antithyroid action of p.a.s

538

ANTITHYROID ACTION OF P.A.S.

I. M. LIBRACH.Ilford Isolation Hospital,Chadwell Heath, Essex.

SIR,—Clausen and Kjerulf-Jensen have describedthree cases of thyroid enlargement with myxcedemaduring p-arikiiiosalieylie acid (P.A.s.) therapy, andKomrower has reported another. I should like to add afurther case. .

An unznairied-woman, aged 23, was admitted to hospitaloU’Jiily -3, 1951, with pulmonary tuberculosis of two years’duration, clinically affecting the right lower lobe. A. chestradiograph showed, in addition to the disease at the rightbase, some apparently new lesions at the left base. In viewQt’ this, cheifnotherapy was decided upon. Thiosemicarbazoner Ethizone ’)(starting dose 50 mg., then 150 mg. daily) andsodium P.A.S. (3 g. four-hourly) were given.On Sept. 17 (eleven weeks later) she complained of a swelling

in the neck, and a soft diffuse, non-pulsatile, slightly tenderswelling of the thyroid gland was felt. The pulse-rate wasnormal and the blood-pressuire was 100/7AO mm. Hg. Therewas no exophthahnos or sweating. Both drugs were stoppedimmediately ; a total of 1170 g. of P.A.S. and 7- 75 g. of ethizonehad been given. She was watched for further signs of disturbedthyroid function, but none developed.

Five weeks later (Oct. 23) the swelling had subsided. Thechest radiograph was unchanged. Further progress wasuneventful ; the -left basal signs subsided, leaving the rightside unchanged.-On June 18, 1952 (about eleven months later), the thyroid

gland was just palpable. Her weight had remained steady at7st. 7½ lb.- The patient has an immature and hysteriaal- personality.She has had an unhappy home life with life-long episodesindicative of instability and insecurity. She is prone to

temper-tantrums and on Jan. 1, 1952, had a prolonged episodeof this sort. A psychiatrist advised certification if she proveddifficult to manage, but she has since been quiet andcooperative.

Investigations.—Sept. 22, 1951: Sputum contained scantyatypical acid-fast bacilli ; barium swallow normal-; laryngo-scopy, no gross tracheal compression ; erythrocyte-sedimenta-tion rate 4 mm. in first hr. (Westergren) at room-temperature ;white blood-cell count 4400 per c.mm. (polymorphs 61 %,lymphocytes 20%, monocytes 4%, eosinophils 14-5%, baso-phils 1%) ; blood-cholesterel 270 mg. per 100 ml. ; basalmetabolic-rate -22 (a further test was refused) ; weight7 st. 9 lb.

Dec. 18 : Hb 87%; blood-cholesterol 100 mg. per 100 ml.weight 7 st. 13 lb.

It was natural to speculate whether either of the twodrugs had caused the thyroid depression.

Bergqvist and de Mare described a patient who died ofhypothyroid goitre and cerebral oedema after treatment with’ Conteben,’ and another who had definite hypothyroidsymptoms after prolonged treatment with P.A.S., dihydro-streptomycin, and conteben. Domagk 4 however had neverheard of an instance during conteben therapy. Mertens and

Bung did not mention thyroid enlargement in a. review ofconteben toxicity, neither did the report of the pilot trialof the British Tuberculosis Association 6 or Nagley’s reviewof thiosemicarbazones" 7 A full account of anti-thyroid drugsby Suter 8 also made no reference to it. For these reasons,ethizone was discounted.

That P.A.S. could be responsible is borne out byKomrower’s case 2 and the 3 Norwegian cases.! In thecase described here. apart from the thyroid swelling,lowered B.M.R., and high normal blood-cholesterol, therewere no overt signs of hypothyroidism, unlike the otherreported cases. Unfortunately the patient refused a

further B.M.R. test, and return to normal had to be

judged clinically. The high eosinophil-count is interestingand may be evidence of drug allergy.1. Clausen, A. K. H., Kjerulf-Jensen. K. Nord. Med. 1951. 45, 475.2. Komrower, G. M. Brit. med. J. 1951. ii. 1193.3. Bergqvist. N., de Mare, O. Nord. Med. 1951. 45, 474.4. Bomagk, G. Irish J. med. Sci. 1951. p. 474.5. Mertens, A., Bung, R. Amer. Rev. Tuberc. 1950, 61, 62.6. British Tuberculosis Association. Tubercle, 1951, p. 217.7. Nagley, M. M. Practitioner, 1952, 168, 523.8. Suter, C. M. In Medicinal Chemistry. New York and London,

1951; vol. I. p. 405.

Kjerulf-Jensen and Wolffbrandt 9 have shown that rats

fed with P.A.S. and rra-aminophenol developed moderatecellular hyperplasia of the thyroid gland. Using radioactiveiodine, Hanngren 10 found that uptake of iodine in the thyroidgland during P.A.S. therapy was inhibited in 3 patients. He

thought that enlargement of the thyroid was compensatony.and caused by increased formation of pituitary thyrotropichormone. He considered that when P.A.S. is given thera-

peutically a certain blood concentration will inhibit thyroxinesynthesis - just as -thiouracil does. Doses in excess of the

patient’s thyroid sensitivity may cause myxoedema.As in the other cases, the therapeutic effect of P.A.S., if any,

did not appear to be antagonised by its antithyroid effect.which may even be beneficial in itself. The metabolic-rate uusually normal in active tuberculosis,l1 but whether a decreasedrate is an advantage is debatable.

Nash 12 however gave thiouracil to 3 patients in 1947, withunexpected spread of the tuberculous lesions as a result. Iremember a girl, aged 16, with thyrotoxicosis and pulmonarytuberculosis who was treated with thiouracil in 1945, and thetuberculosis became worse. It is interesting to note thatMadigan et al.13 suggested that the B.M.R. might rise duringP.A.S. therapy, though whether a rise precedes a fall is speculative in the absence of serial tests.The effect of myxcedema on tuberculosis is of interest.

Pagel 14 merely stated that affections of the thyroid are

reputed to be associated rarely with tuberculosis-i.e., theyare antagonistic to its development. Other authoritiesare more pessimistic, and say that untreated cases of myx.oedema may die of intercurrent infections such as tuberculosis- i.e., their resistance to the disease must be lowered.

In the case reported here gross swelling of the thyroidsubsided within five weeks of stopping the drugs, thoughit was still palpable after one year. Obviously the longeradministration is continued after the thyroid swellinghas appeared, the greater is the risk of myxœdematouschange. Komrower’s case developed after nine months’treatment. The short period of three months in this caseperhaps explains the minimal thyroid changes. Whetherirreversible damage can occur is speculative.

Alternatively the thyroid swelling could be ascribedto an unstable endocrine system associated with mentalinstability, but the lowered B.M.R. is against this. Nash 11wondered whether the antithyroid effect of P.A.S. couldexist without clinically obvious hypothyroidism. This case

suggests that it can.I should like to thank Dr. J. Spencer and Mr. J. Mallard,

A.I.M.L.T., for the metabolic investigations, Mr. L. Whittaker,A.I.M.L.T., for the other investigations, and Dr. G. L. Brownfor his help.

9. Kjerulf-Jensen, K., Wolffbrandt, G. Acta. Pharmacol. scand.1951, 7, 376.

10. Hanngren, A. Lancet, 1952, ii, 117.11. Kayne, G. G. In Pulmonary Tuberculosis by G. G. Kayne.

W. Pagel, and L. O’Shaughnessy. London, 1939; p. 306.12. Nash, F. A. Lancet, Aug. 2, 1952, p. 245.13. Madigan D. G., Griffiths, L. L., Lynch, M. J. G., Bruce, R. A.,

Kay, S., Brownlee, G. Ibid, 1950, i. 239.14. Pagel, W. In Pulmonary Tuberculosis. London, 1939.15. Fishberg, M. Pulmonary Tuberculosis. Philadelphia, 1932.16. Tidy, H. L. Synopsis of Medicine. London, 1939 ; p. 874.17. Rich, A. R. Pathogenesis of Tuberculosis. Springfield, Illinois,

1946.

AMŒBIC ABSCESS OF BONE

SIR,—Amœbic abscesses have now been described inmany tissues of the body. In this part of West Africa,where amoebiasis is heavily endemic, it has to be con-sidered in the differential diagnosis of many clinicalconditions.

I have recently had under my care an African man of theMende tribe who complained of a hard painful lump in themiddle of his thigh. Two years ago he was treated at this

hospital for amoebic dysentery with a course of 6 injections ofgr. 1 of emetine. There was no recurrence of dysenteric orother symptoms until the onset of fever, malaise, and pain inthe left thigh one month before I saw him.The patient was emaciated and looked ill; on the middle

third of the left femur there was a tender mass about 8 cm.

long ; it was fixed to the bone, and though firm it was not

bony hard ; there was no detectable fluctuation, although themass was clearly palpable through the wasted muscles. X.l’3:’