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Postgrad Med J: first published as 10.1136/pgmj.33.381.327 on 1 July 1957. Downloaded from 327

SUBACUTE By SELWYN TAYLOR, M.CH., F.R.C.S. Surgeon, King's College Hospital, Belgrave Hospitalfor Children, and Hammersmith Hospital; Lecturer in Surgery, Postgraduate Medical School of London

The term ' thyroiditis ' implies inflammation of to become much more common in that particular the gland, but by long usage it has come clinic. I had never seen an example before I950, to be used for a number of conditions in which but saw six in the next three years and pro- infection or trauma play apparently no part. Sub- gressively more each year since then. The con- acute thyroiditis is the title given to a condition dition is much commoner in women than men in which was first clearly described by de Quervain the ratio of about six to one. It has not yet been in I904 and which has been rediscovered, or re- reported in a child and is commonest in the fourth described, on a number of occasions since then, and fifth decades, although I have seen it in a with the result that it now has a multiplicity of student teacher of twenty-one. In our own series different names: granulomatous thyroiditis, giant- there was a history of a pre-existing in 50 cell thyroiditis, pseudotuberculous thyroiditis, per cent. of the patients. The incidence, compared creeping thyroiditis, struma granulomatosa, acute with that of Hashimoto's thyroiditis and Riedel's non-infectious thyroiditis, acute non-suppurative thyroiditis, varies widely in different clinics, but thyroiditis and de Quervain's thyroiditis. For those our own figures are most closely in agreement with who prefer eponymous nomenclature, the term those of Lindsay in San Francisco, who finds 'de Quervain's thyroiditis' offers a satisfactory Hashimoto's disease about io times as common as description of the disease. In recent years there de Quervain's and de Quervain's about io times copyright. have been some good reviews of the subject and as common as Riedel's. the reader is referred to Crile (1948), Hazard (I955), Lindsay (1952 and 1954) and Taylor Clinical Picture (I955). The onset is typically acute, the patient com- The article which de Quervain published in I904 plaining of a sore throat, , and a described a condition which he called non-purulent tender or even exquisitely painful thyroid gland, thyroiditis and this distinctly separated from other the pain radiating up towards the ears. The patient thyroid conditions what we here describe as sub- often sweats profusely at night and complains of acute thyroiditis. His article, which was beautifully weakness and lassitude. However, few patients http://pmj.bmj.com/ illustrated with photomicrographs, gave a clear require or wish to be admitted to hospital and they description of the condition which was only recog- may be able to carry on with their work, though nized, and even then under a variety of names, on feeling extremely weak while so doing. some 60 occasions in the next 30 years. In I936 The tenderness may start in one lobe of the Professor de Quervain, together with Dr. Gior- gland, but almost invariably spreads to the other danengo, of Turin, wrote a further account of the side until the whole of the thyroid is involved. The condition, fresh In is then and on adding eight examples. I948 thyroid gland moderately enlarged on October 3, 2021 by guest. Protected Crile again drew attention to the condition and palpation has a distinctive rubbery feel. It is firm emphasized that this was the same as pseudo- as in Hashimoto's thyroiditis, but the edges are tuberculous thyroiditis; it is probably more to this not so well defined, nor does the gland feel so surgeon than to anyone else that we owe the mobile in the neck. This, of course, is in keeping universal interest in this condition today. with the finding of many adhesions of the capsule to the surrounding tissues which tether the gland Incidence to the strap muscles. With the passage of time one It would be a truism to say that subacute of two things happens to the gland: either it thyroiditis occurs most commonly where it is most returns to a normal size and normal consistence commonly recognized, but, in fact, it is only where or fibrosis is so intense that the gland feels hard. clinicians are constantly thinking about the con- In the latter case the surface has the bosselated dition that it is diagnosed. Again, rather as in feel which is 6s typical of Hashimoto's disease, bird-nesting, it is the discovery of the first example and this irregularity, combined with hardness and which leads to the finding of many more; once fibrosis, makes the differentiation from cancer a the condition has been properly recognized it seems difficult one. Postgrad Med J: first published as 10.1136/pgmj.33.381.327 on 1 July 1957. Downloaded from 328 POSTGRADUATE MEDICAL JOURNAL July 1957 The progress of the disease is almost always to Laboratory Findings spontaneous resolution and this usually occurs Just as the clinical findings are so much more between three to six months after the onset. One important than the laboratory findings in Graves' patient under my care complained of symptoms disease, so in subacute thyroiditis too much for a little over a year, but this appears to be reliance should not be placed on special investiga- unusual. tions. However, they may provide valuable sup- portive evidence where the diagnosis remains in Differential Diagnosis doubt, but they also require considerable skill The early stages of de Quervain's disease, with in their interpretation, since they change with the fever, sweating and a painful swollen neck, may progress of the disease, which may extend from well be mistaken for signs of thyroiditis due to three to I2 months. acute bacterial inflammation. Whereas in acute The white cell count remains unaffected and the thyroiditis the causative organism is almost always relative proportions of lymphocytes and poly- discovered, the white cell count is raised and there morphonuclear leucocytes are unchanged. This is is a relative increase of polymorphonuclear leuko- in contrast with the changes seen in bacterial cytes; none of these is found in subacute thy- thyroiditis. The erythrocyte sedimentation rate roiditis. One confusing point, however, is that is raised and may be as high as 50 mm. Westergren both these conditions are often preceded by acute in the first weeks of the disease. No organisms infection in the upper respiratory tract and or viruses have so far been isolated from the especially a sore throat or tonsillitis. thyroid tissue or blood of these patients, but this The commonest condition which is mistaken for does not exclude their presence and, indeed, many subacute thyroiditis is haemorrhage into a nodule workers have felt very strongly that a virus was of a simple nodular goitre. When there is a solitary responsible. nodule almost filling one lobe of the gland and In the early weeks of the disease it is usual to there is haemorrhage into this, it is often very find that the radioactive iodine uptake in the neck difficult to be certain of the right diagnosis. The is zero and, since this is not seen in any other

patient has a painful swollen neck and the pain thyroid condition, it is one of the strongest pointscopyright. may radiate up to the ears, occasionally the tem- in favour of the diagnosis. As the months go by perature is elevated and certainly such patients the radioactive iodine uptake returns and after a almost always complain of malaise and fatigue. One year it is usual for it to be once more normal. important point of differentiation is that the ery- On the other hand, the level of protein-bound throcyte sedimentation rate (E.S.R.) is almost in- iodine in the serum may be high in the first weeks variably elevated in subacute thyroiditis. The of the disease (Lindsay, 1954), but subsequently other important differentiating test between the is lower than normal and does not return to the two conditions is that the radioactive iodine test usually accepted level of approximately 4 vg. per for uptake in the gland is nil in the early stages of cent. until after a year or 8 months has elapsed. http://pmj.bmj.com/ subacute thyroiditis, whereas there is always a fair A most useful ancillary method in coming to a uptake in simple nodular goitre. diagnosis in this disease is the employment of The most serious condition which may be con- needle biopsy. Many types of instrument have fused with subacute thyroiditis is carcinoma of the been used, but one of the simplest, which can be thyroidgland, especially the slow-growingpapillary carried ready sterilized in an ordinary clinical bag, form seen in young adults. Crile and Fisher (I953) is the Vim-Silverman split needle (Crile and described two patients in whom a needle biopsy Hazard, 1951; Taylor, 1955). The patient is asked had been done to confirm the diagnosis of subacute to lie on a couch and the neck is hyperextended by on October 3, 2021 by guest. Protected thyroiditis. When the tissue was examined it was means of a pillow. The skin is prepared with an found to contain carcinoma and the patients were antiseptic and then with a hypodermic needle a then treated by thyroidectomy. Finally, Hashi- tiny weal is raised using 2 per cent. Lignocaine. moto's thyroiditis may be mistaken for that of A tenotomy knife or spear-pointed scalpel is then de Quervain. Occasionally a rather florid form of used to nick the skin and the trocar and cannula Hashimoto's thyroiditis is seen, especially in of the Vim-Silverman needle is introduced, the males, and this offers many of the features of the thyroid being steadied with fingers placed behind clinical picture and pathological findings of sub- the sternomastoid. As soon as the needle is felt to acute thyroiditis. From the clinical point of view engage the surface of the gland, the trocar is the Hashimoto patients progress inevitably towards removed and the split needle inserted in its place myxoedema, which is not seen with the subacute and pushed forward so that the blades enter the cases, and, in addition, the pathologist sees the gland. The most important part of the manoeuvre plump red Askanazy or Hurthle cells together with then follows, which consists of holding the split much lymphoid tissue in the excised gland. part of the needle quite rigidly still and then Postgrad Med J: first published as 10.1136/pgmj.33.381.327 on 1 July 1957. Downloaded from July 1957 TAYLOR: Subacute Thyroiditis 329

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Actual specimen of needle biopsy after section pushing forward the outer cannula over the blades larged and this enlargement may be superimposed http://pmj.bmj.com/ so that they are brought together and grip a piece upon a previous simple goitre. The consistence of thyroid tissue. The needle is then twisted and is firm and the colour paler than usual, there being drawn out and should have between its blades a no increase in vascularity. It is noticeable that the core of biopsied material. The illustrations show capsule is thicker and becomes adherent to the the individual components of the needle and also surrounding structures, though in no way com- an actual specimen after it has been fixed and parable to the intense fibrosis seen in Riedel's sectioned. After the needle has been withdrawn The resembles most of all that

thyroiditis. gland on October 3, 2021 by guest. Protected it is necessary to apply firm pressure for a few seen in Hashimoto's disease, but is not so rubbery, minutes to the neck and then apply a small col- although the surface is similarly bosselated, and, lodion dressing over the skin wound. We have on the whole, it feels tougher when cut with a made a rule of asking the patient to remain lying knife. down for at least a quarter of an hour after this The histological changes depend on the stage form of biopsy and no serious complications have of the disease at which the tissue is examined; in so far resulted. An excellent account of the tech- the beginning there is a generous infiltration by nique has been given by Hamlin (I955, I956). lymphocytes and plasma cells which tend to be Heptinstall and Eastcott (1954) have described the arranged in clumps. The follicles may appear removal of a portion of the isthmus in making the largely normal, but in certain foci follicular cells diagnosis of thyroiditis and this is a very suitable will be seen to have swelled up and disrupted and alternative technique. the aggregations of their nuclei mimic giant cells, hence the name giant-cell thyroiditis. True giant Pathology cells may also appear ad-. itis,possible that they The gland in subacute thyroiditis is always en- phagocytose the colloid from the destroyed fol- Postgrad Med J: first published as 10.1136/pgmj.33.381.327 on 1 July 1957. Downloaded from 330 POSTGRADUATE MEDICAL JOURNAL July 1957

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.' Section showing increase in fibrous stroma, Postgrad Med J: first published as 10.1136/pgmj.33.381.327 on 1 July 1957. Downloaded from July 1957 TAYLOR: Subacute Thyroiditis 331 licles. With the passage of time the fibrous stroma sensitivity to such circulating toxins. The response becomes greatly increased and fibrosis is the most of the condition to cortisone is very suggestive of prominent feature of the histology. The changes such a mechanism, but much further evidence will are seen in the accompanying three photomicro- have to be obtained before a satisfactory working graphs, which illustrate typical areas from biopsy hypothesis is capable of being presented. Finally, specimens obtained by a needle. Perhaps the Perloff (I956) has recently reported five cases of most important point in differential diagnosis his- following proven attacks of sub- tologically is that of papillary carcinoma. Certainly acute thyroiditis. macroscopically the two conditions may appear very similar when confined to focal areas and it is Treatment only by examination under the microscope that an Since subacute thyroiditis is a self-limiting appreciation of the difference is obtained. Most disease any form of treatment may eventually be workers who have studied the histological changes given claims which they do not really deserve and, in subacute thyroiditis have been impressed with in fact, a multitude of different therapies have been the resemblance which it sometimes shows with suggested. The first landmark was the announce- Hashimoto's disease and with certain features of ment by King and Rosellini (i945) that thiouracil hyperthyroidism. Indeed, there are occasionally in ordinary doses caused cessation of pain and patients in whom the diagnosis remains in doubt constitutional symptoms within a few days of being both clinically and histologically and it should not started by mouth. The possible mechanisms be thought that an absolutely clear distinction can which have been put forward to explain this are be made between different forms of thyroiditis. that thiouracil potentiates the action of T.S.H. On the whole, most glands can be put into the from the pituitary. As described above, Robbins category of Hashimoto's, Riedel's or de Quervain's and his colleagues (195i) describe similar good thyroiditis, but this is not always so and only long results with injections of T.S.H. and certainly the observation of the patient gives the final answer. uptake of radioactive iodine by the thyroid is reinstated by this technique. Crile originally

Aetiology advocated the use of radiotherapy for this con- copyright. There is no proven factor in the aetiology of this dition, but most of us have given up its employ- form of thyroiditis, but there is certainly no lack of ment because, although a response can usually be speculation. Cultures of the material have always obtained, it is desirable to avoid X-ray therapy proved negative, but since the condition often when other forms of treatment are equally effec- follows infection in the upper respiratory tract a tive. Recently a number of workers have described virus has been incriminated. Fraser and Harrison good results from the use of cortisone (Clark, (1952) suggested such an aetiology, but Lindsay Nelsen and Raymond, I953; Titleman and Rosen- was unable to demonstrate the histological features, burg, 1953; Lasser, I953; and Kahn and his such as inclusion bodies, which it might be ex- colleagues, I953). On the whole, this has been http://pmj.bmj.com/ pected should be present. Certainly some of the found the best form of therapy and seldom fails to histological changes might be considered, due to produce a response in about a week's time. The the fact that the colloid acts as a foreign body drug has to be continued by mouth until the disease when the follicles disrupt, and some of the phago- reaches a natural remission, and this can only be cytic changes seen would fit in with this. Fraser found by experiment. Small doses of cortisone are suggested that the virus affected the follicular cells usually adequate after the first week and it is most much as thiouracil does in hormone pro- desirable that the dosage be kept to the lowest level blocking on October 3, 2021 by guest. Protected duction, but it is interesting that giving thiouracil which gives an adequate clinical response. It may to such a patient usually relieves the condition and be added that carbimazole in 5-mg. doses three allows iodine uptake. Possibly this is due to the times a day produces an equally good result and potentiation of thyrotrophic hormone which may eventually be reduced to only 5 mg. a day, thiouracil is known to bring about. In support of but it is not unusual to get some increase in the this is the work of Robbins and Rawson, who size of the gland and cortisone provides a more demonstrated that patients with subacute thyroid- satisfactory form of treatment at the present time. itis were relieved of their symptoms and again It should also be added that no kind of antibiotic showed a radioactive iodine uptake in the neck has been found to produce any response. when injected with thyrotrophic (T.S.H.) hor- mone. My own view is that this condition results Postscript from a localized hypersensitivity to toxins, prob- Some interesting new work stems from an ably those from streptococci, as the condition so observation by Cooke and Wilder in 1954 that the commonly follows a sore throat. Just as in Henoch- serum colloidal gold curve in Hashimoto's disease Schonlein's purpura, where there is a hyper- is usually abnormal. They added to this the belief Postgrad Med J: first published as 10.1136/pgmj.33.381.327 on 1 July 1957. Downloaded from 332 POSTGRADUATE MEDICAL JOURNAL July 1957 that liver changes usually accompanied the con- Surgical Progress 1955 for the blocks which appear dition (Cooke and Luxton, 1955) and a larger in this article. confirmatory series appeared from the Cleveland Clinic (Skillern, I956) last year. The raised y globulin levels, their delayed return to normal BIBLIOGRAPHY after thyroidectomy and the infiltration of the CLARK, D. E., and NELSEN, T. S. (I953), Jour. Amer. med. Ass., with cells and COOKE,R. T., and WILDER, E. (I954), Lancet i, 984. thyroid lymphocytes, plasma lym- COOKE, R. T., and LUXTON, R. W. (955), Ibd., i, 968. phoid tissue prompted Roitt et al. (1956) to look CRILE, G., Jr. (I948), Ann. Surg., 127, 640. CRILE G., Jr., and FISHER, E. R. (I953), Cancer, 6, 57. - for an immune response. They have reported a CRILE, G., Jr., and HAZARD, J. B. (i95I), J. clin. Endocr., precipitin reaction of serum with extract of human 1, 1123. thyroid gland and they postulate that it parallels CRILE, G., Jr., and RUMSEY, E. W. (950o), J. Amer. med. Ass., DE QUERAIN F. (1904), Mitt. Grenzgeb. Med. Chir., 2, Supp., the destruction of the patient's own thyroid, and DE QUERVAI, F., and GIORDANENGO, G. (I93S), bid., the an 44 538 especially colloid, by auto-antibody. FRASER R., and HARRISON, R.J. (I952), Lancet, i, 382. It might well be expected that in subacute HAMLIN, E., Jr., and VICKERY, A L. (956), New Eng. J. a Med., 24, 742. thyroiditis similar positive flocculation test would HAZARD, J. B. (955) Amer. din. Path., 25, 399. be obtained and W. R. Trotter and D. Doniach in- HEPTINSTALL, R. I., and..EASTCOTT, H. H. G. (i953). Brit. j. Surg., 41, 471. form me that they have obtained a positive reaction KAHN, J., SPRITZLER, R. J., and SHECTOR, W. E. (g193), in the Ann. intern. Med., 39, I29. serum of two patients with this disease. KING, B. T., and ROSELLINI, L. J. (x94s), J. Amer. med. Ass., For those who are interested in recent advances 12, , 267. LASSER, R. P. (93), Ibid., 152, 133. in problems of immunology and LINDSAY, S., DAILEY, M. E., FRIEDLANDER, J., YEE, G., is and SOLEY, M. H. (1952) .. din. Endocr., 12, 1578; also there an excellent leading article in the Lancet, Trans. Amer. Ass. Goiter (1952), pp. 384-411. Vol. I, p. which reviews the LINDSAY, S., and DAILEY, M. E. (I954), Surg. Gynec. Obstet., May 25, 1957, 1075, 98, 197 whole subject up to the present time. This has PERLOFF, W. H. (x9S6), . clin. Endocr., x6, 542. now become one of the frontiers ROBBINS J., RALL, J. E., TRUNNELL, J. B., and RAWSON, rapidly expanding R.W. (i95x) Ibid.,Ix,txo6. of ROITT, I. M., bONIACH, D., CAMPBELL, P. N., and HUD- thyroid investigation. SON, R.V. (I956) Lancet, ii, 820. SKILLERN, P. G., ChILE, G., McCULLAGH, P., HAZARD, Acknowledgment J. B., LEWIS, L. A., and BROWN, H. (i956), J. din. Endoer., 6, 35. copyright. We are indebted to the publishers of British TAYLOR,T S. (t955), 'Brit. Surg. Progress,' pp. 148-x60, London. RUTHIN CASTLE, NORTH WALES A Clinic for the diagnosis and treatment of Internal Diseases (except Mental or Infectious Diseases). The Clinic is provided with a staff of doctors, technicians and nurses. http://pmj.bmj.com/ The surroundings are beautiful. The climate is mild. There is central heating throughout. The annual rainfall is 30.5 inches, that is, less than the average for England. The Fees are inclusive and vary according to the room occupied. For particulars apply to THE SECRETARY. Ruthin Castle, North Wales. Telegrams: Caetle. Ruthi. Telpomes: Ruchi 66 on October 3, 2021 by guest. Protected

Bibliography continued from page 126--ames Crooks, M.B., M.R.C.P.(Lond. and Ed.), F.R.F.P.S.G. FRANKLIN A. L., LERNER, S. R. and CHAIKOFF, I. L., McCULLAGH, E. P., HUMPHREY, D. C., McGARVEY, C. J., ( 944), 34, 265. and SUNDGREN, V. (I951), J. Amer. med. Ass., 147, xo6. GODLEY, A. F., and STANBURY, J. B. (I95)4, . clin. Endocr. McCULLAGH, E. P., and SURRIDGE, W. T. (x948), J. cin. x4, 70. Endocr., 8, o05I. GOODWIN, J. F., STEINBERG, H., and WILSON, A. (1954). MACGREGOR, A. G., and MILLER, H. (I953), Lancet, i, 88r. Brit. med.J., I, 422. MACGREGOR, A. G., and SOMNER, A. R. (1954) Ibid., ii, 93x. GRIESBACH, W. E., KENNEDY, T. H., and PURVES, H. D. PEMBERTON, J. J., HAINES, S. F., and KEATING, F. R. (1941), Brit. J. exp. Path., 22, 249. (1949), J. din. Endocr., 9, I232. HIMSWORTH H. P. (1948), Brit. med. Y., 2, 6i. PLUMMER, H. S. (1923), 7. Amer. med. Ass., 80, x955. IVERSEN K. (I95), Y. din. Endocr., xI, 298. SOLEY, M. H. (1942), Arch. intern. Med., 70, 2o6. KENNEDY, T. H. (1942), Nature (Lond.), 150, 233. STANLEY, M. M., and ASTWOOD, E. B. (x947), Endocrinology, KRISS, J. P., CARNES, W. H., and GROSS, R. T. (z955), 41 66. 7. Amer. med. Ass., 157, 117. STANLEY, M. M., and ASTWOOD, E. B. (I949), Ibid., 44, 588. LAWSON, A., RIMINGTON, C., and SEARLE, C. E. (r95), WILLIAMS, R. H., TOWERY, B. T., ROGERS W. F., TAG- Lancet, U, 6I9. NON, R., and JAFFE, H. (1949), . clin. Endo., 9, 80. MARINE, D., BAUMANN, E. J., SPENCE, A. W., and CIPRA, A: WOLFF J., CHAIKOFF, I. L., GOLDBERG, R. C., and (1932), Proc. Soc. exp. Biol. (N.Y.), 29, 772. MEER, J. R. (949), Endocrinology, 4, 504.04. MOORE,F. D. (1946), . Amer. med. Ass., 130, 315. WYNGAARDEN, J. B., WRIGHT, B. M., and WAYS, P. (s952), MORGANS, M. E., and TROTTER, W. R. (1954), Lancet, i, 749. Ibid., 50, 537.