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ADRENAL INSUFFICIENCY
130
leave him wide discretion ; but they all have easy personal access to him and he cannot act without being sure of their general support. Naturally, on major issues the comitia must declare its policy formally, and its decision of April 11 in favour of giving evidence to the Royal Commission was reached without dissentient vote in a meeting of over 100 fellows. Though those present were not voting on the instructions of constituents, their decision must have taken account of the general opinion of the people with whom they worked-as was indeed apparent when the other Royal Colleges also expressed their intention of giving evidence to the commission. The truth is that, in times of strain, decisions are, on the whole, more likely to be taken objectively, with full attention to the public interest, by a group of responsible people voting as individuals than by a group of representatives who have to act on resolutions from below. Moreover, the representative cannot always be sure that such resolutions accurately reflect the views of his constituency ; for the constituents who elect him and give him his orders are sometimes no more than an energetic
do so there will be room, -even in medical politics, for representation of professional opinion by smaller bodies -with amateur status. As for the setback in professional unity which has so much disturbed the representative meeting, we see no reason for discouragement. Opinions differed sincerely and deeply on the correct response to the Government’s unhappy decisions on the pay-claim; but they differ -little if at all on the need to reach and a satisfactory settlement ; and if, when the Royal Commission has reported, such a settlement is not forthcoming, few will question the desirability of establishing again, if possible, the united professional front of a year ago. Colleges and association are, after
secure
all,
no
more
servants of
a
than limited
profession
means
to which
to
we
a
great end-
all
belong. But
by consultation between them a policy might be evolved which all would wholeheartedly supportremembering that even unity is worthless unless the strength
it
gives
is used
aright.
Annotations minority. The great advantages of democratic methods of ADRENAL INSUFFICIENCY representation should not blind us to these disadvantages, and the second of them applies conspicuously to TEN years ago adrenal insufficiency was rare ; but notv, the B.M.A. People belong to the association for many as a result of the therapeutic use of the corticosteroids, different reasons-because it is so useful to them ; it is common. Adrenal insufficiency is still often unrecog. because it does much invaluable work for medicine nised, and often it is fatal. A patient who has previously received the drug from a general practitioner may be or because they believe in professional unity and hope that, given support, the association will one day ignorant of the fact ; so may be his surgeon when operais subsequently required. In 1953 Salassa et al.’ develop into a fully representative organisation, satis- tion a that administration of cortisone left gave fying every kind of doctor. As might be expected from patients warning in a state of adrenal insufficiency which became the variety of their motives in joining, a substantial manifest only under the stress of operation, and then bi proportion of the members do not want to take part fatal collapse ; and in these columns Slaney and Brooke’J in medico-political activities, and seldom rise to the and Allanby3 have lately described evidence of thh surface of their silent pool. When, as recently, the sequence. At the Memorial Centre, New York, in one behaviour of a Government engenders emotion even year 1 out of every 300 surgical patients exhibitell among the more deeply submerged, attendances at adrenal hypofunction during or after, operation.4 Accordpractice is growing of administering cortisone meetings become impressive and large majorities are ingly the and after operation to patients who have received during thankfully recorded by the organisers. But these steroid therapy in the previous two years. It is impossible intermittent expressions of opinion cannot always be to detect cases in which adrenal function has been so taken at their face value : for example, there is reason depressed by the original therapy as to cause suscepti. to think that, among the practitioners themselves, the bility to subsequent operative stress ; all patients who B.M.A.’s proposed employment of planned withdrawal are known to have received corticoids have therefore to as a political weapon commanded less genuine support be given cover. Clearly it would be preferable to confine than was generally supposed. As a means of recording the risks inherent in cortisone administration3 to those what doctors really think, more use could perhaps be who are seriously deficient of corticoids, and there is, made of the referendum; but with this instrument, therefore, an urgent need for a test of adrenal insufficiency. of course, the validity of the answer will depend The eosinophil response to administration of cortico. trophin is too variable ; Hasner et awl. observed that little on whether the arguments, pro and con, are equally importance can be attached to responses of less than presented. As a society of educated people with. a 50%. The direct assay of glucocorticoids. in serum and scientific background, the B.M.A. has an exceptional urine after a stimulating dose of corticotrophin, though opportunity to develop a better technique of ascer- an obvious approach if a fairly constant level of normal taining opinion, and this in itself might be a consider- control could be assured, is complex and time-consumiM able service. But what may matter even more-if if the protein and glucuronide bound corticoids in the it seeks to speak for the whole profession-is that it serum are to be assessed ; the decrease in 17-ketosteroi’l should not only discover its minorities but actually excretion might provide a simpler though less direct cherish them and take pains to see that they are approach. High urinary sodium excretion in association with hyponatraemia may indicate a deficiency in mineralorepresented. In a democratic organisation there is corticoids ; Perlmutter has used this as a test6 to always the risk that the majority will acquire a kind 1. Salassa, R. M., Bennet, W. A., Keating, F. R., Sprague, R. G. of sanctity ; but nothing could be more foreign to a J. Amer. med. Ass. 1953, 152, 1509. 2. catholic professional body than the emergence, even Slaney, G., Brooke, B. N. Lancet, 1957, i, 1167. 3. Allanby, K. D. Ibid, p. 1104. in council, of a monolithic party. To suggest in this 4. Howland, W. S., Schewizer, O., Boyan, P., Dotto, A. C. J. Amer med. Ass. 1956, 160, 1271. way that the association should retain its outstanding 5. Hasner, E., Carlsen, K., Engdahl, I., Klaerke, N., Paaby, H. Schultze, B., Sprechler, M., Sprensen, B., Tobiassen, T. Adrenals qualities but shed their complementary defects may in Surgery. Copenhagen, 1952. be asking the impossible ; but until it finds means to 6. Perlmutter, M. J. Amer. med. Ass. 1956, 160, 117.
131 confirm the diagnosis of adrenal insufficiency but only when collapse had already occurred ; latent insufficiency is unlikely to be predictable from sodium metabolism, which becomes significantly distorted only when collapse is at hand. Serum-calcium levels may be worth studying, for Taylor and Cravendiscovered a 20-40% increase in 32 of 36 cats submitted to bilateral adrenalectomy ; further, hypercalcaemia has been reported in Addison’s disease 11 and in patients after adrenalectomy for Cushing’s syndrome.99 But these are circumstances of total adrenal failure, and we are concerned with a threshold state in which the endogenous hormonal production is adequate except when an added stress such as surgery is applied. A quick test is required which will indicate not only whether corticoid function is reduced but also whether the level is so low as to cause the patient to collapse under stress. WHERE DOES HYPERTENSION
BEGIN ? WHEN is a man hypertensive ?z? Many write as though hypertensives formed a clear-cut group like paraplegics; but, as we pointed out,lO the work of Hamilton et al.11 made it doubtful whether essential hypertension could be considered a disease ; and Dr. William Evans, whose article we published last week,l2 implies that some of those with mutable hypertension (hypertonia) are hardly to be regarded as diseased. Two further studies of the distribution of bloodpressure in a population confirm the arbitrariness of any limit set to the normal range. Boe et all managed to record the blood-pressures of no less than three-quarters of the entire adult population of the city of Bergen -some 69,000 people. In general the patterns found by Hamilton et al. are confirmed : the distribution of all pressures is approximately log-normal with considerable variance ; and both mean and variance increase steadily with age. The arithmetical mean of systolic and diastolic pressures behaves with especially striking regularity, suggesting that this value, though not identical with the true mean pressure, is close enough for practical use. Since the true mean pressure is the natural variable appropriate for indicating the stress on heart and arterioles, this estimate might well be used clinically to specify the blood-pressure, the pulse-pressure being usually of little clinical interest. Boe et al. also demonstrate a positive, but not very important, correlation of pressure with excess weight ; and they show that some discrepancies in the highest age-groups can plausibly be attributed to excess mortality among those with the highest pressures. Comstock 14 studied a much smaller sample, but one carefully constructed to be representative of his district in the south of the U.S.A. His figures conform to the pattern described, and he also establishes what had previously been suspected-that the pressures of American Negroes are somewhat higher than those of the Whites. Statistics such as these are an essential complement to clinical experience. The clinician sees many patients suffering from the results of high blood-pressure, but it now appears clear that for every such patient there exist several uncomplaining people of similar age and pressure, some of whom may continue indefinitely without ill effects. The statistics demonstrate the arbitrary nature of the definition of hypertension, and the magnitude of 7. Taylor, N. B., Craven, W. R. Amer. J. Physiol. 1927, 81, 511. 8. Leeksma, C. H. W., de Graff, J., de Cock, J. Acta med. scand. 1957, 156, 455. 9. Sprague, R. G., Kvale, W. F., Priestley, J. T. J. Amer. med. Ass. 1953, 151, 629. 10. Lancet, 1954, i, 1224. 11. Hamilton, M., Pickering, G., Fraser Roberts, J., Sowry, G. Clin. Sci. 1954, 13, 11. 12. Evans, W. Lancet, 1957, i, 53. See Ibid, p. 81. 13. Bøe, J., Humerfelt, S., Wedervang, F. Acta med. scand. suppl. 321. 14. Comstock, G. Amer. J. Hyg. 1957, 65, 271.
any programme of prophylaxis ; and, by implication, they show the need for a more exact prognosis (such as Dr. Evans’s clinical work suggests). At present blood-pressure can only be lowered at the cost, not only of constant medical supervision, but also of various unpleasant effects. Before he exposes symptomless hypertensives to the perils of mecamylamine ileus, veratrine emesis, reserpine psychosis, or hydrallazine lupus, a manometric Procrustes should be sure of his ground. BRAIN FUNCTION a prelude to the Neurological Sciences
As
of
First International
Congress
to be held in Brussels next
week, the Wellcome Historical Medical Library with the cooperation of the National Hospital, Queen Square, and the
Maudsley Hospital, organised a three-day Anglo-American symposium on the history and philosophy of knowledge of the brain and its functions. After the official opening by Mr. M. W. Perrin, chairof the Wellcome Foundation, the American Ambassador opened a number of important exhibitions arranged for the occasion, including centenary exhibitions in honour of J. F. F. Babinski, Victor Horsley, and Charles Sherrington. Formal sessions were held at all three centres on a variety of philosophical, historical, and clinical topics pertinent to present-day research concerning the relation of brain and mind. Evening receptions were held by the Wellcome Foundation and the Royal College of Physicians. The symposium ended with a dinner at Apothecaries’ Hall where guests were welcomed by Dr. Macdonald Critchley, the master, and Sir Henry Dale, chairman of the Wellcome Trust, proposed the toast of Anglo-American Cooperation in Science and Medicine.
man
TUBERCULOSIS AND DIABETES THERE is no doubt that tuberculosis-particularly pulmonary tuberculosis-is commoner in diabetics than in the population at large. At University College Hospital, London, all patients attending the diabetic clinic between January, 1940, and December, 1954, had a chest radiograph. Of 1851 patients, 34 were shown to have active pulmonary tuberculosis-18.2 per 1000, compared with1 4-9 per 1000 in the general population. Turner-Warwick has now described these cases in full and a further 11 in which the disease was discovered while the patients were under surveillance at the clinic. Apart from a preponderance of females, which was as might be expected from the known sex-distribution of diabetes, the tuberculosis had no special features, and the concept of " diabetic tuberculosis " 2 is firmly refuted. On the other hand, Turner-Warwick presents good evidence that the development of tuberculosis is a function of poor diabetic control, thus supporting Dunlop’s3 advocacy of strictness. In the past most tuberculous diabetics did badly ; their diabetes was harder to control and their tuberculosis progressed faster than if the diseases had existed separately. But since the discovery of powerful drugs effective against the tubercle bacillus the position has changed dramatically. At University College Hospital 25% of all diabetics treated for tuberculosis before 1950 died between three and seven years from its onset ; but no patient treated with anti-tuberculosis drugs has yet died from tuberculosis. Thosteson and Tibbits4 treated 294 diabetics with tuberculosis between 1940 and 1952. Of the 167 discharged before 1946 only 50 (30%) were alive in 1953 ; but of the 127 discharged since 1946, 73 (57%) remained well. 1. 2. 3. 4.
Turner-Warwick, M. Quart. J. Med. 1957, 26, 31. Steidl, J. H., Sosman, M. D. Amer. J. Roentgenol. 1927, 17, 625. Dunlop, D. M. Brit. med. J. 1954, ii, 383. Thosteson, G. C., Tibbits, R. S. J. Mich. med. Soc. 1953, 52, 1088
leave him wide discretion ; but they all have easy personal access to him and he cannot act without being sure of their general support. Naturally, on major issues the comitia must declare its policy formally, and its decision of April 11 in favour of giving evidence to the Royal Commission was reached without dissentient vote in a meeting of over 100 fellows. Though those present were not voting on the instructions of constituents, their decision must have taken account of the general opinion of the people with whom they worked-as was indeed apparent when the other Royal Colleges also expressed their intention of giving evidence to the commission. The truth is that, in times of strain, decisions are, on the whole, more likely to be taken objectively, with full attention to the public interest, by a group of responsible people voting as individuals than by a group of representatives who have to act on resolutions from below. Moreover, the representative cannot always be sure that such resolutions accurately reflect the views of his constituency ; for the constituents who elect him and give him his orders are sometimes no more than an energetic
do so there will be room, -even in medical politics, for representation of professional opinion by smaller bodies -with amateur status. As for the setback in professional unity which has so much disturbed the representative meeting, we see no reason for discouragement. Opinions differed sincerely and deeply on the correct response to the Government’s unhappy decisions on the pay-claim; but they differ -little if at all on the need to reach and a satisfactory settlement ; and if, when the Royal Commission has reported, such a settlement is not forthcoming, few will question the desirability of establishing again, if possible, the united professional front of a year ago. Colleges and association are, after
secure
all,
no
more
servants of
a
than limited
profession
means
to which
to
we
a
great end-
all
belong. But
by consultation between them a policy might be evolved which all would wholeheartedly supportremembering that even unity is worthless unless the strength
it
gives
is used
aright.
Annotations minority. The great advantages of democratic methods of ADRENAL INSUFFICIENCY representation should not blind us to these disadvantages, and the second of them applies conspicuously to TEN years ago adrenal insufficiency was rare ; but notv, the B.M.A. People belong to the association for many as a result of the therapeutic use of the corticosteroids, different reasons-because it is so useful to them ; it is common. Adrenal insufficiency is still often unrecog. because it does much invaluable work for medicine nised, and often it is fatal. A patient who has previously received the drug from a general practitioner may be or because they believe in professional unity and hope that, given support, the association will one day ignorant of the fact ; so may be his surgeon when operais subsequently required. In 1953 Salassa et al.’ develop into a fully representative organisation, satis- tion a that administration of cortisone left gave fying every kind of doctor. As might be expected from patients warning in a state of adrenal insufficiency which became the variety of their motives in joining, a substantial manifest only under the stress of operation, and then bi proportion of the members do not want to take part fatal collapse ; and in these columns Slaney and Brooke’J in medico-political activities, and seldom rise to the and Allanby3 have lately described evidence of thh surface of their silent pool. When, as recently, the sequence. At the Memorial Centre, New York, in one behaviour of a Government engenders emotion even year 1 out of every 300 surgical patients exhibitell among the more deeply submerged, attendances at adrenal hypofunction during or after, operation.4 Accordpractice is growing of administering cortisone meetings become impressive and large majorities are ingly the and after operation to patients who have received during thankfully recorded by the organisers. But these steroid therapy in the previous two years. It is impossible intermittent expressions of opinion cannot always be to detect cases in which adrenal function has been so taken at their face value : for example, there is reason depressed by the original therapy as to cause suscepti. to think that, among the practitioners themselves, the bility to subsequent operative stress ; all patients who B.M.A.’s proposed employment of planned withdrawal are known to have received corticoids have therefore to as a political weapon commanded less genuine support be given cover. Clearly it would be preferable to confine than was generally supposed. As a means of recording the risks inherent in cortisone administration3 to those what doctors really think, more use could perhaps be who are seriously deficient of corticoids, and there is, made of the referendum; but with this instrument, therefore, an urgent need for a test of adrenal insufficiency. of course, the validity of the answer will depend The eosinophil response to administration of cortico. trophin is too variable ; Hasner et awl. observed that little on whether the arguments, pro and con, are equally importance can be attached to responses of less than presented. As a society of educated people with. a 50%. The direct assay of glucocorticoids. in serum and scientific background, the B.M.A. has an exceptional urine after a stimulating dose of corticotrophin, though opportunity to develop a better technique of ascer- an obvious approach if a fairly constant level of normal taining opinion, and this in itself might be a consider- control could be assured, is complex and time-consumiM able service. But what may matter even more-if if the protein and glucuronide bound corticoids in the it seeks to speak for the whole profession-is that it serum are to be assessed ; the decrease in 17-ketosteroi’l should not only discover its minorities but actually excretion might provide a simpler though less direct cherish them and take pains to see that they are approach. High urinary sodium excretion in association with hyponatraemia may indicate a deficiency in mineralorepresented. In a democratic organisation there is corticoids ; Perlmutter has used this as a test6 to always the risk that the majority will acquire a kind 1. Salassa, R. M., Bennet, W. A., Keating, F. R., Sprague, R. G. of sanctity ; but nothing could be more foreign to a J. Amer. med. Ass. 1953, 152, 1509. 2. catholic professional body than the emergence, even Slaney, G., Brooke, B. N. Lancet, 1957, i, 1167. 3. Allanby, K. D. Ibid, p. 1104. in council, of a monolithic party. To suggest in this 4. Howland, W. S., Schewizer, O., Boyan, P., Dotto, A. C. J. Amer med. Ass. 1956, 160, 1271. way that the association should retain its outstanding 5. Hasner, E., Carlsen, K., Engdahl, I., Klaerke, N., Paaby, H. Schultze, B., Sprechler, M., Sprensen, B., Tobiassen, T. Adrenals qualities but shed their complementary defects may in Surgery. Copenhagen, 1952. be asking the impossible ; but until it finds means to 6. Perlmutter, M. J. Amer. med. Ass. 1956, 160, 117.
131 confirm the diagnosis of adrenal insufficiency but only when collapse had already occurred ; latent insufficiency is unlikely to be predictable from sodium metabolism, which becomes significantly distorted only when collapse is at hand. Serum-calcium levels may be worth studying, for Taylor and Cravendiscovered a 20-40% increase in 32 of 36 cats submitted to bilateral adrenalectomy ; further, hypercalcaemia has been reported in Addison’s disease 11 and in patients after adrenalectomy for Cushing’s syndrome.99 But these are circumstances of total adrenal failure, and we are concerned with a threshold state in which the endogenous hormonal production is adequate except when an added stress such as surgery is applied. A quick test is required which will indicate not only whether corticoid function is reduced but also whether the level is so low as to cause the patient to collapse under stress. WHERE DOES HYPERTENSION
BEGIN ? WHEN is a man hypertensive ?z? Many write as though hypertensives formed a clear-cut group like paraplegics; but, as we pointed out,lO the work of Hamilton et al.11 made it doubtful whether essential hypertension could be considered a disease ; and Dr. William Evans, whose article we published last week,l2 implies that some of those with mutable hypertension (hypertonia) are hardly to be regarded as diseased. Two further studies of the distribution of bloodpressure in a population confirm the arbitrariness of any limit set to the normal range. Boe et all managed to record the blood-pressures of no less than three-quarters of the entire adult population of the city of Bergen -some 69,000 people. In general the patterns found by Hamilton et al. are confirmed : the distribution of all pressures is approximately log-normal with considerable variance ; and both mean and variance increase steadily with age. The arithmetical mean of systolic and diastolic pressures behaves with especially striking regularity, suggesting that this value, though not identical with the true mean pressure, is close enough for practical use. Since the true mean pressure is the natural variable appropriate for indicating the stress on heart and arterioles, this estimate might well be used clinically to specify the blood-pressure, the pulse-pressure being usually of little clinical interest. Boe et al. also demonstrate a positive, but not very important, correlation of pressure with excess weight ; and they show that some discrepancies in the highest age-groups can plausibly be attributed to excess mortality among those with the highest pressures. Comstock 14 studied a much smaller sample, but one carefully constructed to be representative of his district in the south of the U.S.A. His figures conform to the pattern described, and he also establishes what had previously been suspected-that the pressures of American Negroes are somewhat higher than those of the Whites. Statistics such as these are an essential complement to clinical experience. The clinician sees many patients suffering from the results of high blood-pressure, but it now appears clear that for every such patient there exist several uncomplaining people of similar age and pressure, some of whom may continue indefinitely without ill effects. The statistics demonstrate the arbitrary nature of the definition of hypertension, and the magnitude of 7. Taylor, N. B., Craven, W. R. Amer. J. Physiol. 1927, 81, 511. 8. Leeksma, C. H. W., de Graff, J., de Cock, J. Acta med. scand. 1957, 156, 455. 9. Sprague, R. G., Kvale, W. F., Priestley, J. T. J. Amer. med. Ass. 1953, 151, 629. 10. Lancet, 1954, i, 1224. 11. Hamilton, M., Pickering, G., Fraser Roberts, J., Sowry, G. Clin. Sci. 1954, 13, 11. 12. Evans, W. Lancet, 1957, i, 53. See Ibid, p. 81. 13. Bøe, J., Humerfelt, S., Wedervang, F. Acta med. scand. suppl. 321. 14. Comstock, G. Amer. J. Hyg. 1957, 65, 271.
any programme of prophylaxis ; and, by implication, they show the need for a more exact prognosis (such as Dr. Evans’s clinical work suggests). At present blood-pressure can only be lowered at the cost, not only of constant medical supervision, but also of various unpleasant effects. Before he exposes symptomless hypertensives to the perils of mecamylamine ileus, veratrine emesis, reserpine psychosis, or hydrallazine lupus, a manometric Procrustes should be sure of his ground. BRAIN FUNCTION a prelude to the Neurological Sciences
As
of
First International
Congress
to be held in Brussels next
week, the Wellcome Historical Medical Library with the cooperation of the National Hospital, Queen Square, and the
Maudsley Hospital, organised a three-day Anglo-American symposium on the history and philosophy of knowledge of the brain and its functions. After the official opening by Mr. M. W. Perrin, chairof the Wellcome Foundation, the American Ambassador opened a number of important exhibitions arranged for the occasion, including centenary exhibitions in honour of J. F. F. Babinski, Victor Horsley, and Charles Sherrington. Formal sessions were held at all three centres on a variety of philosophical, historical, and clinical topics pertinent to present-day research concerning the relation of brain and mind. Evening receptions were held by the Wellcome Foundation and the Royal College of Physicians. The symposium ended with a dinner at Apothecaries’ Hall where guests were welcomed by Dr. Macdonald Critchley, the master, and Sir Henry Dale, chairman of the Wellcome Trust, proposed the toast of Anglo-American Cooperation in Science and Medicine.
man
TUBERCULOSIS AND DIABETES THERE is no doubt that tuberculosis-particularly pulmonary tuberculosis-is commoner in diabetics than in the population at large. At University College Hospital, London, all patients attending the diabetic clinic between January, 1940, and December, 1954, had a chest radiograph. Of 1851 patients, 34 were shown to have active pulmonary tuberculosis-18.2 per 1000, compared with1 4-9 per 1000 in the general population. Turner-Warwick has now described these cases in full and a further 11 in which the disease was discovered while the patients were under surveillance at the clinic. Apart from a preponderance of females, which was as might be expected from the known sex-distribution of diabetes, the tuberculosis had no special features, and the concept of " diabetic tuberculosis " 2 is firmly refuted. On the other hand, Turner-Warwick presents good evidence that the development of tuberculosis is a function of poor diabetic control, thus supporting Dunlop’s3 advocacy of strictness. In the past most tuberculous diabetics did badly ; their diabetes was harder to control and their tuberculosis progressed faster than if the diseases had existed separately. But since the discovery of powerful drugs effective against the tubercle bacillus the position has changed dramatically. At University College Hospital 25% of all diabetics treated for tuberculosis before 1950 died between three and seven years from its onset ; but no patient treated with anti-tuberculosis drugs has yet died from tuberculosis. Thosteson and Tibbits4 treated 294 diabetics with tuberculosis between 1940 and 1952. Of the 167 discharged before 1946 only 50 (30%) were alive in 1953 ; but of the 127 discharged since 1946, 73 (57%) remained well. 1. 2. 3. 4.
Turner-Warwick, M. Quart. J. Med. 1957, 26, 31. Steidl, J. H., Sosman, M. D. Amer. J. Roentgenol. 1927, 17, 625. Dunlop, D. M. Brit. med. J. 1954, ii, 383. Thosteson, G. C., Tibbits, R. S. J. Mich. med. Soc. 1953, 52, 1088