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TOTAL ADRENALECTOMY IN RHEUMATOID ARTHRITIS
598
Letters
to
the Editor
TOTAL ADRENALECTOMY IN RHEUMATOID
ARTHRITIS
SiR,-The important role of the adrenal
cortex in the
rheumatoid arthritis was it was shown that administration of cortisone results in prompt and definite improvement in the symptoms of the active rheumatoid stated Selye had previously observed that " rheumatic " disease may represent a disease of adaptation due to endogenous corticoid intoxication, the rheumatic attack resulting from an excessive amount of mineralocorticoid hormone.2 In experiments on rats in which arthritis was produced by local injection of formaldehyde, Selye studied the diametrically opposed effects of mineralocorticoids (such as deoxycortone) and glucocorticoids (such as cortisone).3 On this basis, he suggested that the imbalance in the production of mineralocorticoids and glucocorticoids might be the mechanism of the abnormal response to stress-causing agents in the individual with rheumatic disease. Caughey and -MeCoy4 reported a case of Addison’s disease associated with recurrent polyarthritis, in which treatment with deoxycortone and salt repeatedly resulted in aggravation of joint symptoms, while remissions were consistently obtained when cortisone was administered and deoxycortone reduced. They subscribed in part to the contention of Selye that, in subjects with a preexisting tendency toward arthritic lesions, an imbalance between the mineralocorticoids and the glucocorticoids may precipitate an attack of rheumatic joint disease. The derangement of the normal relationship between corticosteroids and joint tissue may conceivably be due
pathological physiology firmly established when
to other factors.
It is
of
for instance, that an might be produced in a diseased state and result in rheumatoid joint disturbances; but such a hormone has not yet been identified. And again, the fault may lie somewhere along the metabolic pathway of the normal corticosteroid in its progression to the end-organ. No doubt, still other variations can be advanced on this hypothetical basis. Such theoretical assumptions might be clarified by observations in a rheumatoid patient subjected to total extirpation of the adrenals. It is also conceivable that total adrenalectomy followed by replacement therapy may result in remission of the active rheumatoid state, Since it or even in termination of the disease process. has been amply demonstrated that totally adrenalectomised patients can be maintained in a state of good health through proper replacement therapy, it is felt that this procedure is justified in carefully selected patients with severe rheumatoid arthritis.
possible,
abnormal adrenal corticosteroid
A 38-year-old Caucasian woman with rheumatoid arthritis of 14 years’ duration (stage III, class in, according to the classification of the American Rheumatism Association) was selected for total adrenalectomy because of her rapidly deteriorating condition, in spite of all standard therapeutic measures. Rheumatoid arthritis had been only partially controlled by cortisone in doses of 50-100 mg. daily for a period of nine months. The patient presented a " Cushingoid" appearance. After careful clinical appraisal and complete laboratory investigation, the patient was subjected to total adrenalectomy on July 28, 1954. Pathological specimens have been sent for study to the Worcester Foundation for Experimental Biology. The clinical aspects of this patient’s disease were profoundly altered immediately after the operation and have remained so up to the time of writing-42 days after the
operation. 1. Hench, P. S., Kendall, E. C., Slocumb, C. H., Polley, II. P. Proc. Mayo Clin. 1949, 24, 181. 2. Selye, H. Textbook of Endocrinology. Montreal, 1947 ; p. 863. 3. Selye, H. Brit. med. J. 1949, ii, 1129. 4. Caughey, J. E., McCoy, J. E. Ibid, 1951, ii, 1189.
Objective evidence so far indicates a favourable response. The classical signs of the active rheumatoid state, such as joint inflammation and effusions and signs of extra-articular activity, were abruptly terminated after surgery. The erythrocyte-sedimentation rate, which was 43 mm. in 1 hour (Westergren) just before the operation returned to 16 mm. in 1 hour by the 35th postoperative day. It is, however, premature to make a final evaluation of the response, and we want to make it particularly clear that these comments are not to be construed as a claim for permanent and complete remission of the rheumatoid state. The possibility of the presence and hypertrophy of aberrant adrenocortical tissue must be considered. Such tissue may have the capability of either normal or abnormal endocrine function. Appropriate studies of the clinical course of this Tta.tient
are
in
Ttrofrfsa
and will be TmbHshed later.
Pasadena, Ca,lifornia.
RICHARD D. MILLER ROBERT W. GENTRY HANS H. ZINSSER FRANCIS E. SCHLUETER.
LONDON’S PLANE TREES SIR,—The professional careers of many of us are linked with a number of London squares. Graduating at Queen Square, we travel on through Lincoln’s Inn Fields or Trafalgar Square to reach a haven in the vicinity of Cavendish Square. The tall and gracious plane trees of the last of these constitute a precious amenity of London life which is now threatened by the Government’s consideration of a plan to construct an underground car-park. The planners still hesitate to affirm that removal of the trees is essential ; but trial borings have been completed, and recent experienceof the cost to private sentiment of bureaucratic tidymindedness suggests that, unless we protest before they can say they have gone too far to draw back, all will be lost. The destruction of irreplaceable beauty for short-term advantage is the bane of existence in this country today. Any temporary improvement in parking facilitieswhether for doctors or others-would be far outweighed by the permanent loss to the spirit. I would far rather continue to abandon my car half a mile away than have it tidily at hand beneath a concrete desert garnished with a few consolatory flower-beds. All who share these feelings should take every opportunity, both as individuals and as members of the influential medical societies in the vicinity, to make the most forceful protests to the Minister of Transport and members of parliament before the demolition squads arrive. DAVID LE VAY. London, W.l. MEPHENESIN CARBAMATE IN SPASTIC DISORDERS
SIR,—The treatment of long-standing muscle spasm and I think that there may be interest in this preliminary note on the effects of mephenesin carbamate. Twenty mental defectives suffering from severe spastic disorders from birth were selected for the study ; ten were treated with standard mephenesin tablets (0-5 g.) and the other ten with mephenesin carbamate (’ Tolseram ’) tablets (0-5 g.)
presents major difficulties
All the patients had previously been treated with physiotherapy for long periods without any appreciable benefit. Following the start of drug therapy in September, 1953, they all continued to receive physiotherapy in the standard hospital class, the extent of their limb movement being accurately measured by the remedial gymnast, who was not informed of the particular drug being administered to individual patients. The investigation continued until last June, but both drugs were discontinued for several months at the middle of the trial because supplies of mephonesin carbamate could
This interval was used to observe any under the influence of physiotherapy alone.
not be maintained.
relapse
Letters
to
the Editor
TOTAL ADRENALECTOMY IN RHEUMATOID
ARTHRITIS
SiR,-The important role of the adrenal
cortex in the
rheumatoid arthritis was it was shown that administration of cortisone results in prompt and definite improvement in the symptoms of the active rheumatoid stated Selye had previously observed that " rheumatic " disease may represent a disease of adaptation due to endogenous corticoid intoxication, the rheumatic attack resulting from an excessive amount of mineralocorticoid hormone.2 In experiments on rats in which arthritis was produced by local injection of formaldehyde, Selye studied the diametrically opposed effects of mineralocorticoids (such as deoxycortone) and glucocorticoids (such as cortisone).3 On this basis, he suggested that the imbalance in the production of mineralocorticoids and glucocorticoids might be the mechanism of the abnormal response to stress-causing agents in the individual with rheumatic disease. Caughey and -MeCoy4 reported a case of Addison’s disease associated with recurrent polyarthritis, in which treatment with deoxycortone and salt repeatedly resulted in aggravation of joint symptoms, while remissions were consistently obtained when cortisone was administered and deoxycortone reduced. They subscribed in part to the contention of Selye that, in subjects with a preexisting tendency toward arthritic lesions, an imbalance between the mineralocorticoids and the glucocorticoids may precipitate an attack of rheumatic joint disease. The derangement of the normal relationship between corticosteroids and joint tissue may conceivably be due
pathological physiology firmly established when
to other factors.
It is
of
for instance, that an might be produced in a diseased state and result in rheumatoid joint disturbances; but such a hormone has not yet been identified. And again, the fault may lie somewhere along the metabolic pathway of the normal corticosteroid in its progression to the end-organ. No doubt, still other variations can be advanced on this hypothetical basis. Such theoretical assumptions might be clarified by observations in a rheumatoid patient subjected to total extirpation of the adrenals. It is also conceivable that total adrenalectomy followed by replacement therapy may result in remission of the active rheumatoid state, Since it or even in termination of the disease process. has been amply demonstrated that totally adrenalectomised patients can be maintained in a state of good health through proper replacement therapy, it is felt that this procedure is justified in carefully selected patients with severe rheumatoid arthritis.
possible,
abnormal adrenal corticosteroid
A 38-year-old Caucasian woman with rheumatoid arthritis of 14 years’ duration (stage III, class in, according to the classification of the American Rheumatism Association) was selected for total adrenalectomy because of her rapidly deteriorating condition, in spite of all standard therapeutic measures. Rheumatoid arthritis had been only partially controlled by cortisone in doses of 50-100 mg. daily for a period of nine months. The patient presented a " Cushingoid" appearance. After careful clinical appraisal and complete laboratory investigation, the patient was subjected to total adrenalectomy on July 28, 1954. Pathological specimens have been sent for study to the Worcester Foundation for Experimental Biology. The clinical aspects of this patient’s disease were profoundly altered immediately after the operation and have remained so up to the time of writing-42 days after the
operation. 1. Hench, P. S., Kendall, E. C., Slocumb, C. H., Polley, II. P. Proc. Mayo Clin. 1949, 24, 181. 2. Selye, H. Textbook of Endocrinology. Montreal, 1947 ; p. 863. 3. Selye, H. Brit. med. J. 1949, ii, 1129. 4. Caughey, J. E., McCoy, J. E. Ibid, 1951, ii, 1189.
Objective evidence so far indicates a favourable response. The classical signs of the active rheumatoid state, such as joint inflammation and effusions and signs of extra-articular activity, were abruptly terminated after surgery. The erythrocyte-sedimentation rate, which was 43 mm. in 1 hour (Westergren) just before the operation returned to 16 mm. in 1 hour by the 35th postoperative day. It is, however, premature to make a final evaluation of the response, and we want to make it particularly clear that these comments are not to be construed as a claim for permanent and complete remission of the rheumatoid state. The possibility of the presence and hypertrophy of aberrant adrenocortical tissue must be considered. Such tissue may have the capability of either normal or abnormal endocrine function. Appropriate studies of the clinical course of this Tta.tient
are
in
Ttrofrfsa
and will be TmbHshed later.
Pasadena, Ca,lifornia.
RICHARD D. MILLER ROBERT W. GENTRY HANS H. ZINSSER FRANCIS E. SCHLUETER.
LONDON’S PLANE TREES SIR,—The professional careers of many of us are linked with a number of London squares. Graduating at Queen Square, we travel on through Lincoln’s Inn Fields or Trafalgar Square to reach a haven in the vicinity of Cavendish Square. The tall and gracious plane trees of the last of these constitute a precious amenity of London life which is now threatened by the Government’s consideration of a plan to construct an underground car-park. The planners still hesitate to affirm that removal of the trees is essential ; but trial borings have been completed, and recent experienceof the cost to private sentiment of bureaucratic tidymindedness suggests that, unless we protest before they can say they have gone too far to draw back, all will be lost. The destruction of irreplaceable beauty for short-term advantage is the bane of existence in this country today. Any temporary improvement in parking facilitieswhether for doctors or others-would be far outweighed by the permanent loss to the spirit. I would far rather continue to abandon my car half a mile away than have it tidily at hand beneath a concrete desert garnished with a few consolatory flower-beds. All who share these feelings should take every opportunity, both as individuals and as members of the influential medical societies in the vicinity, to make the most forceful protests to the Minister of Transport and members of parliament before the demolition squads arrive. DAVID LE VAY. London, W.l. MEPHENESIN CARBAMATE IN SPASTIC DISORDERS
SIR,—The treatment of long-standing muscle spasm and I think that there may be interest in this preliminary note on the effects of mephenesin carbamate. Twenty mental defectives suffering from severe spastic disorders from birth were selected for the study ; ten were treated with standard mephenesin tablets (0-5 g.) and the other ten with mephenesin carbamate (’ Tolseram ’) tablets (0-5 g.)
presents major difficulties
All the patients had previously been treated with physiotherapy for long periods without any appreciable benefit. Following the start of drug therapy in September, 1953, they all continued to receive physiotherapy in the standard hospital class, the extent of their limb movement being accurately measured by the remedial gymnast, who was not informed of the particular drug being administered to individual patients. The investigation continued until last June, but both drugs were discontinued for several months at the middle of the trial because supplies of mephonesin carbamate could
This interval was used to observe any under the influence of physiotherapy alone.
not be maintained.
relapse