1346

1. Lancet, Feb. 27, 1960, p. 480.2. Lawson, J. D. New Engl. J. Med. 1958, 259, 761.

Letters to the Editor

" METABOLIC INSUFFICIENCY "

MARSHALL GOLDBERG.

SIR,- Your editorial, Goodbye to "Metabolic In-

sufficiency" made the strong inference that the lastword had been written concerning this controversialsyndrome, and further investigation had better beabandoned lest euthyroid hypometabolism (a preferabletitle) be denied its " quiet disappearance from the medicalliterature ". Unfortunately the argument cited, the

report by M. E. Levin-based on a " double-blind " studyconducted on only 6 patients-hardly supports such adecisive stand.

One might gather from the editorial comments of several ofthe medical journals that the " double-blind " study hasbecome a modern-day Holy Grail, relegating less ambitiousresearchers to ignoble ends. Be this as it may, one all-importantfactor which must be firmly established-particularly when ahormone is used in a " double-blind " study-is proper andadequate dosage. One can easily imagine the opportunitywhich might have been missed had Best and Banting decidedto put 5 units of insulin to the "double-blind

" test in the

treatment of diabetes. One might also recall the erroneous con-clusions reached in the British study comparing salicylates andcortisone (100 mg.) in the treatment of acute rheumatic fever.The experience of Kurland, Hamolsky, and Freedberg, as wellas my own in 32 cases, has clearly shown that the majority of" hypometabolic

" cases require a minimum daily dosage of

100,ug. triiodothyronine, and even then there is usually a timelag of two or three weeks before subjective or objectiveimprovement is observed. Thus, considering that a final

dosage of 75 f-lg. was given by Levin, and this for only twoweeks in one-third of patients and four weeks in two-thirds, it ishardly surprising that his results were equivocal. The time-

lag in the euthyroid hypometabolic patient before triiodo-thyronine affects the basal metabolism is in striking contrastto the prompt metabolic response to triiodothyronine in threeto five days in cases of true hypothyroidism.During the past three years, approximately 500 patients have

been screened in our endocrine clinic for euthyroid hypo-metabolism ; the majority of them were suspected of beingpsychoneurotic or hypothyroid. Among this group, 32

patients (6-4%) were believed to have euthyroid hypo-metabolism as judged by the following diagnostic criteria:

(1) A symptom-complex resembling hypothyroidism in certainrespects and psychoneurosis in others.

(2) Presumably normal thyroid (thyroxine) function as shown bya normal protein-bound iodine value (P.B.I.) and a normal rise inP.B.I. following the administration of thyrotrophic hormone.

(3) Objectively, a B.M.R. below minus 10% and a prolongedelectrometric recording of the free Achilles reflex. 2

(4) No response to placebo or desiccated thyroid, the latter givenin daily dosages up to gr. 5 or intolerance.

(5) A favourable response, both objectively (B.M.R. and reflexrecording) and subjectively, to proper amounts of triiodothyronine-on the average of 100-125 /(g. daily-and maintenance of suchimprovement over a minimum follow-up period of six months.

Previously a major drawback to screening patients for hypo-metabolism has been the absence of an objective parameter ofend organ metabolism, which is consistently abnormal in suchcases, and of a higher degree of accuracy, reliability, andreproducibility than the conventional B.M.R. procedure. (Only50% of B.M.R.s were abnormally low in these 32 cases whendone for the first time. The majority of patients had B.M.R.Srecorded on three consecutive days.) This situation has beenremedied by the finding that the contraction phase of theAchilles reflex (as measured electrometrically by the Lawsonapparatus) is significantly prolonged in both hypothyroidismand euthyroid hypometabolism in over 90% of cases, and .thatsuch an abnormality is only rarely encountered in otherdiseases affecting metabolic or neuromuscular function.

1. Segall, J. J. Lancet, 1953, i, 524.

Furthermore, neither the B.M.R. nor reflex recording showsimprovement in truly euthyroid hypometabolic patients givendesiccated thyroid or placebos or positive suggestion, butreturns to normal levels when triiodothyronine in adequatedoses is given. Since the " hypometabolic " patient oftenmasquerades clinically as a psychoneurotic and is usually mis-diagnosed as such, and since triiodothyronine is completelyeffective in relieving the so-called " psychoneurotic " com-plaints in the vast majority of " hypometabolic

" patients, itseems well worth screening such patients for hypothyroidismor euthyroid hypometabolism and thus spare them the fate ofthe true neurotic-dependence on tranquillisers or prolongedexpensive psychotherapy.The relationship between euthyroid hypometabolism

and " neurotic " behaviour is probably more than acasual one, although a precise cause-and-effect mechanismremains unknown. In fact, considering that all the tests ofthe functional capacity of the thyroid gland itself (incontrast to end organ metabolism) have been found to bewithin normal limits in the euthyroid hypometabolicpatient, the possibility remains that this syndrome is nota thyroid disease at all, but results from some cortico-hypothalamic factor or bodily dysfunction which affectsthe thyroid gland-particularly the formation and releaseof triiodothyronine-only secondarily, as happens, for

example, in hypopituitary myxoedema. In summary, it ismy present belief and experience that a syndrome ofeuthyroid hypometabolism does, in all likelihood, existand is worthy of further consideration and study-particularly, as to its pathophysiology and incidenceamong patients with psychodynamic complaints. Thestudy conducted by Levin should be regarded as a praise-worthy and important contribution to this enigma, buthardly the last word. The scepticism professed by TheLancet concerning the unsettled existence of euthyroidhypometabolism is looked upon as healthy and challenging,but an obituary is decidedly premature.

Worcester,Mass.

** Our annotation was intended as a challenge to

those who believe in the existence of this syndrome, andwe are delighted that Dr. Goldberg has responded. He

rightly points out that a " double-blind " trial is not

ipso facto sacrosanct and is often open to criticism onother grounds. Nevertheless, it seems to us that no firmconclusions can be drawn about the effects of therapy in acondition which " often masquerades as a psycho-neurosis " (Dr. Goldberg’s words), unless a double-blind procedure is employed. The obvious answer to ourcriticism would be for Dr. Goldberg to repeat Levin’sobservations, using the dosage and duration of therapywhich he considers adequate. Until he has done so (andthere is no indication in his letter that he has), we feeljustified in reserving judgment on his claim that " tri-iodothyronine is completedly effective in relieving theso-called psychoneurotic’ complaints in the vast

majority of’ hypometabolic ’ patients ".-ED. L.

CAUSE OF ŒDEMA IN " COR PULMONALE "

SIR,-In their article of May 28, Dr. Campbell andDr. Short state that oedema in chronic lung disease isnot closely correlated with a raised venous pressure.An absence of the urinary abnormalities of heart-failure (high specific gravity, proteinuria, cells, andcasts) 1 is further evidence against attributing the oedemain these cases to myocardial failure. Similarly, abdominalpalpation may fail to show the signs of passive venous