Safety and Efficacy of Surgical Management of Hyperthyroidism: 15-year Experience from a Tertiary Care Center in a Developing Country

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Background Ideal management of toxic goiter still remains elusive. Though surgical management of toxic multinodular goiter (MNG) is well accepted, surgical treatment of Graves’ disease (GD) is still controversial in view of the presumed increased
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  Safety and Efficacy of Surgical Managementof Hyperthyroidism: 15-year Experience froma Tertiary Care Center in a Developing Country P. V. Pradeep, MS, DNB, MRCSEd, 1 Amit Agarwal, MS, 1 Mukta Baxi, MS, 1 Gaurav Agarwal, MS, PDCC, 1 Sushil Kumar Gupta, MD, DM, 2 S. K. Mishra, MS, DNB, FACS 1 1 Department of Endocrine Surgery, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae-Bareillei Road, Lucknow,Uttar Pradesh 226014, India  2 Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Rae-Bareillei Road, Lucknow,Uttar Pradesh 226014, India  Abstract Background:   Ideal management of toxic goiter still remains elusive. Though surgical managementof toxic multinodular goiter (MNG) is well accepted, surgical treatment of Graves’ disease (GD) isstill controversial in view of the presumed increased incidence of complications. In this paper, wediscuss the experience of the surgical management of hyperthyroidism at a specialized tertiarycare endocrine center in a developing country, highlighting the minimal morbidity and satisfactoryoutcome in experienced hands. Materials and methods:   We retrospectively reviewed 325 consecutive patients with hyperthy-roidism managed surgically from 1990 to 2005. The etiologic diagnoses were Graves’ disease(185), toxic MNG (105), and autonomously functioning thyroid nodules (AFTN) (n = 35). Theindications for surgery in Graves’ patients were large goiter, relapse after antithyroid drug therapy(ATD), Graves’ ophthalmopathy, and presence of nodule. The indications for surgery in toxic MNGwere retrosternal extension (n = 15), compressive symptoms (n = 20), and large size (grade II).Among the AFTN nodule size, those greater than 4 cm (85%) formed the major indication forsurgery. Subjects with GD and toxic MNG were subjected to subtotal thyroidectomy (n = 93 priorto 1995) or total thyroidectomy (n = 205 post-1995). Hemithyroidectomy was the procedure ofchoice in patients with AFTN. Results:   Patients with Graves’ disease were younger in age, with shorter mean duration of goiterwhen compared with the other 2 groups. Eight percent of patients with Graves’ disease without aclinically palpable nodule and 25% of those with nodules had associated differentiated carcinoma,including papillary, follicular, and medullary thyroid cancer. Four percent of patients with toxicMNG had malignancy. Complications included temporary hypocalcemia (24%), permanenthypocalcemia (3%), and permanent vocal-cord palsy (1%). Conclusions:   Surgery for hyperthyroidism has negligible mortality and acceptable morbidity inexperienced hands. It is a definite option in selected cases. Immediate and permanent cure ofhyperthyroidism is achieved, with no recurrences, after total thyroidectomy. The cosmeticoutcome is good, with excellent patient satisfaction and acceptance. Correspondence to: Amit Agarwal, MS, e-mail: amit@sgpgi. ac.in   2007 by the Socie´te´ Internationale de Chirurgie World J Surg (2007)Published Online: 5 January 2007 DOI: 10.1007/s00268-006-0572-9  S urgery forms an important therapeutic modality in aselected subset of patients with hyperthyroidism. Inthe United States, radioiodine has been described as theinitial definitive treatment modality, with very few surgicalindications for patients with hyperthyroidism. 1 Higherincidence of surgical morbidity has been suggested forthis preference of radioiodine treatment over surgicalintervention. 1 However, the Indian patient profile is dif-ferent from that of patients in developed countries formany reasons. Patients with Graves’ disease usuallyrequire antithyroid medication for a period of 12–18months, 2 which many of our Indian patients cannot afford;neither can they come for prolonged follow-up. Most ofour patients have large goiters (mean gland weight75.734  –  52.1 gm in patients with Graves’ disease and155.5  –  115.1gms in toxic multinodular goiter (MNG); P   = < 0.0001). So 1-time treatment becomes an attrac-tive option and saves many follow-up visits and loss ofwork hours. Medical treatment with antithyroid drugsrequires repeated hormonal assays, dosage adjustment,prolonged medication, and low remission rates. Radioio-dine therapy produces unpredictable hypothyroidism andrequires long-term follow-up. In our country, surgicaltreatment is not the preferred option in toxic goiters. Theaim of this study was to look at the efficacy of surgicalmanagement in terms of curing the disease and safety interms of morbidity and mortality related to the surgicalprocedure. One-time treatment by surgery and life-longthyroxine replacement becomes an attractive alternativeoption in patients for whom the follow-up is difficult. MATERIALS AND METHODS We retrospectively analyzed the data of patients whowere referred for surgical treatment at our institution from1990 to 2005 from the hospital records and their out-comes after the surgical treatment. This group of patientswho undergo surgical treatment form less than 25 % of thetotal hyperthyroid patients seen in our hospital. Specificdata obtained included demographics, indications forsurgery, surgical procedure, pathology, and postopera-tive short- and long-term complications, including per-manent hypoparathyroidism and permanent recurrentlaryngeal nerve (RLN) palsy. Preoperative evaluation inour patients included thyroid function tests, Tc 99 thyroidscan, ultrasound (US) scan, and indirect laryngoscopy.Prior to surgery, we achieve euthyroidism with thiona-mides, and Lugol’s iodine was started 10 days prior to theprocedure. In those patients who continued to be toxicdespite a high dose of thionamides, we use propranololand glucocorticoids for rapidly preparing them for surgery.Surgical treatment was either with subtotal thyroidectomy(STT) (n = 93, prior to 1995) or total thyroidectomy(n = 205, post-1995). Hemithyroidectomy was the pro-cedure in patients with autonomously functioning thyroidnodule (AFTN). It is a routine policy of the department tocheck serum calcium at 24, 48, and 72 hours and 2weeks postoperatively. All patients with biochemical and/ or symptomatic hypocalcemia were treated with calciumand vitamin D analogues, which were tapered over thenext 6 months. All our patients underwent routine indirectlaryngoscopy at 1 week postoperatively by an otorhino-laryngologist. Those with vocal cord palsy and/orhoarseness were followed up till recovery. The follow-updata was collected by retrieval from hospital records,correspondence, and telephonic review. The follow-upwas done with free T4 and thyroid-stimulating hormone(TSH) estimation and clinical examination at 6 weeks, 6months, and yearly. Follow-up ranged from 12 to 180months. RESULTS A total of 325 patients with hyperthyroidism wereoperated. These included patients with Graves’ disease(n = 185), toxic MNG (n = 105), and AFTN (n = 35). Themale to female ratio was 1:3.3. Mean patient age was39.86  –  12.08 years. Patient characteristics are depictedin the Table 1. Patients with Graves’ disease were com-paratively younger in age than those in the group withtoxic MNG and AFTN. Among patients with Graves’ dis-ease, 43 %  (n = 76) had infiltrative ophthalmopathy and26 %  (n = 48) had nodules. Nodules detected either clin-ically or by imaging were included in this subgroup.Ninety-one percent of patients with Graves’ disease, 95 % with toxic MNG, and 87 %  with AFTN had large goiters.Patients with toxic MNG had long-standing goiters(11.11  –  9.71; range: 0.2–40 years) compared withGraves’ disease patients (3.93  –  4.38; range: 0.2–20years). Retrosternal extension and compressive symp-toms were seen in the toxic MNG group. Indications forsurgery in patients with Graves’ disease are summarizedin Table 2. Relapse after antithyroid drug therapy (ATD),presence of infiltrative ophthalmopathy, and large goiterwere the most common indications for surgery in patientswith Graves’ disease (Table 2). Indications for surgery intoxic MNG included retrosternal extension (n = 15),compressive symptoms (n = 20), and more than 90 % being large goiter. Among AFTN, more than 85 %  of thenodes were larger than 4 cm in size, which formed the Pradeep et al.: Safety and Efficacy of Surgical Management of Hyperthyroidism  indication for surgery. Of patients with associated malig-nancies, 8 %  (15 out of 185) had Graves’ disease and25 %  (12 out of 48) had Graves’ disease with nodule.Papillary thyroid carcinoma was the most common can-cer (8 out of 12) in patients who had Graves’ disease withnodule, followed by patients with follicular thyroid cancer(3 out of 12) and medullary thyroid cancer (1 out of 12).Four percent of patients wtih toxic MNG had associatedincidental malignancy. Among the 76 patients withGraves’ ophthalmopathy, follow-up was available in 65patients. The response was assessed subjectively bycomparison of preoperative patient photographs withphotographs taken 6 and 12 months postoperatively. Thedetails are depicted in Table 3. Surgical proceduresperformed during the period 1990–2005 are depicted inFig. 1. The change in policy of doing total over STT wasbought about by the concerns for recurrence (4 % ) andhigher rates of unpredictable hypothyroidism (26 % )associated with STT. Associated complications of the 2procedures are shown in Table 4. Vocal-cord palsy wasdefined as permanent if it persisted beyond 1 year, andwe had 1 % incidence rate. Permanent hypocalcemia wasdefined as that lasting beyond 6 months of surgery. Theaverage tumor weight and size were greater in the toxicMNG group (Table 5). There was no mortality in ourpatients. DISCUSSION Treatment options for toxic goiters are medical, surgi-cal, and radioiodine. However, each of these has its ownadvantages and disadvantages, and the ideal treatmentfor hyperthyroidism is still elusive. The ideal treatment ofthyrotoxicosis should produce prompt control of diseasemanifestations and return to and maintenance of euthy-roidism with minimal morbidity and mortality andreasonable cost. Patient preference, physician prefer-ence, local practice patterns, and conventional wisdomhas been responsible for choosing one modality over theother. In this study, we have analyzed data of patientsreferred for surgical treatment for hyperthyroidism at atertiary-level health care center (which is also a teachingand training hospital). Graves’ disease is the mostcommon cause of hyperthyroidism, and worldwide, itaccounts for 60–80 % of all cases. 3 In our surgical series, Table 1. Patient characteristicsCharacteristics Graves’ disease (n = 185) Toxic MNG (n = 105) AFTN n = 35Gender (M:F) 1:2.2 1:7.5 1:3Age in years (mean  –  SD) 16–62 (34.7  –  10.66) 19–71 (45.3  –  12.2) 18–65 (43.5  –  10.1)Ophthalmopathy 76 (43 % ) – –Nodule 48 (18 % ) – –Grades II and III 91 %  95 %  87 % > 4cmDuration of goiter (range in years) 3.93  –  4.38 (0.2–20 ) 11.11  –  9.71 (0.2–40) 11.67  –  14.4 (1–40 years)Duration of ATD (mean  –  SD years) 0.2–10 (2.9  –  2.33) 0.2–15 (2.5  –  2.5) 0.3–8 (3.1  –  2.4)Compressive symptoms 0 20 0Retrosternal extension 0 15 0MNG: multinodular goiter; AFTN: autonomously functioning thyroid nodules; M: male; F: female; ATD: antithyroid drug therapy;SD: standard deviation. Table 2. Indications for surgery in patients with Graves’ diseaseIndications n = 185 PercentRelapse after ATD therapy 140 75.6Persistent hyperthyroidism 20 10.8Large goiter (grades II and III) 121 65.4Allergic reactions to thionamides 5 2.7Drug noncompliance 20 10.8Nodule 48 25.9Eye disease (infiltrative ophthalmopathy) 76 41.1Pregnancy current/planned 4 2.1Many patients had multiple indications.ATD: antithyroid drug therapy. Table 3. The outcome of Graves’ ophthalmopathy following thyroidsurgeryProcedure performed STT (n = 30) TT (n = 35)OutcomeStationary 22 (73.3 % ) 28 (80 % )Regression 7 (23.3 % ) 7 (20 % )Progression 1 (3.3 % ) –STT: subtotal thyroidectomy; TT: total thyroidectomy;n: cases where follow-up was available.Pradeep et al.: Safety and Efficacy of Surgical Management of Hyperthyroidism  Graves’ disease constituted 57 %  of the cases and toxicMNG 32 % . In the series of Linos  et al  . Graves’ constituted28 %  and toxic MNG 57 %  of the cases. 4 This differencecould be attributed to the different practice patterns in thedifferent parts of the world in choosing the definitive modeof treatment. Most of the affected patients were women,as autoimmune diseases are more common in the femalegender. The major indications for surgery in our patientswith Graves’ disease were large goiter, relapse after ATDtherapy, ophthalmopathy, and presence of nodules.Weber  et al  ., 5 in their series, reported failure of medicaltherapy and presence of nodule as the most commonindications of surgery in Graves   disease. Patient prefer-ence, cold nodule, eye symptoms, large goiter size,allergy to antithyroidal medications, and age youngerthan 16 years were reported as the most common sur-gical indication by Lal  et al  . 6 Prior to 1995, we performed subtotal thyroidectomy,which involved leaving a remnant of 4 gm on either sideafter identification of the RLN. After 1995, we switched tototal thyroidectomy. Our technique of total thyroidectomyinvolves capsular dissection, identification of the externalbranch of the superior laryngeal nerve (EBSLN), andidentification of RLN palsy in its entire course. We rou-tinely identify all 4 parathyroid glands and autotransplantthe at-risk parathyroids. It is essential to look for thepyramidal lobe and other embryological and anatomicalextensions of the thyroid, such as the tubercle of Figure 1.  Surgical procedure performed (1990–2005). Table 4. Short- and long-term complications following thyroidectomy inGraves’ disease and toxic multinodular goiter (MNG)Pre-1995 Post-1995Procedure STT (n = 93) TT (205)ComplicationsHematoma/seroma 5 (5 % ) 5 (2 % )Temporary hypocalcemia 9 (10 % ) 49 (24 % )Permanent hypocalcemia 2 (2 % ) 6 (3 % )Temporary VC palsy 4 (4 % ) 5 (2 % )Permanent VC palsy 1 (1 % ) 2 (1 % )Tracheostomy 1 1Recurrence of thyrotoxicosis 4 (4 % ) 0Hypothyroidism 24 (26 % ) AllSTT: subtotal thyroidectomy; TT: total thyroidectomy; n:cases where follow-up was available; VC: vocal chord. Table 5. Mean gland weight and gland size observed in the differentgroups of hyperthyroid patientsMean weight (gm) Size (cm)Graves’ disease 75.734  –  52.1 7.033  –  1.69Toxic multinodal goiter 155.5  –  115.1 8.77  –  2.48 P  -value < 0.0001 < 0.0001Pradeep et al.: Safety and Efficacy of Surgical Management of Hyperthyroidism  Zuckerkandl, and detached thyroid lobes to avoid futurerecurrences. With this technique, we have been able tokeep our complication rates and recurrences to anacceptable minimum. Surgery avoids long-term risks ofradioactive iodine, such as the increased risk of cancerand unpredictable hypothyroidism. 7 Surgical treatmentnow has an almost zero mortality, few complications, andfew recurrences, with the euthyroid state being achievedrapidly and consistently.Permanent hypocalcemia occurred in 3 % of our cases.Our protocol for management of hypocalcemia involvesassessment of clinical signs [Trousseau’s sign (T sign),Chvostek’s sign], symptoms (perioral numbness, tin-gling), and biochemical parameters (serum calcium,inorganic phosphorus). If there is biochemical hypocal-cemia, we start the patient on oral calcium; if there aremild symptoms, such as tingling and numbness alongwith biochemical hypocalcemia, we also add vitamin Danalogues along with the oral calcium. For patients whodevelop frank hypocalcemia with a positive T sign andtetany, we start them on intravenous calcium infusion atthe rate of 1–2 mg/kg per hour, along with oral calciumand vitamin D supplements. We prepare the calciuminfusion by adding 6 ampoules of 10 % calcium gluconate(90 mg elemental calcium) in 540 ml of saline, whichprovides around 1 mg/ml. This is infused at the above-mentioned rate of 1–2 mg/kg per hour for 36–48 hours,along with oral calcium and vitamin D supplements.Patients who continue to have hypocalcemia 6 monthspostoperatively are labeled as permanently hypocalce-mic. Permanent hypocalcemia is a distressing and diffi-cult problem to tackle because these patients have totake lifelong calcium and vitamin D supplements. How-ever, the incidence of this dreaded complication can beminimized in experienced hands by meticulous dissectiontechnique and saving viable parathyroids in situ, and bykeeping a low threshold for autotransplantation of ische-mic parathyroids. We emphasize making every attempt topreserve parathyroids in situ wherever possible, ratherthan doing autotransplantation. Patients who developedpermanent hypocalcemia in our series are now on lifelongcalcium and vitamin D supplements. The rate of perma-nent RLN palsy was 1 %  in this series. Similar lowincidences of RLN palsy have been reported by Harada et al  . 8 (0 %  of 157 patients with Graves’ disease), Linos et al  . (1 %  of 400 patients of hyperthyroidism), andEricksen  et al  . (2 %  of 174 patients with toxic MNG). 9 Surgery is the preferred therapy for toxic MNG, Graves’ophthalmopathy, for children, in pregnancy, for psycho-logically or mentally incompetent patients’ and for pa-tients who are unable to maintain long-term follow-up.Unlike radioiodine therapy in which the patient has toavoid pregnancy for 6–12 months after surgery, child-bearing is immediately possible. 7 Advancements such aspreoperative preparation and intraoperative PTH moni-toring have the potential to decrease risks and improveoutcomes; 7 however, this needs to be ratified by moreliterature support. We did not perform intraoperative PTHdue to economic constraints and relied on visual identi-fication of all the parathyroids. Lack of availability ofexperienced thyroid surgeons has been very often citedas a reason for choosing the other modalities of therapy,such as radioiodine and ATDs. Our study 10 and that ofothers 11 have shown that thyroid surgery can thereforebe safely and effectively performed by residents. Theother major concerns of surgical treatment have beenrecurrence. We at the Sanjay Gandhi PostgraduateInstitute of Medical Sciences also shifted to total thy-roidectomy after 1996 when we reviewed our initialexperience and found a recurrence of 4 %  and unpre-dictable hypothyroidism of 28 %  in our patients whounderwent subtotal thyroidectomy. Major centers world-wide have now reported negligible morbidity with totalthyroidectomy for toxic MNG and Graves’ disease. 4,12 The concern for coincidental malignancy has alwaysbeen there. 13 Total thyroidectomy provides adequateinitial treatment of any associated malignancy. In ourseries, 8 %  of patients with Graves’ disease and 4 %  withtoxic MNG had malignancy. In Graves’ disease, theconcern for malignancy is higher in the presence ofnodules. Kraimps  et al  . 14 reported a 3.8 %  incidence inGraves’ disease and a 15 % incidence in Graves’ diseasewith nodules. In the present series, patients with Graves’disease and nodule had a 25 % incidence of malignancy.This may, however, be due to a referral bias. Linos  et al  .,in their series, found 8 % of AFTN patients had associatedmalignancy. 4 However, in our series, no associatedmalignancy was detected in AFTN patients. Presence ofeither palpable or sonographically detected nodules inpatients with Graves’ disease increases the concern ofassociated malignancy. Kraimps  et al  . showed that USdetected 83 %  of nodules compared with 39 %  by thyroidscintigraphy. US-guided fine-needle aspiration cytology(FNAC) can be employed in these patients; however, theinterpretation may be difficult due to the hyperplastictissue in Graves’ disease. 15 In endemically iodine-defi-cient areas, such as those in some parts of India, have ahigher incidence of associated nodules in Graves’ dis-ease. 16 In the present series, 26 %  of the patients withGraves’ disease had a nodule. With surgical treatment,there is quick control of disease, early return to work,minimum morbidity in experienced hands, and minimum Pradeep et al.: Safety and Efficacy of Surgical Management of Hyperthyroidism
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