205

THYROIDECTOMY IN NON-THYROTOXIC HEART DISEASE.

By J o s ~ H LgWlS.

F OR many years a relationship between toxic thyroid conditions and cardiac disease has been reeognised, and actually Graves' disease was by some observers believed to be primarily a

disease of the heart. In more recent years methods introduced for the determination

of metabolism have revealed a persistent elevation of the metabolic rate in hyperthyroid conditions and a persistent lowering of metabolism in depressed thyroid states.

The high B.M.R. accompanying toxic goitres, when lowered by appropriate surgical or medical measures, is followed by a distinet improvement in the condition of the heart within a comparatively short time; indeed, auricular fibrillation of long standing may dis- appear entirely. This improvement in the cardiac condition, the slowing of the heart rate, and the increase in weight can only be attri.buted to and coincides with the lowering of the metabolic rate.

Blumgart has shown that a relationship exists between blood velocity and metabolism. Detailed observations on a large number of cases has clearly demonstrated that the velocity of the blood is determined by the metabolic requirements of the tissues. Thus, if the tissue metabolism increases there results from this elevated metabolic rate an increase in the speed of the blood proportionate to th8 rise in the metabolic rate. On the other hand, if the rate of metabolism falls the velocity of the blood slows correspondingly.

This relationship between blood velocity and metabolism is admir- ably demonstrated in the thyrotoxicoses and in the diametrically opposite condition, myxcedema; in the former both are increased~ and in the latter both speed and metabolism are reduced.

It would thus appear that an equilibrium exists between meta- bolism and blood velocity, and on the knowledge of this physiological fact lies the rationale of the treatment of certain ease8 of non- thyrotoxic heart disease by total ablation of the thyroid gland.

Blood Velocity. The blood velocity in normal adults as determined by the intra-

venous administration of sodium dehydrocholate (Decholin) is 16-18 seconds. This being a subjective test is open to a slight though insignificant error in time. The preparation is injected slowly into the median cubital vein, 5 c.cs. being given. The time of the commencement of the injection is noted and the patient indieate~ by raising his finger the moment he notices a peculiar taste in hi~ mouth. By using a 0"7 ram. diameter needle the blood velocity is determined as cited above.

Patients with valvular disease but with a fully compensated myocardium conform to these normal time measurements, but in subjects with decompensation the velocity rate is slowed, the rate varying with the degree of congestive failure.

206 IRISH JOURNAL OF MEDICAL SCIENCE

The metabolic rate in cardiac decompcnsation varies little if at all from the normal measurements of + 15 per cent. to - 15 per cent.

The accompanying chart shows the variations in velocity in normal individuals and in treated and untreated cases of cardiac disease.

Name Disease Cardiac Symptoms Velocity

None. None. Mr. L.

Mr. S.

M r . B . E .

Miss K.

Mr. B. (a)

Mr. B. (b)

Mr. W. (a)

Mr. W. (b)

Mr. X.

None.

Mitral stenosis.

Mitral s tenosis-- fibrillation.

Myocardial fai lure-- fibrillation.

Myocardial failure: given digitalis and aspirated.

Myocardial fa i lure-- fibrillation.

Myocardial fa i lure-- fibrillation.

Exophthalmic goitre.

None.

None.

Complete decompensation.

Oedema to groins, hydrothorax, etc.

Oedema to groins, hydrothorax, etc.

Thyroidectomy.

17 secs.

I6 secs.

16 sees.

42 secs.

31 secs.

21 sees.

28 sees.

29 sees.

1 2 s e e s .

The foregoing chart shows an acceleration of the blood in treated eases of heart failure, e.g., the velocity increas'mg from 31 to 21 soconds in the case of Mr. B. following digitalis, removal of transudate fluid and Salyrgan injections.

I t will be seen that while there are variations in the speed of the blood, the degree of retardation of the blood-flow depends on the degree of heart failure and that no matter what the blood speed may be the metabolic rate remains w~.thin nOlmlal limits.

I t is evident then that in congestive heart failure the equilibrium between the B.M.R. and the blood speed becomes upset--a dispro- portion exists between them, the blood velocity becoming retarded while the B.M.R. remains normal. Further, as the symptoms of the congestive failure become more pronounced the disproportion becomes more marked, the velocity of the blood becoming slower as the symptoms of decompensation become more manifest.

M yxo~dema. In this condition the reduced speed of the blood corresponds

closely, with the reduction in the B.M.R. This reduced blood velocity approximates closely to that observed in some cases of con- gestive heart failure, but in myxcedema no symptoms of decom- pensation were observed in spite of the greatly reduced blood velocity. It would appear, therefore, that the speed of the blood in myxcedema is adequate for the lowered tissue requirements in this disease.

This interesting observation demonstrates that the adequacy of a given speed of blood-flow can be decided only in relation to the metabolic requirements of the tissues.

I t was thought that if the equilibrium between blood velocity and

T t t Y R O I D E C T O M Y IN H E A R T D I S E A S E 207

B.M.R. could be re-established then symptoms of decompensation would improve. This can be done by either increasing the blood velocity or reducing the B.M.R. in patients with congestive failure. I f the B.M.R. could be reduced then the blood supply might be adequate at the reduced velocity to meet the lowered metabolic requirements of the tissues.

Angina Pectoris. This theory of lowering the metabolic rate of the body also applies

in the case of angina pectoris. Anginal pain results from an added load on the myocardium consequent on an increased demand by the tissues. The pain is due to a temporary isch~emia of the myocard[um following an insufficiency of blood travelling through narrowed coronary arteries. I f the B.M.R. be lowered then the tissue require- ments together with the intrinsic demands of the heart would be lessened and the coronary ar tery supply would become adequate for the needs of the myocardium at this artificially lowered rate of metabolism.

Methods of Reduction of Basal Met~balic Rate. The earlier attempts to reduce the B.M.R. were of only temporary

benefit owing to the remarkable powers of regeneration and hyper- plasia of the thyroid gland.

I rradiat ion of the gland was not attended by much success, Hemithyroidectomy and later subtotal thyroidectomy were per-

formed and brought about an improvement of short duration, but hyperplasia of the residual gland tissue restored the metabolic rate to its original level in a comparatively short time.

On account of the extraordinary powers of regeneration of the thyroid it was decided to remove the entire thyroid gland, thereby producing an artificial myxoedema.

The comparatively good results claimed by American workers from total ablation of the thyroid gland encouraged me to t ry this t reatment on two intractable cardiac cases both of whom had undergone prolonged medical treatment without lasting benefit:

Angina Pectoris. Cas~ I. A. F., a mate, aged 65 years, first complained of prmcordia!

pain in 193I. It commenced with effort, radiated to the left arm, and was accompanied by a feeling of tightness around the chest. The attacks became more frequent with time, and less effort was required to precipi- tate the pain, until it became impossible for him to pursue his occupation as a telephone mechanic. A short period of treatment in hospital brought about no lasting benefit, and by this time he had exhausted all the usual therapeutic remedies for this agonising and incapacitating disease.

In 1935 he was referred ~o me by Dr. Lynch. At this stage the slightest effort brought on a spasm. The effort of writing was impossible, while concentrated reading was at times too much. The pain radiated to the left side of his neck and face and down his arm. I t was of a very severe cramping nature and rendered the victim almost helpless. The pain ~as of variable duration, lasting from a few seconds to 20 or 30 minutes, and was of very frequent occurrence.

As his history of treatment had exhausted all the therapeutic remedies available and as the attacks occurred with the merest effort, I sugge6t~l an operation to him. Wish this suggestion he did not agree.

I saw him some months later, when his condition had become even more acute. I found him in a continuous anginal state. The pain was

208 I R I S H J O U R N A l , O F M E D I C A L S C I E N C E

more or less constant, turning in bed caused a spasm of pain, walking a few yards was almost impossible, writing was impossible. In this state of utter helplessness he volunteered for the operation which I had pre- viously suggested for, as he said, " his life was just a misery to him " in that state.

I admitted him to hospital on May 6th, 1935. He was confined to bed as a preoperative measure and while inve.~tigations were being carried out. Durin~ this period ~le had several attacks of anginal pain while in bed which w-ere relieved by amyl nitrite. On May 21st a severe attack was unrelieved by amyl ni tr i te but relieved by morphine sulphate (gr. i)-

Clinical In~es~igaf.ions. Cardio-vascular System.--The peripheral arteries soft and palpably

normal. Apex beat normal in position and in character of pulsation. Hear t sounds not abnormal and there were no organic murmurs. Systolic B.P. 120, diastolic 80 mm. Hg. Pulse, 70.

Elcctrocardiogram.--When first seen by me there were no electrographic abnormalities except for a slight left-sided ventricular preponderance (o|d nomenclature). At a, further tracing on May 18th, after some attacks

T wave became inverted in leads I and III . of anginal pain, the " Blood Ezaminations.--Wassermann test negative. Urea: 48 mgms. per

cent. Calcium: 10.5 mgms. per cent. Cholesterol: 190 mgms. per cent. Urine.--No deposit. No albumen. Urea concentration 2.7 per cent.

fasting, reaching 4 per cent. after two hours. Basal metabolic rate performed under difficulties in a large ward was

estimated at +43 per cent. Radiogram.--Some cardiac enlargement with calcified plaques in the

aorta. The appearance suggested atheroma of the aorta. Operation.--The investigations proving satisfactory, and as the

patient 's general condition was excellent, the total removal of the thyroid was undertaken on May 27th, 1935. Local anmsthesia was employed. There was little difficulty in removing the gland, which was adherent to its capsule over a small area. At this point o[ attachment a small piece of the gland was unfortunately left behind. The parathyroids were found and left in sit~. During the operation there was practically no disturb- ance in the pulse rate or in the blood-pressure, and under the influence of morphia the patient felt quite confident.

Postoperative His~ory.--Hoarseness and some dysphagia were com- plained of on the day following operation: these persisted for three weeks, after which his voice became normal again.

The anginal pain which he had experienced while in bed before opera- tion ceased immediately after removal of the gland. This complete freedom from pain persisted to the time of his discharge from hospital on June 25th, 1935, one month after the operation.

On this date his B.M.R. had fallen to +5 per cent., and his blood cholesterol had risen to 250 mgms. per cent. I s a w him periodically a f t e r his discharge from hospital, when he had compm~e aesence ot au pr~cardial discomfort. At first he feared to make any effort, but as his confidence grew and as, to his surprise, there was no repetition of pain, he grew somewhat bolder, until he was able to walk two to three miles at a time at an average walking pace of two and a half miles per hour. This newly-found lease was so complete that he expressed a desire to return to his former occupation.

Unfortunately the benefit, which had lasted for more than six months, was not maintained. Slowly and gradually the pain returned until i t reached the same intensity and frequency as before. I readmitted him to h~Jspital and made the following inves t iga t ions :~

Basal metabolic ra te : +22 per cent. Blood cholesterol: 276 mgms. per cent. Bloo~ calcium: 10.8 mgms. per cent.

I t will be observed that his B.M.R. has risen to +22 per cent. This elevation of metabolism can be accounted for only by the hyperplasia of the small residual piece of thyroid tissue left behind at operation, as the presence of an accessory thyroid was excluded at operation.

I t is seen t h a t whi le the B.M.R. was low there was comple te f r eedom f r o m pain, bu t on res tora t ion to a h ighe r level pa in : recurred; tha t is, a t a low level of metabo l i sm the coronary blood supp ly was adequa te fo r the t issue requ i rements , b u t a t the h i g h e r

T H Y R O I D E C T O M Y I N H E A R T D I S E A S E 209

level the blood s u p p l y to the m y o c a r d i u m was insufficient. This case demons t ra tes the necessi ty fo r comple te and total

e x t i r p a t i o n of the t h y r o i d fo r the re l ief of ang ina l pa in ; i t i l lus t ra tes also the degree of h y p e r p l a s i a which a t i n y piece o f t hy ro id t issue can unde rgo - - su f f i c i en t to res tore a no rma l B.M.R.

Congestive Hear~ Failure. CASE II. Mr. W., aged 67 years, was admitted to hospital in July,

1935, with unilateral a~dema of his legs extending to the groins. His scrotum was also (edematous, and there was a collection of transudato fluid in both pleural sacs. He had a persistent cough with marked dyspncea. His pulse was irregular (auricular fibrillation) and rather slow, 70-80 per minute. Two pints of fluid were removed from his left chest, and he was given digitalis and salyrgan. After several weeks he was discharged free from all symptoms and signs of cardiac failure.

In spite of maintenance treatment with digitalis the condition recurred. He was readmitted within five weeks of discharge. I t was decided, in view of the rapid recurrence of symptoms, te investigate his case with a view to thyroidectomy.

Physical Ezamination.--The apex beat was wavy, diffuse and outwardly displaced. A soft, mitral systolic murmur due to dilatation was present, and h., had auricular fibrillation. His pulse rate was 70, the apex rate 81 per minute. His peripheral arteries were not abnormally sclerosed for his age.

Inves~igations.-- Blood velocity: 28 seconds. B.M.R. : +~3 per cent. taken under unsuitable conditions. Blood urea: 32 mgms. per cent. Blo.~d calcium: 10.2 mgms. per cent. B13o=l cholesterol: 125 mgms. per cent.

Blood Wassermann test was negative. Urine--Deposit not pathological. Urea Concentration---2.2 per cent., reaching 3 per cent. in 2 hours. X~ray l~eport---Some transverse enlargement of the heart.

Congestion of lungs. Fluid in left chest. Electrocardiogram--Auricular fibrillation. ]'he clin:'cal, biochemic:~i and pathological examinations proving satis-

factory a total thyroidectomy was performed on Oct. 23rd, 1935, under local anmsthe.~i~ without any unpleasant events arising either during the operathm ~r in convalescence.

Histological examination of the thyroid revealed normal colloid features. Ten days after the operation he was allowed up for 20 minutes. A

month after the operation investigations revealed the fo l lowing :~ B.M.R. : +20 per cent. Blood velocity: 29 secs. Blood urea: 30 mgms. per cent. Blood cholesterol: 210 mgms. per cent. Blood calcium: 10.4 mgms. per cent.

X-ray showed the heart shadow slightly reduced. Electrocardiogram--Auricular fibrillation. No visible change. Subsequent History.--He was discharged from hospital nine weeks after

his operation. There was no evidence of cedema in either leg, though the patient had been walking about the ward for several weeks prior to his discharge. His cardiac reserve had greatly improved, and though he fel~ the cold somewhat more than usual he suffered no ill-effects whatever.

Later History.--Four months after his operation I admitted him to hospital again on account of. abdominal swelling. He was completely free from oedema of his legs, there was a complete absence of fluid in his pleural sacs and there was little or no respiratory distress, but the abdominal distension caused a certain degree of discomfort.

Investigations showed-- B.M.R.: +12 per cent. Blood cholesterol: 320 mgms. per cent. Blood calcium: 9.4 mgms. per cent. Blood urea: 48 mgms. per cent.

Electrocardiogram revealed auricular fibrillation of a slow rate and a lowering of the cardiac voltage.

210 I R I S H J O U R N A L OF M E D I C A L S C I E N C E

The abdomen was tapped and 6 pints of dark-coloured fluid were removed. Pathological examination of this fluid showed it to be an exudate and not transudation fluid. ]t was sterile. Abdominal examina- tion after removal of the fluid failed to reveal any cause for its presence. This fluid recurred with monotonous regularity every three weeks and necessitated removal of eight to ten pints on each occasion. In a series of 12 cases reported by S. A. Levine3 and others, one case had a recurring ascites following thyroidectomy, which they attributed to a Zuekevgu~ss- leber. ~lhis local peritonitis around the liver (perihepatitis) could readily have accounted for this fluid in view of a history of chronic alcoholism in ahis patient, but this alcoholic Etiology was not maintained by subsequent event~.

Two grains of thyroid extract were given thrice daily and the fluid completely disappeared, and has not since recurred. This dose of thyroid was not suificient to cause a recurrence of his symptoms of cardiac failure. At the same time the unpleasant feature of constant coldness was alleviated by the addition of thyroid extract without at the same time defeating the purpose of the thyroidectomy.

In view of the complete disappearance of the ascitie fluid by replace- ment therapy the " sugar-ice " liver cannot be responsible for this fluid. I am unable to supply a suitable explanation of Vhis relationship between the thyroid gland and this particular type of ascites. I t cannot be a mere coincidence.

Present history.--At the time of reporting this patient is entirely free from all symptoms of cardiac failure. He suffers very little from dyspnoea, and since the administration of thyroid extract suffers little if at all from cold. The ascites has entirely disappeared since he commenced taking thyroid extract, the dose being insufficient to cause a return of symptoms.

Mvc, hanism of Relief of Anginal Pai~. ~ The rapid and immediate relief of anginal pain following

thyroidectomy cannot be due to lowering of the B.M.R. The fall in the B.M.R. is slow and gradual. Weinstein, Berlin and others studied a series of cases and concluded that the early relief of pain was due to interruption of nerve impulses and was temporary.

This early relief is analagous to the early effects of cervical sympathectomy. Unilateral relief of pain following hemi- thyroidectomy would support this nervous factor in the early relief of pain. The pe rmanen t relief, however, is unassociated with nervous interruption, but is due to and coincident with a lowering of the metabolic rate in the consequent lessening of the demands on the myocardium. These two mechanisms are independent in their action and occur at different times post-operatively.

Chaz~es l~ollowing Campletr Thyroidectamy. 1. Blood Velocity.--The speed of the blood in heart failure is

unaffected by thyroidectomy; in fact, it may be slightly retarded. I t does not, however, increase the symptoms of failure because the supply is now adequate for the reduced requirements resulting from the lowered metabolic demands.

With a lowered blood velocity and a lowered B.M.R. the hear t ' s work is greatly lessened; in fact, it may be said to possess a " reserve ", i.e., the difference between the actual work at rest and at work.

2. Basal M~tabolic Rale.- -This falls in each case, and the greater the reduction in the B.M.R. the more marked appears the clinical improvement. When the B.M.R. reaches to - 2 0 per cent. symptoms

THYROIDECTOMY IN HEART DISEASE 211

of myxcedcma arise, such as coldness of the hands and feet and some roughening of the skin.

3. Myxeedema..--This develops slowly and may take several months. Symptoms begin to manifest themselves at - 20 per cent. and are definite at - 30 per cent. These symptoms can be readily kept under control by the administration of small doses of thyroid. The thyroid elevates the B.M.R. sufficient only to keep the symptoms of thyroid insufficiency in check, but has not the effect of reproduc- ing the original symptoms unless pushed to effect.

4. The H e a r t - - I n spontaneous myxcedema, the heart is usually enlarged. In artificial myx0edema similar cardiac changes are noticed. This enlargement has been variously attributed to dilata- tion and to myx~edematous infiltration. I t is possible that both factors are responsible, but the myx~<lematous factor is the more important causative agent. The beneficial effect on the size of the heart with thyroid administration would tend to support the myxoedematous agent.

The electrocardiogram shows a lowering of the Q.R.S. complete with a prolongation of the Q.R.S. time. The " T " wave may be flatter than usual and fibrillation if present becomes slower.

Indications for Operation. The operation is advisable only in selected eases after other

therapeutic measures have been given trial and proved insufficient. I t is considered advisable in chronic recurrent cases of cardiac dropsy in which medical measures have failed to give a more or less prolonged freedom from recurrence. In angina pectoris it would appear the benefits derived are best. I t should be advised only in cases with severe and frequent seizures and in those in whom little effort precipitates the attack. A low B.M.R. prior to operation ( - 15 per cent. or less) would render operation ineffective.

Condus/ons. 1. Two cases are reported in whom beneficial results followed

total thyroidectomy. 2. Complete ablation of the gland is absolutely necessary on

account of the regenerative capabilities of the thyroid. 3. Immediate relief of pain followed operation in the anginal

case and was maintained until the B.M.R. reasserted itself through incomplete thyroid removal.

4. An interesting relationship appears to exist between the thyroid gland and one variety of ascites.

5. The operation is attended with little if any risk to life in spite of a damaged myocardium, and is best performed under local anaesthesia.

6. Symptoms of myxcedema can be kept at bay by small doses of thyroid extract if neccesary.

References. 1. Blurngart: Arch. Int. Med., 19%, 52, 165. 2. Berlin, 1). : Am. Jo. Sur.q., 1933, 21, 173. 3. Levine, S. A. : New England Jo. Med., 1933, 209, 667. 4. Weinstein, A. : Am. Jr Med. Sei.; 1934, 187, 753.