1084 1100 and 1600) while he continued on bromocriptine (increased to 7-5 mg daily) and dexamethasone (0-5 mg daily). A four-week course of pituitary irradiation (4500 rads) was started at eight weeks. The patient has continued to gain strength. He has lost his Cushingoid appearance and is no longer thirsty. There has been a return of sexual potency and his blood pressure has fallen to 135/90 mm Hg. His ECG is now normal. We hope to phase out his medical therapy when pituitary irradiation has taken effect. It is apparent that in this case bromo-
criptine has successfully lowered the plasma ACTH levels, thereby maintaining normal plasma cortisol levels with relief of symptoms and signs of Cushing's syndrome. One could
postulate that the action of bromocriptine on ACTH release may be similar to its action on growth hormone release and, as in some cases of acromegaly treated with bromocriptine, there is the bonus of return of sexual finction. A L KENNEDY D A D MONTGOMERY
BRITISH MEDICAL JOURNAL
23 APRIL 1977
to 235 nmol (68 mg)!24 h. The ACTH response to too little on the stepfather, who, as all fathers, a loading dose of 12 mg of cyrpoheptadine is shown is assuming in our society a much more in the table. Treatment was continued for six significant role in child rearing"; and only last weeks, the dose being 24 mg daily for the last three month the review panel on the case of Wayne weeks. At the end of this period there was subjective and objective improvement in muscle weak- Brewer published its findings on yet another ness. The mean UFC was reduced to 394 nmol case of a child killed by his stepfather. A recently completed research project (143 ,ug)/24 h (seven samples. A pituitary adenoma was subsequently removed at operation, with carried out in Norfolk, which studied all restoration of normal pituitary function in all children placed on the county's Nonrespects. Accidental Injury Register in a 12-month
The levels of UFC in both these patients were reduced by cyproheptadine and in the patient treated for six weeks clinical improvement was noted. ACTH levels appear to be reduced acutely by cyproheptadine, although this may be difficult to evaluate in view of the normal fluctuations of the hormone. We agree with others2 that cyproheptadine may be useful and free of side effects in patients with mild Cushing's disease who are unsuitable for surgery. In severe cases in which it is desired to improve preoperative fitness it may not be as effective as combined metyrapone-aminoglutethimide therapy. A W BuRRows C W BURKE
period, has found that male abusers outnumber females by three to two; and nearly one-third of the male abusers were stepfathers. The lesson seems clear: we cannot continue to ignore the role of the father in cases of nonaccidental injury. GEORGE MEREDITH Director of Social Services, Norfolk County Council Norwich
Fatal oxprenolol poisoning
SIR,-While Drs C J C Roberts and H McNulty (26 March, p 840) may be right in suggesting that hypernatraemia and cerebral Lamberts, S W J, and Berkenhager, J C, Abstracts Vth International Congress of Endocrinology, Radcliffe Infirmary, oedema may have contributed to the rapid Hamburg, 1976. No 492, p 201. Oxford loss of consciousness in a patient who had Besser, G M, Jeffcoate, W J, and Tomlin, S, Abstracts L H REES taken an overdose of oxprenolol and received Vth International Congress of Endocrinology, Hamburg, 1976, No 494, p 202. St Bartholomew's Hospital, a salt emetic, it has recently been demonstrated' London EC1 that oxprenolol in a single oral dose of 480 mg ' Child, D F, et al, Acta Endocrinologica, 1976, 82, 330. produced marked drowsiness in healthy Cyproheptadine and Cushing's disease 2 Krieger, D T, et al, New England journal of Medicine, volunteers, comparable to that produced by 1975, 293, 893. lorazepam 2 mg. A direct central depressant SIR,-We read with interest the recent report action of oxprenolol must therefore be conby Dr Jeremy Allgrove and others (12 March, sidered in an unconscious patient who has p 686) of the lack of response of a patient with Children at risk taken a dose in excess of this. Cushing's disease to cyproheptadine treatment. PAUL TURNER We would like to report the findings in two SIR,-Dr Margaret A Lynch and Ms Bartholomew's Hospital patients with pituitary-dependent Cushing's Jacqueline Roberts (5 March, p 624) have St Medical College, disease treated with cyproheptadine before researched the value of information available London EC1 pituitary surgery. in the perinatal period in the prediction of Farhoumand, N, et al, British Journal of Clinical Case 1-A 16-year-old boy presented with a child abuse. A significant number of the Pharmacology, 1977, in press. three-week history of headaches and altered facial abused group had two or more of the perinatal appearance. His blood pressure was 150/102 risk factors suggested, all of which were taken mm Hg. Mean (four samples) urinary free cortisol from information recorded routinely at the (UFC) was 2650 nmol (960,ug)/24 h (normal 28-280 maternity hospital. However, the fact that Tuberculin reversion rate nmol (10-100 ,g)/24 h). Midnight plasma cortisol was 825 nmol/l (30 4g/100 ml) (normal 140-280 100% of the controls also had two or more of SIR,-The result of the tuberculin survey nmol/l (5-10 ,ug/l00 ml)) and midnight plasma these risk factors suggests that we might have carried out in Glasgow in 1974 by Dr K M ACTH (corticotrophin) 76 ng/l (normal 10-80 to investigate about 10 % of all newborns. This Goel and others (12 March, p 676) is surprisng/l). Pituitary dependence was also confirmed by would seem too large a number for the inten- ing. According to table V in the paper only a positive response to metyrapone, 17-oxogenic sive follow-up necessary to prevent child six of 500 immigrant and native children steroid excretion rising from 85 lsmol (24-5 mg)/ abuse. It would be useful to have more infor- reacted positively to the Tine test although 24 h to 230 ,umol (66 mg)/24 h. Preoperatively he mation from the present survey on the per- 470 of them had previously been vaccinated was treated with metyrapone and aminoglut- centage of total births associated with two or with BCG. This is a remarkably high reversion ethimide.' This reduced the UFC to a mean of more risk factors and the percentage associated rate in vaccinated children whose mean age 315 nmol (114 jLg)/24 h (two samples). Cyprowas only 71 years. Postvaccinal tuberculin heptadine was added to his other treatment and later with child abuse. ACTH levels in response to a loading dose of sensitivity is usually much more enduring. PETER C CORRY 12 mg are shown in the accompanying table. The authors do not state what criterion they Area Craigavon Hospital, treatment During eight days' cyproheptadine used in interpreting the results of the Tine Co Armagh mean was reduced further UFC (16 mg daily) the tests. h exnmol On samples). to 182 (66 ug)/24 (four H G CALWELL ploration of the pituitary fossa two weeks later B T Adams) a necrotic adenoma was found SIR,-The article by Dr Margaret A Lynch Carrickfergus, (Mr C which was selectively removed with complete and Ms Jacqueline Roberts. on "Predicting Co Antrim relief of the Cushing's disease. child abuse: signs of bonding failure in the Case 2-A 51-year-old woman was investigated maternity hospital" (5 March, p 624) fails to ***We sent a copy of this letter to Dr K M for weight gain and generalised muscular weakness. consider the possibility that the father may Goel and his colleagues, whose reply is Her mean UFC was 605 nmol (220 jig)/24 h (two printed below.-ED, BM7. samples), midnight plasma cortisol 633 nmol/l sometimes be involved in cases of non(23 jig/100 ml), and midnight plasma ACTH accidental injury. Yet in 1974 the Maria 45 ng/l. A metyrapone test produced a rise of Colwell Committee observed that "too much SIR,-We accept Dr Calwell's point about our 17-oxogenic steroids from 71 nmol (20-5 mg)/24 h attention may be centred upon the mother and apparently high tuberculin reversion rate. We chose the intradermal Tine test (Lederle Laboratories) for convenience, although we are ACTH responses (ng/l) to 12 mg cyproheptadine more familiar with the Mantoux. The Tine procedure delivers 5 tuberculin units (TU) + 24h + 48h + 72h Basal (2 samples) + 2h + 4h + 8h Case No and is the equivalent of a 1/2000 Mantoux 92 24 85 23 27 62 67 1 test. The "positives" in our paper (12 March, 44 2 36 29 37 55 38 25 p 676) conformed to the following criteria: the test leaves four puncture sites at the corners Further doses of 4 mg cyproheptadine given 6-hourly.
criptine has successfully lowered the plasma ACTH levels, thereby maintaining normal plasma cortisol levels with relief of symptoms and signs of Cushing's syndrome. One could
postulate that the action of bromocriptine on ACTH release may be similar to its action on growth hormone release and, as in some cases of acromegaly treated with bromocriptine, there is the bonus of return of sexual finction. A L KENNEDY D A D MONTGOMERY
BRITISH MEDICAL JOURNAL
23 APRIL 1977
to 235 nmol (68 mg)!24 h. The ACTH response to too little on the stepfather, who, as all fathers, a loading dose of 12 mg of cyrpoheptadine is shown is assuming in our society a much more in the table. Treatment was continued for six significant role in child rearing"; and only last weeks, the dose being 24 mg daily for the last three month the review panel on the case of Wayne weeks. At the end of this period there was subjective and objective improvement in muscle weak- Brewer published its findings on yet another ness. The mean UFC was reduced to 394 nmol case of a child killed by his stepfather. A recently completed research project (143 ,ug)/24 h (seven samples. A pituitary adenoma was subsequently removed at operation, with carried out in Norfolk, which studied all restoration of normal pituitary function in all children placed on the county's Nonrespects. Accidental Injury Register in a 12-month
The levels of UFC in both these patients were reduced by cyproheptadine and in the patient treated for six weeks clinical improvement was noted. ACTH levels appear to be reduced acutely by cyproheptadine, although this may be difficult to evaluate in view of the normal fluctuations of the hormone. We agree with others2 that cyproheptadine may be useful and free of side effects in patients with mild Cushing's disease who are unsuitable for surgery. In severe cases in which it is desired to improve preoperative fitness it may not be as effective as combined metyrapone-aminoglutethimide therapy. A W BuRRows C W BURKE
period, has found that male abusers outnumber females by three to two; and nearly one-third of the male abusers were stepfathers. The lesson seems clear: we cannot continue to ignore the role of the father in cases of nonaccidental injury. GEORGE MEREDITH Director of Social Services, Norfolk County Council Norwich
Fatal oxprenolol poisoning
SIR,-While Drs C J C Roberts and H McNulty (26 March, p 840) may be right in suggesting that hypernatraemia and cerebral Lamberts, S W J, and Berkenhager, J C, Abstracts Vth International Congress of Endocrinology, Radcliffe Infirmary, oedema may have contributed to the rapid Hamburg, 1976. No 492, p 201. Oxford loss of consciousness in a patient who had Besser, G M, Jeffcoate, W J, and Tomlin, S, Abstracts L H REES taken an overdose of oxprenolol and received Vth International Congress of Endocrinology, Hamburg, 1976, No 494, p 202. St Bartholomew's Hospital, a salt emetic, it has recently been demonstrated' London EC1 that oxprenolol in a single oral dose of 480 mg ' Child, D F, et al, Acta Endocrinologica, 1976, 82, 330. produced marked drowsiness in healthy Cyproheptadine and Cushing's disease 2 Krieger, D T, et al, New England journal of Medicine, volunteers, comparable to that produced by 1975, 293, 893. lorazepam 2 mg. A direct central depressant SIR,-We read with interest the recent report action of oxprenolol must therefore be conby Dr Jeremy Allgrove and others (12 March, sidered in an unconscious patient who has p 686) of the lack of response of a patient with Children at risk taken a dose in excess of this. Cushing's disease to cyproheptadine treatment. PAUL TURNER We would like to report the findings in two SIR,-Dr Margaret A Lynch and Ms Bartholomew's Hospital patients with pituitary-dependent Cushing's Jacqueline Roberts (5 March, p 624) have St Medical College, disease treated with cyproheptadine before researched the value of information available London EC1 pituitary surgery. in the perinatal period in the prediction of Farhoumand, N, et al, British Journal of Clinical Case 1-A 16-year-old boy presented with a child abuse. A significant number of the Pharmacology, 1977, in press. three-week history of headaches and altered facial abused group had two or more of the perinatal appearance. His blood pressure was 150/102 risk factors suggested, all of which were taken mm Hg. Mean (four samples) urinary free cortisol from information recorded routinely at the (UFC) was 2650 nmol (960,ug)/24 h (normal 28-280 maternity hospital. However, the fact that Tuberculin reversion rate nmol (10-100 ,g)/24 h). Midnight plasma cortisol was 825 nmol/l (30 4g/100 ml) (normal 140-280 100% of the controls also had two or more of SIR,-The result of the tuberculin survey nmol/l (5-10 ,ug/l00 ml)) and midnight plasma these risk factors suggests that we might have carried out in Glasgow in 1974 by Dr K M ACTH (corticotrophin) 76 ng/l (normal 10-80 to investigate about 10 % of all newborns. This Goel and others (12 March, p 676) is surprisng/l). Pituitary dependence was also confirmed by would seem too large a number for the inten- ing. According to table V in the paper only a positive response to metyrapone, 17-oxogenic sive follow-up necessary to prevent child six of 500 immigrant and native children steroid excretion rising from 85 lsmol (24-5 mg)/ abuse. It would be useful to have more infor- reacted positively to the Tine test although 24 h to 230 ,umol (66 mg)/24 h. Preoperatively he mation from the present survey on the per- 470 of them had previously been vaccinated was treated with metyrapone and aminoglut- centage of total births associated with two or with BCG. This is a remarkably high reversion ethimide.' This reduced the UFC to a mean of more risk factors and the percentage associated rate in vaccinated children whose mean age 315 nmol (114 jLg)/24 h (two samples). Cyprowas only 71 years. Postvaccinal tuberculin heptadine was added to his other treatment and later with child abuse. ACTH levels in response to a loading dose of sensitivity is usually much more enduring. PETER C CORRY 12 mg are shown in the accompanying table. The authors do not state what criterion they Area Craigavon Hospital, treatment During eight days' cyproheptadine used in interpreting the results of the Tine Co Armagh mean was reduced further UFC (16 mg daily) the tests. h exnmol On samples). to 182 (66 ug)/24 (four H G CALWELL ploration of the pituitary fossa two weeks later B T Adams) a necrotic adenoma was found SIR,-The article by Dr Margaret A Lynch Carrickfergus, (Mr C which was selectively removed with complete and Ms Jacqueline Roberts. on "Predicting Co Antrim relief of the Cushing's disease. child abuse: signs of bonding failure in the Case 2-A 51-year-old woman was investigated maternity hospital" (5 March, p 624) fails to ***We sent a copy of this letter to Dr K M for weight gain and generalised muscular weakness. consider the possibility that the father may Goel and his colleagues, whose reply is Her mean UFC was 605 nmol (220 jig)/24 h (two printed below.-ED, BM7. samples), midnight plasma cortisol 633 nmol/l sometimes be involved in cases of non(23 jig/100 ml), and midnight plasma ACTH accidental injury. Yet in 1974 the Maria 45 ng/l. A metyrapone test produced a rise of Colwell Committee observed that "too much SIR,-We accept Dr Calwell's point about our 17-oxogenic steroids from 71 nmol (20-5 mg)/24 h attention may be centred upon the mother and apparently high tuberculin reversion rate. We chose the intradermal Tine test (Lederle Laboratories) for convenience, although we are ACTH responses (ng/l) to 12 mg cyproheptadine more familiar with the Mantoux. The Tine procedure delivers 5 tuberculin units (TU) + 24h + 48h + 72h Basal (2 samples) + 2h + 4h + 8h Case No and is the equivalent of a 1/2000 Mantoux 92 24 85 23 27 62 67 1 test. The "positives" in our paper (12 March, 44 2 36 29 37 55 38 25 p 676) conformed to the following criteria: the test leaves four puncture sites at the corners Further doses of 4 mg cyproheptadine given 6-hourly.
