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1 Radiidine therapy in vluminus multindular nn-txic gitre Jean Vereist, Marc Bnnyns, and Daniel Gliner Departments f Internal Medicine and Radiistpes, University Hspital Saint-Pierre, Brussels, Belgium Abstract. Large dses f radiidine were administered since 1969 t 15 euthyrid patients with cmpressive vluminus gitres. A decrease in gitre size was bserved in all patients (between 15 and 63%, average 39%). Maximal effect n gitre size was attained rapidly, partially already after less than ne year and was almst maximal after 24 t 30 mnths. N significant lcal adverse reactins were bserved; n patient required sterid administratin. Hypthyridism fllwed radiidine administratin in 30% f the patients after 2 years; after 8 years, all thse wh had survived were hypthyrid, requiring substitutin therapy. In all patients there was a marked imprvement in cmpressin symptms. The use f radiactive idine therapy cnstitutes an alternative t surgery in selected patients with large cmpressive gitres in whm surgery is cntraindicated because f age r ther medical cnditins. Preliminary results f the present studies were presented at the Annual Meeting f the Eurpean Assciatin f Nuclear Medicine, Milan, 1988, and at the 17th Annual Meeting f the Eurpean Thyrid Assciatin, La Grande Mtte-Mntpellier, September The therapeutic administratin f radiidine has nw gained large acceptance thrughut the wrld fr the management f hyperthyridism (1-3). In this clinical cnditin, it is assumed that radiidine induces radiatin damage t the thyrid fllicular cells, leading t impaired replicatin and eventu ally t reductin in the size f the thyrid (4). Rad iidine therapy is, hwever, als emplyed in ther clinical cnditins, such as treatment f mé tastases frm thyrid differentiated cancer and ab latin f cervical remnants after incmplete surgery fr thyrid cancer. It is therefre apparent that thyrid tissue mass can be reduced by admin istratin f radiidine. Hence, this tl may be applicable t euthyrid patients with multindular gitre wh present lcal cmpressin symptms. In the present article we reprt n the retrspec tive results f radiidine administratin ver a perid f 20 years in a grup f inperable euthy rid patients with vluminus multindular gitre. These elderly patients were cnsidered inperable fr reasns related t their age and/r assciated medical disease, r because they refused surgery (and in sme cases because surgens refused t p erate n them). The patients required therapy be cause f recent increase in gitre size, respiratry distress symptms due t trachéal cmpressin, and in rare instances because f discmfrt related t dysphagia. Patients and Methds A grup f 15 patients (11 females and 4 males), aged 62 t 86 years, were treated since It is ntewrthy that 9 f 15 patients (mean age 67 years) were treated between 1969 and 1978, but nly 6 patients (mean age 76 years) after The higher mean age f patients during the latter decade indicates that during recent years lder pa tients were mre frequently referred t surgery. All pa tients had a multindular gitre, in mst instances asym metrical and with variable degrees f substernal exten sin. Gitre had been present since many years (sme times decades) and was mst frequently stable in size. In sme patients hrmne substitutin therapy had been given previusly fr lng perids f time, mst generally

2 withut reductin f gitre size. All patients had always been cnsidered as clinically euthyrid and were cn firmed t be bth clinically and bichemically euthyrid after the initial evaluatin in ur institutin. X-rays ex aminatin revealed trachéal deviatin in all cases and tra chea! cmpressin in 60% f them. g S ï 10 <TSH) X <UT=9» V Results Thyrid scintiscan with 131I ( MBq) was perfrmed befre treatment, and shwed hetergenus tracer distributin. The thyridal 24-h uptake ranged frm 9 t 69% (mean ± sem 43±5). The mean value f prtein-bund 131I, measured 24-h after tracer administratin, was within the ref erence range f ur nrmal ppulatin, i.e. belw 0.10% dse/1. The thyrid size was estimated frm scintigraphy by planimetry, fllwing the methd f Mandart & Erbsmann (5). Glandular size ranged > J Befre RI Alter RI Cmparisn f thyrid vlumes befre and after radii dine (Ri) therapy in 15 patients. Mean±sEM are repre sented by the symbl Thyrid vlume was estimated by planimetry frm scintigraphy f the gland carried ut 24 h after the administratin f 50 r 100 nci 131I ( MBq) HO Mnths After Radiidine 2. Changes in thyrid vlume after radiidine administra tin, expressed as percent f the initial glandular vlume. In sme cases, mre than ne scintigraphy was btained during the fllw-up. Only the data frm the first scin tigraphy btained (with the shrtest delay) after radii dine administratin is illustrated in the figure and was taken int accunt t calculate the reductin in size. O see text. between 106 and 252 g, with a mean (±sem) f 175±13g. The therapeutic radiidine dse administered was calculated taking int accunt the determina tin f thyridal uptake in the preliminary tracer study in rder t deliver 75 t 100 pci (2.8 t 3.7 MBqVgram tissue. Dses given varied between 740 and 1850 MBq, with a mean (±sem) f 1184± cmpares the thyrid vlume befre rad iidine therapy t the vlume estimated frm a scintigraphy btained at varius intervals during the fllw-up perid in each patient. A reductin in size was evident in every patient treated, in the very large (abve 200 g) as well as in the less vluminus glands. Individual changes in vlume were rughly parallel and the mean decrease fr the grup was 39%, frm 175 t 110 g. 2. illustrates the decrease in thyrid size, as a percent f the initial vlume, during the fllwup f patients. The figure cmpares thyrid scin tigraphy in the 15 patients, perfrmed at different time intervals after radiidine administratin, be tween 0.5 and 13 years (median 2). Reductin in the vlume f gitre was rapid, already evident after less than ne year in 3 patients (in whm it was assessed at this early stage). Maximal effect was b tained after mnths; thereafter, changes in size were nly minr. Tw patients were f special interest (indicated by O in the figure 2). In ne, the

3. Typical example f thyrid scintigraphy befre radiidine administratin (left panel) and at different time intervals after radiidine administratin (right panels).

In this patient, radiidine had been given despite a lw 24-h uptake (9%) and the treatment bviusly did nt cmpletely fulfil its jb.

This patient had been given radiidine after thyrid stimulatin with bvine TSH, thereby explaining the "super" effect. Fr radiprtectin reasns and 4.

3 3. Typical example f thyrid scintigraphy befre radiidine administratin (left panel) and at different time intervals after radiidine administratin (right panels). effect f radiidine n vlume reductin was small, reaching nly 17% f the initial vlume after 5 years. In this patient, radiidine had been given despite a lw 24-h uptake (9%) and the treatment bviusly did nt cmpletely fulfil its jb. In the secnd patient, a marked and rapid vlume reduc tin was bserved, reaching 63% after 1 year. This patient had been given radiidine after thyrid stimulatin with bvine TSH, thereby explaining the "super" effect. Fr radiprtectin reasns and 4. See legend t allw fr a careful bservatin, all patients were taken int the hspital during 3-7 days after rad iidine. Thereafter patients were discharged and examined regularly n an utpatient basis during the first 6 weeks. Fllwing treatment, there was n single instance f acute increase in gitre size, nr acute exacerbatin f bstructive symptms, nr episdes f thyrid dysfunctin. N patient re quired sterid administratin. During the lngterm fllw-up, hypthyridism develped in 30% t 3.

4 f the patients after 2 years. After 8 years all thse wh survived had becme hypthyrid, requiring hrmne substitutin therapy. Figs. 3 and 4 illustrate the thyrid scintigraphic changes in tw typical patients befre and after radiidine therapy shwing the reductin in glan dular size with time. Discussin Nn-txic multindular gitre is a relatively cmmn cnditin. The natural histry f such gitres is usually that f a slw and prgressive grwth with frequent increase in number and size f ndules. Spntaneus reductin in size is ex ceedingly rare. Furthermre, when thyrid hr mne substitutin is administered with the aim t reduce r stabilize the size f lng-standing gitre, it remains frequently ineffective. Radical therapy, if required fr csmetic reasns r lcal cmpres sin symptms, generally cnsists in surgical re mval, especially in yunger patients. In 10 t 15% f perated patients, hwever, recurrence f gitre has been reprted (6). The grup f patients reprted herein cmprises 15 elderly patients with lng-standing nn-txic multindular gitre, wh fr varius reasns culd nt be submitted t surgery. The patients required therapy because f recent increase in gitre size, symptms related t trachéal cmpressin r dysphagia. The pssible ccurrence f thyrid cancer was assessed using the available clinical criteria and in a few recent patients by benign cytlgy btained frm fine-needle aspiratin. In the absence f sur gical data, cancer culd nt strictly be ruled ut, but it was never disclsed in any f the patients during the fllw-up perid and was therefre unlikely. The patients were treated with a single administra tin f a relatively large dse f radiidine ( 1184 MBq n the average). The results indicate that a significant reductin in gitre vlume was btained in all patients, averaging 40%. Radilgical cm pressin f the trachea shwed an imprvement in all patients. Similarly, the subjective symptms im prved in all patients. There was n serius adverse reactins and sterid administratin was nt nec essary. Fr cmparisn, we als analysed retrspectively the changes in thyrid vlume resulting frm rad iidine administratin in 22 thyrtxic patients with gitres greater than 100 grams (results nt shwn). Decrease f thyrid vlume with time was similar t that f ur patients with nn-txic gi tres, indicating that there was n»radiresistance«in the latter patients. Recently, tw reprts have been published deal ing with the same questin in different grups f patients. Kay et al. (6) shwed similar results in patients previusly perated fr gitre and with subsequent recurrence. One difference between the results f Kay et al. and urs is that, while hypthyridism ccurred infrequently in their pa tients (presumably because they were yunger than urs), hypthyridism was frequent in ur series. Hence, careful fllw-up f elderly patients is man datry and thyrid hrmne substitutin shuld be initiated when required. In the article f Hegedüs et al. (7), the patients had smaller gitres and were fllwed during nly the first 12 mnths after rad iidine administratin. The authrs als bserved changes in thyrid vlume, ccurring already during the first year, with n adverse reactins frm therapy. In cnclusin, surgical remval is the treatment f chice fr multindular gitre. Hwever, the use f radiactive idine cnstitutes a valuable alterna tive in selected patients with large nn-txic mul tindular gitres, in particular in thse wh, be cause f age r ther medical cnditins, are un suitable fr surgery. Acknwledgments The authrs wish t thank Prf A. M. Ermans fr his cnstant supprt and interest in their wrk. The authrs gratefully acknwledge Mrs Brigitte De Brauwer fr expert secretarial help. References 1. Beierwaltes WH. The treatment f hyperthyridism with idine-131. Semin Nucl Med 1978;8: Henneman G, Krenning EP, Sankaranarayanan K. Place f radiactive idine in treatment f thyrtxicsis. Lancet 1986;1: OrgiazziJ. Management f Graves'hyperthyridism. Endcrinl Metab Clin Nrth Am. 1987;16: Gldsmith RE. Radiistpe therapy fr Graves' dis ease. May Clin Prc 1972;47: Mandan G, Erbsmann F. Estimatin f thyrid

5 weight by scintigraphy. Intern J Nucl Med Bil 1975;2: Kay TWH, d'emden MC, Andrews JT, Martin FIR. Treatment f nn-txic multindular gitre with ra diactive idine. Am J Med 1987;84: Hegediis L, Hansen BM, Knudsen N, Hansen JM. Reductin f size f thyrid with radiactive idine in multindular nn-txic gitre. Br Med J 1987; 297: Received September 8th, Accepted January 8th, Dr D. Gliner, Hôpital Saint-Pierre, Université Libre de Bruxelles, Department f Internal Medicine, 322, rue Haute, B-1000 Bruxelles, Belgium.

DATA RELEASE: UPDATED PRELIMINARY ANALYSIS ON 2016 HEALTH & LIFESTYLE SURVEY ELECTRONIC CIGARETTE QUESTIONS

DATA RELEASE: UPDATED PRELIMINARY ANALYSIS ON 216 HEALTH & LIFESTYLE SURVEY ELECTRONIC CIGARETTE QUESTIONS This briefing has been specifically prepared fr the Ministry f Health t prvide infrmatin frm this