EVALUACIJA NODOZNIH STRUMA NA PODRU JU ZDRAVSTVENOG CENTRA NOVI PAZAR

38 MEDICINSKI GLASNIK / str. 38-47 Mersudin Muli *, Bilsana Muli EVALUACIJA NODOZNIH STRUMA NA PODRU JU ZDRAVSTVENOG CENTRA NOVI PAZAR Sažetak: Pojam tiroidni nodus odnosi se na bilo kakav nepravilan rast, koji formira izbo inu u štitastoj žlezdi. Cilj ispitivanja: evaluacija anamnesti kih, klini kih, laboratorijskih i ultrasonografskih parametara u ispitanika sa poreme ajem gra e štitaste žlezde na podru ju Zdravstvenog centra Novi Pazar. Metode: Ispitivanjem je obuhva eno 61 ispitanik sa poreme enom gra om štitaste žlezde, od kojih 58 ženskog i 3 muškog pola. Svaki ispitanik obuhva en je klini kim pregledom i ultrazvu nim pregledom štitaste žlezde. Kod svakog ispitanika procenjena je globalna funkcija štitaste žlezde merenjem serumske koncentracije trijodtironina (T-3), tiroksina (T-4), tirostimulišu eg hormona (TSH) i titra tiroglobulinskih (TGAb) i mikrozomalnih (TPOAb) antitela. Rezultati: U estalost pojave tiroidnih nodusa najve a je u periodu 35 39 godina sa 16.39% i 55 59 godina sa 18.03%. Analizom ultrazvu nog nalaza štitaste žlezde ispitanika dobijena je slede a distribucija: Kod 13 (21.31%) na ena je difuzna i nodozna struma; 17 (27.87%) je imalo nodoznu strumu; 20 (32.79%) polinodoznu strumu; 5 (8.19%) cisti ni nodus; 3 (4.92%) mikronodusnu strumu i 3 (4.92%) su recidiv nodusi. Zaklju ak: Na podru ju Zdravstvenog centra Novi Pazar, u estalost pojave tiroidnih nodusa najve a je u periodu od 55. do 59. godine, a naj- eš i oblik poreme aja gra e štitaste žlezde je polinodozna struma. Klju ne re i: tiroidni nodus, štitasta žlezda. * Mr sc. med Mersudin Muli, e-mail: merko@ptt.rs

EVALUACIJA NODOZNIH STRUMA NA PODRU JU ZDRAVSTVENOG CENTRA NOVI PAZAR 39 Summary: The term thyroid nodus refers to any irregular growth which forms a lump in the thyroid gland. Objective: The evolution of illness history, clinical, laboratory and ultrasonography ndings in patients with the disorder of thyroid gland structure in the region of Healthcare Center of Novi Pazar. Methods: the study involved 61 patients, 58 female and 3 male, with a disorder of thyroid gland structure. Each patient underwent clinical examination and ultrasound imaging of the thyroid gland. In each patient a global function of the thyroid gland was assessed by the determination of serum concentration of triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), and titres of thyroglobulin (TGAb) and microsomal (TPOAb) antibodies. Results: The frequency of the occurrence of a thyroid nodus is highest at age 35-39 years (16.39%) and at age 55-59 years (18.03%). By analyzing the ultrasound ndings of the patients the following distribution was obtained: 13 (21.31%) patients had a diffuse and nodose struma, 17 (27.87%) nodose struma, 20 (32.79%) polynodose struma, 5 (8.19%) cystic node, 3 (4.92%) micronodular struma and 3 (4.92%) had recurrence of noduses. Conclusion: In the region of the Healthcare Centre of Novi Pazar the frequency of thyroid nodus if highest at age 55-59 years, while the most frequent disorder of thyroid gland structure is polynodose struma. Key words: thyroid nodus, thyroid gland UVOD Tiroidni nodusi predstavljaju jednu od naj eš ih patologija u celokupnoj medicini. Oni obuhvataju sve promene u kojima se ograni eni, jedan ili više, delovi štitaste žlezde strukturno (morfološki) razlikuju od normalnog, zdravog tkiva. Tiroidni nodusi mogu da budu ciste, adenomi, karcinomi, lobulacije normalnog tkiva ili bilo koja druga fokalna promena u štitastoj žlezdi (1). Prevalenca palpatorno detektovanih nodusa i strume iznosi oko 3% u celoj populaciji, oko 6.4% kod žena i 1.5% kod muškaraca (2, 3). Sa druge strane, prilikom istraživanja koje je obuhvatalo zdravu populaciju, ehosonografski su detektovani nodusi kod 60% ispitanika (4). Autopsijski, tiroidni nodusi se detektuju u preko 50% pregledanih žlezda (5). Prevalenca tiroidnih nodusa raste sa godinama, de citom joda i sa izlaganjem jonizuju em zra enju. Klini ki zna aj ovako na enih nodusa još uvek nije potpuno i podrobno procenjen. Ve ina vorova u štitastoj žlezdi potpuno su asimptomski i najverovatnije nikada ne e izazvati pojavu simptoma. Ukoliko elije u nodusu produkuju tiroidne hormone samostalno, nodus može dati simptome poja anog rada štitaste žlezde (hipertireoidizam). Mali

40 MEDICINSKI GLASNIK / str. 38-47 broj pacijenata se žali na bol na mestu nodusa, koji se širi ka uhu ili vilici. Ukoliko je nodus veoma velikih dimenzija, može vršiti kompresiju jednjaka i traheje sa otežanim gutanjem i disanjem. U nekim slu ajevima pacijent se može žaliti na promuklost i otežan govor zbog kompresije larinksa. Ipak, u oko 10 do 15% nodusa u štitastoj žlezdi postoji karcinom. Za ove pacijente je rano otkrivanje i odgovaraju e le enje uslov za izvanredno dobru prognozu u ve ini slu ajeva. Zbog toga je potreba da se dijagnostikuju i dalje le e vorovi u štitastoj žlezdi, koji potencijalno mogu biti maligni, dovela do rasprostranjenog uverenja da sve noduse ve e od 1 do 1.5 cm treba podrobno ispitati. Glavni zadatak klini ara je, prema tome, da prepozna noduse koji su maligne prirode ili sumnjivi na karcinom radi blagovremenog le enja, a da se izbegnu nepotrebne operacije benignih nodusa (6). Evaluacija ima za cilj da se me u vrlo estim tiroidnim nodusima otkriju relativno retki karcinomi tiroideje (6). CILJ ISPITIVANJA Cilj ispitivanja je da: evaluacijom anamnesti kih, klini kih, laboratorijskih i ultrasonografskih parametara ocenimo osobenosti tiroidne gra e u bolesnika sa poreme ajem gra e štitaste žlezde u regionu Novog Pazara. U našoj sredini ovakve studije do sada nisu ra ene, te je ovo prva studija koja se bavi evaluacijom nodusa na ovom podru ju. Za ove pacijente je rano otkrivanje i odgovaraju e le enje uslov za dobru prognozu. Zbog toga je opravdana potreba da se blagovremeno dijagnostikuju i dalje le e osobe sa vorovima u štitastoj žlezdi i da se naro ito izdvoje bolesnici sa nodusima koji potencijalno mogu biti maligni. MATERIJAL I METODE Ispitivanjem je obuhva en 61 ispitanik, sa poreme enom gra om štitaste žlezde, na podru ju ZC Novi Pazar. Tokom metodološke obrade koriš eni su: Klini ki pregled u proceni veli ine vora. Ultrazvu ni pregled štitaste žlezde. Laboratorijski parametri za procenu funkcije štitaste žlezde (merenje serumske koncentracije trijodtironina (T-3), tiroksina (T-4), tirostimulišu eg hormona (TSH), i titra tiroglobulinskih (TGAb) i mikrozomalnih (antiperoksidaza, TPOAb) antitela. Upitnik za procenu kvaliteta života (koji je sadržao: ime i prezime, godinu ro- enja, pol, zanimanje, bra no stanje, TV, TT, ITM, socioekonomske uslove života, prethodno zra enje regije vrata, porodi na optere enost karcinomom, kao i pitanje zašto se ispitanik javio lekaru). Statisti ka obrada podataka.

EVALUACIJA NODOZNIH STRUMA NA PODRU JU ZDRAVSTVENOG CENTRA NOVI PAZAR 41 REZULTATI Istraživanjem je obuhva en 61 ispitanik od kojih je 58 bilo ženskog a ostala trojica muškog pola ( tabela 1). Tabela 1. Pol f % Muški 3 4.92 Ženski 58 95.08 Ukupno 61 100.00 Najmla i ispitanik imao je 22 godine a najstariji 76 godina. Prose na starost ispitanika ženskog pola iznosila je 50,76 13,4 godina, a ispitanika muškog pola 54,33 2,3 godina. Distribucija u estalosti tiroidnih nodusa po godinama starosti ispitanika, uzimaju i grupni interval od 5 godina, data je u tabeli 2. Tabela 2. Godine života f % 20-24 1 1.64 25-29 30-34 4 6.56 35-39 10 16.39 40-44 7 11.47 45-49 8 13.11 50-54 3 4.92 55-59 11 18.03 60-64 7 11.47 65-69 6 9.84 70-74 75-79 4 6.56 80-84 Ukupno 61 100.00 Iz tabele broj 2 vidi se da je u estalost pojave tiroidnih nodusa kod ispitanika najve a u periodu od 35. do 39. godine i od 55. do 59. godine starosti. Analizom zaklju aka ispisanih u ultrazvu nom nalazu tiroidne žlezde uo ena je slede a distribucija, tabela 3, gra kon 1.

42 MEDICINSKI GLASNIK / str. 38-47 Tabela 3. Struma f % Difuzna i nodozna 13 21.31 Nodozna 17 27.87 Polinodozna 20 32.79 Mikronodozna 3 4.92 Cistni nodusi 5 8.19 Recidiv nodus 3 4.92 Ukupno 61 100.00 Kod 13 ispitanika na ena je difuzna i nodozna struma, 17 ispitanika ima pojedina ni nodus štitastoj žlezdi. Najve i broj ispitanika (njih 20) ima polinodoznu strumu, 3 ispitanika mikronodoznu a kod 5 ispitanika na en je cistni nodus. Kod 3 ispitanika u pitanju je recidiv nodusa u preostalom lobusu nakon prethodno ura ene lobektomije. Evidentno je da najve i procenat pripada polinodoznim strumama (oko 33%). Recidiv-nodus Mikronodozna Cistni nodusi 8% 5% 5% 21% Difuzna I nod ozna TIP STRUME Polinodozna 33% 28% Nodozna Gra kon 1. Raspodela ispitanika u odnosu na morfološke nalaze Distribucija ispitanika u odnosu na vrednosti nalaza T3, T4, TSH prikazana je u tabeli 4.

EVALUACIJA NODOZNIH STRUMA NA PODRU JU ZDRAVSTVENOG CENTRA NOVI PAZAR 43 Tabela 4. T3 fn % 1 ispod opsega RV 2 u opsegu RV 47 77.05 3 iznad opsega RV 14 22.95 Ukupno 61 100.00 T4 fn % 1 ispod opsega RV 2 u opsegu RV 47 77.05 3 iznad opsega RV 14 22.95 Ukupno 61 100.00 TSH fn % 1 ispod opsega RV 14 22.95 2 u opsegu RV 47 77.05 Ukupno 61 100.00 RV: referentna vrednost Nalaz T3 u 77% ispitanika (njih 47) u opsegu je referentnih vrednosti, a 23 % ispitanika (njih 14) imalo je vrednosti T3 iznad opsega referentnih vrednosti. Distribucija bolesnika u odnosu na vrednosti nalaza za tiroglobulinska i mikrozomalna antitela prikazana je u tabeli 5. Tabela 5. Raspodela ispitanika prema vrednostima laboratorijskih nalaza za tireoglobulinska i mikrozomalna antitela Tireoglobulinska antitela fn % 2 u opsegu RV 49 80.33 3 iznad opsega RV 12 19.67 Ukupno 61 100.00 Mikrozomalna antitela f % 2 u opsegu RV 46 75.41 3 iznad opsega RV 15 24.59 Ukupno 61 100.00 Vrednosti nalaza za nivo tiroglobulinskih antitela kod 49 ispitanika (oko 80%) u opsegu je referentnih vrednosti, a kod 12 ispitanika (oko 20%) je iznad opsega referentnih vrednosti.

44 MEDICINSKI GLASNIK / str. 38-47 Vrednosti nalaza za nivo mikrozomalnih antitela kod 46 ispitanika (oko 75%) u opsegu je referentnih vrednosti, a kod 15 ispitanika (oko 25 %) iznad opsega istih. DISKUSIJA Tiroidni nodusi se esto otkrivaju prilikom klini kog pregleda, pogotovu ako se on dopuni još i ehotomografskom evaluacijom predela štitaste žlezde. U zemljama kao što su SAD, gde je nedostatak joda korigovan jodnom pro laksom, tiroidni nodusi su klini ki uo ljivi u oko 4 7% celokupne populacije. Prevalenca je ve a u zemljama pogo enim srednjim ili ozbiljnijim nedostatkom joda, gde je bolest endemska (7). U estalost supklini kih (nepalpabilnih) vorova otkrivenih tiroidnom ultrasonogra- jom dostiže 50% kod žena starijih od 50 godina. U našoj seriji bolesnika pri ultrazvu nom pregledu na eno je 21.31% bolesnika sa difuznom i nodoznom strumom, dok je samo nodoznu strumu imalo 27.87%. Zbir ove dve kategorije ukazuje da se i u našem podru ju zastupljenost vorova pri ehotomografskom pregledu kre e oko 49%, što navodi na injenicu da je incidenca nodoznih promena u ispitivanom stanovništvu Novog Pazara i okoline na nivou svetske zastupljenosti vorova. Tokom ispitivanja pronašli smo povišena antitiroglobulinska antitela u 12 bolesnika, što bi moglo govoriti u prilog postojanja zapaljenja štitaste žlezde, i to 3 u difuznoj i nodoznoj strumi, 3 u nodoznoj strumi, 3 u polinodoznoj strumi i 3 u recidivima nodusa. Sli an nalaz je dobijen i kod ispitivanja zastupljenosti povišenog titra antimikrozomalnih (peroksidaza) antitela na eno je povišenje nalaza u 15 ispitanika, odnosno u 25% ispitivane populacije, što bi moglo da ukaže na postojanje Hashimotovog tireoiditisa. Radionuklidnim ispitivanjem, scintigrafski izoaktivni,,topli nodusi predstavljaju 3 20% tiroidnih nodusa i njihova incidenca je ve a u zemljama gde postoji nedostatak joda. Oko 10% ove grupe je maligno. Oni su 3 do 4 puta eš i kod žena i to posle 40. godine života. U velikoj ve ini slu ajeva, topli nodusi su benigni. Hladni nodusi ine više od 80% svih tiroidnih nodusa i do 17% mogu biti maligne prirode. Tiroidnom ultrasonogra jom razlikuju se tri vrste nodusa: cisti ni, solidni i mešoviti (sadrže solidnu i cisti nu komponentu). Cisti ni nodusi (10 20% svih nodula) skoro su uvek benigni (sa stopom maligniteta od oko 10%). U našem istraživanju na eno je 5 cisti nih nodusa me u ispitivanim stanovništvom Novog Pazara i okoline, što ini 8.19% ispitivane populacije. Na eni podatak ukazuje da je zastupljenost cistnih nodusa na našem ispitivanom materijalu nešto niža od svetskog proseka. Tiroidni malignitet se nalazi u oko 10% hladnih nodusa, koji su solidni ili mešoviti na ultrasonogra ji. Kako se topli i cisti ni nodusi uslovno mogu smatrati neoplasti nim bolestima, prevalenca tireoidnog maligniteta je približno 5%. Kako je ultrasonogra ja vrata rutinska procedura u dijagnostici, otkrivanje mikronodusa je u porastu. Generalno, mikronodusi nemaju klini ki zna aj i, u odsustvu drugih

EVALUACIJA NODOZNIH STRUMA NA PODRU JU ZDRAVSTVENOG CENTRA NOVI PAZAR 45 klini kih nalaza, ne zahtevaju dalje ispitivanje ili tretman. Naj eš e, preporuka je da se ultrasonogra ja ponavlja u odre enim intervalima, tj. kroz 6 do 12 meseci. U našem ispitivanom materijalu mikronodozne promene imalo je 3 ispitanika, odnosno 4.91% ispitivane populacije. Tokom dijagnostike benignih lezija, jednako je važno zapaziti klini ke znake ili simptome kao što su kompresija traheje, ezofagusa ili laringealnog rekurentnog nerva koji, sami za sebe, zahtevaju hirurški tretman. Uobi ajeno se smatra da i starije osobe imaju 1.5 do 2 puta ve u verovatno u za malignu prirodu nodusa nego osobe od 20 do 60 godina, ali ovaj stav nije potvr en (8). Tiroidni nodus je u ve oj meri suspektan na malignitet kada se otkrije kod muškaraca, starijih (preko 60 godina), i kod dece i adolescenata (ispod 20 godina). U našoj seriji ispitivanih bolesnika tiroidni vorovi su otkriveni u svega 3 bolesnika muškog pola, što je inilo 4.92% ispitivane populacije. Najve a u estalost vorova bila je u dobnoj skupini bolesnika izmedju 55 i 59 godina. Drugu vremensku grupu po u estalosti javljanja tiroidnih vorova u našem ispitivanju ini grupa ispitanika izme u 35 i 39 godina starosti. U studiji u kojoj je tražena korelacija suspektnih klini kih nalaza i histološke dijagnoze, benigna bolest je na ena kod 29% pacijenata sa palpabilnim cervikalnim limfnim vorovima, kod 50% pacijenata sa vrstim vori ima, kod 29% pacijenata sa vidljivom ksacijom vorova, i kod 17% pacijenata sa paralizom glasnih žica. Prema tome, raspoloživi podaci ukazuju da klini ke osobenosti mogu da pove aju verovatno u ocene da je neki nodus ve i od 1 cm u pre niku zlo ude prirode i to može da bude od pomo i u tuma enju citopatološkog nalaza neodre ene prirode (9). Opšti klini ki pregled je zna ajan za otkrivanje znakova i simptoma hipo- ili hipertiroidizma i zdravstvenog stanja, gde je kontraindikovana hirurška procedura. Dve grupe istraživa a ispitivale su koncentraciju TSH u bolesnika sa tiroidnim vorovima i obe potvr uju da je viši TSH u vezi sa pove anom opasnoš u od maligniteta. Uopšteno re eno, koncentracija TSH iznad gornje granice referentnih vrednosti povezana je sa 2 do 3 puta ve om opasnoš u da je nodus kancerogen. Do sada još uvek nema prospektivnih kontrolisanih studija koje se bave ovim problemom (10). U našem ispitivanju pokazano je da je normalnu vrednost T3 imalo 47 bolesnika, odnosno 77.05% ispitivanih bolesnika. 14 bolesnika, odnosno 22.95% imalo je povišenu vrednost T3. Nijedan ispitanik nije imao snižene vrednosti tiroidnih hormona. Povišene vrednosti T3 u ispitivanih bolesnika mogle bi da ukažu na postojanje toplih vorova u štitastoj žlezdi sa pove anom funkcijom. Merenje T4 je pokazalo normalne vrednosti u 47 ispitanika, odnosno u 77.05% ispitivane populacije. Nijedan bolesnik nije imao snižene vrednosti T4. Povišene vrednosti T4 imalo je 14 bolesnika, odnosno 22.95% ispitivane populacije. Nivo TSH je bio normalan kod 47 ispitanika, odnosno u 77.05% ispitivane populacije. Ispod opsega referentnih vrednosti, TSH je na en u 14 bolesnika, odnosno u 22.95% ispitane populacije. Zajedno uzevši, postojanje povišenih vrednosti T3 i T4 uz suprimovane vrednosti TSH u 14 ispitivanih osoba

46 MEDICINSKI GLASNIK / str. 38-47 ukazuje na postojanje hipertireoze u ovih ispitanika, koji ine ukupno 22.95% ispitane populacije me u stanovništvom Novog Pazara i okoline. Distribucija ispitanika u našem ispitivanju, na osnovu zaklju ka ultrazvu nog pregleda, data je u tabeli broj 3 u odeljku Rezultati rada. Najzastupljeniji nalaz u ultrazvu nom pregledu u naših ispitanika bio je postojanje polinodozne strume (32.79%), drugi po u estalosti bio je postojanje nodozne strume (27.87%), dok je tre u grupu po u estalosti nalaza inila kombinacija di zne i nodozne strume (21.31%). Mnogi centri daju prednost skoro potpunoj tiroidektomiji kod nodusa sumnjivih na papilarnu neoplazmu, kod nalaza folikularne promene ili atipi ne slike manjeg stepena opasnosti u promeni ozna enoj kao neodre en citološki nalaz (11,12). Merenje TSH u serumu, ultrasenzitivnim postupkom, tiroidna ultrasonogra ja, tiroidna 99m Tc scintigra ja i FNB se mogu smatrati prvom linijom ispitivanja. U zemljama gde je nedostatak joda korigovan, mnogi klini ari smatraju FNB testom izbora i podatkom da dodatna ispitivanja treba bazirati na rezultatima FNB. Ukoliko su noduli topli na scintigra ji, dalji postupak generalno zavisi od prisustva tirotoksikoze i od veli ine nodula. U slu aju cisti nog oblika, FNB se izvodi i u terapijske svrhe (evakuacija sadržaja), i kao dijagnosti ka procedura u otkrivanju malog procenta cisti nih karcinoma. Ako je nodul hladan na tiroidnoj scintigra ji i mešovit ili solidan na tiroidnoj ultrasonogra ji, odluka o daljem postupku e zavisiti od rezultata FNB. ZAKLJU AK 1. U estalost pojave tiroidnih nodusa na podru ju Zdravstvenog centra Novi Pazar najve a je u periodu od 55. do 59. godine sa 18.03%. 2. Naj eš i oblik poreme aja gra e štitaste žlezde na podru ju Zdravstvenog centra Novi Pazar je polinodozna struma sa 32.7%. 3. Adekvatan pregled je zlatni standard u evaluaciji pacijenata sa nodusom u štitastoj žlezdi. 4. Aspiraciona biopsija tankom iglom je zbog svoje jednostavnosti i ta nosti prva dijagnosti ka metoda u evaluaciji pacijenata sa solitarnim nodusom. 5. Metode i testovi, sprovedeni tokom ovog istraživanja, mogu biti korisni u evaluaciji pacijenata sa nodusom i izvode se u skladu sa lokalnim nalazom i protokolima. LITERATURA 1. DeGroot LJ, Pacini F. Thyroid Nodules. http://www.thyroidmanager.org/chapter18/18 nodulesframe.htm 1-5-2006. 13-2-2009.

EVALUACIJA NODOZNIH STRUMA NA PODRU JU ZDRAVSTVENOG CENTRA NOVI PAZAR 47 2. Tunbridge WM, Evered DC, Hall R et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Endocrinol (Oxf) 1977; 7(6): 481 493. 3. Vander JB, Gaston EA, Dawber TR. The signi cance of nontoxic thyroid nodules. Final report of a 15-year study of the incidence of thyroid malignancy. Ann Intern Med 1968;69(3): 537 540. 4. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997; 126(3): 226 231. 5. Mortensen JD, Woolner LB, Bennett WA. Gross and microscopic ndings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955; 15(10): 1270 1280. 6. Jankovi R. Hirurgija tiroidne i paratiroidnih žlezda. Zavod za udžbenike i nastavna sredstva, Beograd, 2001. 7. Bel ore A, La Rosa G.L, La Porta G.A, Giuffrida D, Milazzo G, Lupo L, Regalbuto C, Vigneri R. Cancer risk in patients with cold thyroid nodules: relevance of iodine intake, sex, age, and multinodularity. Am J Med 1992,93:363 369. 8. Yang J, Schnadig V, Logrono, R Wasserman PG. Fine-needle Aspiration of Thyroid Nodules: A Study of 4703 Patients With Histologic and Clinical Correlations CANCER (CANCER CYTOPATHOLOGY) 2007, 111 /, 5, 306 315. 9. Gerhard R., Cunha Santos G da. Inter- and intraobserver reproducibility of thyroid ne needle aspiration cytology: an analysis of discrepant cases Cytopathology 2007, 18, 105 111. 10. K. Boelaert, J, Horacek, R. L, Holder, J. C, Watkinson, M. C, Sheppard, and J. A. Franklyn. Serum Thyrotropin Concentration as a Novel Predictor of Malignancy in Thyroid Nodules Investigated by Fine- Needle Aspiration J Clin Endocrinol Metab 2006, 91: 4295 4301. 11. Delbridge L, Symposium on Evidence-Based Endocrine Surgery (2): Benign Thyroid Disease World J Surg 2008, 32:1235 1236. 12. White ML, Doherty GM, Gauger PG. Evidence-Based Surgical Management of Substernal Goiter World J Surg, 2008, 32:1285 1300.

48 MEDICINSKI GLASNIK / str. 48-57 Mersudin Muli *, Bilsana Muli NODULAR GOITRE EVALUATIONIN THE REGION OF THE HEALTHCARE CENTER OF NOVI PAZAR Summary: The term thyroid nodus refers to any irregular growth which forms a lump in the thyroid gland. Objective: The evaluation of medical history, clinical, laboratory and ultrasonography ndings in patients with the disorder of thyroid gland structure in the region of the Healthcare Center of Novi Pazar. Methods: The study included 61 patients, 58 females and 3 males, with a disorder of the thyroid gland structure. Each patient underwent clinical examination and ultrasonography of the thyroid gland. In each patient the global function of the thyroid gland was assessed by measuring serum concentrations of triiodothyronine (T3), thyroxine (T4), thyroidstimulating hormone (TSH), and titres of thyroglobulin (TGAb) and microsomal (TPOAb) antibodies. Results: The frequency of the occurrence of a thyroid nodus is highest at the age 35-39 (16.39%) and at the age 55-59 (18.03%). By analyzing the ultrasound ndings of the patients thyroid glands, the following distribution was obtained: 13 (21.31%) patients had a diffuse and nodose struma, 17 (27.87%) had nodose struma, 20 (32.79%) had polynodose struma, 5 (8.19%) had cystic node, 3 (4.92%) had micronodular struma and 3 (4.92%) had a recurrence of nodules. Conclusion: In the region of the Healthcare Centre of Novi Pazar, the frequency of thyroid nodus is highest at the age 55-59, and the most common disorder of the thyroid gland structure is polynodose struma. Keywords: thyroid nodus, thyroid gland * Mr. Med Sci Mersudin MULI Specialist in Internal Medicine Subspecialist in Endocrinology. Address: Sutjeska C/11.36300 Novi Pazar. E-mail: merko@ptt.rs

NODULAR GOITRE EVALUATIONIN THE REGION OF THE HEALTHCARE CENTER OF NOVI PAZAR 49 INTRODUCTION Thyroid nodules are one of the most common diseases in medicine in general. They include all the changes in which limited, one or more, parts of the thyroid gland structurally (morphologically) differ from the normal, healthy tissue. Thyroid nodules can be cysts, adenomas, carcinomas, lobulations of the normal tissue or any other focal changes in the thyroid gland (1). The prevalence of nodules and struma detected by palpation is about 3% in the entire population, about 6.4% in women and 1.5% in men (2, 3). On the other hand, during the research which included the healthy population, nodules were detected by echosonography in 60% of the patients (4). Autopsy studies detected thyroid nodules in over 50% of the examined glands (5). The prevalence of thyroid nodules increases with age, iodine de ciency and exposure to ionizing radiation. The clinical signi cance of the nodules detected in this way has not been fully and thoroughly evaluated yet. Most nodules in the thyroid gland are completely asymptomatic and most likely will never cause any symptoms. If the cells in the nodus produce thyroid hormones independently, the nodus can give the symptoms of an increased thyroid gland (hyperthyroidism). A small number of patients complain of the pain which spreads from the nodus to the ear or the jaw. If the nodus is of a very large size, it may perform compression of the esophagus and trachea causing dif cult swallowing and breathing. In some cases, the patient may complain of hoarseness and dif culty in speaking due to the compression of the larynx. However, in about 10 to 15% of nodules in the thyroid gland there is a carcinoma. For these patients, early detection and proper treatment is the condition for an exceptionally good prognosis in most cases. Therefore, the need to diagnose and continue the treatment of the nodules in the thyroid gland which can potentially be malignant has led to a widespread belief that all nodules greater than 1-1.5 cm should be thoroughly investigated. The main task of the doctor, therefore, is to identify the nodules that are of suspicious or malignant nature in order to begin a timely treatment of cancer, and to avoid unnecessary surgery of benign nodules (6). The evaluation aims to identify relatively rare cases of thyroid carcinoma among very common thyroid nodules (6). OBJECTIVE The aim of the research is, by evaluating medical history, clinical, laboratory, and ultrasonography parameters, to assess the features of the thyroid structure in patients with disorders of the thyroid gland structure in the region of Novi Pazar. In our region, such studies have not been done in the past, and this is the rst study that deals with the evaluation of the nodules in this area. For these patients, early detection and proper treatment are the conditions for a good prognosis. Therefore, it is necessary to timely diagnose and treat people with nodules in the thyroid gland and, in particular, to distinguish patients with the nodules that can be potentially malignant.

50 MEDICINSKI GLASNIK / str. 48-57 MATERIAL AND METHODS The study involved 61 patients with an irregular thyroid gland structure in the region of the HC Novi Pazar. During the research, the following methodology was used: 1. Clinical examination in the assessment of the nodule size. 2. Ultrasound examination of the thyroid gland 3. Laboratory parameters for the evaluation of the thyroid function (measurement of serum concentrations of triiodothyronine (T-3), thyroxine (T-4), thyroid-stimulating hormone (TSH), and the titer thyroglobulin (TgAb) and microsomal (antiperoxidase, TPOAb) antibodies). 4. Questionnaire on life quality assessment (which included: full name, date of birth, gender, occupation, marital status, TV, TT, BMI, socioeconomic living conditions, pre-radiation of the neck region, the family history of cancer, as well as the question of why a patient came to see a doctor). 5. Statistical data processing RESULTS The study included 61 patients of whom 58 were female and three were male patients (Table 1). Table 1 Gender f % Male 3 4.92 Female 58 95.08 Toal 61 100.00 The youngest patient was 22 years old and the oldest was 76. The average age of females was 50.76 ± 13.4 years, while male patients were 54.33 ± 2.3 years of age. The prevalence and distribution of thyroid nodules according to the age of patients, taking a group interval of 5 years, is given in Table 2 Table 2 Age f % 20-24 1 1.64 25-29 30-34 4 6.56

NODULAR GOITRE EVALUATIONIN THE REGION OF THE HEALTHCARE CENTER OF NOVI PAZAR 51 35-39 10 16.39 40-44 7 11.47 45-49 8 13.11 50-54 3 4.92 55-59 11 18.03 60-64 7 11.47 65-69 6 9.84 70-74 75-79 4 6.56 80-84 Total 61 100.00 Table 2 shows that the incidence of thyroid nodules in patients is highest at the age of 35-39 and 55-59. The analysis of the ndings listed in the thyroid ultrasound examination revealed the following distribution, Table 3, Figure 1 Table 3 Struma f % Diffuse and nodular 13 21.31 Nodose 17 27.87 Polynodose 20 32.79 Micronodular 3 4.92 Cystic nodules 5 8.19 Node recurrence 3 4.92 Total 61 100.00 13 patients were diagnosed with diffuse and nodular struma, 17 patients had a single thyroid nodule. Most patients (20 of them) had multinodular struma, 3 patients had micronodular struma and cystic nodules were found in 5 patients. In 3 patients there was the recurrence of nodules in the remaining lobe after lobectomy. It is evident that there is the highest percentage of multinodular struma (about 33%).

52 MEDICINSKI GLASNIK / str. 48-57 Figure 1. The distribution of patients according to the morphological ndings Node Recurrence - Micronodular Cystic nodules 8% 5% 5% 21% Diffuse and nodular Type of struma Polynodosea 33% 28% Nodose The distribution of patients according to the value of the ndings of T3, T4, TSH is shown in Table 4. Table 4 T3 fn % 1 below RR 2 within RR 47 77.05 3 above RR 14 22.95 Total 61 100.00 T4 fn % 1 below RR 2 within RR 47 77.05 3 above RR 14 22.95 Total 61 100.00 TSH fn % 1 below RR 14 22.95 2 within and above RR 47 77.05 Total 61 100.00 RR: reference range

NODULAR GOITRE EVALUATIONIN THE REGION OF THE HEALTHCARE CENTER OF NOVI PAZAR 53 T3 ndings in 77% of patients (47 of them) were within the normal range, and 23% (14 of them) had T3 values above the reference range. The distribution of patients in relation to the values of the ndings of thyroglobulin and microsomal antibodies is shown in Table 5. Table 5. Distribution of patients according to the values of laboratory tests for thyroglobulin and microsomal antibodies Thyroglobulin antibodies fn % 2 within RR 49 80.33 3 above RR 12 19.67 Total 61 100.00 Microsomal antibodies f % 2 within RR 46 75.41 - above RR 15 24.59 Total 61 100.00 The values found for the level of thyroglobulin antibodies in 49 patients (80%) were within the reference range and in 12 patients (20%) they were above the reference range. The values found for the level of microsomal antibodies in 46 patients (75%) were within the reference range and in 15 patients (25%) they were above the reference range. DISCUSSION Thyroid nodules are often discovered during clinical examination, especially if it was supplemented with echotomographic assessment of the thyroid gland. In countries like the U.S., where iodine de ciency is corrected with iodine prophylaxis, thyroid nodules are clinically evident in about 4-7% of the entire population. The prevalence is higher in countries affected by high or severe iodine de ciency, where the disease is endemic (7). The incidence of sub-clinical (non-palpable) nodes detected by means of thyroid ultrasonography reaches 50% in women older than 50. In our series of patients, ultrasound examination showed that there were 21.31% patients with diffuse and nodular struma, whereas 27.87% of patients had only nodular struma. The sum of these two categories shows that in our area, too, the percentage of nodes detected by means of echotomographic assessment is around 49%, which indicates that the incidence of nodular changes in the study population of Novi Pazar and the surrounding area is at the global level.

54 MEDICINSKI GLASNIK / str. 48-57 In our study, we discovered elevated antithyroglobulin antibodies in 12 patients, which could speak in favor of the existence of in ammation of the thyroid gland, 3 patients with diffuse and nodular struma, 3 patients with nodular struma, 3 patients with polynodose struma and 3 patients with node recurrences. A similar result was obtained when testing the presence of high titer antimicrosomal (peroxidase) antibodies there was an increase in 15 patients, or 25% of the study population, which could indicate the presence of Hashimoto s thyroiditis. Radionuclide examination shows that scintigraphy isoactive hot nodules represent 3-20% of thyroid nodules and their incidence is higher in countries with iodine de- ciency. About 10% of nodules in this group were malignant. They are 3 to 4 times more common in women, particularly after the age of 40. In most cases, warm nodules are benign. Cold nodules make more than 80% of all thyroid nodules and up to 17% of them may be malignant. Thyroid ultrasonography can distinguish three different types of nodes: cystic, solid or mixed (containing solid and cystic component). Cystic nodules (10-20% of all nodules) are almost always benign (malignancy rate is of about 10%). In our study, 5 cystic nodules were found among the study population of Novi Pazar and the surrounding area, which is 8.19% of the study population. Discovered data indicate that the presence of nodes in examined material is lower than the world average. Thyroid malignancy is found by means of ultrasonography in about 10% of cold nodules that are solid or mixed. Since hot and cystic nodules can be tentatively considered as neoplastic diseases, the prevalence of thyroid malignancy is approximately 5%. As neck ultrasonography is a routine procedure in the diagnostics, the detection of micro nodes is increasing. Generally, micro nodes have no clinical signi cance and, in the absence of other clinical ndings, they do not call for further examination or treatment. Most often, it is recommended that ultrasound is repeated at regular intervals, i.e. in 6 to 12 months. In our examined material, micronodular changes were observed in 3 patients or 4.91% of the study population. When diagnosing benign lesions, it is equally important to note clinical signs or symptoms, such as compression of the trachea, esophagus, or recurrent laryngeal nerve, which all require surgical treatment. Normally, it is considered that the elderly are 1.5 to 2 times more likely to have malignant nodules than those aged 20 to 60, but this has not been con rmed yet (8). A thyroid nodule is more suspicious of malignancy when detected in older men (over 60), and in children and adolescents (under the age of 20). In our series of patients, thyroid nodules were detected in only 3 male patients, accounting for 4.92% of the study population. The highest incidence of nodes was found in the age group of patients between 55 and 59. The second group in terms of incidence of thyroid nodes in our study is the group of patients between 35 and 39 years of age. In the study, in which the correlation between suspicious clinical ndings and histological diagnosis was required, a benign disease was found in 29% of patients with palpable cervical

NODULAR GOITRE EVALUATIONIN THE REGION OF THE HEALTHCARE CENTER OF NOVI PAZAR 55 lymph nodes, in 50% of patients with solid nodules, in 29% of patients with a visible xation of nodes, and in 17% of patients with vocal cord paralysis. Thus, the available data indicate that the clinical characteristics may increase the likelihood that an evaluation of a nodule greater than 1 cm in diameter is of malignant nature and this may be helpful in interpreting cytopathological ndings of unspeci ed nature (9). General clinical examination is important to detect signs and symptoms of hypoor hyperthyroidism and health conditions where a surgical procedure is contraindicated. Two groups of researchers have investigated the concentration of TSH in patients with thyroid nodules and both con rm that the higher TSH is related to an increased risk of malignancy. In general, the concentration of TSH above the upper limit of the reference range is linked to the 2 to 3 times greater risk of the nodule being cancerous. So far, there are still no prospective and controlled studies that address this issue (10). In our study, it is shown that 47 patients or 77.05% of the patients had the normal value of T3. 14 or 22.95% of patients had elevated T3 values. None of the subjects had lower levels of thyroid hormones. Elevated serum T3 in the patients could indicate the existence of hot nodes in the thyroid gland with increased functionality. T4 measurement showed normal values in 47 patients, or 77.05% of the study population. None of the patients had lower levels of T4. 14 patients, or 22.95% of the study population, had elevated serum T4. TSH was normal in 47 patients, or 77.05% of the study population. TSH reference values below the range were found in 14 patients, or 22.95% of the study population. Together, given the existence of elevated T3 and T4 values with supreme TSH values, hyperthyroidism was indicated in 14 patients, who make up 22.95% of the study population among the entire population of Novi Pazar and the surrounding area. The distribution of the patients in our study based on the conclusion of ultrasound examination is given in Table 3 in the work results section. The most frequent nding in the ultrasound scan in our patients was the existence of polynodular goiter (32.79%), the second most common was the presence of nodular goiter (27.87%), while the third group, in terms of frequency, combined diffuse and nodular goiter (21.31%). Many centers prefer almost total thyroidectomy for papillary nodules suspected of neoplasia, the ndings of follicular changes or atypical images with a lower risk degree identified as indeterminate cytological findings (11, 12). Measurement of serum TSH by means of an ultra-sensitive process, thyroid ultrasonography, thyroid scintigraphy and 99m Tc FNB can be considered the rst line of examination. In countries where iodine de ciency is improved, many doctors believe FNB choice test and additional testing should be based on the results of FNB. If the nodules are shown as hot in scintigraphy, further examination generally depends on the presence of hyperthyroidism, and the size of the nodule. In the cases of cystic forms, FNB is performed for therapeutic purposes (contents evacuation) and as a diagnostic procedure it is used to detect a small percentage of cystic carcinomas. If a

56 MEDICINSKI GLASNIK / str. 48-57 nodule is cold in thyroid scintigraphy and mixed or solid in thyroid ultrasonography, the decision on further treatment will depend on the results of FNB. CONCLUSION 1. The incidence of thyroid nodules in the Healthcare center of Novi Pazar is highest at the age between 55-59 with 18.03%. 2. The most common form of the disorder of the thyroid gland structure in the Healthcare center of Novi Pazar is multinodular goitre with 32.7%. 3. Adequate examination is the gold standard in the evaluation of patients with nodules in the thyroid gland. 4. Fine needle aspiration biopsy is performed because it is the rst diagnostic tool in the evaluation of patients with solitary pulmonary nodule due to its simplicity and accuracy. 5. Methods and tests performed during this study may be useful in the evaluation of patients with a nodus and performed in accordance with local protocols and ndings. LITERATURE 1. DeGroot LJ, Pacini F.Thyroid Nodules.http://www.thyroidmanager.org/Chapter18/18 nodulesframe.htm 1-5-2006. 13-2-2009. 2. Tunbridge WM, Evered DC, Hall R et al.the spectrum of thyroid disease in a community:the Whickham survey. Clin Endocrinol (Oxf) 1977; 7(6): 481 493. 3. Vander JB, Gaston EA, Dawber TR.The signi cance of nontoxic thyroid nodules.final report of a 15-year study of the incidence of thyroid malignancy. Ann Intern Med1968; 69(3): 537 540. 4. Tan GH, Gharib H. Thyroid incidentalomas: management approaches to nonpalpable nodules discovered incidentally on thyroid imaging. Ann Intern Med 1997; 126(3): 226 231. 5. Mortensen JD, Woolner LB, Bennett WA. Gross and microscopic ndings in clinically normal thyroid glands. J Clin Endocrinol Metab 1955; 15(10): 1270 1280. 6. Jankovi R. Surgery of thyroid and parathyroid glands. Institute for textbook publishing and teaching aids, Belgrade, 2001. 7. Bel ore A.,La Rosa G.L.,La Porta G.A.,Giuffrida D.,Milazzo G.,Lupo L.,Regalbuto C.,Vigneri R. Cancer risk in patients with cold thyroid nodules:relevance of iodine intake,sex,age,and multinodularity.am J Med 1992,93:363-369 8. Yang J, Schnadig V, Logrono,R Wasserman PG, Fine-needle Aspiration of Thyroid Nodules: A Study of 4703 Patients With Histologic and Clinical Correlations CANCER (CANCER CYTOPATHOLOGY) 2007, 111 /, 5, 306-315

NODULAR GOITRE EVALUATIONIN THE REGION OF THE HEALTHCARE CENTER OF NOVI PAZAR 57 9. Gerhard R Cunha Santos G da: Inter- and intraobserver reproducibility of thyroid ne needleaspiration cytology: an analysis of discrepant cases Cytopathology 2007, 18, 105 111 10. K. Boelaert, J. Horacek, R. L. Holder, J. C. Watkinson, M. C. Sheppard, and J. A. Franklyn: Serum Thyrotropin Concentration as a Novel Predictor of Malignancy in Thyroid Nodules Investigated by Fine- Needle Aspiration J Clin Endocrinol Metab 2006, 91: 4295 4301 11. Delbridge L Symposium on Evidence-Based Endocrine Surgery (2): Benign Thyroid Disease World J Surg 2008, 32:1235 1236 12. White ML, Doherty GM, Gauger PG: Evidence-Based Surgical Management of Substernal Goiter World J Surg, 2008, 32:1285 1300