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Page 1: SUBACUTE THYROIDITIS - Postgraduate Medical Journal · 327 SUBACUTE THYROIDITIS BySELWYNTAYLOR, M.CH., F.R.C.S. Surgeon, King's College Hospital, Belgrave Hospitalfor Children, andHammersmithHospital;

327

SUBACUTE THYROIDITISBy SELWYN TAYLOR, M.CH., F.R.C.S.

Surgeon, King's College Hospital, Belgrave Hospital for Children, and Hammersmith Hospital;Lecturer in Surgery, Postgraduate Medical School of London

The term ' thyroiditis ' implies inflammation ofthe thyroid gland, but by long usage it has cometo be used for a number of conditions in whichinfection or trauma play apparently no part. Sub-acute thyroiditis is the title given to a conditionwhich was first clearly described by de Quervainin I904 and which has been rediscovered, or re-described, on a number of occasions since then,with the result that it now has a multiplicity ofdifferent names: granulomatous thyroiditis, giant-cell thyroiditis, pseudotuberculous thyroiditis,creeping thyroiditis, struma granulomatosa, acutenon-infectious thyroiditis, acute non-suppurativethyroiditis and de Quervain's thyroiditis. For thosewho prefer eponymous nomenclature, the term'de Quervain's thyroiditis' offers a satisfactorydescription of the disease. In recent years therehave been some good reviews of the subject andthe reader is referred to Crile (1948), Hazard(I955), Lindsay (1952 and 1954) and Taylor(I955).The article which de Quervain published in I904

described a condition which he called non-purulentthyroiditis and this distinctly separated from otherthyroid conditions what we here describe as sub-acute thyroiditis. His article, which was beautifullyillustrated with photomicrographs, gave a cleardescription of the condition which was only recog-nized, and even then under a variety of names, onsome 60 occasions in the next 30 years. In I936Professor de Quervain, together with Dr. Gior-danengo, of Turin, wrote a further account of thecondition, adding eight fresh examples. In I948Crile again drew attention to the condition andemphasized that this was the same as pseudo-tuberculous thyroiditis; it is probably more to thissurgeon than to anyone else that we owe theuniversal interest in this condition today.Incidence

It would be a truism to say that subacutethyroiditis occurs most commonly where it is mostcommonly recognized, but, in fact, it is only whereclinicians are constantly thinking about the con-dition that it is diagnosed. Again, rather as inbird-nesting, it is the discovery of the first examplewhich leads to the finding of many more; oncethe condition has been properly recognized it seems

to become much more common in that particularclinic. I had never seen an example before I950,but saw six in the next three years and pro-gressively more each year since then. The con-dition is much commoner in women than men inthe ratio of about six to one. It has not yet beenreported in a child and is commonest in the fourthand fifth decades, although I have seen it in astudent teacher of twenty-one. In our own seriesthere was a history of a pre-existing goitre in 50per cent. of the patients. The incidence, comparedwith that of Hashimoto's thyroiditis and Riedel'sthyroiditis, varies widely in different clinics, butour own figures are most closely in agreement withthose of Lindsay in San Francisco, who findsHashimoto's disease about io times as common asde Quervain's and de Quervain's about io timesas common as Riedel's.

Clinical PictureThe onset is typically acute, the patient com-

plaining of a sore throat, malaise, fever and atender or even exquisitely painful thyroid gland,the pain radiating up towards the ears. The patientoften sweats profusely at night and complains ofweakness and lassitude. However, few patientsrequire or wish to be admitted to hospital and theymay be able to carry on with their work, thoughfeeling extremely weak while so doing.The tenderness may start in one lobe of the

gland, but almost invariably spreads to the otherside until the whole of the thyroid is involved. Thethyroid gland is then moderately enlarged and onpalpation has a distinctive rubbery feel. It is firmas in Hashimoto's thyroiditis, but the edges arenot so well defined, nor does the gland feel somobile in the neck. This, of course, is in keepingwith the finding of many adhesions of the capsuleto the surrounding tissues which tether the glandto the strap muscles. With the passage of time oneof two things happens to the gland: either itreturns to a normal size and normal consistenceor fibrosis is so intense that the gland feels hard.In the latter case the surface has the bosselatedfeel which is 6s typical of Hashimoto's disease,and this irregularity, combined with hardness andfibrosis, makes the differentiation from cancer adifficult one.

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Page 2: SUBACUTE THYROIDITIS - Postgraduate Medical Journal · 327 SUBACUTE THYROIDITIS BySELWYNTAYLOR, M.CH., F.R.C.S. Surgeon, King's College Hospital, Belgrave Hospitalfor Children, andHammersmithHospital;

328 POSTGRADUATE MEDICAL JOURNAL July 1957

The progress of the disease is almost always tospontaneous resolution and this usually occursbetween three to six months after the onset. Onepatient under my care complained of symptomsfor a little over a year, but this appears to beunusual.

Differential DiagnosisThe early stages of de Quervain's disease, with

fever, sweating and a painful swollen neck, maywell be mistaken for signs of thyroiditis due toacute bacterial inflammation. Whereas in acutethyroiditis the causative organism is almost alwaysdiscovered, the white cell count is raised and thereis a relative increase of polymorphonuclear leuko-cytes; none of these is found in subacute thy-roiditis. One confusing point, however, is thatboth these conditions are often preceded by acuteinfection in the upper respiratory tract andespecially a sore throat or tonsillitis.The commonest condition which is mistaken for

subacute thyroiditis is haemorrhage into a noduleof a simple nodular goitre. When there is a solitarynodule almost filling one lobe of the gland andthere is haemorrhage into this, it is often verydifficult to be certain of the right diagnosis. Thepatient has a painful swollen neck and the painmay radiate up to the ears, occasionally the tem-perature is elevated and certainly such patientsalmost always complain of malaise and fatigue. Oneimportant point of differentiation is that the ery-throcyte sedimentation rate (E.S.R.) is almost in-variably elevated in subacute thyroiditis. Theother important differentiating test between thetwo conditions is that the radioactive iodine testfor uptake in the gland is nil in the early stages ofsubacute thyroiditis, whereas there is always a fairuptake in simple nodular goitre.The most serious condition which may be con-

fused with subacute thyroiditis is carcinoma of thethyroid gland, especially the slow-growing papillaryform seen in young adults. Crile and Fisher (I953)described two patients in whom a needle biopsyhad been done to confirm the diagnosis of subacutethyroiditis. When the tissue was examined it wasfound to contain carcinoma and the patients werethen treated by thyroidectomy. Finally, Hashi-moto's thyroiditis may be mistaken for that ofde Quervain. Occasionally a rather florid form ofHashimoto's thyroiditis is seen, especially inmales, and this offers many of the features of theclinical picture and pathological findings of sub-acute thyroiditis. From the clinical point of viewthe Hashimoto patients progress inevitably towardsmyxoedema, which is not seen with the subacutecases, and, in addition, the pathologist sees theplump red Askanazy or Hurthle cells together withmuch lymphoid tissue in the excised gland.

Laboratory FindingsJust as the clinical findings are so much more

important than the laboratory findings in Graves'disease, so in subacute thyroiditis too muchreliance should not be placed on special investiga-tions. However, they may provide valuable sup-portive evidence where the diagnosis remains indoubt, but they also require considerable skillin their interpretation, since they change with theprogress of the disease, which may extend fromthree to I2 months.The white cell count remains unaffected and the

relative proportions of lymphocytes and poly-morphonuclear leucocytes are unchanged. This isin contrast with the changes seen in bacterialthyroiditis. The erythrocyte sedimentation rateis raised and may be as high as 50 mm. Westergrenin the first weeks of the disease. No organismsor viruses have so far been isolated from thethyroid tissue or blood of these patients, but thisdoes not exclude their presence and, indeed, manyworkers have felt very strongly that a virus wasresponsible.

In the early weeks of the disease it is usual tofind that the radioactive iodine uptake in the neckis zero and, since this is not seen in any otherthyroid condition, it is one of the strongest pointsin favour of the diagnosis. As the months go bythe radioactive iodine uptake returns and after ayear it is usual for it to be once more normal.On the other hand, the level of protein-boundiodine in the serum may be high in the first weeksof the disease (Lindsay, 1954), but subsequentlyis lower than normal and does not return to theusually accepted level of approximately 4 vg. percent. until after a year or 8 months has elapsed.A most useful ancillary method in coming to a

diagnosis in this disease is the employment ofneedle biopsy. Many types of instrument havebeen used, but one of the simplest, which can becarried ready sterilized in an ordinary clinical bag,is the Vim-Silverman split needle (Crile andHazard, 1951; Taylor, 1955). The patient is askedto lie on a couch and the neck is hyperextended bymeans of a pillow. The skin is prepared with anantiseptic and then with a hypodermic needle atiny weal is raised using 2 per cent. Lignocaine.A tenotomy knife or spear-pointed scalpel is thenused to nick the skin and the trocar and cannulaof the Vim-Silverman needle is introduced, thethyroid being steadied with fingers placed behindthe sternomastoid. As soon as the needle is felt toengage the surface of the gland, the trocar isremoved and the split needle inserted in its placeand pushed forward so that the blades enter thegland. The most important part of the manoeuvrethen follows, which consists of holding the splitpart of the needle quite rigidly still and then

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Page 3: SUBACUTE THYROIDITIS - Postgraduate Medical Journal · 327 SUBACUTE THYROIDITIS BySELWYNTAYLOR, M.CH., F.R.C.S. Surgeon, King's College Hospital, Belgrave Hospitalfor Children, andHammersmithHospital;

July 1957 TAYLOR: Subacute Thyroiditis 329

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pushing forward the outer cannula over the bladesso that they are brought together and grip a pieceof thyroid tissue. The needle is then twisted anddrawn out and should have between its blades acore of biopsied material. The illustrations showthe individual components of the needle and alsoan actual specimen after it has been fixed andsectioned. After the needle has been withdrawnit is necessary to apply firm pressure for a fewminutes to the neck and then apply a small col-lodion dressing over the skin wound. We havemade a rule of asking the patient to remain lyingdown for at least a quarter of an hour after thisform of biopsy and no serious complications haveso far resulted. An excellent account of the tech-nique has been given by Hamlin (I955, I956).Heptinstall and Eastcott (1954) have described theremoval of a portion of the isthmus in making thediagnosis of thyroiditis and this is a very suitablealternative technique.PathologyThe gland in subacute thyroiditis is always en-

larged and this enlargement may be superimposedupon a previous simple goitre. The consistenceis firm and the colour paler than usual, there beingno increase in vascularity. It is noticeable that thecapsule is thicker and becomes adherent to thesurrounding structures, though in no way com-parable to the intense fibrosis seen in Riedel'sthyroiditis. The gland resembles most of all thatseen in Hashimoto's disease, but is not so rubbery,although the surface is similarly bosselated, and,on the whole, it feels tougher when cut with aknife.The histological changes depend on the stage

of the disease at which the tissue is examined; inthe beginning there is a generous infiltration bylymphocytes and plasma cells which tend to bearranged in clumps. The follicles may appearlargely normal, but in certain foci follicular cellswill be seen to have swelled up and disrupted andthe aggregations of their nuclei mimic giant cells,hence the name giant-cell thyroiditis. True giantcells may also appear ad-. it is, possible that theyphagocytose the colloid from the destroyed fol-

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Page 4: SUBACUTE THYROIDITIS - Postgraduate Medical Journal · 327 SUBACUTE THYROIDITIS BySELWYNTAYLOR, M.CH., F.R.C.S. Surgeon, King's College Hospital, Belgrave Hospitalfor Children, andHammersmithHospital;

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July 1957 TAYLOR: Subacute Thyroiditis 331

licles. With the passage of time the fibrous stromabecomes greatly increased and fibrosis is the mostprominent feature of the histology. The changesare seen in the accompanying three photomicro-graphs, which illustrate typical areas from biopsyspecimens obtained by a needle. Perhaps themost important point in differential diagnosis his-tologically is that of papillary carcinoma. Certainlymacroscopically the two conditions may appearvery similar when confined to focal areas and it isonly by examination under the microscope that anappreciation of the difference is obtained. Mostworkers who have studied the histological changesin subacute thyroiditis have been impressed withthe resemblance which it sometimes shows withHashimoto's disease and with certain features ofhyperthyroidism. Indeed, there are occasionallypatients in whom the diagnosis remains in doubtboth clinically and histologically and it should notbe thought that an absolutely clear distinction canbe made between different forms of thyroiditis.On the whole, most glands can be put into thecategory of Hashimoto's, Riedel's or de Quervain'sthyroiditis, but this is not always so and only longobservation of the patient gives the final answer.

AetiologyThere is no proven factor in the aetiology of this

form of thyroiditis, but there is certainly no lack ofspeculation. Cultures of the material have alwaysproved negative, but since the condition oftenfollows infection in the upper respiratory tract avirus has been incriminated. Fraser and Harrison(1952) suggested such an aetiology, but Lindsaywas unable to demonstrate the histological features,such as inclusion bodies, which it might be ex-pected should be present. Certainly some of thehistological changes might be considered, due tothe fact that the colloid acts as a foreign bodywhen the follicles disrupt, and some of the phago-cytic changes seen would fit in with this. Frasersuggested that the virus affected the follicular cellsmuch as thiouracil does in blocking hormone pro-duction, but it is interesting that giving thiouracilto such a patient usually relieves the condition andallows iodine uptake. Possibly this is due to thepotentiation of thyrotrophic hormone whichthiouracil is known to bring about. In support ofthis is the work of Robbins and Rawson, whodemonstrated that patients with subacute thyroid-itis were relieved of their symptoms and againshowed a radioactive iodine uptake in the neckwhen injected with thyrotrophic (T.S.H.) hor-mone. My own view is that this condition resultsfrom a localized hypersensitivity to toxins, prob-ably those from streptococci, as the condition socommonly follows a sore throat. Just as in Henoch-Schonlein's purpura, where there is a hyper-

sensitivity to such circulating toxins. The responseof the condition to cortisone is very suggestive ofsuch a mechanism, but much further evidence willhave to be obtained before a satisfactory workinghypothesis is capable of being presented. Finally,Perloff (I956) has recently reported five cases ofhyperthyroidism following proven attacks of sub-acute thyroiditis.Treatment

Since subacute thyroiditis is a self-limitingdisease any form of treatment may eventually begiven claims which they do not really deserve and,in fact, a multitude of different therapies have beensuggested. The first landmark was the announce-ment by King and Rosellini (i945) that thiouracilin ordinary doses caused cessation of pain andconstitutional symptoms within a few days of beingstarted by mouth. The possible mechanismswhich have been put forward to explain this arethat thiouracil potentiates the action of T.S.H.from the pituitary. As described above, Robbinsand his colleagues (195i) describe similar goodresults with injections of T.S.H. and certainly theuptake of radioactive iodine by the thyroid isreinstated by this technique. Crile originallyadvocated the use of radiotherapy for this con-dition, but most of us have given up its employ-ment because, although a response can usually beobtained, it is desirable to avoid X-ray therapywhen other forms of treatment are equally effec-tive. Recently a number of workers have describedgood results from the use of cortisone (Clark,Nelsen and Raymond, I953; Titleman and Rosen-burg, 1953; Lasser, I953; and Kahn and hiscolleagues, I953). On the whole, this has beenfound the best form of therapy and seldom fails toproduce a response in about a week's time. Thedrug has to be continued by mouth until the diseasereaches a natural remission, and this can only befound by experiment. Small doses of cortisone areusually adequate after the first week and it is mostdesirable that the dosage be kept to the lowest levelwhich gives an adequate clinical response. It maybe added that carbimazole in 5-mg. doses threetimes a day produces an equally good result andmay eventually be reduced to only 5 mg. a day,but it is not unusual to get some increase in thesize of the gland and cortisone provides a moresatisfactory form of treatment at the present time.It should also be added that no kind of antibiotichas been found to produce any response.PostscriptSome interesting new work stems from an

observation by Cooke and Wilder in 1954 that theserum colloidal gold curve in Hashimoto's diseaseis usually abnormal. They added to this the belief

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332 POSTGRADUATE MEDICAL JOURNAL July 1957

that liver changes usually accompanied the con-dition (Cooke and Luxton, 1955) and a largerconfirmatory series appeared from the ClevelandClinic (Skillern, I956) last year. The raised yglobulin levels, their delayed return to normalafter thyroidectomy and the infiltration of thethyroid with lymphocytes, plasma cells and lym-phoid tissue prompted Roitt et al. (1956) to lookfor an immune response. They have reported aprecipitin reaction of serum with extract of humanthyroid gland and they postulate that it parallelsthe destruction of the patient's own thyroid, andespecially the colloid, by an auto-antibody.

It might well be expected that in subacutethyroiditis a similar positive flocculation test wouldbe obtained and W. R. Trotter and D. Doniach in-form me that they have obtained a positive reactionin the serum of two patients with this disease.For those who are interested in recent advances

in problems of immunology and thyroid diseasethere is an excellent leading article in the Lancet,May 25, 1957, Vol. I, p. 1075, which reviews thewhole subject up to the present time. This hasnow become one of the rapidly expanding frontiersof thyroid investigation.AcknowledgmentWe are indebted to the publishers of British

Surgical Progress 1955 for the blocks which appearin this article.

BIBLIOGRAPHYCLARK, D. E., and NELSEN, T. S. (I953), Jour. Amer. med. Ass.,

COOKE,R. T., and WILDER, E. (I954), Lancet i, 984.COOKE, R. T., and LUXTON, R. W. (955), Ibd., i, 968.CRILE, G., Jr. (I948), Ann. Surg., 127, 640.CRILE G., Jr., and FISHER, E. R. (I953), Cancer, 6, 57. -

CRILE, G., Jr., and HAZARD, J. B. (i95I), J. clin. Endocr.,1, 1123.

CRILE, G., Jr., and RUMSEY, E. W. (950o), J. Amer. med. Ass.,DE QUERAIN F. (1904), Mitt. Grenzgeb. Med. Chir., 2, Supp.,DE QUERVAI, F., and GIORDANENGO, G. (I93S), bid.,

44 538FRASER R., and HARRISON, R.J. (I952), Lancet, i, 382.HAMLIN, E., Jr., and VICKERY, A L. (956), New Eng. J.

Med., 24, 742.HAZARD, J. B. (955) Amer. .. din. Path., 25, 399.HEPTINSTALL, R. I., and EASTCOTT, H. H. G. (i953).

Brit. j. Surg., 41, 471.KAHN, J., SPRITZLER, R. J., and SHECTOR, W. E. (g193),

Ann. intern. Med., 39, I29.KING, B. T., and ROSELLINI, L. J. (x94s), J. Amer. med. Ass.,

12, , 267.LASSER, R. P. (93), Ibid., 152, 133.LINDSAY, S., DAILEY, M. E., FRIEDLANDER, J., YEE, G.,

and SOLEY, M. H. (1952) .. din. Endocr., 12, 1578; alsoTrans. Amer. Ass. Goiter (1952), pp. 384-411.

LINDSAY, S., and DAILEY, M. E. (I954), Surg. Gynec. Obstet.,98, 197

PERLOFF,W. H. (x9S6), . clin. Endocr., x6, 542.ROBBINS J., RALL, J. E., TRUNNELL, J. B., and RAWSON,

R.W. (i95x) Ibid.,Ix,txo6.ROITT, I. M., bONIACH, D., CAMPBELL, P. N., and HUD-

SON, R.V. (I956) Lancet, ii, 820.SKILLERN, P. G., ChILE, G., McCULLAGH, P., HAZARD,

J. B., LEWIS, L. A., and BROWN, H. (i956), J. din. Endoer.,T

6, 35.TAYLOR, S. (t955), 'Brit. Surg. Progress,' pp. 148-x60, London.

RUTHIN CASTLE, NORTH WALESA 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.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

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.,

( 944), Endocrinology 34, 265.GODLEY, A. F., and STANBURY, J. B. (I95)4, . clin. Endocr.

x4, 70.GOODWIN, J. F., STEINBERG, H., and WILSON, A. (1954).

Brit. med.J., I, 422.GRIESBACH, W. E., KENNEDY, T. H., and PURVES, H. D.

(1941), Brit. J. exp. Path., 22, 249.HIMSWORTH H. P. (1948), Brit. med. Y., 2, 6i.IVERSEN K. (I95), Y. din. Endocr., xI, 298.KENNEDY, T. H. (1942), Nature (Lond.), 150, 233.KRISS, J. P., CARNES, W. H., and GROSS, R. T. (z955),

7. Amer. med. Ass., 157, 117.LAWSON, A., RIMINGTON, C., and SEARLE, C. E. (r95),

Lancet, U, 6I9.MARINE, D., BAUMANN, E. J., SPENCE, A. W., and CIPRA, A:

(1932), Proc. Soc. exp. Biol. (N.Y.), 29, 772.MOORE,F. D. (1946), . Amer. med. Ass., 130, 315.MORGANS, M. E., and TROTTER, W. R. (1954), Lancet, i, 749.

McCULLAGH, E. P., HUMPHREY, D. C., McGARVEY, C. J.,and SUNDGREN, V. (I951), J. Amer. med. Ass., 147, xo6.

McCULLAGH, E. P., and SURRIDGE, W. T. (x948), J. cin.Endocr., 8, o05I.

MACGREGOR, A. G., and MILLER, H. (I953), Lancet, i, 88r.MACGREGOR, A. G., and SOMNER, A. R. (1954) Ibid., ii, 93x.PEMBERTON, J. J., HAINES, S. F., and KEATING, F. R.

(1949), J. din. Endocr., 9, I232.PLUMMER, H. S. (1923), 7. Amer. med. Ass., 80, x955.SOLEY, M. H. (1942), Arch. intern. Med., 70, 2o6.STANLEY, M. M., and ASTWOOD, E. B. (x947), Endocrinology,

41 66.STANLEY, M. M., and ASTWOOD, E. B. (I949), Ibid., 44, 588.WILLIAMS, R. H., TOWERY, B. T., ROGERS W. F., TAG-

NON, R., and JAFFE, H. (1949), . clin. Endo., 9, 80.WOLFF J., CHAIKOFF, I. L., GOLDBERG, R. C., and

MEER, J. R. (949), Endocrinology, 4, 504.04.WYNGAARDEN, J. B., WRIGHT, B. M., and WAYS, P. (s952),

Ibid., 50, 537.

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