tmng surgical indication

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CHIRURGIA ITALIANA 2005 - VOL. 57 N. 5 PP 597-606 597

Surgical indications for toxicmultinodular goitre

ADOLFO PISANU, ALESSANDRO MONTISCI, ALESSANDRO COIS, ALESSANDRO UCCHEDDU

Dipartimento di Chirurgia - Semeiotica Chirurgica - Universit di CagliariCentro di Studio per la Chirurgia Endocrina e Metabolica

Riassunto Lo scopo di questo studio era di chiarire le indicazioni chirurgiche e lefficacia della tiroi-dectomia totale (TT) nel trattamento del gozzo multinodulare tossico (TMNG). Dal gennaio1998 al maggio 2004, 70 pazienti affetti da TMNG sono stati sottoposti a TT presso il nostroDipartimento. In 46 pazienti (65.7%) le indicazioni alla TT erano: 25 casi di gozzo com-pressivo; 12 di gozzo immerso; 2 di sindrome di Pemberton; 5 noduli follicolari con atipiecitologiche; 2 casi di sospetto carcinoma papillare. In 24 pazienti (34.3%), per il fallimentoo lintolleranza a precedenti terapie, le indicazioni chirurgiche erano: 9 casi di ipertiroidi-smo persistente; 5 di ipertiroidismo ricorrente dopo terapia medica; 6 pazienti con cardio-tossicit; 3 con recidiva di malattia dopo iniezione percutanea di etanolo; 1 con intolleran-za agli antitiroidei. La degenza postoperatoria media stata di 3.2 giorni (range: 2-9).Lipocalcemia transitoria si verificata in 6 pazienti (8.6%) e la paralisi ricorrenziale tran-sitoria in altri 3 (4.2%). Tutti i 70 pazienti hanno risolto i sintomi e sono diventati ipotiroideidopo lintervento. La TT risultata una soluzione rapida e affidabile dellipertiroidismo,rimuove il gozzo e le neoplasie associate, evitando recidive di tossicit e lipotiroidismopostchirurgico semplice da trattare.Parole chiave: ipertiroidismo, gozzo multinodulare tossico, tiroidectomia, ablazioneradioiodio

Summary Surgical indications for toxic multinodular goitre. A. Pisanu, A. Montisci, A. Cois,A. UcchedduThe aim of this study was to clarify the surgical indications and the effectiveness of total

thyroidectomy in the treatment of toxic multinodular goitre. From January 1998 to May2004, 70 patients underwent total thyroidectomy in our department because of toxic multi-nodular goitre. In 46 patients (65.7%) the indications for total thyroidectomy were: 25 com-pressive goitres, 12 cervico-mediastinal goitres, 2 cases of Pembertons sign, 5 follicularnodules with cytological atypia, and 2 cases of suspected papillary carcinoma. In 24patients (34.3%) with failure or intolerance of previous treatment, surgical indications were:9 persistent and 5 recurrent hyperthyroidism after medical treatment; 6 patients with car-diotoxicity; 3 patients with recurrent disease after percutaneous ethanol injection; 1 patientwith antithyroid drug intolerance. The mean postoperative hospital stay was 3.2 days (ran-ge: 2-9). Transient hypocalcaemia occurred in 6 patients (8.6%) and transient unilateral

Correspondence to: Prof. Alessandro Uccheddu - Semeiotica Chirurgica - Ospedale San Giovanni di Dio - Via Ospedale, 46 -09124 Cagliari.This study was supported by a grant from the University of Cagliari, Italy.


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598 SURGICAL INDICATIONS FOR TOXIC MULTINODULAR GOITRE

endocrine disorders in our surgical department. In115 patients (21.5%) hyperthyroidism was also pres-ent. The medical records of 70 patients with TMNG

were analysed retrospectively. TMNG was defined asa multinodular thyroid gland with at least oneautonomously functioning thyroid nodule secretingexcess thyroid hormone and producing typical signsand symptoms of hyperthyroidism. Laboratory evi-dence supporting the diagnosis of hyperthyroidismwas defined as suppressed thyroid-stimulating hor-mone (TSH) less than 0.400 IU/ml, associated withan elevated plasma level of free triiodithyronine (FT3> 4.2 pg/ml) or free thyroxin (FT4 > 1.9 ng/dl), whilesubclinical hyperthyroidism was defined as sup-pressed TSH, associated with normal plasma values ofFT3 and FT4. Definition of TMNG excluded the pres-ence of autoimmune disease and its related autoanti-bodies such as antithyroglobulin (antiTG Ab), antithy-roid peroxidase (antiTPO Ab) and thyrotropin recep-tor antibodies (TSHr Ab). Moreover, criteria for TMNGincluded clinical findings, imaging studies, and nodu-lar goitre on palpation, which proved to be multin-odular at pathology. Thyrotoxicosis was originally aterm that described the clinical appearance of affect-ed patients. Hyperthyroidism is a condition in whichthe thyroid gland secretes excessive hormone. Like

other Authors

7

, we use the terms interchangeably.

Study design

We carried out a retrospective study to assess theindications and effectiveness of total thyroidectomy inthe treatment of TMNG. The present study involvedevaluation of demographic data (age and sex), med-ical history, laboratory data, ultrasonography, andTc99-scintigraphy, and fine needle aspiration cytol-ogy (FNAC) findings in patients with TMNG. A sampleof TMNG patients with full information about their

case history was also evaluated in order to clarify thenatural history of the disease.The indications for surgery were defined for two

groups of patients with TMNG. Those patients having

Introduction

Toxic multinodular goitre (TMNG) is a common

cause of hyperthyroidism, especially in areas ofiodine deficiency1. The steps in the pathogenesis ofthe disease have been described2 and TMNG usuallyfollows a growing process with multiple nodules thatbecome autonomous3. The natural history involvesprogression from overproduction of thyroid hormonesin autonomous functioning nodules toward thyrotoxi-cosis and its related symptoms and complications4.Three different modalities are commonly used for thetreatment of TMNG: antithyroid drugs, surgery, andradioiodine (131I)5,6. First-line treatment is oftenantithyroid drugs but the relapse rate after medicaltherapy is reported as high6,7. Surgical treatmentquickly eliminates the hyperthyroid state, but it ischarged with having a higher rate of complications5.Radioiodine 131I ablation therapy takes longer toachieve a euthyroid state, but presents low complica-tion risks8. More recently, radioiodine 131I ablationhas been regarded as the most appropriate treatmentfor TMNG, with surgery performed only in patientswith large goitres or severe hyperthyroidism9-11. Onthe other hand, some Authors favour surgical treat-ment, stressing the inferior efficacy of radioiodine that

requires multiple doses and may produce only a lowreduction in goitre size3,6. Ethanol injection of toxicnodules is also reported in the literature as an effectivetreatment depending on nodule size3,12,13. However,optimal treatment remains controversial and treat-ment decision-making in TMNG is debatable with dif-ferent options reported in the literature3,6,8-11. Becauseof the unresolved debate, we reviewed our own expe-rience with the aim of clarifying the surgical indica-tions and the effectiveness of total thyroidectomy inthe treatment of TMNG and to assess and plan appro-priate management of the disease.

Patients and methodsOver the period from January 1998 to May 2004,

534 patients underwent thyroidectomy for a variety of

recurrent laryngeal nerve injury in another 3 patients (4.2%). None of the patients had per-manent hypocalcaemia or permanent recurrent laryngeal nerve injury. All 70 treatedpatients relieved their symptoms and became biochemically hypothyroid after the opera-tion. Total thyroidectomy results in a rapid, reliable resolution of hyperthyroidism and remo-val of multinodular goitre, requires no re-treatment, removes any coexisting malignancy,and post-surgical hypothyroidism is simple to treat.Key words:hyperthyroidism, toxic multinodular goitre, thyroidectomy, radioiodine ablationChir Ital 2005; 57, 5: 597-606


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a primary disease in whom thyroidectomy was firstindicated and those patients with failure or intoler-ance of previous treatment of hyperthyroidism inTMNG. Patients with failure of medical treatment

(methimazole and beta-adrenergic blocking drugs for18 months) were classified as having recurrent dis-ease if symptoms of hyperthyroidism relapsed 6months after drug discontinuation. Patients whorelapsed within 6 months were classified as havingpersistent disease.

Management characteristics and surgical compli-cations, such as recurrent laryngeal nerve andparathyroid injury were also evaluated in all patients.Pathological findings of multinodular disease andweight of all specimens were also recorded, as well asevidence of associated thyroid carcinoma.

Despite not being part of the subject of the currentstudy, the results relating to demographic data, surgi-cal indications and prevalence of associated carcino-ma were compared with those of patients operated onin our department during the same period for toxicadenoma (Plummer disease) and Graves disease.

All patients with TMNG entered a follow-up study inthe endocrinological outpatient department. Early fol-low-up was defined as evaluation on day 30 after surgi-cal treatment, and late follow-up was then updated.

Treatment was defined as being successful ifpatients were relieved of their symptoms and were nolonger clinically or biochemically hyperthyroid.

Surgical procedure

In patients with TMNG, thyroidectomy was per-formed when restoration of euthyroidism wasachieved. Preoperative medication with Lugols solu-tion (iodine-iodide) 5% was combined with the preex-isting antithyroid therapy according to a schedule oforal administration of 15 drops of Lugols solution 3times/day for 10 days before operation. Lugols solution

limits intraoperative bleeding and its related complica-tions resulting from a reduction in thyroid gland vascu-larisation and friability, and also preventing thyroidstorm during surgery14. A number of patients were pre-pared with iopanoic acid administration. The scheduleof oral administration was one 500 mg tablet once dai-ly for 10 days before operation (333.4 g of iodine pertablet) or two 500 mg tablets twice daily for 5 daysbefore operation. Iopanoic acid is a cholecystographicoral agent with iodine excess that decreases thyroidblood flow and the release of thyroid hormone from thegland. Iopanoic acid also affects the peripheral metab-

olism of thyroid hormones, mainly by inhibiting deiod-ination of T4 to T315.Each surgical operation on patients with TMNG

consisted of a total thyroidectomy managed extracap-

sularly. A little transverse skin incision was performedat the base of the neck. After creating a short superiorand inferior flap, the strap muscles were divided in themidline and separated from the thyroid gland. The

pyramidal lobe was first dissected and then lowered.After visualization of the external branch of the supe-rior laryngeal nerve on the right, the superior pole wasligated and divided. Dissection was then performed toidentify and respect the recurrent laryngeal nerve andthe superior and inferior parathyroid glands. The thy-roid was elevated and dissected from the pretrachealfascia. The contralateral lobe of the thyroid wasapproached in a similar fashion. The dissection wascompleted by mobilising the gland from the trachea.In all patients, three parathyroid glands at least wereidentified and preserved after identification of their

vascular pedicles, and very mild dissection by ultrali-gature and bipolar coagulation. When a venousinfarction of the parathyroid gland was recognized, asmall decompressing incision and hydration of thegland were performed with careful checking of theend result. A highly compromised parathyroid glandwas autotransplanted in the ipsilateral sternocleido-mastoid muscle. A drain was positioned and neckincision was closed in layers, with a 4/0 subcuticularmonocryl suture to the skin.

Data collection and statistical analysis

Data were collected in a planned relational com-puter database including patient characteristics, casehistory, and laboratory, FNAC, and imaging study find-ings. Operative and postoperative results and any com-plications or follow-up information were also recorded.

Age data were presented as mean standard errorof the mean (SEM) and as median value. Data werecompared for statistical analysis using the chi-squaretest and Students t-test, and analysis of variance(ANOVA) on categorical and continuous variables,

respectively. Differences were considered significantwhen p< 0.05.

Results

Seventy patients met the inclusion criteria andwere classified as having TMNG. The prevalence ofpatients treated for TMNG during the period consid-ered was 13.1%. Among those patients surgicallytreated in our department for hyperthyroidism, theprevalence of TMNG was 63.0% (Table I). Patients

with TMNG included 57 females and 13 males (F:M =4.4:1.0) with a mean age of 56.4 years (range: 23-79),and were significantly older than those with Gravesdisease (p= 0.000) (Table I).


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cell carcinoma. Moreover, histological examinationrevealed 5 case of incidental papillary carcinoma. Theprevalence of malignancy in all treated TMNG patientswas 12.8%. Nevertheless, the prevalence of malignan-cy was significantly higher in Graves disease than inTMNG (p= 0.036) (Table IV).

After total thyroidectomy, the mean postoperativehospital stay was 3.2 days (range: 2-9). No deaths andmorbidity were encountered in 10 patients (14.2%)(Table V). Reoperation for postoperative haemorrhage

occurred in one patient (1.4%), within 6 hours of thy-

roidectomy and without any sequelae. Transienthypocalcaemia occurred in 6 patients (8.6%) and intwo of these cases one parathyroid gland was auto-transplanted in the ipsilateral sternocleidomastoidmuscle. Transient unilateral recurrent laryngeal nerveinjury was observed in 3 patients (4.2%). None of thepatients had permanent hypocalcaemia or permanentrecurrent laryngeal nerve injury (Table V).

Surgical treatment was defined as a success,because symptom relief occurred in all 70 treated

TMNG patients and all were biochemically hypothy-

Table III. Indications for total thyroidectomy in TMNG as compared to toxic adenoma and Graves disease.

Indication TMNG Toxic adenoma Graves disease p (Plummer)

Compressive goitre 25(35.8%) 3(42.8%) 6(17.6%)Cervico-mediastinal goitre 12(17.2%) Pembertons sign 2(2.8%) Follicular nodule with atypia 5(7.1%) 5(14.7%)Suspected papillary thyroid carcinoma 2(2.8%) 4(11.8%)

Subtotal 1 46(65.7%) 3(42.8%) 15(44.1%) 0.059

* Persistent after medical treatment 9(12.9%) 1(14.3%) 7(20.8%)** Recurrent or multi-recurrent after medical treatment 5(5.0%) 1(14.3%) 3(8.8%)Recurrent after percutaneous ethanol injection 3(4.3%) Cardiotoxicity 6(8.6%) 2(28.6%) 1(2.9%)Severe ophthalmopathy 3(8.8%)Antithyroid drug intolerance (methimazole) 1(1.4%) 2(5.9%)Agranulocytosis (methimazole) 1(2.9%)Cholestasis (methimazole) 1(2.9%)Hepatocellular damage (prophylthiouracil) 1(2.9%)

Subtotal 2 24(34.3%) 4(57.2%) 19(55.9%) 0.059

Total 70 7 34

TMNG = toxic multinodular goitre* Persistent hyperthyroidism: if symptoms relapsed within 6 months of drug discontinuation.** Recurrent hyperthyroidism: if symptoms relapsed 6 or more months after drug discontinuation.

Table IV. Coexisting thyroid carcinoma and TMNG as compared to toxic adenoma and Graves disease.

Diagnosis TMNG Toxic adenoma Graves disease p (Plummer)

Suspected papillary thyroid carcinoma on cytology 2 7Incidental papillary thyroid carcinoma 2 2Incidental multicentric papillary carcinoma 3 2Hrthle cell carcinoma 2

Total 9 out of 70 11 out of 3412.8% 0% 32.3% 0.036

TMNG = toxic multinodular goitre.


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Table V. Perioperative data, postoperative results and follow-up of 70 patients with TMNG.

TMNG %

Preparation with Lugols solution before thyroidectomy 67 95.7

Preparation with iopanoic acid before thyroidectomy 3 4.3

Total thyroidectomy 70 100%

Mean weight of thyroid gland 93 g (range: 23-350)

Mortality

Morbidity 10 14.2Postoperative haemorrhage 1 1.4Temporary hypocalcaemia 6 8.6Permanent hypocalcaemia 0 0Unilateral temporary recurrent nerve palsy 3 4.2Permanent recurrent nerve palsy 0 0

Postoperative stay (days) 3.2 days (range: 2-9)

Early follow-upPatients hypothyroid after one month 70 100%

Late updated follow-upPatients with recurrent hyperthyroidism 0 0%

Patients undergoing 131I ablation therapy becauseof an associated thyroid carcinoma 9 12.8%

TMNG = toxic multinodular goitre.

roid within one month of the operation. Sixty-onepatients received lifelong thyroxin substitution thera-py. Nine patients (12.8%) with associated thyroid car-cinoma received 131I ablation therapy after total thy-roidectomy, and thyroxin suppressive therapy. A lateupdated follow-up failed to detect recurrent disease(Table V).

Discussion

The prevalence of hyperthyroidism is approximate-ly 2% in women and 0.2% in men.16 Hyperthyroidismfrom toxic multinodular goiter (TMNG) is especiallycommon in areas of iodine deficiency.1 The develop-ment of various form of hyperthyroidism dependsmainly on the iodine intake of the population. An epi-demiological survey compared an area of normaliodine intake (Iceland) and an area of low iodineintake (East Jutland, Denmark). Graves diseaseaccounted for at least 80% of new cases of hyperthy-roidism in Iceland, whereas TMNG caused over halfthe new cases of hyperthyroidism in Denmark.17 In

some Sardinian geographical areas iodine intake isdeficient18 and it may be for this reason that in ourexperience the prevalence of TMNG was 63.0% ascompared to a 30.6% incidence of Graves disease

(Table I). Moreover, during the toxic evolution of amultinodular goitre a major part is played by theintroduction of oral iodine supplementation in areaswith iodine deficiency19, and the highest incidence ofTMNG is detected mainly in the initial phase of sup-plementation intake19.

TMNG is a heterogeneous disease producinghyperthyroidism and encompasses a spectrum of dif-ferent clinical entities, ranging from a single hyper-functioning nodule within an enlarged thyroid glandwith other nonfunctioning nodules to multiple hyper-

functioning areas scattered over non-adenomatousnodules20. The exact cause of TMNG is unknown2,but it is probably related to mutations in individualcells and clonal expansion of individual nodules withautonomous thyroid function20. As in toxic thyroidadenoma, autonomous function has been linked toactivating mutations in the thyrotropin receptor(TSHr), or further downstream in the stimulatory Gprotein pathway producing cyclic AMP21,22.Activating TSHr mutations are present in single hyper-functioning nodules, either in adenoma or hyperplas-tic areas, in the context of TMNG20.The expression of

TSHr mutation both in adenomatous and hyperplasticareas of the thyroid gland could explain the scinti-graphic evidence of different patterns of intenseuptake20, as recorded in the current study.


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The natural history of TMNG involves progressionfrom multinodular goitre to an overproduction of thy-roid hormones in autonomous functioning nodules,followed by thyrotoxicosis and its related symptoms4.

The present study showed a significant progressive age-ing in the toxic evolution of a multinodular goitrewhich was first classified as euthyroid, in a sample ofpatients with full information as to their medical histo-ry (Table II). On the basis of evidence from the litera-ture, most patients with TMNG are women older than50 years7. In our experience, the mean age of patientswith TMNG was 56.4 years as compared to 41.7 yearsin cases of Graves disease (Table I) which is commonin areas of the world with iodine deficiency7,17.

Patients who have symptoms of hyperthyroidismdue to TMNG always need treatment to avoid subse-

quent cardiovascular, skeletal, or psychological sec-ondary effects. Antithyroid drugs are used as primarytreatment, with the aim of achieving remission, usual-ly defined as normal thyroid function for 1 year afterdrug discontinuation. However, the average treatmentcure rate with antithyroid drugs ranges only from 40%to 50% of cases7.

As in our practice, some Authors classified patientswith failure of medical treatment (antithyroid drugsand beta-adrenergic blocking drugs for 18 months) ashaving recurrent disease if symptoms of hyperthy-roidism relapse occurred 6 or more months after drugdiscontinuation6. On the other hand, patients whorelapsed within 6 months were classified as havingpersistent disease6. When relapse occurs after med-ical therapy, a number of physicians prefer anothercourse of drug treatment.

In any event, in most cases the essential goal of thetreatment, i.e. definitive reduction of hypersecretion ofthyroid hormone, can be achieved only with surgery orradioiodine 131I ablation therapy, although the optimaltreatment still remains controversial6-11. The analysis ofour experience suggests that total thyroidectomy in the

treatment of TMNG can be defined as a successbecause all treated patients experienced symptomrelief and became hypothyroid within one month of theoperation, with a low incidence of morbidity, and with-out permanent hypocalcaemia or permanent recurrentlaryngeal nerve injury (Table V). On the other hand,when a partial thyroid resection is the first-choice treat-ment, some cases of hyperthyroidism relapse arereported23. Surgical indications for TMNG were moreoften related to surgical concerns because 65.7% ofpatients underwent thyroidectomy for compressivegoitre or suspected malignancy, in whom, however,

total thyroidectomy should have been indicated evenwithout hyperthyroidism (Table III). The 34.3% ofpatients with TMNG underwent surgery because med-ical therapy failed and patients were classified as hav-

ing persistent or recurrent hyperthyroidism or severecardiotoxicity related to thyroid hormone excess.Moreover, 3 patients underwent thyroidectomybecause relapse followed percutaneous ethanol injec-

tion (PEI) and one patient underwent surgery followingantithyroid drug intolerance (Table III). An alternativetreatment to surgery, such as radioiodine ablation,might have been indicated in this subgroup of 24patients, as advocated by other Authors9-11. A potentialconcern is the post-radioiodine exacerbation of hyper-thyroidism due to radiation-related thyroiditis7. Manyinvestigators recommend pretreatment with antithyroiddrugs for the patients underlying cardiovascular dis-ease24. Pretreatment results in a higher failure rate ofradioactive iodine treatment25. In our practice, surgeryis likely to be effective sooner, which could minimise

the cardiac effects of coexisting severe cardiotoxicity.In fact, rapid control of thyrotoxicosis is the majoradvantage of surgical therapy of TMNG5,26.

As can be seen from our early and late follow-upresults, when surgery is performed in the form of totalthyroidectomy, re-treatment is not required and postop-erative hypothyroidism is relatively simple to treat3,5,6.Therefore, total thyroidectomy is an effective optioneven for benign conditions if the risk of recurrence issignificantly high27,28. In experienced hands the inci-dence of complications after total thyroidectomy hasrecently been reported as low, ranging from 0.4% to0.9% of permanent nerve injuries28,29 and from 0.5% to2.2% of permanent hypoparathyroidism30-32.

On the other hand, in the USA and in someNorthern European countries, TMNG is usually man-aged by radioiodine ablation therapy3,7 regardless ofgoitre size or nodularity9. Several Authors recom-mend radioiodine ablation as the most appropriatetreatment for TMNG9-11, because it is relatively safeand cost-effective7,9. Kang and co-workers report that,in their experience, the number of patients treatedwith radioiodine from 1990 to 1999 was greater than

the number of patients treated by surgery

3

. Possibleexplanations include the desire to completely avoidany surgical risk or malpractice litigation8, the highercosts of surgery, and older patients with more co-mor-bidities and consequently higher inherent surgicalrisk, and milder thyrotoxicosis or smaller goitre sizeamenable to non-surgical treatment3,5,8,33.

However, a potential hurdle in treating patientswith TMNG is the low radioiodine uptake noted inmany patients and higher doses of radioiodine may beneeded7. The ideal dose of radioiodine remains con-troversial because higher doses exacerbate hyperthy-

roidism and the resolution of thyrotoxicosis is usuallydelayed, requires multiple doses and often fails toreduce goitre size3,7. Complete failure of radioiodineablation therapy ranges in the literature from 0% to


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Ethanol injection of toxic nodules is also reportedin the literature as effective treatment depending onnodule size12,13, but in our study population 3 patientsunderwent thyroidectomy because of recurrenthyperthyroidism after percutaneous ethanol injection.

Treatment of patients with hyperthyroidism has notchanged over half a century, the aim being to inhibit,destroy, or remove the thyroid gland7, and surgical andradioiodine treatments are associated with different

advantages and disadvantages, respectively (Table VI).Standardisation of management guidelines for patientswith TMNG will, however, continue be a controversialissue for a long time. In our opinion and practice, sur-gery in the form of total thyroidectomy results in rapidand reliable resolution of hyperthyroidism and removalof multinodular goitre, requires no re-treatment, andremoves any coexisting malignancy, and post-surgicalhypothyroidism is simple to treat. A skilled surgeonwith good experience in endocrine surgery can per-form total thyroidectomy for TMNG with no mortalityand low morbidity. On the basis of evidence from the

literature, radioiodine is not so harmless and the reso-lution of hyperthyroidism is delayed. It may perhaps bemore suitable for those patients who are considered athigh risk for surgical treatment.

33% of cases with a mean figure of 10% requiring sur-gical treatment4 .

According to another study34, coexisting carcino-ma was found in 12.8% of our patients with TMNG,which is higher than the 5-9% reported by otherAuthors35,36. The figure of 32.3% of associated malig-nancy was especially high in Graves disease (TableIV). It is unlikely that 131I treatment would have provedeffective for these malignancies. Moreover, a poten-

tial major side effect of

131

I treatment is an increasedthyroid cancer risk mainly in patients with TMNG9.Increased mortality was seen during the first 5 yearsafter radioiodine treatment, indicating that thyroidcancer was present before 131I treatment37,38.

A recent epidemiological survey has shown that,among patients with hyperthyroidism treated withradioiodine, mortality from all causes and mortalitydue to cardiovascular and cerebrovascular diseaseand fracture were increased10.

Despite the fact that several small long-term fol-low-up studies have shown no evidence that radioio-

dine treatment is associated with birth defects or infer-tility in women, radioiodine is strongly contraindicat-ed in pregnancy, and pregnancy testing must be donebefore treatment3.

Table VI. Surgery versus radioiodine in the treatment of TMNG.

Treatment Advantages Disadvantages

Surgery Effective and rapid resolution Most invasive

of hyperthyroidismRemoval of multinodular goitre Potential complications (recurrent laryngeal nerveand relief of compressive symptoms injury, hypoparathyroidism)

Removal of coexisting malignancy Malpractice litigation

No recurrence after total thyroidectomy Permanent hypothyroidism (simple to treat)

Option for patients refusing radioiodine Most expensive

Potential in pregnancy if major side effects Pain, scarfrom antithyroid drugs

Effective in patients with coexistingcardiotoxicity

RAI Cure of hyperthyroidism Delayed resolution of hyperthyroidismLow complication risk Multiple doses of radioiodine

Most cost-effective Potential complete failure and recurrenceof hyperthyroidism

Effective in elderly and high Potential risk of hyperthyroidism exacerbationsurgical risk patients

Option in patients refusing surgery Contraindicated in pregnancyIncreased thyroid cancer riskIncreased mortality for all causesSurgery more difficult after radioiodine treatment

TMNG = toxic multinodular goitre; RAI = radioactive iodine 131I.


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