1408
Cortisol, LPH, and corticotropin values before and during treatment with octreotide in
patient with paraneoplastic Cushing’s syndrome of pulmonary origin. ACTH corticotropin. =
A 56-year-old man was referred to our institute because of worsening of his paraneoplastic Cushing’s syndrome. Six months earlier, endocrine symptoms had been treated successfully by removal of
an
undifferentiated adenocarcinoma of the left upper
pulmonary lobe. At admission, signs of Cushing’s syndrome were obvious: plasma cortisol was at 627 u.g/1 (normal 60-230) with loss of nychthemeral profile, free urinary cortisol was 2175 mg per day (30-100), plasma corticotropin 220 pg/ml (19-55), and plasma p-LPH was 961 pg/ml (47-123). Subcutaneous octreotide treatment was begun in the absence of any neoplastic recurrence after extensive screening: day 1, 3 x 50 ug, day 2, 3 x 100 J.lg; days 3-14,x200 g daily. Blood samples were obtained from day 3 to day 14. Cortisol, corticotropin, and &bgr;-LPH values are shown in the figure. All showed a striking increase. No clinical improvement was noticed. The patient died from heart failure a few days after octreotide withdrawal. Necropsy showed multiple small metastases of the pleura. Hormone values were stable before treatment was started and for about 15 days. Octreotide provoked pronounced hypercortisolism, which may account for the death of our patient. This response remains unexplained and has not been reported in the treatment of other peptide-secreting tumours.2,3 Further use of octreotide for paraneoplastic Cushing’s syndrome of pulmonary origin should be preceded by preliminary evaluation of therapeutic efficacy. M. DUQUENNE B. DOUSSET G. WERYHA
O. FADE-SCHNELLER Department of Internal Medicine and Endocrinology, T. DURIEZ Biochemistry Laboratory, D. ANTHOINE and Department of Pneumology, J. LECLERE CHV de Nancy, 54000 Nancy, France P. HARTEMANN 1. Bertagna X, Favrod-Coune C, Escourolle H, et al. Suppression of ectopic adrenocorticotropin secretion by the long-acting somatostatin analog octreotide. J Clin Endocrinol Metab 1989; 68: 988-91. 2. Hearn PR, Reynolds CL, Johansen K, Woodhouse NY. Lung carcinoid with Cushing’s syndrome control of serum ACTH and cortisol levels using SMS 201-995 (Sandostatin). Clin Endocrinol 1988; 28: 181-85 3. Maton PN, Gargdner JD, Jensen RT. Use of long-acting of somatostatin analog (SMS 201-995) in patients with pancreatic islet cell tumours. Dig Dis Sci 1989; 34: 28-39S
Secondary leukaemia after epipodophyllotoxins SIR,-Dr Pedersen-Bjergaard and colleagues (Nov 16,
p
1269) raise the possibility that the secondary myelodysplasias and leukaemias may have developed as part of the natural history of the initial germ-cell tumours. Are p
epipodophyllotoxin. We conclude that the epipodophyllotoxins, acting alone or together with alkylating agents or radiation, seem to be implicated in the development of secondary leukaemia after childhood cancer. Childhood Cancer Research University of Oxford, Oxford OX2 6JH. UK
Group,
M. M. HAWKINS
Management of childhood fever SIR,-Iagree with your Oct 26 editorial that febrile children given antipyretics. But doctors are left with a major difficulty: we banned aspirin because it induced Reye’s syndrome, and so we prescribe paracetamol despite its well-known hepatotoxicity. Now we are faced not only with its fatal acute poisoning-albeit rare in children-but also with its chronic toxicity, which seems to be more of a danger.’ Is ibuprofen the better choice? What about this drug’s side-effects, including gastrointestinal disturbances, agranulocytosis, thrombocytopenia, toxic amblyopia, blurred vision, and many others?2 Has not the time come to admit that we have made the wrong deductions, that there is no scientific proof for a link between aspirin and Reye’s syndrome?3-6 Or shall we go on and thus expose our young patients to other risks, known and unknown? should be
Department of Paediatrics, University Hospital Gasthuisberg, 3000 Leuven, Belgium
M. CASTEELS-VAN DAELE
1. Penna A, Buchanan N. Paracetamol poisoning m children and hepatotoxicity. Br J Clin Pharmacol 1991; 32: 143-49. 2. Martindale. The extra pharmacopoeia, 29th ed. London: Pharmaceutical Press, 1989. 20-21 3. Clark JH, Fitzgerald JF. Doubts relationship of salicylate and Reye’s syndrome. Pediatrics 1981; 68: 467 4. Daniels SR, Greenberg RS, Ibrahim MA. Scientific uncertainties in the studies of salicylate use and Reye’s syndrome. JAMA 1983; 249: 1311-16. 5. Orlowski JP, Gillis J, Kilham HA. A catch m the Reye. Pediatrics 1987; 80: 638-42. 6. Casteels-Van Daele M. Reye syndrome or side-effects of anti-emetics? Eur J Pediatr 1991; 150: 456-59
1270)
affirm their original interpretation (Aug 10, p 359) that secondary myelodysplasia and leukaemia after chemotherapy for germ-cell tumours were probably due to etoposide either acting alone or in combination with cisplatin and bleomycin. Dr Donatini and Dr
Krupp (Nov 16,
epipodophyllotoxins related to the development of secondary leukaemia? With colleagues I have carried out a case-control study of secondary acute leukaemia in survivors of childhood cancer diagnosed in Great Britain between 1940 and 1983. Ascertainment was through the population based National Register of Childhood Tumours maintained by the Childhood Cancer Research Group. Cases and controls were matched for sex, type of first cancer, and age at first cancer, and controls had to have survived, free of secondary neoplasms, at least as long as the interval between the first cancer and secondary leukaemia in the corresponding case. We attempted to select four controls per patient. 96 controls for 26 cases were eventually selected as satisfying the criteria for matching. This study will be published in full elsewhere, but because of the important clinical and scientific issues raised, we report our general conclusions in relation to epipodophyllotoxins. 10 acute leukaemias were diagnosed after administration of an epipodophyllotoxin, 9 after tenitoside, and 1 after etoposide. Each patient who received an epipodophyllotoxin also received at least one alkylating agent, and most had radiotherapy. A strong dose response was demonstrated by the relative risk of secondary leukaemia which rose strikingly with increasing exposure to epipodophyllotoxins (likelihood ratio test p < 0’001), and this remained after controlling for exposure to other cytotoxic drugs and averaged dose of radiation to the patients’ active bone marrow (p=0012). Translocations at llq23 were noted in one-third of secondary leukaemias for which there were successful chromosome studies after exposure to an
CORRECTION India: Missing women -In this Round the World report (Sept 14, p 685) the last sentence of paragraph 2 should read: "Because of disturbances ... In the last paragraph many men working there as agricultural labourers (p 688) the population of India should be 844 million (not 84 million). ....
Cortisol, LPH, and corticotropin values before and during treatment with octreotide in
patient with paraneoplastic Cushing’s syndrome of pulmonary origin. ACTH corticotropin. =
A 56-year-old man was referred to our institute because of worsening of his paraneoplastic Cushing’s syndrome. Six months earlier, endocrine symptoms had been treated successfully by removal of
an
undifferentiated adenocarcinoma of the left upper
pulmonary lobe. At admission, signs of Cushing’s syndrome were obvious: plasma cortisol was at 627 u.g/1 (normal 60-230) with loss of nychthemeral profile, free urinary cortisol was 2175 mg per day (30-100), plasma corticotropin 220 pg/ml (19-55), and plasma p-LPH was 961 pg/ml (47-123). Subcutaneous octreotide treatment was begun in the absence of any neoplastic recurrence after extensive screening: day 1, 3 x 50 ug, day 2, 3 x 100 J.lg; days 3-14,x200 g daily. Blood samples were obtained from day 3 to day 14. Cortisol, corticotropin, and &bgr;-LPH values are shown in the figure. All showed a striking increase. No clinical improvement was noticed. The patient died from heart failure a few days after octreotide withdrawal. Necropsy showed multiple small metastases of the pleura. Hormone values were stable before treatment was started and for about 15 days. Octreotide provoked pronounced hypercortisolism, which may account for the death of our patient. This response remains unexplained and has not been reported in the treatment of other peptide-secreting tumours.2,3 Further use of octreotide for paraneoplastic Cushing’s syndrome of pulmonary origin should be preceded by preliminary evaluation of therapeutic efficacy. M. DUQUENNE B. DOUSSET G. WERYHA
O. FADE-SCHNELLER Department of Internal Medicine and Endocrinology, T. DURIEZ Biochemistry Laboratory, D. ANTHOINE and Department of Pneumology, J. LECLERE CHV de Nancy, 54000 Nancy, France P. HARTEMANN 1. Bertagna X, Favrod-Coune C, Escourolle H, et al. Suppression of ectopic adrenocorticotropin secretion by the long-acting somatostatin analog octreotide. J Clin Endocrinol Metab 1989; 68: 988-91. 2. Hearn PR, Reynolds CL, Johansen K, Woodhouse NY. Lung carcinoid with Cushing’s syndrome control of serum ACTH and cortisol levels using SMS 201-995 (Sandostatin). Clin Endocrinol 1988; 28: 181-85 3. Maton PN, Gargdner JD, Jensen RT. Use of long-acting of somatostatin analog (SMS 201-995) in patients with pancreatic islet cell tumours. Dig Dis Sci 1989; 34: 28-39S
Secondary leukaemia after epipodophyllotoxins SIR,-Dr Pedersen-Bjergaard and colleagues (Nov 16,
p
1269) raise the possibility that the secondary myelodysplasias and leukaemias may have developed as part of the natural history of the initial germ-cell tumours. Are p
epipodophyllotoxin. We conclude that the epipodophyllotoxins, acting alone or together with alkylating agents or radiation, seem to be implicated in the development of secondary leukaemia after childhood cancer. Childhood Cancer Research University of Oxford, Oxford OX2 6JH. UK
Group,
M. M. HAWKINS
Management of childhood fever SIR,-Iagree with your Oct 26 editorial that febrile children given antipyretics. But doctors are left with a major difficulty: we banned aspirin because it induced Reye’s syndrome, and so we prescribe paracetamol despite its well-known hepatotoxicity. Now we are faced not only with its fatal acute poisoning-albeit rare in children-but also with its chronic toxicity, which seems to be more of a danger.’ Is ibuprofen the better choice? What about this drug’s side-effects, including gastrointestinal disturbances, agranulocytosis, thrombocytopenia, toxic amblyopia, blurred vision, and many others?2 Has not the time come to admit that we have made the wrong deductions, that there is no scientific proof for a link between aspirin and Reye’s syndrome?3-6 Or shall we go on and thus expose our young patients to other risks, known and unknown? should be
Department of Paediatrics, University Hospital Gasthuisberg, 3000 Leuven, Belgium
M. CASTEELS-VAN DAELE
1. Penna A, Buchanan N. Paracetamol poisoning m children and hepatotoxicity. Br J Clin Pharmacol 1991; 32: 143-49. 2. Martindale. The extra pharmacopoeia, 29th ed. London: Pharmaceutical Press, 1989. 20-21 3. Clark JH, Fitzgerald JF. Doubts relationship of salicylate and Reye’s syndrome. Pediatrics 1981; 68: 467 4. Daniels SR, Greenberg RS, Ibrahim MA. Scientific uncertainties in the studies of salicylate use and Reye’s syndrome. JAMA 1983; 249: 1311-16. 5. Orlowski JP, Gillis J, Kilham HA. A catch m the Reye. Pediatrics 1987; 80: 638-42. 6. Casteels-Van Daele M. Reye syndrome or side-effects of anti-emetics? Eur J Pediatr 1991; 150: 456-59
1270)
affirm their original interpretation (Aug 10, p 359) that secondary myelodysplasia and leukaemia after chemotherapy for germ-cell tumours were probably due to etoposide either acting alone or in combination with cisplatin and bleomycin. Dr Donatini and Dr
Krupp (Nov 16,
epipodophyllotoxins related to the development of secondary leukaemia? With colleagues I have carried out a case-control study of secondary acute leukaemia in survivors of childhood cancer diagnosed in Great Britain between 1940 and 1983. Ascertainment was through the population based National Register of Childhood Tumours maintained by the Childhood Cancer Research Group. Cases and controls were matched for sex, type of first cancer, and age at first cancer, and controls had to have survived, free of secondary neoplasms, at least as long as the interval between the first cancer and secondary leukaemia in the corresponding case. We attempted to select four controls per patient. 96 controls for 26 cases were eventually selected as satisfying the criteria for matching. This study will be published in full elsewhere, but because of the important clinical and scientific issues raised, we report our general conclusions in relation to epipodophyllotoxins. 10 acute leukaemias were diagnosed after administration of an epipodophyllotoxin, 9 after tenitoside, and 1 after etoposide. Each patient who received an epipodophyllotoxin also received at least one alkylating agent, and most had radiotherapy. A strong dose response was demonstrated by the relative risk of secondary leukaemia which rose strikingly with increasing exposure to epipodophyllotoxins (likelihood ratio test p < 0’001), and this remained after controlling for exposure to other cytotoxic drugs and averaged dose of radiation to the patients’ active bone marrow (p=0012). Translocations at llq23 were noted in one-third of secondary leukaemias for which there were successful chromosome studies after exposure to an
CORRECTION India: Missing women -In this Round the World report (Sept 14, p 685) the last sentence of paragraph 2 should read: "Because of disturbances ... In the last paragraph many men working there as agricultural labourers (p 688) the population of India should be 844 million (not 84 million). ....
