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Total thyroidectomy for Graves’disease: Compliance with AmericanThyroid Association guidelines maynot always be necessaryMyrick C. Shinall, Jr, MD,a James T. Broome, MD,a,b Ratnam Nookala, MBBS,a

JenniferB.Shinall, JD,PhD,cColleenKiernan,MD,aLeeParks III,MD,dandCarmenC.Sol�orzano,MD,a,b

Nashville, TN

Background. Total thyroidectomy (TT) is the preferred operative approach to Graves’ disease. Currentguidelines of the American Thyroid Association call for the administration of potassium iodide (KI) andachievement of euthyroid state before operation. Small numbers and a mixture of operative approachesspanning several decades hinder previous operative series. We present the outcomes for TT at a singlehigh-volume center.Methods. A retrospective cohort study was conducted on 165 patients undergoing TT for Graves’ diseasefrom July 2007 to May 2012.Results. Mean age was 43 years (range, 17�78), and 128 patients (78%) were female. A total of 95%of patients were on methimazole or propylthiouracil, and 42% remained hyperthyroid at time of TT.Only 3 (2%) patients received KI. Mean operative time was 132 minutes (range, 59�271). Meangland size and blood loss were 41 g (range, 8�180) and 55 mL (range, 10�1050), respectively. Nopatient developed thyroid storm. Median follow-up was 7.5 months. Temporary and permanenthypocalcemia developed in 51 (31%) and 2 patients (1.2%), respectively. Temporary and permanentrecurrent laryngeal nerve paresis occurred in 12 (7%) and one (0.6%) patient, respectively. Sixty-one(37%) patients experienced at least one complication. On multivariate analysis, patient age youngerthan 45 years (odds ratio 2.93, 95% confidence interval 1.39–6.19) and obesity (odds ratio 2.11,95% confidence interval 1.00–4.43) were associated with the occurrence of complications.Conclusion. This high-volume surgeon experience demonstrates no appreciable detriment to patientoutcomes when recommendations of the American Thyroid Association for routine use of KI andeuthyroid state before thyroidectomy are not met. Transient hypocalcemia and hoarseness are frequentcomplications of TT for Graves’ disease, resolving within 6 months in most patients. Age younger than45 years and obesity are risk factors for postoperative complications. (Surgery 2013;154:1009-15.)

From the Department of Surgery,a Division of Surgical Oncology and Endocrine Surgery,b VanderbiltUniversity School of Law,c and Division of Endocrinology,d Vanderbilt University Medical Center,Nashville, TN

GRAVES’ DISEASE (GD) remains one of the most com-mon causes of thyrotoxicosis in the United States.1

Patients and their physicians can manage GD with3 modalities: antithyroid medications, radioactiveiodine (RAI), or thyroidectomy. Making an

d at the 82nd Annual Meeting of the American Thyroidion, Quebec City, Quebec, Canada.

d for publication April 26, 2013.

requests: Myrick C. Shinall, Jr, MD, 1161 21st Ave, CCC-CN, Nashville, TN 37232. E-mail: Ricky.shinall@ilt.edu.

60/$ - see front matter

Mosby, Inc. All rights reserved.

x.doi.org/10.1016/j.surg.2013.04.064

informed decision about which therapy for GD topursue requires an understanding of the risksand benefits of each modality. Although remissionof GD can be achieved with antithyroid medica-tions, remission rates are variable (ranging from14–80%), and it is difficult to predict which pa-tients will achieve it with medical therapy.2 Forthese reasons, patients and physicians frequentlyopt for definitive treatment with either thyroidec-tomy or RAI. Choosing between these 2 modalitiesrequires weighing anesthetic and operative risks ofthyroidectomy versus symptoms, recurrence rates,and complications related to RAI therapy.

In the past, subtotal thyroidectomy was thepreferred operative approach used in an attempt

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to prevent hypothyroidism and to protect both therecurrent laryngeal nerves and the parathyroidglands. Hyperthyroidism recurred, however, in asmany as 8% of patients treated with subtotalthyroidectomy. Moreover, reoperative completionthyroidectomy in this setting is fraught with com-plications.3 In contrast, total thyroidectomy (TT)carries a nearly 0% risk of recurrence, and the pa-tient avoids undergoing complex reoperative sur-gery.3 Therefore, current guidelines from theAmerican Thyroid Association (ATA; Recommen-dation 24) recommend total or near-total thyroid-ectomy as the operative therapy of choice for GD.4

Most recent series on operative treatment of GDinvolve either small numbers or a long time spanwith a mix of subtotal and TT.5-12 In the last decade,our center has seen an increase in the number ofpatients referred for operative treatment of GD.Here, we evaluate the perioperative outcomes of alarge and contemporary series of patients undergo-ing TT for GD at a high-volume center.

Current guidelines of the ATA (Recommenda-tion 22 and Recommendation 23) also recom-mend that patients be rendered euthyroid withmethimazole preoperatively and that potassiumiodide (KI) be given in the immediate preopera-tive period.4 The recommendation to render pa-tients euthyroid with antithyroid medication is aneffort to decrease the risk of thyrotoxic crisis (thy-roid storm) that the stress of the procedure couldprecipitate. KI is recommended to decrease thevascularity of the thyroid gland with the goal ofimproving operative visualization and decreasingoperative complications. In this series, we also eval-uate the extent to which these recommendationswere met and the extent to which failure to achievethese goals results in untoward effects.

MATERIALS AND METHODS

After approval by the institutional review board atVanderbilt University, a retrospective analysis of themedical records at a large, urban, academic hospitalwas conducted. All patients undergoing TT with apreoperative diagnosis of GD from July 1, 2007,through May 30, 2012 were included. During thistime period, no patients underwent subtotal thy-roidectomy for GD. Information on preoperativemedical history, operative characteristics, and post-operative complications was collected.

The diagnosis of GD generally was established bythe referring endocrinologist or other referringprovider by the use of clinical signs and symptoms,thyroid hormone and thyroid-stimulating hormoneassays, RAI uptake and scan, and/or measurementof thyrotropin receptor antibodies. Patients were

deemed ready for the procedure based on thejudgment of the surgeon in consultation with thereferring endocrinologist if they were not clinicallytoxic and treatment had been initiated with antith-yroidal medication and/or beta-blockers. Prethyr-oidectomy KI was not used routinely, although it wasnot discontinued if another provider prescribed it.TT was performed at a single center by 1 of 6endocrine surgeons. Recurrent laryngeal nervemonitoring was used in all cases. Operative sitedrains were not used. Patients were discharged thesame day or after overnight observation unless acomplication developed requiring greater inpatienthospitalization. Serumcalciumconcentrations wereobtained the following morning and patients wereplaced on standard calcium supplements (1 g ofelemental calcium TID). Calcium levels were re-checked 2 weeks after thyroidectomy. Calcitriol wasadded when calcium levels were <7.8 mg/dL orwhen the patient was symptomatic. Parathyroidhormone (PTH) levels were not checked routinelyunless indicated clinically.

Thyroid hormone status was defined by the lastset of laboratory values before operation. Becausethe increase in thyroid-stimulating hormone(TSH) after initiation of medical therapy lagsbehind the decrease in thyroid hormone levels,T4 and T3 levels are used to gauge thyroid status inthe early course of medical management ratherthan TSH values. As such, unless the TSH wasfrankly elevated, thyroid hormone status wasdefined by T4 and T3 levels rather than TSH,consistent with clinical practice, as follows: hypo-thyroidism was defined as an increased TSH levelor a T4 or T3 level less than the reference value;euthyroidism was defined as normal or low TSHlevel with normal T4 and T3 levels; mild hyperthy-roidism was defined as either T3 or T4 level greaterthan the reference range but less than 1.5 timesthe upper limit of normal; moderate hyperthyroid-ism was defined as T3 or T4 level greater than 1.5times the upper limit of normal but not requiringhospitalization, and severe hyperthyroidism wasdefined as patients who were hospitalized forhyperthyroidism at the time of their operation,regardless of hormone levels.

The primary outcome of interest was any periop-erative complication occurring within the first sixmonths after TT. Postoperative hypocalcemia wasdefined as either a serumcalciumconcentration lessthan the reference range or complaints of hypocal-cemic symptoms requiring treatment during theimmediate postoperative period. Prolonged post-operative hypocalcemia was hypocalcemia persist-ing beyond 6 months after TT. Permanent

Table I. Characteristics of 165 patients withGraves’ disease

Characteristic n (%)

Age, yrs, mean ± SD 43 ± 14SexMale 37 (22)Female 128 (78)

BMI status*Underweight 8 (5)Normal weight 45 (29)Overweight 46 (27)Obese 56 (36)

History of Graves’ ophthalmopathy 65 (39)Smoker 53 (32)Preoperative medicationsMethimazole 133 (81)PTU 23 (14)KI 3 (2)Steroids 15 (9)Beta blockers 92 (57)

Thyroid hormone statusEuthyroid 87 (53)Hypothyroid 8 (5)Hyperthyroid 70 (42)Mildly hyperthyroid 31 (19)Moderately hyperthyroid 27 (16)Severely hyperthyroid 12 (7)

ASA class1 2 (1)2 102 (62)3 60 (36)4 1 (0.6)

Median follow-up (months, range) 7.50 (0�52)

*There were 10 missing observations for BMI; percentages given are calcu-lated based on the 155 patients with BMI information.Values are n (%) unless otherwise specified.ASA class, American Society of Anesthesiologists Physical Status Classifica-tion System; BMI, body mass index; KI, potassium iodide; PTU, propylth-iouracil; TSH, thyroid-stimulating hormone; T4, thyroxine.

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hypoparathyroidism was a requirement for calciumsupplements above a normal daily supplement withlow PTH levels beyond 12 months. Recurrentlaryngeal nerve (RLN) paresis was defined as sub-jective complaints of hoarseness at the first post-operative visit (2 weeks), whereas prolonged RLNpalsy was defined as hoarseness and documentedRLN paralysis at laryngoscopy persisting beyond6 months.

Risk factors for complications were compared inboth bivariate and multivariate analyses. Statisticalsignificance on bivariate analysis was determinedwith the v2 test. Given the sample size, a maximumof 6 variables was set for regression analysis to limitloss of power from multiple comparisons. A subsetof the patient characteristics were chosen formultivariate analysis based on the authors’ hypoth-eses that these were the most likely to be clinicallyrelevant. A logistic regression of the ‘‘any complica-tion’’ variable on the selected risk factors was per-formed with heteroskedasticity-robust standarderrors using Stata (StataCorp LP, College Station,TX). In the reported regression, subjects withmissing observations were dropped. Continuousvariables are presented as mean ± SD.

RESULTS

Patient factors. A total of 165 patients underwentTT for GD during the period studied (Table I).Mean age was 43 years, and 78% of the patientswere female. Mean body mass index was 28 kg/m2,and 39%of thepatients had ahistory ofGraves’ oph-thalmopathy, defined as preoperative diagnosis ofGraves’ ophthalmopathy by a referring physicianon the basis of history and physical examination. Ahistory of smoking was present in 32%. Preopera-tively, themajority (95%)of patients were takingme-thimazole or propylthiouracil. Three patients (2%)received KI preoperatively, as prescribed by their en-docrinologists, whereas 15 (9%) were on steroids atthe time of operation. The majority of patients(58%) were euthyroid or hypothyroid at the timeof operation on the basis of the aforementioned def-initions. Basedon the anesthesiologist assessment ofpatient comorbidities according to the AmericanSociety of Anesthesiologists Physical Status Classifi-cation system (ASA class), almost all patients wereASA Class 2 or 3, or 62% and 36%, respectively.Median duration of hospital stay was 1 day (range,0�10); the patient with the 10-day stay was hospital-ized for psychiatric reasons not related to her oper-ation; the next longest duration of stay was 4 days. Atotal of 156 patients (95%) were discharged within23 hours of their operation. Patients were followedfor a median of 7.5 months (range, 0�52).

Thereasonswhypatients choseTT, rather thanRAIor medical management, are presented in Table II.The most common reason (38%) given was patientpreference without specific references to indicationsor contraindications for any therapy. For 6%of thepa-tients, no reason for TTover other therapies was givenin the record. For the remaining patients, reasonsincluded concern for the exacerbation of ophthalm-opathy with RAI, allergy or intolerance to medica-tions, failed medical therapy, large thyroid withcompressive symptoms or thyroid nodule(s) in addi-tion to GD, contraindications to RAI, failed RAI, ordesire for childbearing in the near future. Some pa-tients had more than one reason for preferring TT,so the numbers sum to greater than 100%.

Operative factors and complications. Operativecharacteristics were as follows. Mean procedure

Table II. Reasons for choosing totalthyroidectomy over medical or RAI therapy

Reason for choosing operation n (%)

Patient preference 62 (38)Large thyroid/thyroid nodules 37 (22)Ophthalmopathy 28 (17)Failed RAI 14 (8)Failed medical therapy 11 (7)Allergy/intolerance to medications 10 (6)Desire to bear children 10 (6)Reason not addressed 10 (6)Contraindications to RAI 1 (0.6)

Total patients = 165; total sum is greater than 100% because more thanone reason could be given for each patient.RAI, Radioactive iodine.

Table III. Complications after total thyroidectomyfor Graves’ disease (n = 165 patients)

Complication n (%)

Any complication 61 (37)Postoperative hypocalcemia 51 (31)

Transient postoperative hypocalcemia 45 (27)Prolonged postoperative hypocalcemia* 6 (4)

RLN paresis 12 (7)Transient RLN paresis 11 (7)Permanent RLN palsy 1 (0.6)

Postoperative hematoma 1 (0.6)Seroma 3 (2)Tracheal injury 1 (0.6)

*See text for details; only 2 patients had permanent hypocalcemia.RLN, Recurrent laryngeal nerve.

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time was 132 ± 39 minutes (range, 59�271), andthe median estimated blood loss was 30 mL (range,10�1,050). Parathyroid autotransplantation wasperformed in 23 (14%) patients, and in 13 (8%)patients, pathologic analysis demonstrated para-thyroid tissue inadvertently excised with the spec-imen. The mean weight of the excised gland was41 ± 29 g (range, 8�180).

Complications are presented in Table III. Sixty-eight distinct complications occurred in 61 of the165 patients (37%). The most common complica-tion was hypocalcemia, which occurred in 51(31%) patients. To what extent transient hypocal-cemia represented transient hypoparathyroidismversus bone hunger is difficult to determinebecause routine PTH levels were not available onall patients. The majority of cases were transient,with only 6 patients (4%) experiencing hypocalce-mia beyond 6 months. Of these 6 patients, 4 havereturned to eucalcemia off supplements at 12months follow-up. The remaining 2 patientscontinued to require calcium and calcitriol

supplements; one had PTH level less than the limitof detection at 12 months, and the other had PTHlevel of 5 pg/mL. Permanent hypoparathyroidismwas, therefore, seen in 2 (1.2%) patients. RLNparesis was identified in 12 (7%) patients, but inonly 1 (0.6%) did hoarseness persist beyond 6months. Of these 12 patients, one (0.6%) had aRLN transection, which was identified and re-paired intraoperatively. Although this patient hadpostoperative hoarseness, it did not persist beyond6 months, and the patient declined to undergolaryngoscopy because she felt her voice had re-turned to normal. One patient (0.6%) developeda postoperative hematoma requiring emergentre-exploration. Three patients (2%) developed aseroma that required drainage at the first clinicvisit, and one patient (0.6%) experienced a smalltracheal injury that was identified and repaired in-traoperatively with no sequelae. No patient devel-oped thyroid storm perioperatively, nor did anypatients develop hypertensive, cardiovascular, orneurologic complications.

Patient and operative factors were examined viabivariate analysis to identify risk factors of anycomplication (Table IV). On bivariate analysis theonly risk factor found to be statistically significantfor any complication was age younger than 45years. On multivariate regression analysis, ageyounger than 45 years remained a risk factor andobesity became significant (Table V).

Given that such a large proportion of thepatients in this series were hyperthyroid at thetime of operation (42%), we sought to examinethe implications for thyroid hormone status onoutcomes. On bivariate and multivariate analysis,thyroid hormone status was not correlated withcomplications. In the absence of any discernableeffect on outcome, we used intraoperative beta-blocker administration as a surrogate for hemody-namic instability. Of the 70 patients who werehyperthyroid (mildly, moderately, or severely) atoperation, 18 (26%) received intraoperative beta-blocker, compared with 15 of the 95 (16%)euthyroid or hypothyroid patients (P = .12).Comparing the moderately and severely hyperthy-roid patients as a group to all other patients, theformer did have a greater rate of beta-blocker us-age (odds ratio 2.65, 95% confidence interval1.16�6.01).

DISCUSSION

TT is a safe and effective therapy for GD. In thisseries, the most common complication, hypocalce-mia, was, in general, transient. The most fearedcomplication, RLN paresis, was uncommon and

Table V. Multivariate logistic regression of riskfactors for any complication after totalthyroidectomy for Graves’ disease

Risk factorOddsratio

95% Confidenceinterval

Pvalue

SexMale 1.00 —Female 1.53 0.65–3.59 .331

Age$45 yrs 1.00 —<45 yrs 2.93 1.39–6.19 .005

ObesityBMI #30 kg/m2 1.00 —BMI >30 kg/m2 2.11 1.00–4.43 .049

Smoking historyNonsmoker 1.00 —Smoker 1.23 0.59–2.59 .579

Thyroid status at operationHypothyroid

or euthyroid1.00 —

Hyperthyroid 1.75 0.86–3.53 .120ASA class1 or 2 1.00 —3 or 4 0.96 0.45–2.04 .917

ASA, American Society of Anesthesiologists Physical Status Classificationsystem; BMI, body mass index.

Table IV. Bivariate analysis of risk factors forany complication after total thyroidectomy forGraves’ disease

Risk factor

Patientswith no

complications(n = 104),n (%)

Patientswith any

complications(n = 61),n (%)

Pvalue

Female 76 (73) 51 (84) .121Age <45 yrs 48 (46) 42 (69) .005Obese* 32% 42% .189History of Graves’

ophthalmopathy43 (41) 22 (36) .503

Smoker 33 (32) 20 (33) .741Hyperthyroid at

operation39 (38) 31 (51) .095

ASA class 3 or 4 39 (38) 22 (36) .854Operative time

>150 min28 (27) 19 (31) .562

Parathyroidautotransplantation

11 (11) 12 (20) .103

Parathyroid excised 8 (8) 5 (8) .908Thyroid weight >40 g 34 (34) 22 (38) .651

*Obesity defined as BMI greater than 30 kg/m2. There were 10 missingobservations for BMI; percentages given are calculated based on the 155patients with BMI information.ASA, American Society of Anesthesiologists Physical Status Classificationsystem; BMI, body mass index.

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also generally transient. Rates of both complica-tions (transient and permanent) were comparablewith those demonstrated in previous studies oftotal and subtotal thyroidectomy for GD and afterTT for nontoxic multinodular goiter. In thesestudies the incidence of transient hypocalcemiaranged from 3 to 40%, with the incidence of long-term hypocalcemia ranging from 0.6 to 6%.Similarly, the incidence of transient and perma-nent RLN palsy ranged from 0 to 24%, and 0 to2%, respectively.5-15 In the current series, othercomplications such as hematoma, seroma, andtracheal injury, occurred at very low rates. Thesedata reconfirm the consensus that TT is a safeand appropriate initial therapy for GD when per-formed by high-volume surgeons.

Current ATA guidelines recommend that pa-tients be rendered euthyroid with methimazolepreoperatively and that KI be given in the imme-diate preoperative period.4 The recommendationto render patients euthyroid with anti-thyroidmedication stems from a concern that the stressof the operation could precipitate thyroid storm.In this series, the majority of patients were treatedwith antithyroid medications, and no patient expe-rienced thyroid storm, even though a large propor-tion (42%) remained biochemically hyperthyroid

at the time of operation. Although the moderatelyand severely hyperthyroid patients did requiremore intraoperative beta-blockers, there was no ev-idence for any other untoward cardiovascular out-comes resulting from hyperthyroidism. Onbivariate analysis, association between hyperthy-roidism and complications approached statisticalsignificance (P = .059). Adjusting for other factorsvia multivariate analysis, we found that the associa-tion between hyperthyroidism and complicationsfailed to reach statistical significance (P = .120).Thus, although we believe preoperative medicalmanagement is justified on the basis of symptommanagement, these data suggest that patientswho remain biochemically hyperthyroid beforethe procedure can still have good operativeoutcomes.

The recommendation to administer KI preoper-atively arose originally from the observation ofPlummer’s more than 50 years ago that the admin-istration of KI decreasd the risk of thyroid storm.16

Later, the administration of KI was noted todecrease the vascularity of the thyroid on histologicexamination.17 Only after the introduction of thio-namides was the decrease in vascularity put forwardas the primary justification for the administration ofKI, because its thyrostatic properties were less clini-cally important.18 The evidence for the utility of KI

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administration has beenmixed, andmuch of the ev-idence in its favor comes from imaging studiesassessing thyroid blood flow.19-21 The clinical impor-tance of these imaging studies is difficult to extrapo-late. Clinical studies have not demonstratedconsistently any benefit to KI administration. Anolder double-blinded, randomized controlled trialshowed no appreciable difference in blood loss atthyroidectomy or surgeon reports of operative diffi-culty whether or not KI was administered.22 Anotherretrospective study came to a similar conclusion thatKI did not make an appreciable clinical differ-ence.23 In a more recent unblinded, randomizedtrial Erbil et al24 did report a difference with admin-istration of KI. In this trial 36 patients with GD wereassigned either to preoperative treatment with KIor to no treatment. These investigators demon-strated a difference in intraoperative blood loss(108 mL in the control vs 54 mL in the KI group)favoring the KI group.

In the study by Erbil et al,24 the estimated bloodloss in the KI group (mean 54 mL) is similar to theblood loss we found in our series in which KI wasalmost never administered (mean 55 mL). More-over, the 0.6% rate of reoperation for hematomain our series is comparable with an 0.8% rate re-ported for a large series of parathyroid and thyroidoperations of all types.25 The number of patientstaking KI preoperatively in the current study wastoo small to allow statistically meaningful compari-son with those who did not. Because large amountsof intraoperative blood loss can potentially lead topoor visualization, longer operating times, andincreased incidence of hypocalcemia, RLN injury,and hematomas, we cannot advocate that all sur-geons should stop using KI preparation. Large,blinded randomized studies may be needed tofurther clarify the routine use of KI, but thesedata do add to the studies that show that KI admin-istration may have less clinical importance in mod-ern thyroidectomy by high-volume surgeons.

This series also permits investigation into riskfactors for complications. Young age (<45 years)was associated with complications on both bivar-iate and multivariate analysis. The most commoncomplication overall was transient hypocalcemia(Table IV), which correlates with a large registry-based study in which the authors found youngerpatients have an increased incidence of hypocalce-mia after TT for GD.13 Because definitions of hypo-calcemia in these series include (in part) thedevelopment of symptoms, this was hypothesizedto be attributable to younger patients possibly be-ing more sensitive to and having more symptomsof hypocalcemia in the postoperative period,

consistent with a previous analysis of hypocalcemiaafter TT for GD.26 This result, however, is notconsistent across studies, and some studies haveidentified older age as a risk factor for postthyroi-dectomy complications.27,28 The data suggest clini-cians may need to counsel younger patients aboutan increased risk of hypocalcemia when theydiscuss treatment plans.

On multivariate analysis, obesity also was associ-ated with occurrence of at least one complication.Previous studies have demonstrated that morbidityand operative time for thyroidectomy and para-thyroidectomy are greater in overweight and obesepatients.29 It is plausible to assume that TT is moretechnically challenging in the neck of an obese pa-tient and that postoperative complications wouldtherefore arise more frequently in obese patients.Obese patients may also have more comorbid con-ditions that predispose to complications, butincluding ASA class in the regression shouldpartially control for such confounding.

The current study has several limitations. Aswith any retrospective investigation, this study islimited to the data already present in the medicalrecord. This report reflects the results of high-volume surgeons (>100 thyroidectomy proce-dures per year), and our findings may not begeneralizable. To the authors’ knowledge, thepresent study represents the largest contemporary,U.S. experience of TT for GD.8,10,12 Nevertheless,the current study remains relatively small, and sta-tistical inference on risk factors is thus limited.Even so, this observational study does shed furtherlight on outcomes of TT for GD. It also points tothe need for further comparative studies on theefficacy of KI.

This series demonstrates that, in the hands ofhigh volume surgeons, TT for GD can be accom-plished with minimal morbidity. TT rightly has aplace as the initial operative treatment for GD. Asexperience accumulates, recommendations forpreoperative management of GD may changeand potentially be simplified. With accurate infor-mation on the risks of complications, physicianscan counsel their patients to choose the therapyfor GD that maximizes benefit and minimizesharms and best fits the patient’s wishes.

REFERENCES

1. Singer PA, Cooper DS, Levy EG, et al. Treatment guidelinesfor patients with hyperthyroidism and hypothyroidism.Standards of Care Committee, American Thyroid Associa-tion. JAMA 1995;273:808-12.

2. Klein I, Becker DV, Levey GS. Treatment of hyperthyroiddisease. Ann Intern Med 1994;121:281-8.

SurgeryVolume 154, Number 5

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3. Palit TK, Miller CC 3rd, Miltenburg DM. The efficacy of thy-roidectomy for Graves’ disease: a meta-analysis. J Surg Res2000;90:161-5.

4. BahnChairRS,BurchHB,CooperDS, et al.Hyperthyroidismand other causes of thyrotoxicosis: management guidelinesof the American Thyroid Association and American Associa-tion of Clinical Endocrinologists. Thyroid 2011;21:593-646.

5. Werga-Kjellman P, Zedenius J, Tallstedt L, Traisk F, LundellG, Wallin G. Surgical treatment of hyperthyroidism: a ten-year experience. Thyroid 2001;11:187-92.

6. Barakate MS, Agarwal G, Reeve TS, Barraclough B, Robin-son B, Delbridge LW. Total thyroidectomy is now thepreferred option for the surgical management of Graves’disease. ANZ J Surg 2002;72:321-4.

7. Chiang FY, Wang LF, Huang YF, Lee KW, Kuo WR. Recur-rent laryngeal nerve palsy after thyroidectomy with routineidentification of the recurrent laryngeal nerve. Surgery2005;137:342-7.

8. Lal G, Ituarte P, Kebebew E, Siperstein A, Duh QY, ClarkOH. Should total thyroidectomy become the preferred pro-cedure for surgical management of Graves’ disease? Thy-roid 2005;15:569-74.

9. Ku CF, Lo CY, Chan WF, Kung AW, Lam KS. Total thyroid-ectomy replaces subtotal thyroidectomy as the preferredsurgical treatment for Graves’ disease. ANZ J Surg 2005;75:528-31.

10. Weber KJ, Solorzano CC, Lee JK, Gaffud MJ, Prinz RA. Thy-roidectomy remains an effective treatment option forGraves’ disease. Am J Surg 2006;191:400-5.

11. Gaujoux S, Leenhardt L, Tresallet C, et al. Extensive thyroid-ectomy in Graves’ disease. J Am Coll Surg 2006;202:868-73.

12. Feliciano DV, Lyons JD. Thyroidectomy is optimal treat-ment for Graves’ disease. J Am Coll Surg 2011;212:714-20;discussion 720-1.

13. Hallgrimsson P, Nordenstrom E, Almquist M, BergenfelzAO. Risk factors for medically treated hypocalcemia aftersurgery for graves’ disease: a Swedish multicenter study of1,157 patients. World J Surg 2012;36:1933-42.

14. Zambudio AR, Rodriguez J, Riquelme J, Soria T, CanterasM, Parrilla P. Prospective study of postoperative complica-tions after total thyroidectomy for multinodular goiters bysurgeons with experience in endocrine surgery. Ann Surg2004;240:18-25.

15. Agarwal G, Aggarwal V. Is total thyroidectomy the surgicalprocedure of choice for benign multinodular goiter? Anevidence-based review. World J Surg 2008;32:1313-24.

16. Plummer HS. Results of administering iodine to patientshaving exophthalmic goiter. JAMA 1955;1923:80.

17. Rienhoff WF. The histological changes brought about incases of exophthalmic goiter by the administration ofiodine. Bull Johns Hopkins Hospital 1925;37:285-306.

18. Langley RW, Burch HB. Perioperative management of thethyrotoxic patient. Endocrinol Metab Clin North Am2003;32:519-34.

19. Ansaldo GL, Pretolesi F, Varaldo E, et al. Doppler evaluationof intrathyroid arterial resistances during preoperativetreatment with Lugol’s iodide solution in patients withdiffuse toxic goiter. J Am Coll Surg 2000;191:607-12.

20. Marigold JH, Morgan AK, Earle DJ, Young AE, Croft DN.Lugol’s iodine: its effect on thyroid blood flow in patientswith thyrotoxicosis. Br J Surg 1985;72:45-7.

21. Chang DC, Wheeler MH, Woodcock JP, et al. The effect ofpreoperative Lugol’s iodine on thyroid blood flow in pa-tients with Graves’ hyperthyroidism. Surgery 1987;102:1055-61.

22. Coyle PJ, Mitchell JE. Thyroidectomy: is Lugol’s iodinenecessary? Ann Roy Coll Surg Engl 1982;64:334-5.

23. Marmon L, Au FC. The preoperative use of iodine solutionin thyrotoxic patients prepared with propranolol. Is itnecessary? Am Surg 1989;55:629-31.

24. Erbil Y, Ozluk Y, Giris M, et al. Effect of lugol solution onthyroid gland blood flow and microvessel density in the pa-tients with Graves’ disease. J Clin Endocrinol Metab 2007;92:2182-9.

25. Abbas G, Dubner S, Heller KS. Re-operation for bleeding af-ter thyroidectomy and parathyroidectomy. Head Neck 2001;23:544-6.

26. Pesce CE, Shiue Z, Tsai HL, et al. Postoperative hypocalce-mia after thyroidectomy for Graves’ disease. Thyroid 2010;20:1279-83.

27. Thomusch O, Machens A, Sekulla C, et al. Multivariate anal-ysis of risk factors for postoperative complications in benigngoiter surgery: prospective multicenter study in Germany.World J Surg 2000;24:1335-41.

28. Erbil Y, Barbaros U, Temel B, et al. The impact of age,vitamin D(3) level, and incidental parathyroidectomy onpostoperative hypocalcemia after total or near total thyroid-ectomy. Am J Surg 2009;197:439-46.

29. Buerba R, Roman SA, Sosa JA. Thyroidectomy and para-thyroidectomy in patients with high body mass index aresafe overall: analysis of 26,864 patients. Surgery 2011;150:950-8.