THE LIFE-HISTORY
OF THE FIRST CASE OF
MYXOEDEMA
TREATED BY THYROID
EXTRACT.
By GEORGE R. MURRAY, MD, D.C.L., F.R.C.P.,
Professor of Systematic Medicine in the Victoria
University,
and Physician. to the Royal Infirmary, Manchester;
Lately Colonel A.M.R. AND Consulting
Physician in Italy.
The development of the principles and practice of endocrinology during the last thirty years has been rapid and progressive. The practice of this branch of medicine has unfortunately not always been based o-sound physiological principles, so that glandular extracts have been given indiscriminately in many conditions with disappointing results. In the case of some preparations there is little evidence that the hormones they are supposed to contain are able to exert their normal physiological action when given by the mouth. It therefore may be of interest to complete the life-history of the first case of myxoedema successfully treated by thyroid extract – it has recently terminated at the age of 74 – the results obtained in this case not only afforded definite proof that the thyroid gland produced an internal secretion, but showed that the thyroidal insufficiency of myxoedema in man could be made good by maintaining an adequate supply of thyroidal hormones from an external source.
During the war we learned to appreciate more fully the value of the collective investigation of disease for which the aggregation of large numbers of men under military discipline and the co-operation of groups of medical officers provided the opportunity. A striking example of the results. to be obtained by this method had, however, already been furnished by the publication, in 1888, of the report of the special committee which was appointed by the Clinical Society[i] in 1883 to investigate the relation of myxoedema and allied conditions to the thyroid gland.
The history of the subsequent
developments of the treatment of these maladies as a direct result of the work
of this committee has just been so clearly given by Mr. Stephan Paget[ii](2)
that further reference to it is not necessary. It is, of course, well known
that the experimental work of Sir Victor Horsley, which was undertaken at the
request of this committee, first definitely proved that myxoedema, cretinism,
and cachexia strumipriva were due to loss of function of the thyroid gland. Although
at that time it had, not been proved that this function was to provide an. internal
secretion he suggested that grafting a portion of healthy thyroid gland would
be a rational method of treating these maladies.[iii](3)
The striking improvement which followed the adoption of this suggestion in
Bettencourt and Serrano's[iv](4)
case led me to suggest and carry out the treatment of myxoedema by thyroid extract
in the case whose complete life-history I now wish to record as an example of
the value of observation of individual cases over long periods of time in the
elucidation of certain problems in medicine.
Mrs. S., aged 46, was shown at a meeting of the Northumberland and Durham Medical Society on February 12th, 1891.[v](5) She had had a family of nine children, of whom six were living. At the. age of 40 she had a miscarriage, after which she had menstruated once, at the age of 42. When she was 41 or 42 years of age her relations had noticed that she was becoming slow in speech and action, and she herself began to find that it required a great effort to carry on her ordinary housework. The features gradually became enlarged and thickened and the hands and feet increased in size and changed in shape, so that at the time of this meeting she presented the typical features of an advanced case of myxoedema of at least four years' duration. After showing the patient, I stated my intention of, treating her with thyroid extract, and described the principles upon which this treatment was based and the reasons for expecting that it would be successful. The treatment was not commenced until two months later, and the following note taken on April 13th, 1891, describes her condition at that time:
She complains of languor, a disinclination to see strangers, and great sensitiveness to cold. The temperature is subnormal, and varies, between, 95.6° and 97.2° in the mouth. The pulse varies between 60 and 70. The face is blank and expressionless and the features are notably thickened. This change is well seen in the alae nasi and lips. The subcutaneous connective tissue of the eyelids is so swollen that she finds it difficult to look upwards. There is also considerable swelling beneath the eyes and of the cheeks. The hands and feet are both enlarged; the former have that peculiar shape which has been described as spade-like. The skin is very dry, there is no perspiration, and the superficial layers of the epidermis are continually being shed as a fine white powder. The hair is very fine in texture, and a considerable quantity of it has been lost. She is slow in answering questions; all her actions are slow and are performed with difficulty. The speech is remarkably slow and drawling and the memory is bad. No thyroid gland can be felt in the neck. The urine contains no albumin or sugar.
The experimental nature of the treatment was explained, and the patient, realizing the otherwise hopeless outlook, promptly consented to its trial. In order to ensure that the extract was properly prepared, the thyroid gland was removed from a freshly killed sheep with sterilized instruments and conveyed at once in a sterilized bottle to the laboratory where the glycerin extract was prepared, as elsewhere described.[vi](6) This extract was afterwards included in the British Pharmacopoeia of 1898 as "liquor thyroidei."
At that time care in obtaining the actual thyroid gland was necessary, as was shown by the experience of the late Dr. Michell Clarke, who, in the course of a discussion on a paper read by me at the annual meeting of the British Medical Association at Nottingham in 1892,[vii](7) stated that he had carried out the treatment without any benefit in two cases. Several years later Dr. Clarke kindly told me he had subsequently discovered that his want of success was due to the fact that. the butcher had been supplying thymus instead of thyroid gland for the preparation, of the extract. Even in recent years some thyroid preparations have proved to be inactive. In the treatment of this first case a hypodermic injection of 25 minims of the extract was given twice a week at first, and later on at longer intervals. The patient steadily improved, and three months later, on July. 13th, the condition was thus described:
The swelling has gradually diminished, and has practically disappeared from the backs of the hands, the skin over them being now loose and freely movable. The lips are much smaller. The swelling of the upper eyelids has diminished so much that she can look upwards quite easily. The swelling beneath the eyes and of the cheeks has also much diminished& The face consequently, as a whole, has greatly improved in appearance and has much more expression, as many of the natural wrinkles, especially about the forehead, have returned. The speech has become more rapid and fluent, the drawl being. scarcely noticeable at the present time. . She answers questions much more readily, the mind has become-more active, and the memory has improved. She' is more active In all her movements, and finds that it requires much less effort than formerly to do her housework. She now walks about the streets without any hesitation without a companion.
She has menstruated normally during -the last six weeks at the regular interval. For the last four weeks the skin has been much less dry and she perspires when walking. The hair remains as before. She is no longer so sensitive to cold. Unfortunately owing to circumstances a daily record of the temperature has not been kept, but out of four observations that have been made lately, about 11 a.m., three times the temperature has been 98.2℉ and once 97.4°.
After this the injections were given at fortnightly intervals, and later on, when the oral administration had been shown by Dr. E. L. Fox and Dr. Hector Mackenzie[viii](8) to be equally efficient, she took 10 minims by the mouth six nights a week, so that 1 drachm was consumed in the course of each week. On this dose she remained in good health, and free from' the signs of myxoedema. I have only seen this patient once during the last eleven years but Dr. Helen Gurney, medical registrar at the Royal Victoria Infirmary, Newcastle, has kindly kept her under observation, and has informed me that she continued to take liquid thyroid extract regularly until early in 1918, when it became difficult to obtain, so that she was given dry thyroid extract in a tablet instead. She enjoyed excellent health until early in 1919, when she developed oedema of the legs, and died in May of that year at the age of 74 from cardiac failure.
This patient was thus enabled, by the regular and continued use of thyroid extract, to live in good health for over twenty-eight years after she had reached an advanced stage of myxoedema. During this period she consumed over nine pints of liquid thyroid extract or its equivalent, prepared from the thyroid glands of more than 870 sheep.
The results obtained in this case show that:
1 The thyroid is purely an internal secretory gland.
2 The symptoms of myxoedema can be entirely removed, and the patient maintained in good health, by the continuous administration of thyroid extract.
3
The functions of this gland
in man can be fully and permanently carried on by the continued supply of thyroidal
hormones obtained from one of the lower
animals.
4 The duration of life need not be shortened by atrophy of the thyroid gland provided this substitution treatment is fully maintained, and so under these circumstances the prognosis of myxoedema is very good.
References
[i] Clinical Society's Transactions, Supplement, to vol. xxi.
[ii] Sir Victor Horsley: A Study of his Life and Works, by Stephen. Paget pp. 52-67.
[iii] British Medical Journal. February 8th, 1890f. p. 257
[iv] La Semaine Medicale, August -13th. 1890.
[v] Transactions of the Northumberland & and Durham, Medical Society., February. 1891
[vi] British Medical Journal, October 10th, 1891.
[vii] Ibid., August 27th,1892.
[viii] Ibid., October 29th, 1892
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