aplastic antithyroid icpl4

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have been reduced if the patients had remained confined to bedor chair.

ALEXANDER KAHAN.St. James’ Hospital,

Balham, London S.W.12.

SIR,-Dr. Spencer, in his interesting paper last week,does not mention the blood-uric-acid levels of the two patientswho died. Hyperuricxmia is an invariable accompaniment ofthe fasting state,’ and the only two patients I have treated bythis method achieved blood-levels of 10’5 and 15.6 mg. per100 ml. Could hyperuricæmia sensitise the myocardium to theaction of catecholamines ?

A. M. W. PORTER.Church Hill,

Camberley, Surrey.

APLASTIC ANÆMIA AFTERPROPYLTHIOURACIL

SIR,—Antithyroid drugs (thiouracil, methylthiouracil, pro-pylthiouracil, methimazole, and carbimazole) are usuallylisted among agents associated with the development of

agranulocytosis, but bone-marrow aplasia rarely 2 followstheir use.3—5 The only case of aplastic anxmia which has beendescribed after propylthiouracil therapy is the one recentlyreported by Martelo et al. But, though their patient had bonemarrow aplasia with pancytopenia, the clinical course was "morein keeping with that of agranulocytosis " in the author’s ownwords. We report here a typical case of aplastic anaemia withsevere hmmorrhagic manifestations which followed propyl-thiouracil therapy.The patient, a 39-year-old man, was admitted to this

department with weakness, fatigue, palpitation, weight-loss,pallor, epistaxis, and petechiæ. Two months before he hadbeen diagnosed as having Graves’ disease and treated withpropylthiouracil in another hospital. In 3 weeks, he hadreceived 80 x 50 mg. tablets of this drug. A week after stop-ping propylthiouracil, he had begun to complain of epistaxisand weakness, for which he had been treated with blood-transfusions without much success.At admission the patient was well developed but looked

very pale and tired, with purpuric spots all over his body.He had pronounced exophthalmos and moderate diffusethyroid enlargement. Blood-pressure (B.P.) was 125/50 mm.Hg.; pulse-rate regular, 119 beats per minute; temperature37°C.

Investigations were as follows: red blood-cells (R.B.C.)1,350,000 per c.mm.; haemoglobin 35 g. per 100 ml.; packed-cell volume 13%; platelets 10,800 per c.mm.; white blood-cells 2600 per c.mm. (14% segmented neutrophils, 8% neutro-philic band forms, 10% monocytes, and 68% lymphocytes);bone-marrow aspirates from sternum and iliac crest were

hypocellular with 62% lymphocytes, 8% neutrophilic myelo-cytes, 10% neutrophilic metamyelocytes, 6% neutrophilicband forms, 4% segmented neutrophils, 1% plasma cells, 1%polychromatic macroblasts, 7% polychromatic normoblasts,and 1 % orthochromatic normoblasts; foetal haemoglobin5-7%, serum-iron 180;jt.g. per 100 ml., serum-cholesterol 135mg. per 100 ml., serum-protein-bound-iodine 7.5µg. per 100ml., basal metabolic rate +58%. No agglutination could bedemonstrated in the leucoagglutinin and platelet-agglutinintests,7 performed with and without propylthiouracil, usingpatient’s serum, with drug concentrations of 20, 30, and 40(l.g. per 100 ml.

Aolastic anaemia due to oroovlthiouracil was diasnosed.

1. Thomson, T. J., Runcie, J., Miller, V. Lancet, 1966, ii, 992.2. Trotter, W. R. J. New Drugs, 1962, 2, 333.3. Burrell, C. D. Br. med. J. 1956, i, 1456.4. Levine, B., Rosenberg, D. V. Ann. intern. Med. 1954, 41, 844.5. Poate, H. R. G. Med. J. Aust. 1957, ii, 208.6. Martelo, O. J., Katims, R. B., Yunis, A. A. Archs intern. Med. 1967,

120, 587.7. Dausset, J., Colombani, J., Okochi, K. Leukocyte and Platelet Agglu-

tination Immunological Methods; p. 539. Philadelphia, 1964.8. Harrington, W. J., Minnich, V., Arimura, A. K. Progress in Hæma-

tology; p. 166. New York, 1956.

Despite energetic treatment, which consisted of seven whole-blood transfusions in 3 weeks, the last two in plastic bags,250 mg. methyltestosterone (’ Testoviron’) weekly, and 12x 0-5 mg. tablets of dexamethasone daily, R.B.c. count increasedonly to 2,130,000 per c.mm., haemoglobin to 56 g. per 100ml., and platelets to about 100,000 per c.mm. In the mean-

time, an episode of sore throat was treated with penicillin.Unlike the case reported by Martelo et al.,6 spontaneous

clinical and haematological improvement did not follow dis-continuation of propylthiouracil. Now, about 2 months afterstopping propylthiouracil, the condition of the patient is verycritical. Hxmorrhagic manifestations (epistaxis, bleedingfrom the gums, and widespread purpuric spots) dominatethe clinical picture.The pathogenesis of drug-induced aplastic anaemia is still

obscure.9 No satisfactory evidence supporting an immunemechanism could be obtained from experimental investiga-tions. No leucocyte or platelet agglutinins could be found inour patient or in the patient of Martelo et al.6 Our patientreceived a moderate dose of propylthiouracil, daily and overall.Therefore it seems likely that the amount of the drug that hereceived did not play a significant role. Overall haematologicalside-effects occur in roughly 1-5% of patients treated withpropylthiouracil, and there is no consistent relation betweenthe dosage and the occurrence of haematological side-effects.10It seems likely that their occurrence depends on personalsusceptibility rather than on the quantity of drug used. Theavailable evidence does not enable us to say which, but thispersonal susceptibility might involve some essential metabolicprocess as yet undetermined.

MUZAFFER AKSOYSAKIR ERDEM.

Section of Hæmatology,2nd Internal Clinic of Istanbul Medical School,

Istanbul, Turkey.

TONSILLECTOMY AND ADENOIDECTOMY

SIR,—I am grateful to Dr. Alpert and his colleagues (lastweek, p. 1319) for confirming my impression that the mortalityfigures which they gave for the operations of tonsillectomy andadenoidectomy had been calculated before they drafted theiroriginal letter (May 25, p. 1149) and for explaining theirestimations in detail. They have been sadly misled by acceptingall the figures on which their calculations were based. Perhapsthey had some right to assume that figures quoted in theHospital In-Patient Enquiry would be completely accurate,but a calculation giving a mortality figure of 1 in 1355 is soclearly erroneous that it is surprising that it was cited withoutany attempt at verification, and that it has been repeated despitethe figures which I gave in my letter.

It is now known that a few hospitals committed fundamentalerrors in submitting their returns to the Hospital In-PatientEnquiry, and it has been verified that almost all of the fewpatients recorded in the survey as having died after theseoperations are in fact very much alive and well. It is not a case,as Dr. Alpert and his colleagues now suggest, that some ofthese deaths have been attributed to other events-they justdid not occur at all. As a result, the ratio which they calculatedso precisely has no basis in reality. A careful analysis of allpossible sources of information, including those referred to byDr. Alpert and his colleagues, has been undertaken by theGeneral Register Office and, as pointed out previously, thesefigures show that in the last three years for which there arerecords available there have been an average of 7 deaths peryear at a rate of 1 in approximately 27,000 operations.

It is unfortunate that any erroneous figures should beincluded in an official publication, but I think it is possible tounderstand how they could find their way into a large volumepacked with statistics. It is not so easy to understand the un-critical acceptance of such figures by workers submitting acritical apppraisal of the results of these operations.

D. RANGER.London W.I.

9. Wintrobe, M. M. Clinical Hæmatology; p. 785. Philadelphia, 1967.10. Bartels, E. C. Am. J. Med. 1948, 5, 48.