SS Thyroidectomy for Selected Patients With Thyrotoxicosis Elizabeth A. Mittendorf, MD; Christopher R. McHenry, MD Objective: To examine the indications for operation and the frequency, efficacy, and outcome of surgical therapy for thyrotoxicosis, Metheds: The medical records of all patients who un- derwent thyroidectomy between 1990 and 1008 were re viewed. Operative indications, laboratory evaluations, ex- tent of thyroidectomy, pathologic findings, and morbidity and mortality were determined for patients with thyro- Results: Of the 347 patients who underwent thyroid- ‘ectomy, 54 (16%) had thyrotoxicosis, secondary to Graves disease (32 patients), toxic multinodular goiter (18 pa- tients), thyroiditis (2 patients) or amiodarone (2 patients) The indications for operation were compressive symp- toms or substernal extension or both (35 patients), pa- tient preference (12 patients), thyrotoxicosis (+ pa- tients), ora dominant nodule (3 patients). Most patients received pharmacological preparation, followed by total (62 patients), near-total (13 patients), subtotal (8 pa- tients), or unilateral (1 patient) thyroidectomy. The ini- thyroidectomy, and after a mean 28-month follow-up, 1 was euthyroid; 2, hyperthyroid; and 5, hypothyroid. As- sociated carcinoma was present in 4 (7%) of the 54 pa- jents. Symptomatic hypocalcemia occurred in 10 pa- tients (19%), with a mean free thyroxine level of 60.494 16.09 pmol/L vs 40.41 419.56 pmoVL (4.70.4 1.25 ng/L vs 3.1441.52 ng/dL) in 25 patients (46%) with asymptomatic hypocalcemia (P<.03). Vocal cord pare sis and a hematoma requiring operative evacu: curred in 1 patient each, There was 1 mortality ina pa- dent with amiodarone-induced thyrotoxicosis, Conelusions: Massive thyroid enlargement with com- pressive symptoms, a dominant nodule, and patient pref- erence are indications for surgical treatment of thyro- toxicosis. Near-total or total thyroidectomy is safe and more effective than subtotal thyroidectomy in prevent- ing recurrence and should be considered in most pa- lents referred for surgical treatment of thyrotoxicosis. Transient postoperative hypocalcemia is common and is related to the severity of thyrotoxicosis, tial 8 pati ts with Graves’ disease underwent subtotal Arch Otolaryngol Head Neck Surg. 2001;127:61-65 From the Department of ‘Surgery, MetroHealth Medical ‘Genter, Case Wester Reserve University School of Medicine, Cleveland, Ohio, Downloaded From: on 06/01/2018 HYROTONICOSIS is a syn- drome characterized by signs and symptoms of hyperme- labolismand increased sym- pathetic nervous system ac- tivity that results from excessive thyroid hormone. The most common cause of thy- rotoxicosis is Graves' disease, accounting for (60% to 90% of all cases of thyrotoxicosis! Toxic multinodular goiter and a solitary toxic nodule are less common causes of thy- roloxicosts, The treatment alternatives for thyrotoxicosis include antithyroid drugs, thyroid ablation with iodine 131 (°"), and thyroidectomy. In the United States, Lis the predominant modality used for treat- ‘ment of thyrotoxicosis"? Many clinicians have questioned the necessity of surgical therapy for thyrotoxicosis. Atone large te Uiary care institution, only 3 patients with Graves’ disease were treated with thyroid- ceclomy during « 25-year period.’ Factors that need to be considered when deciding fon an appropriate treatment plan for pa- tients with thyrotoxicosis inelude patient (©2001 American Med age; associated ophthalmopathy: the size of the thyroid gland: the presence of compres- sive symptoms, substernal thyroid exten- sion, or a concomitant dominant nodule; contraindications to the use of radioio- dine; intolerance to antithyroid drugs; re- sponse to previous therspy and patient pref erences. The purpose of this study was to determine how olten thyroidectomy is per- formed for treatment of thyrotoxicosis, de- lineate the reasons why patients with thy- roloxicosis are referred for thyroidectomy’ and assess the eflicacy and outcome of sur” gical therapy for thyrotoxicosis. et SS Of the 347 patients undergoing thyroid- ectomy, 5+ (16%) were referred for treat- ment of thyrotoxicosis. Of these, #3 (80%) were women. Ages ranged from 23 10 83 years (mean age, 42 years). The cause of thyrotoxicasts was Graves’ disease in 32 patients (50%), toxic multinodular gol- {erin 18 (33%), relapsing thyroiditis in 2 Association, All rights reserved.PATIENTS AND METHODS A retrospective ree ofall patients undergoing hy- roldectomy between 1990 and 1998 was completed, ful those who underwent yrldetiomy forthyro™ tentang wer ented. Ther medial econds ere reviewed for demographe daa, the case of tyro- tenons, lineal manlfesaions, result of baseline thyroid fancion test, laine phosphatase evel, fn the presence of dominant node or susie tal extension patients wth Graves dease, the presenceofophihdimopay was noted. Whether pa tents underwent penpeaiepharnacologeal preps tll was determined and tages sed wert Ce {terized The indiatons for persion, extent of thyroidectomy, management af the parathyotd lands, weight ofthe esced thyroid gland, post Speraivecu evel nal phology and morbidity and morality werealse denied. Opera- tive sepors were reviewed lo determine succes at idening the ecrent ryngeal nervecand hee ‘lueny of perahyro gland sutotransparaton ' comparative analyse of fe thyroxine (FT) and alkaline phosphatase levels was completed for pallens withepmpiomatc vs ssympomalc postop. Efave hypocalcemia, The svc of iyrtencons inpatients wth Grave’ dase was compared with that in patients with other causes of thyrotoxcose ‘The elerence ranges forthe laboratory Indices ne Iyzed were FI, 940102587 pmol (073 0 201 fifa) thyrotropin, 04010336 asec, 2 toa Stel. (2410100 mg/dL) andallalin phos phatase, 25 to 136 UML. The statist significance ES dferences was determined using {lest P03 sas consiered sigan (496), and amiodarone-induced thyrotoxicosis in 2 (4%) patients. The means SD PT, level in patients with Graves disease was 54.184 10.43 pmol/L vs 33.084 17.63 pmol. (4.214151 ng/L vs 2.5741.37 ng/dL) in patients with thyrotoxicosis from other causes (P<.05). Preoperative pharmacological preparation varied ac- cording to the catise and severity of thyrotoxicosis. All| patients with Graves’ disease received 10 days of iodine treatment before surgery to reduce the vascularity of the thyroid gland. Twenty-eight of 32 patients with Graves! disease received an antithyroid drug, 17 of whom also received a B-receplor antagonist. Two patients with in- tolerance to antithyroid drugs received a B-receptor an- tagonist, and 2 patients with subclinical thyrotoxicosis received preoperative iodine alone. Twelve of 18 pa- tients with toxie multinodular gotter received an anti- thyroid drug preoperatively, 4 of whom also received a B-receplor antagonist. No pharmacological preparation ‘was necessary in 6 patients with toxie multinodular got ter, all of whom had subclinical thyrotoxicosis. The 2 pa- Liens with relapsing thyroiditis were treated with a B-re ‘ceptor antagonist alone. The 2 patients with amiodarone- induced thyrotoxicosis were treated with an antithyroid drug, 1 of whom also received prednisone (aepniy ep) SECHOTOCARTNGOL HERD NECRSURGN ONT (©2001 American Medical Assoc Downloaded From: on 06/01/2018 The indications for operation in the 32 patients with, Graves disease were massive thyroid enlargement with com- pressive symptoms (17 patients),a dominant nodule (3 pa- tients), and patient preference (12 patients), including 2 who had failed radioiodine treatment and 6 patients with concems about radioiodine-induced aggravation of their ophthalmopathy. The extent of thyroidectomy in patients with Graves’ disease included 17 total, 7 near-total, and 8 subtotal thyroidectomies. The average weight of the re- sected thyroid gland was 72 g (range, 20-210 g). nour early experience, we performed subtotal thyroidectomy, leav- ing bilateral 3-g remnants of thyroid issue in patients, 1 of whom after 4 mean 28-month follow-up was euthy- roid: 2, hyperthyroid: and 5, hypothyroid. Pathologic evalu- ation ofthe dominant nodule in 3 patients with Graves dis- case revealed a 2-cm papillary carcinomain | anda follicular adenomain 2, One patient without a dominant nodule had an incidental occult microscopic papillary carcinoma Eighteen patients underwent thyroidectomy for toxic multinodular goiter, with substernal extension in 11 and compressive symptoms in 13. A total thyroidectomy was performed in 12 patients, near-total thyroidectomy in 5, and a unilateral resection ofa large substernal goiter in a single elderly patient with subclinical thyrotoxicosis, ‘minimal disease in the contralateral thyroid lobe, and a markedly attenuated recurrent laryngeal nerve on the side of the substernal goiter. The average weight of the re- sected gland in patients with toxic multinodular goiter was 184 g (range, 34-1025 g). One patient had an in: dental 2.5-em medullary earcinoma diagnosed on final pathologic examination. Two patients with relapsing thyroiditis experi enced alternating episodes of symptomatic hyper- and hypothyroidism for 5 and 10 years’ duration. Their PT, levels were 30.37 pmol/L (2.36 ng/dL) and 55.34 pmol/L, (43 ng/L), and both had a low radioiodine uptake. Near- total and total thyroidectomies were performed, with e cision of a 10-g and 24-g thyroid gland. The final patho- logic finding was chronic lymphocytic thyroiditis in both patients, 1 of whom also had an incidental 0.4-em pap- illary carcinoma, Two patients underwent total thyroidectomy for amiodarone-induced thyrotoxicosis that was resistant to antithyroid medications. One patient, previously de- scribed,’ was a 72-year-old man with significant cardio- pulmonary disease and refractory ventricular arrhyth- miss, who had a 30.7-g thyroid resected. The second patient was an 85-year-old paraplegic man with signil ‘ant cardiopulmonary disease, refractory supraventrict Jararrhythmias, anda massive multinodular goiter, caus- ing shortness of breath, dysphagia, and swelling of his face and neck. He had a computed tomographic scan that showed a large substernal goiter displacing the trachea and esophagus (Figure 1). At operation, the patient was, noted to have a massive substernal goiter (Figure 2). The weight of the resected thyroid gland was 202 g. On the filth postoperative day. the patient developed acute respiratory distress, secondary to an aspiration pneumo- na. Because of his comorbid diseases and in accordance with his living will, the family allowed him to die, with comfort measures only. This was the only mortality in TVET WW ARTOTOCOM on, AU rights reserved,Figure 4. Computed tomographi scan ofa patent wth amiodaron-nducedtyrtoicoss and multinodular ole showing (A) age substenal goer optagu an (8) extersion Intraoperatively, the recurrent laryngeal nerves were identified in all patients. There was no incidence of netv transection, Two or more parathyroid glands were pre- served in situ inall patients, Thirteen patients (24%) had or 2 parathyroid glands autotransplanted into the ster- nocleidomastoid muscle Postoperative complications included vocal cord pa resis in 1 patient that resolved 1 month alter near-total thyroidectomy for Graves’ disease, One patient devel- oped a hematoma that requited operative evacuation fol- lowing subtotal thyroidectomy for Graves’ disease. Two palients, both with Graves disease treated by subtotal thy- roidectomy, developed recurrent thyrotoxicosis. Pastop- erative hypocalcemia oceurred in 35 patients (65%), 10 (20%) of whom were symptomatic. The mean pretreat- ment PT, level in patients with symptomatic hypocalee- mia was 60.494 16.09 pmol/L vs 40.412 19.56 pmol/L (4.704125 ng/dl. vs 3.1441.52 ng/dL) in patients with asymptomatic hypocalcemia (P<.05). The mean pretreal- ment alkaline phosphatase level in patients with symp- tomatic hypocalcemia was 147 £55 U/L vs 145480 U/L in patients with asymptomatic hypocalcemia (P>.05). No pa- tient developed permanent recurrent laryngeal nerve in- jury, permanent hypoparathytoidism, or thyroid storm. The average follow-up forthe entire group was 22 months —_1KIiZ:n”m”_—_@y_§_ Graves’ disease, an autoimmune disorder of uncertain ori- ‘gin, accounted for 50% (32 patients), and toxic multi- nodular goiter, a disease characterized by multiple au tonomously functioning thyroid nodules, accounted for 18 (3%) of the patients with surgicaly-treated thyro- toxicosis in our series, Patients with toxic multinodular {goiter were noted to have larger thyroid glands and more Frequent substernal extension and compressive symp- toms, Although patients with toxic multinodular goiter were more likely to have local symptoms related to marked thyroid enlargement, patients with Graves’ disease had more severe thyrotoxicosis, as evidenced by signifi- cantly higher pretreatment FT levels. Thyrotoxicosis from thyroiditis oF amiodarone-induced thyrotoxicosis was uncommon, No patient with asolitary toxie nodule was referred for surgery in our series, nyo othe eel a the ach the aot, Figure 2. aopeatve photo pte with amldaronensiced th pitens heads ote rit). ho ge subsea iyo gland ina hats and malta goer ihe Patients with thyrotoxicosis constituted 16% (54/ 347) ofall patients referred for thyroidectomy at our in stitution during the 9-year study. The most common re son for recommending surgical therapy was marked thyroid enlargement, with associated substernal exten- sion or compressive symptoms or both. In patients with massive thyroid enlargement, multiple radioiodine teat ments are often required to treat thyrotoxicosis, with litle ellect on the size of the thyroid gland. This was true for 2 of our patients with Graves’ disease, who opted for sur- gical treatment after 1 and 2 treatments with '"L failed to ameliorate their thyrotoxicosis, An associated dominant nodule with abnormal find ings on fine-needle aspiration biopsy was the principal indication for surgery in 3 (9%) of our patients with Graves’ disease, 1 di noma and 2 as having «follicular adenoma. This under- thyroid scin- gnosed as having a papillary carci- scores the importance of obtaining an " Uiscan in patients with a dominant thyroid nodule and a fine-needle aspiration biopsy that is consistent with a fol licular neoplasm when a serum thyrotropin level is low.©| This is necessary to differentiate a hypofunctioning nod- ule in a patient with Graves’ disease, where the risk of ‘malignancy varies from 10% to 50%, from a hyperfune- Ldoning nodulle, where the incidence of malignancy is less than 19% (©2001 American Medical Association, AI rights reserved, Downloaded From: on 06/01/2018Rates of Recurent Hyperthyroidism in Patients ‘Undergoing Sublotal Thyroldectomy> BadlyandLeiey™ — 10 =D 0 “083 Daverportand Tabet” 69 43y 13 “00 Kasuga etal"1990 812 t8y 180 Frankymetal2 001 WR toy 108, Olameoetal1002 NR By 162 Patardhanstal"1009 35° ame-2y 12 Sugioetal!" 10055 28y 146 Wiecletal 10964 = EABmo TS Towingetal* 10061 ty 60 WR ates 0 corded Patient preference was the primary reason for oper tion in 12 8%) of the 32 patients with Graves’ disease. Two patients had failed either 1 oF 2 radioiodine treat. ments, and 6 patients were concerned about the potential forradioiodine-induced aggravation of their ophthlimops- thy. Tallstedt and colleagues" have previously reported the potential for worsening of Graves’ eye disease in patients treated with "1. Total thyroidectomy has been recom- mended for patients with severe or progressive ophihal- ‘mopathy and high levels of thyrotropin receptor antibod- ies. Total removal of the abnormal thyroid antigens is advocated to decrease thyrotropin receptor antibodies and ‘other antibodies that are directed against the extraocular muscles and optic nerve.” One ofthe major advantages of ‘surgical treatment that appeals to many patients is the rapid reversal of symptomatic thyrotoxicosis, whereas.a6- 10 12- week delay in symptom resolution is not unusual for pa- tients receiving radioiodine therapy. These reasons under- score the clinician's responsibility to discuss all therapeutic alternatives for thyrotoxicosis with the patient ‘Another generally accepted indication or surgical man- agement of Graves disease is for pregnant women who are intolerant to antithyroid drugs, This isan uncommon see: nario. Optimally, the surgery should be performed during the second trimester, with the use of an intravenous B ‘ceptor antagonist, if necessary. No pregnant patients with thyrotoxicosis and intolerance to antithyroid drugs were referred for surgical therapy in ou series. The overall incidence of carcinoma in our surgically treated patients with thyrotoxicosis was 7% 4 patients) This included an incidentally discovered 2-cm medul- lary carcinoma in 1 (6%) of our 18 patients with toxic multinodular goiter; a papillary carcinoma in 2 (6%) of, 32 patients with Graves disease, 1 of whom had an oc- ‘cull microscopic lesion; and a 0.4-cm occult papillary carcinoma in 1 of our 2 patients with lymphocytic thy- roiditis, Pellegriti and colleagues" have previously re- ported a 4.7% incidence of clinically relevant and 3.3% ineidence of occult differentiated thytoid carcinoma in a series of 450 patients with Graves’ disease. Bilateral subtotal thyroidectomy has been advo- ‘cated for patients with Graves’ disease to establish a eu thyroid state and to reduce the risk of recurrent laryn- geal nerve injury and hypoparathyroidism, How much (©2001 American Med Downloaded From: on 06/01/2018 thyroid tissue to leave to achieve a euthyroid state re- ‘mains controversial Bradley and Liechly" described their technique of leaving two 5-g remnants, each attached to an intact inferior thyroid artery, and reported that a eu- thyroid state was achieved in 92% of 107 patients fol- lowed up for more than 2 years. Others have not been able to demonstrate a clear-cut relationship between the size of the remnant and achievement ofa euthyroid state." Even if such a determination could be made, standard- {ing the remnant size is inherently difficult. The reported incidence of recurrent hyperthyroid {sm in patients undergoing subtotal thyroidectomy vaties between 1.2% and 16.2% (Table) *!!!™" This can be e plained in part by the differences in remnant size and may also be related to differences in length of follow-up. Itis four belief that recurrent Graves’ disease is an unaceept- able outcome as it ay subject patients to" therapy, which they may have chosen not to receive initially or to reop- erative surgery, which has an increased risk of injury to the recurrent laryngeal nerves and the parathyroid glands. Early in our experience, subtotal thyroidectomy with 3-g rem- nants was routinely performed for Graves’ disease. How- ever, only 1 patient remained euthyroid, 2 developed 1 ‘current hyperthyroidism, and 5 developed hypothyroidism alter a mean 28-month Follow-up, Near-total or total thyroidectomy is our operation of choice for most patients with thyrotoxicosis. Patients with a solitary toxic nodule are the exception, and they are treated with thyroid lobectomy. Near-total or total thy- roidectomy eliminates the possibility of recurrent thyro- Loxicosis, which is always concern when any sizable rem- nant of thyroid tissue is left behind. It also simplifies the long-term assessment of patients’ thyroid function post- operatively. Since more than 30% of patients with thyro- toxicosis treated by bilateral subtotal thyroidectomy be- come hypothyroid within 20 years of surgery, close follow-up is required to prevent delay in recognition and treatment of hypothyroidism.*"* Following near-total or total thyroidectomy, all patients are immediately started ona replacement dose of thyroid hormone. Our results demonstrate that near-toal and total thy roidectomy in patients with thyrotoxicosis can be per- formed with a low morbidity. We attribute this to several factors, The first isthe use of preoperative pharmacologi- cal preparation that has elfecively eliminated thyroid storm, Iodine administration in patients with Graves’ disease has been helpful in reducing intraoperative bleeding, which can affect the identification and preservation ofthe recur- rent laryngeal nerves and the parathyroid glands. Opers- Live visualization ofthe recurrent laryngeal nerves through fut their entire course has been important in eliminating permanent vocal cord paralysis. Meticulous technique ‘maintaining parathyroid gland blood supply and auto- transplantation of parathyroid glands that cannot be pre- served in sits have been important in reducing the ine dence of permanent hypoparathyroidism. Other authors have documented that total thyroidectomy can be performed safely in patients with Graves’ disease fo multinodular goiter. Patients with chronic, remitting thyrotoxicosis se ondary to thyroiditis or amiodarone-induced thyrotox cosis also benefit from near-total of total thyroidec- TVET WW ARTOTOCOM Association, All rights reserved.tomy. Amiodarone-induced thyrotoxicosis is a rare disorder, reported in fewer than 3% of patients taking this antiarehythmic agent. Amiodarone is taken up by the thyroid gland, and its high iodine content produces an increase in iodine stores available for hormone synthe- sis. Ithas also been shown to damage thyroid cell mem- branes, resulting in increased release of large stores of thyroid hormone.” Amiodarone-induced thyrotoxicosis has also been reported to occur in patients with preex- isting thyroid disease, most commonly multinodular goi- ter" Its often resistant to amiodarone withdrawal and conventional pharmacological therapy. Mulligan et al demonstrated that near-lotal thyroidectomy is safe and celfective in producing rapid resolution of symptoms in patients with amiodarone-induced thyrotoxicosis. The ‘only mortality in our series occurred in a patient with, amiodarone-induced thyrotoxicosis, emphasizing that these patients may be at higher risk for surgery related to their underlying comorbid diseases, Transient postoperative hypocalcemia is common following thyroidectomy for thyrotoxicosis, occurring in 35 (65%) of our patients. The causative mechanism is not completely understood. Postoperative hypocalee- mia has been altributed to parathyroid insufficiency due to injury, devascularization, or inadvertent excision of parathyroid glands." In patients with thyrotoxicosis, ther ‘causes of temporary hypocalcemia include calcium up- take by bone in patients with thyrotoxic osteodystrophy ‘or parathyroid suppression from increased calcium re- sorbed from the bone of patients with hyperthyroid- ism.” Transient postoperative hypocalcemia was symp- tomatic in only 10 (19%) of our patients, with a mean pretreatment FT level that was significantly higher than that in patients with asymptomatic hypocalcemia (P<05). This supports earlier findings from our institution that the development of symptomatic postoperative hypocal- ‘cemia is related to the severity of thyrotoxicosis. In most patients, symptomatic postoperative hypocalcemia re- solved within 2 weeks of surgery In conclusion, our results demonstrate that surgl- cal therapy has an important role in patients with thy- rotoxicosis, accounting for 54 (16%) of the 347 thyroid- ‘ectomies performed at our institution during a 9-year period. Our series emphasizes that massive thyroid en- largement with compressive symptoms, adominant nod- ule with abnormal fine-needle aspiration biopsy find- ings, failed radioiodine therapy, or patient preference, ‘especially when there are concerns about radioiodins induced aggravation of ophthalmopathy, are estab- lished indications for surgical treatment of thyrotoxico- sis. Near-total or total thyroidectomy, when it can be performed safely, should be considered fordefinitive man- agement of Graves’ disease, toxic multinodular goiter, chronically remitting thyrotoxicosis secondary to thy” roiditis, and amiodarone-induced thyrotoxicosis. Tran- sient symptomatic postoperative hypocalcemia is com- ‘mon in patients with surgically-treated thyrotoxicosis and is related to the severity of thyrotoxicosis. Accepted for publication June 28, 2000. Corresponding author and reprints: Christopher R. ‘McHenry, MD, Department of Surgery, MetroHealth Med (aerniyreD) TECHOTORRET (©2001 American Medical Downloaded From: on 06/01/2018 Ass cal Center, Case Western Reserve University School of Medicine, 2500 MetroHealth Dr, Cleveland, OH 44109- 1998. Es} 1. Brun, ger RD nveduconta hci ave LE ier Ds. War and Inbar Te Mya, Te Pha P: pia ven one 524 Frm JA Day Dro Z, Fre, Sheppard MC. Long rm flew-ap feznen of tytazsisby the cient meted. 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Aan Surg 1057.208-82 70 NagenarK Por, Sgh Hershman JM. Ardaree and yd fureson Prog Caras is 10893112737 Mario Aghin-Lombud Marit, etal Anodroe:2coneron ouce stieing-ndued tyros. Horn Res. 1087.26-88-171. Hans Se OT. Pos-hyroecomyhypopaathyris, Ar Sr. 7642 0.08. Michie W, Duncan T, Haver Hodoes DW ea Mecanismo ypcleania afer yoitecony fr hycoess, Lancet 8711306514, oak Cvastnsen HS Decreased uray uncon ype ism: itrsonstipsbaween seu pray hormone, elu, pos nus matablsm ad hyd freon Aca Endocnne 1778385 75, eto Spar, Wentworth, Murty Tika for ostyi tomy hypocaleemia. Suey. DK 165588, 20 2 of 909 patos 2 Es En 8 6 a. 28 TT lation, All rights reserved.