Postgrad Med J: first published as 10.1136/pgmj.29.330.215 on 1 April 1953. Downloaded from

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ACUTE By PAUL FOURMAN, M.D., M.R.C.P. Nuffield Department of Clinical Medicine, University of Oxford

In acute adrenal insufficiency we are faced with common in patients whose adrenal insufficiency is the interaction of many factors ; if in trying to due to than in patients with disentangle them I have cut some knots it is for Addison's disease. the sake of brevity. Addison's disease is characterized by a failure to Acute adrenal insufficiency may result from conserve sodium and we usually think of the crisis sudden loss of adrenal function by haemorrhage, of acute adrenal insufficiency as a condition of thrombosis or ablation. More often it-occurs in a brought about by salt depletion. This patient with chronic adrenal insufficiency, either might be true in a patient with Addison's disease in the natural course of the illness or following who is in crisis when he first presents ; in him the an such as'infection, operation or exposure. crisis is the climax of a long illness during which

Acute adrenal insufficiency is characterized by there has been time for the sodium stores to by copyright. prostration and collapse with low blood pressure become depleted. The sodium depletion may and rapid pulse. It is usually accompanied by represent a stress that released the crisis rather gastro-intestinal symptoms: anorexia, than the immediate cause of the shock-like state. and diarrhoea, and sometimes and Sodium depletion is not an essential feature of hiccup. Headache is common. The patient is at adrenal crisis. Adrenal crisis can develop in a first weak and apathetic but he may become rest- matter of hours, but it takes a few days for the loss less and confused, sometimes with high and swing- of sodium to produce a serious depletion. If the ing , before he finally lapses into a fatal coma. adrenal insufficiency has arisen suddenly depletion to if the Now, in patients with intact adrenal glands who of sodium has not had time develop ; http://pmj.bmj.com/ have been exposed to different types of injury or crisis has arisen in a patient already under treat- " stress " there is, underlying the specific response ment for Addison's disease depletion of sodium to each type of injury, a general response common will have been prevented by the previous treat- to all. This is the alarm reaction of Selye and is ment. These patients may show little bio- partly a result of discharge of adrenal . In chemical evidence of acute adrenal insufficiency the alarm reaction adrenal hormone is liberated beyond hypoglycaemia, and even this may be in large amounts and is probably rapidly con- lacking. In our ignorance we take refuge in saying sumed by the tissues. In Addisonian patients the that stress has produced an increased demand for on September 28, 2021 by guest. Protected alarm reaction cannot occur, but the response to adrenal hormone to which the adrenal glands are stress again follows a general pattern which we unable to respond. know as an adrenal crisis, so that in Addisonian It is important to distinguish between cases with patients too there is a non-specific response to and without salt depletion, for their treatment will injury. Presumably the reaction to injury of differ. In both instances the patients will need an patients with intact adrenals combines the effects active preparation of adrenal hormone to control of a discharge of adrenal hormone and another collapse and hypoglycaemia, and the greater the mechanism which is unmasked in adrenal in- precipitating stress the greater the demand for sufficiency. This other mechanism should account hormone; but the one group will also need to be for the rapid utilization of adrenal hormone in the given salt and may need to be helped to conserve alarm reaction. What this mechanism is we do not salt ; the other may be killed by an excess of salt know. Thyroid is one hormone that may increase and salt-retaining hormone, for the patient with the need for adrenal hormone, for thyroid may adrenal insufficiency can no more excrete salt in precipitate adrenal crisis in patients with hypo- the face of excess than conserve it in the face of pituitarism ; apart from this, adrenal crisis is less depletion. Postgrad Med J: first published as 10.1136/pgmj.29.330.215 on 1 April 1953. Downloaded from 1.6 POSTGRADUATE MEDICAL JOURNAL April 1953 It is possible that there is only one adrenal freely. Fever is no guide to whether or not these hormone in nature, but in practice among the patients have an infection. artificial hormone preparations that are available 3. If the patient is depleted of sodium; give 5 to us two important actions are divorced. The first per cent. glucose in normal saline intravenously, is to conserve sodium and discharge potassium; but not more than 3 litres in 24 hours. Stop-the the second is to control glycogen metabolism and drip as soon as possible after the patient begins to prevent hypoglrcaemia-associated ·with this take by mouth. Control the treatment by following second action isthe ability to resist stress. The two the serum sodium and the haematocrit. Watch for types of preparation are represented by the any sign of overloading with fluid. If the patient artificial compound deoxycortone acetate (DCA) is not depleted of sodium, very little saline may be on the one hand, and by cortisone on the other. needed; give io per cent. glucose in water intra- Whole adrenal extract probably combines both venously and glucose by mouth as soon as possible. actions, but compared to the whole extract DCA Control the treatment by the blood glucose. Here has an exaggerated effect on s6dium retention. the intake of fluid should not exceed z litres in the DCA has very little action other than to restore first 24 hours and thereafter depends on the electrolyte balance, but if the balance is upset this urinary output. An intake of I litre in excess of action may be life-saving. The main action of the urinary output is safe. Do not give large deoxycortone on electrolytes is to cause retention doses of DCA routinely. If needed at all, io mg. of sodium. It cannot retain sodium unless sodium or less may suffice on the first day and 5 mg. or less is given and the effect depends not so much on the on succeeding days. dose of deoxycortone as on the amount of sodium 4. Be extravagant with whole adrenal extract. that the patient is receiving. DCA has another Give 20 or 40 cc. into the drip and then io cc. effect on electrolyte balance, to cause a discharge every hour until the systolic blood pressure is of accumulated potassium from the body. This 8o mm., and every 2 hours until , vomiting, effect is greater, the greater the dose of DCA and abdominal pain and diarrhoea lhave stopped.

is excessive if DCA is given in e£cess. With cortisone it is possible to use less adrenalby copyright. DCA does not bear much relation to the hor- extract than hitherto but, because the extract can mone that is normally called forth and rapidly be given intravenously and cortisone cannot, we consumed in stress. This is more nearly.repre- still rely on adrenal extract for-a rapid effect. Two sented by the whole extract of the gland, and milligrams of cortisone are equivalent to I0 c.c. nowadays by cortisone, and perhaps in the future of extract. Cortisone acts more rapidly by mouth by (compound F) if it should be than intramuscularly, but if the patient cannot economically synthesized. These preparations swallow, cortisone must be given intramuscularly, ckuse a discharge of potassium but have only say 00oo or 200 mg. if no excess of DCA has been

minor effects on sodium. We know that this type given. As soon as the patient can take by mouth, http://pmj.bmj.com/ of hormone will prevent the hypoglycaemia of give 50 mg. followed by 25 mg. every 6 hours. adrenal insufficiency, but this is not enough to When symptoms have receded and for 3 days after explain why it should be essential to survival in that, the patient should have either extract, Io c.c. the face of stress such as exposure, operation, or every 4 hours, or cortisone I2.5 mg. every 6'hours. infection. It is hardly possible to give an overdose The patient is then ready for maintenance therapy of adrenal extract, but an' excess of DCA will and a small dose of cortisone, say 12.5 or 25 mg. limit the amount of cortisone that can safely be daily, can be given partly to replace DCA. The given, owing to the risk of potassium deficiency. cbrtisone may be given by mouth in four divided on September 28, 2021 by guest. Protected Adrenal crisis is an emergency during which the doses daily, in a mixture, or as an intramuscular patient may at any moment die ; treatment must injection of 50-Ioo mg. twice a week. These be prompt. In treatment our aim is: dosage schemes provide only a rough guide. In I. To treat the shock. particular the patient may require more adrenal 2. To remove the stress. hormone if there is persistent infection or other 3. To replenish sodium and give sugar. stress such as operation. 4. To supply adrenal hormone as required, and Some patients have a very stormy course and the 5. Not to kill the patient. blood pressure fails to rise. Infusions of plasma This may be elaborated: may be added to the treatment. Injections of i. Keep the patient warm and disturb him as adretaline (0.3- mg.) have been recommended but little' as possible--even a blanket bath may be may have an undesirable effect in increasing the lethal. Morphia is dangerous. Chart the pulse and pulse rate. Nor-adrenaline may have a place in the' blood pressure, at first hourly and later every the treatment of the , particularly to four hours, as in a patient with shock. prevent the sudden'collapse produced by adrenal 2. Look for any infection and use antibiotics surgery. It is given in a drip at a rate of 5-35 Postgrad Med J: first published as 10.1136/pgmj.29.330.215 on 1 April 1953. Downloaded from April 1953 FOURMAN: Acute Adrenal Insuffciency 217 micrograms a minute, with careful watch on the crisis. Patients with Addison's disease need much blood pressure. less cortisone than patients with rheumatoid arthri- The absolute count be a tis; tuberculosis is probably not aggravated when eosinophil may helpful cortisone is given in these physiological doses. guide to treatment but probably only after the Appetite improves, strength returns and mental first emergency is over. It is reasonable to aim at powers increase. Hypoglycaemia is controlled. The a count below 50 per cu. mm. in the presence of risk of sudden crisis and death is diminished. stress. Acute adrenal insufficiency can be forestalled 5. The patient may be killed by an excess of if one recognizes that any stress such as hard salt, fluid or DCA; the venous pressure does not physical work, infection or operation leads to an give warning of this. Autopsy may reveal pleural increased demand for hormone. In a patient who and pericardial effusions when there was no rise of cannot respond to this demand because he lacks venous pressure in life. adrenal glands large amounts of adrenal extract or Chronic adrenal insufficiency is usually due to cortisone should be given. Patients with adrenal destruction or atrophy of the adrenal glands but atrophy secondary to hypopituitarism or with it may complicate hypopituitarism and it may unilateral atrophy due to a contralateral tumour accompany adreno-genital virilism. In all these which is to be removed present a special case; diseases cortisone has a rational place in main- in them the adrenal glands may be stimulated with tenance treatment as well as in the treatment of adreno-corticotropic hormone. by copyright. .CORRESPONDENCE REQUEST FOR REPRINTS CONCERNING individual reprint requests to authors of whom we STRESS AND THE ADAPTIVE knew that they are currently engaged in research on stress and allied topics. Even this procedure DEAR SIR, did not give us the wide coverage which would be In perusing the current literature with which desirable, because it is materially impossible to this is concerned, we note that an ever- journal contact all these authors individually and it often http://pmj.bmj.com/ increasing number of its articles deals with prob- takes too much time to get the requested reprints. lems pertaining to research on ' stress' and the It is evident that in order to ensure prompt in- so-called 'adaptive hormones' (ACTH, STH, clusion of publications in the annual reports, these corticoids, adrenergic substances, etc.). surveys must develop into a co-operative effort We are writing you because, in our opinion, the between the authors of original papers and the re- success of research in this complex and rapidly' viewers. This co-operation has been greatly en- developing field largely depends upon the prompt hanced of late by the publication of announce- availability and evaluation of relevant publications, ments, in several medical journals, encouraging on September 28, 2021 by guest. Protected a task for which we should like to solicit the investigators interested in stress research to send assistance of your readers. us their reprints for this purpose as soon as they In 1950 our Institute initiated the publication become available. of a series of reference volumes entitled ' Annual We should be grateful if by the publication of Reports on Stress' (Acta Medical Publishers, this note you would also bring this problem to Montreal) in which the entire current world litera- the attention of your readers. ture is surveyed every year (usually between 2,000 We are, Sir, and 4,0oo publications). Up to now we have had Very sincerely yours, to compile the pertinent literature partly from HANS SELYE, M.D., Ph.D., D.Sc., F.R.S.(C.). medical periodicals, monographs, abstract journals and partly from reprints sent to us by the authors Professor and Director of the Institute of Ex- themselves. Of all these, reprints proved to be perimental Medicine and Surgery. the best source of data which we felt deserved ALEXANDER HoRAVA, M.D., prompt attention in our annual reports. Hence, Co-author of the 'Annual Reports on in the past, we have sent out several thousand Stress.'