non-isolation nursing. These circumstances presented an opportunity to assess the risk of infection to the ward and laboratory staff. Blood-samples were taken from staff within ten days of admission of the affected patients and "convalescent" samples were taken up to 80 days later. The staff included doctors, nurses, and porters on the admitting ward and intensive-care 7
8
Svien, H J, Colby, M. Y. Treatment for Chromophobe Adenomas Springfield, Illinois, 1967 Thorner, M. O, McNeilly, A. S., Hagan, C., Besser, G. M. Br. med. J. 1974,
9
Kleinberg,
ii, 419. D.
L., Noel,
G. L.,
Frantz, A. G. New Engl. J Med 1977, 296,
589 10 Fossati, P., Strauch, G., Tournaire, J. Nouv. Presse méd. 1976, 1 McDade, J. E., and others New Engl.J.Med. 1977, 297, 1197. 2 Frazer, D W , and others ibid. 1977, 297, 1189. 3 Sanford. J.P ibid. 1979, 300, 654.
unit, the staff of the medical microbiology, haematology, and medical biochemistry laboratories, and X-ray staff. All sera were tested by the indirect fluorescent antibody technique’ with a formalin-killed yolk-sac suspension of Legionella pneumophila (supplied by Dr P. Taylor, Public Health Laboratory Service, Colindale). Serological testing of 122 staff members revealed that no sera yielded positive fluorescence at a reciprocal dilution greater than 1:16 and no rise in specific antibody titre was observed. These two cases of legionnaires’ disease seem to have posed no particular infection hazard to the ward staff caring for the patients or to the laboratory staff handling the patients’ blood, sputum, stool, or urine. We do not know for certain whether the patient with hepatic coma contracted legionnaires’ disease in Spain or from the other case of legionnaires’ disease on the same ward. However, there was no direct contact between the two patients and we have not been able to find a clinical or subclinical case among the staff. Secondary cases of legionnaires’ disease are, at most, uncommonand our findings suggest that the agent is adequately contained even in routine hosnital laboratories. J. R. MORGAN Departments of Medical Microbiology R. RYDER and Medicine, A. PAULL Welsh National School of Medicine, Heath Park, Cardiff J. P. THOMAS
ENTERITIS NECROTICANS IN CHINA
SIR,-Lawrence and Walker4suggested that enteritis necroticans (pigbel) in Papua New Guinea is due to reduced levels of trypsin in the gut caused by a low protein diet, the presence of Ascaris lumbricoides (which secretes a trypsin inhibitor), and the ingestion of trypsin inhibitor in poorly cooked sweet potato. When ingestion of protein (usually pig meat) leads to rapid growth of Clostridium welchii type C, there is insufficient trypsin present to destroy the beta-toxin produced by this organism and the toxin produces the characteristic intestinal lesion. The role of beta-toxin in the pathogenesis of enteritis necroticans is supported by our finding (Feb. 3, p. 227) that immunisation of Papua New Guinea children with C. welchii type C beta-toxoid protects them against the disease. Apart from an outbreak in post-war Germany, few cases of enteritis necroticans have been recorded outside Papua New Guinea. We wish to report the occurrence in the People’s Republic of China of a disease that is almost certainly enteritis necroticans. The condition is well documented in the Chinese ’medical literature, and it is more common in the south of China than in the north. One hospital serving 30 000 people in the south sees 5-10 cases a year, and this suggests that many cases of enteritis necroticans occur each year in southern China’s very large rural population. The clinical features of the disease in China are similar to those in Papua New Guinea.5 It is commonest in children, and there is usually an acute onset of abdominal pain with varying degrees of blood in the stool, intestinal obstruction, shock, and occasionally perforation. Most cases occur in rural children, who have a lower protein intake than urban dwellers. Some cases follow a feast where the meat is cooked the day before and about half the cases follow a meal of raw sweet potato, peanuts, or water chestnut. Ascaris infestation is a frequent association. Untyped C. welchii were isolated in 18 of 19 cases in one series, and were also commonly found in people not suffering from enteritis necroticans. These features are consistent with Lawrence and Walker’s suggested pathogenesis of the disease in Papua New Guinea. The availability of a vaccine that protects against enteritis nec-
5, 1687. 4. Lawrence, G., Walker, P. D. Lancet, 1976, i, 125. 5. Murrell, T. G. C., Roth, L., Egerton, J., Sands, J.,
i, 219.
Walker, P. D. ibid. 1966,
creas
tests.
Department of Radiology, Royal Free Hospital, London NW3
2QG
L. A. BERGER
REGRESSION OF PITUITARY PROLACTINOMA AFTER TREATMENT WITH BROMOCRIPTINE
A
Nov. 3, 1976, showed no change in the adensize (see figure) and revealed a moderate internal hydrocephalus. On Nov. 6, 1976, bromocriptine treatment was started at 2-5 mg, increasing to 10 mg daily within 4 weeks. Higher doses caused nausea and unsteadiness. After 6 weeks the serum-prolactin was normal (9 ng/ml), and the patient noted an improvement in his headaches after 2 months of treatment. This improvement has now lasted 21years. The headaches have not disappeared but the continuous pain is diminished, and severe attacks are rare. A third c.T. scan showed a considerable decrease in the tumour size on Sept. 27, 1977 (figure)-i.e., 11 months after starting bromocriptine treatment. The serum-prolactin has fallen below 2 ng/ml. A fourth c.T. scan demonstrated an unchanged picture on Oct. 30, 1978. In this case we have direct radiographic evidence of a reduction in a pituitary prolactinoma during bromocriptine treatment. With one exception previous evidence has been indirect. The reduction in size may have been due to spontaneous necrosis, a late effect of radiotherapy, bromocriptine treatment, or a combination of the effects of bromocripc.T. scan on
oma
SiR,—The beneficial endocrine effects of bromocriptine in the treatment of pituitary adenomas are well known, but evidence for changes in tumour size is less clear-cut. Improvement in visual-field defects has been reported in some cases;I-4 temporary regression of an incomplete cavernous sinus syndrome has been reported in a man with invasive prolactinoma;5 there has been one brief report of "radiographic improvement";2 and Sobrinho et a1.6 observed a reduction of an infrasellar softtissue mass in the sphenoid sinus in a patient with a prolactinoma. We have seen a case of tumour regression demonstrated by computerised axial tomography (c.T.). A 56-year-old man with congenital amaurosis of the right eye presented at the age of 49 with progressive visual loss in the left eye of 6 years’ duration, worsening headaches, impotence, and apathy. He had a small atrophic optic disc on the right and a concentric narrowing of the left visual field. Endocrinological examination revealed hypogonadism, adrenal insufficiency, and myxredema. Radiographic studies revealed an enlarged pituitary fossa with suprasellar extension. In March, 1973, a chromophobe adenoma was removed. Postoperatively the patient had transitory diabetes insipidus. Cortisone and levothyroxine were prescribed. His clinical condition improved considerably, though the headaches did not disappear completely. 2 years later the headaches became much
worse. A c.T. scan Oct. 28, 1975, demonstrated tumour recurrence (see figure). Endocrine evaluation revealed continuing hypopituitarism and hyperprolactinaemia (620 ng/ml, normal 6-14 ng/ml). Prolactin had not been measured previously. X-rays showed that the adenoma had extended again into the suprasellar space and broken into the sphenoid sinus and upper clivus. A subtotal removal of the adenoma was done via the transsphenoidal route. The headaches immediately got better. In March, 1976, 1 month after radiotherapy (4000 rad in 22 fractions), the serum-prolactin was 400 ng/ml. The headaches soon returned, and increasingly severe attacks required injections of 20 mg scopolamine butylbromide and 2.5 g dipyrone once or twice a week. Treatment of his labile arterial hypertension failed to improve his condition.
on
Carenblum, B., Webster, B. R., Mortimer, C. B., Ezrin, C. Clin. Res. 1975, 23, 614A. 2. Linquette, M. in La bromocriptine (edited by H. Bricaire); p. 173. Sandoz, Rueil Malmaison, 1977. 3. Vaidya, R., Aloorkar, S., Shet, A. Fertil. Steril. 1977, 28, 363. 4. Werder, K., Fahlbusch, R., Landgraf, R., Pickardt, C. R., Rjosk, H. K., Scriba, P. C. J. Endocr. Invest. 1978, 1, 47. 5. Landolt, A. M. in Advances and Technical Standards in Neurosurgery (edited by H. Krayen buhl); vol. v, p. 3. Vienna, 1978. 6. Sobrinho, L. G., Nunes, M. C. P., Santos, M. A., Mauricio, J. C. Lancet, 1978, ii, 257.
1.
Basal and
higher C.T.
sections.
(a) Oct. 28, 1975: before second operation. (b) Nov. 3, 1976: 1 year after operation. (c) Sept. 28, 1977: 11 months after bromocriptine therapy size diminution of adenoma visible in last
examination.
Note
1083
radiotherapy. However, spontaneous necrosis due to infarction of the adenoma is often accompanied by hoemorrhage into the tumour, and in this case neither the clinical course nor the c.T. scans suggest that this happened. Reporting results of radiotherapy in pituitary adenoma Svien and Colby7 state that vision improved within 6 months, though in many cases 6-9 months was required; most radiotherapy failures became evident within a year of treatment. 9 months after a course of radiotherapy our patient still had his headaches and the c.T. showed no reduction in adenoma size. Bromocriptine does not usually seem to affect the size of prolactinomas. Morphological studies of human prolactinomas treated with bromocriptine have shown that the drug blocks the release of prolactin granules from the tumour cel1,5 but there has been no evidence for drug-induced tumour-cell reduction. Furthermore hyperprolactinxmia promptly reappears when bromocriptine tine and
is discontinued.8 This leaves the possibility of synergism between bromocriptine and radiotherapy. Our patient’s serum-prolactin fell to normal within 6 weeks on bromocriptine but after 1½years prolactin values were below normal. Bromocriptine does not usually lower prolactin concentrations below the normal
additional therapeutic effect after the first prolactin determination during bromocriptine treatment. We believe that a synergistic action of radiotherapy (which is notoriously inefficient if applied as the only treatment of hyperprolactinæmia2,7,10) and bromocriptine caused the necrosis of this adenoma. We now give combined radiotherapy and bromocriptine treatment in patients with invasive prolactinomas which cannot be extirpated radically.
range,9 suggesting some
We thank Dr E. del
Pozo, Sandoz Ltd., Basle for his help.
Department of Neurosurgery, University Hospital, 8091 Zurich, Switzerland
Department of Neurology, University of Basle
A. M. LANDOLT
R. WÜTHRICH H. FELLMANN
Lucerne
ANTIBODIES IN HOSPITAL STAFF EXPOSED TO LEGIONNAIRES’ DISEASE
SIR,-The publicity engendered by the first recognised outbreak of legionnaires’ diseasel,2 and subsequent reports suggesting the ubiquity of this disease have raised questions about the safety of those caring for affected patients or handling biological samples in hospital laboratories. Two patients returning from holiday in Spain were admitted 2 days apart as emergencies to a medical ward of this teaching hospital. Legionnaires’ disease was diagnosed 48 h after the admission of one patient with pneumonia who was then nursed under strict isolation facilities. The second patient was admitted in hepatic coma and pneumonia subsequently developed. A serological diagnosis of legionnaires’ disease was made post mortem after the patient had received 11 days of standard non-isolation nursing. These circumstances presented an opportunity to assess the risk of infection to the ward and laboratory staff. Blood-samples were taken from staff within ten days of admission of the affected patients and "convalescent" samples were taken up to 80 days later. The staff included doctors, nurses, and porters on the admitting ward and intensive-care 7
8
Svien, H J, Colby, M. Y. Treatment for Chromophobe Adenomas Springfield, Illinois, 1967 Thorner, M. O, McNeilly, A. S., Hagan, C., Besser, G. M. Br. med. J. 1974,
9
Kleinberg,
ii, 419. D.
L., Noel,
G. L.,
Frantz, A. G. New Engl. J Med 1977, 296,
589 10 Fossati, P., Strauch, G., Tournaire, J. Nouv. Presse méd. 1976, 1 McDade, J. E., and others New Engl.J.Med. 1977, 297, 1197. 2 Frazer, D W , and others ibid. 1977, 297, 1189. 3 Sanford. J.P ibid. 1979, 300, 654.
unit, the staff of the medical microbiology, haematology, and medical biochemistry laboratories, and X-ray staff. All sera were tested by the indirect fluorescent antibody technique’ with a formalin-killed yolk-sac suspension of Legionella pneumophila (supplied by Dr P. Taylor, Public Health Laboratory Service, Colindale). Serological testing of 122 staff members revealed that no sera yielded positive fluorescence at a reciprocal dilution greater than 1:16 and no rise in specific antibody titre was observed. These two cases of legionnaires’ disease seem to have posed no particular infection hazard to the ward staff caring for the patients or to the laboratory staff handling the patients’ blood, sputum, stool, or urine. We do not know for certain whether the patient with hepatic coma contracted legionnaires’ disease in Spain or from the other case of legionnaires’ disease on the same ward. However, there was no direct contact between the two patients and we have not been able to find a clinical or subclinical case among the staff. Secondary cases of legionnaires’ disease are, at most, uncommonand our findings suggest that the agent is adequately contained even in routine hosnital laboratories. J. R. MORGAN Departments of Medical Microbiology R. RYDER and Medicine, A. PAULL Welsh National School of Medicine, Heath Park, Cardiff J. P. THOMAS
ENTERITIS NECROTICANS IN CHINA
SIR,-Lawrence and Walker4suggested that enteritis necroticans (pigbel) in Papua New Guinea is due to reduced levels of trypsin in the gut caused by a low protein diet, the presence of Ascaris lumbricoides (which secretes a trypsin inhibitor), and the ingestion of trypsin inhibitor in poorly cooked sweet potato. When ingestion of protein (usually pig meat) leads to rapid growth of Clostridium welchii type C, there is insufficient trypsin present to destroy the beta-toxin produced by this organism and the toxin produces the characteristic intestinal lesion. The role of beta-toxin in the pathogenesis of enteritis necroticans is supported by our finding (Feb. 3, p. 227) that immunisation of Papua New Guinea children with C. welchii type C beta-toxoid protects them against the disease. Apart from an outbreak in post-war Germany, few cases of enteritis necroticans have been recorded outside Papua New Guinea. We wish to report the occurrence in the People’s Republic of China of a disease that is almost certainly enteritis necroticans. The condition is well documented in the Chinese ’medical literature, and it is more common in the south of China than in the north. One hospital serving 30 000 people in the south sees 5-10 cases a year, and this suggests that many cases of enteritis necroticans occur each year in southern China’s very large rural population. The clinical features of the disease in China are similar to those in Papua New Guinea.5 It is commonest in children, and there is usually an acute onset of abdominal pain with varying degrees of blood in the stool, intestinal obstruction, shock, and occasionally perforation. Most cases occur in rural children, who have a lower protein intake than urban dwellers. Some cases follow a feast where the meat is cooked the day before and about half the cases follow a meal of raw sweet potato, peanuts, or water chestnut. Ascaris infestation is a frequent association. Untyped C. welchii were isolated in 18 of 19 cases in one series, and were also commonly found in people not suffering from enteritis necroticans. These features are consistent with Lawrence and Walker’s suggested pathogenesis of the disease in Papua New Guinea. The availability of a vaccine that protects against enteritis nec-
5, 1687. 4. Lawrence, G., Walker, P. D. Lancet, 1976, i, 125. 5. Murrell, T. G. C., Roth, L., Egerton, J., Sands, J.,
i, 219.
Walker, P. D. ibid. 1966,
