Thyroid Disease and Compressive Symptoms

The Laryngoscope VC 2011 The American Laryngological, Rhinological and Otological Society, Inc.

Caroline A. Banks, MD; Christopher M. Ayers, BS; Joshua D. Hornig, MD; Eric J. Lentsch, MD; Terry A. Day, MD; Shaun A. Nguyen, MD, MA; M. Boyd Gillespie, MD, MSc

Objectives/Hypothesis: Compressive symptoms are common in thyroid disease, but few studies have focused on the presence, associated factors, and etiology of compressive symptoms. Study Design: Retrospective review. Methods: Patients who underwent thyroidectomy from 2005 through 2009 were reviewed. The data included demo- graphics, indication for surgery, compressive symptoms, complications, diagnosis, volume of thyroid gland, presence of inflammation, and follow-up. Results: Three hundred thirty-three patients were identified. The mean age was 51 years, and 82% were female. Fifty- two percent (n ¼ 172) of patients experienced compressive symptoms preoperatively, including dysphagia (n ¼ 131) and shortness of breath (n ¼ 83). Twenty-six percent (n ¼ 86) of patients presented with voice changes, and 8% (n ¼ 27) complained of odynophagia. Postoperatively, 25 patients (8%) continued to have compressive symptoms (P < .0001), and 10 patients (3%) developed new compressive symptoms. Compressive symptoms were present in 72% (n ¼ 21) of patients with lymphocytic thyroiditis, 71% (n ¼ 5) of patients with anaplastic thyroid cancer, and 60% (n ¼ 92) of patients with goiter. The average volume of the gland in patients with compressive symptoms was 75.5 mL compared to 37.1 mL in asymptomatic patients (P < .0001). There was not a significant relationship between compressive symptoms and the presence of inflammation (P ¼ .869). Conclusions: Patients with thyroid disease frequently present with compressive symptoms, and the majority of patients experience relief postoperatively. The volume of the thyroid gland is associated with compressive symptoms along with addi- tional contributing factors. Key Words: Thyroid, dysphagia, compressive symptoms, thyroidectomy, goiter. Level of Evidence: 4 Laryngoscope, 122:13–16, 2012

INTRODUCTION thyroid disease.8 Thyroidectomy may be effective in Compressive symptoms are common among patients relieving compressive symptoms.9 with thyroid disease and represent an indication for thy- Although diffuse thyroid enlargement is associated roidectomy.,2 Compressive symptoms range from mild, with tracheoesophageal compression, compressive symp- presenting with neck pressure or globus sensation, to toms are also commonly observed in patients with only severe, characterized by significant dysphagia or dysp- mild to moderate thyroid enlargement. In addition to nea.,2 In rare cases, tracheal or esophageal compression direct compression from an enlarged thyroid gland, dys- leads to acute airway distress that requires emergent phagia and shortness of breath may be a manifestation of treatment with intubation or tracheostomy.5 thyrotoxicosis, Hashimoto thyroiditis, de Quervain thyroid- Compressive symptomatology is associated with itis, and other inflammatory diseases of the thyroid.10–14 both benign and malignant thyroid disease.6 Patients Previous studies suggest that inflammation of the thyroid with multinodular goiter frequently complain of dyspha- gland may be an etiology of compressive symptoms, but gia or dyspnea.7 Marked thyroid enlargement and this association has not been fully elucidated. This study substernal goiters have a higher incidence of compres- explores the incidence of compressive symptoms in thyroid sive symptoms.1,5,8 Although compressive symptoms are disease over a 5-year period and describes associated fac- found in thyroid malignancy, the majority of patients tors and possible etiologies of compressive symptoms. In presenting with aerodigestive compression have benign addition, the study seeks to determine if there is a clear association between compressive symptoms and thyroid inflammation on surgical pathology. From the Department of Otolaryngology–Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina, U.S.A. Editor’s Note: This Manuscript was accepted for publication June 28, 2011. MATERIALS AND METHODS The authors have no funding, financial relationships, or conflicts A retrospective review was performed on patients under- of interest to disclose. going thyroidectomy by the Medical University of South Send correspondence to Caroline A. Banks, MD, Department of Carolina (MUSC) Head and Neck Tumor Program from 2005 Otolaryngology, Medical University of South Carolina, 135 Rutledge through 2009. Patients were identified through billing records Avenue, MSC 550, Charleston, SC 29425. E-mail: [email protected] using procedure codes for partial, total, and completion thyroid- DOI: 10.1002/lary.22366 ectomy. Exclusion criteria included patients under the age of

Laryngoscope 122: January 2012 Banks et al.: Thyroid Disease and Compressive Symptoms 13 ¼ TABLE I. diagnosis was most commonly goiter (46%, n 152), Patient Characteristics papillary thyroid carcinoma (22%, n ¼ 72), follicular adenoma (10%, n ¼ 32), and thyroiditis (9%, n ¼29). The Age, yr, mean (6SD) 51.1 (15.2) most frequent complications were unilateral true vocal Sex, no. (%) cord paresis or paralysis (5%, n ¼ 17), postoperative hypocalcemia (4%, n ¼ 13), and superior laryngeal nerve Female 274 (82.3) injury (2%, n ¼ 5). Other complications included hema- Male 59 (17.7) toma, keloid, cellulitis, and wound dehiscence. Fifty-two percent (n ¼ 172) of all patients under- Race/ethnicity, no. (%) going thyroidectomy described compressive symptoms Caucasian 215 (64.6) preoperatively. Common compressive symptoms included dysphagia in 39% (n ¼ 131) and shortness of breath (or- African American 111 (33.3) thopnea), most commonly when supine, in 25% (n ¼ 83) Hispanic 3 (0.9) of patients. Unspecified compressive symptoms charac- ¼ Asian 1 (0.3) terized by neck pressure were observed in 10% (n 32) of patients. Twenty-six percent (n ¼ 86) of patients pre- Native American 1 (0.3) sented with voice changes, and 8% (n ¼ 27) of patients Other 2 (0.6) complained of odynophagia. The presence of compressive symptoms varied with SD ¼ standard deviation. disease state. Seventy-two percent of patients with lymphocytic thyroiditis, 71% of patients with anaplastic 18 years, a diagnosis of squamous cell carcinoma, thyroidectomy thyroid cancer (ATC), and 60% of patients with goiter for reasons other than thyroid disease, and patients with multi- had compressive symptoms. Odynophagia occurred in ple recurrent thyroid cancer. Electronic medical records and 14% (n ¼ 4) of patients with thyroiditis, 13% (n ¼ 4) of archived paper charts were reviewed to obtain the following patients with follicular adenoma, and 9% (n ¼ 1) of data: sex, age, race, indication for surgery, presence of neck patients with Graves disease. Voice changes occurred in mass, presence of compressive symptoms, postoperative compli- 100% (n ¼ 2) of patients with medullary thyroid carci- cations, fine needle aspiration (FNA) result, final pathologic noma, 71% (n ¼ 5) of patients with ATC, and 41% (n ¼ diagnosis, tumor size, volume and weight of thyroid gland, 12) of patients with thyroiditis. These results are histologic presence of aggressive features, presence of inflamma- described in Table 3. tion, length of hospitalization, and follow-up time. The volume of the thyroid gland was determined using the accepted ellip- The average volume of the gland in patients with ¼ soid formula of p/6 multiplied by the height, width, and depth compressive symptoms was 75.5 mL (SD 84.9; range, of each lobe.15 Permission for this study was obtained from the 0.4–479.2 mL) compared to 37.1 mL (SD ¼ 51.6; range, MUSC institutional review board through an expedited review 0.6–314.4 mL) in asymptomatic patients (P < .001). approval. Patients with marked thyroid enlargement, defined as a All analyses were performed with Sigma Stat 3.5, SPSS 15.0, and Sample Power 2.0 (SPSS, Inc., Chicago, IL). Categori- cal variables were presented as percentage, and continuous TABLE II. variables were presented as mean and range or as mean 6 Indications for Surgery. standard deviation (SD). All continuous variables were normal distributed as determined by Kolmogorov-Smirnov test. Com- No. (%) parisons of baseline patient characteristics and clinical outcomes were performed using the v2 or Fisher exact test (cat- Goiter 6 compression 120 (36.0) egorical variables) and the t test (continuous variables). Rapidly enlarging mass 13 (3.9) Spearman rank order correlation was used to determine relationship between variables. A P value of <.05 was considered Atypical cells/malignancy indicative of statistical significance. PTC 60 (18) Follicular lesion 49 (14.7) RESULTS Atypical cells NOS 11 (3.3) Three hundred thirty-three patients were identified. The mean age was 51 years (range, 18 –90; SD ¼ 15 ATC 4 (1.2) ¼ years), and 82% (n 274) were female. Patient charac- MTC 1 (0.3) teristics are described in Table 1. The mean follow-up time was 5 months (range, 0–59 months). Nodule(s) 42 (12.6) Forty-four percent (n ¼ 145) of patients underwent Graves 27 (8.1) hemithyroidectomy or completion thyroidectomy, and 57% (n ¼ 188) of patients underwent total thyroidec- TVC paralysis 4 (1.2) tomy. The most common indications for surgery were Other 2 (0.6) goiter or enlarging neck mass (40%) and atypical or PTC ¼ papillary thyroid carcinoma; NOS ¼ not otherwise specified; malignant cells on FNA cytology (38%). Indications for ATC ¼ anaplastic thyroid carcinoma; MTC ¼ medullary thyroid carcinoma; surgery are summarized in Table II. The final pathologic TVC ¼ true vocal cord.

Laryngoscope 122: January 2012 Banks et al.: Thyroid Disease and Compressive Symptoms 14 ¼ TABLE III. 91.7 mL (SD 103; range, 6.6–425 mL). The difference Diagnosis and Compressive Symptoms. between the volume of gland in patients with resolution of symptoms compared to continued symptoms was not Compression, Odynophagia, Voice Changes, ¼ Diagnosis (No.) No. (%) No. (%) No. (%) statistically different (P .330).

Goiter (152) 92 (60.5) 11 (7.2) 36 (23.7) DISCUSSION PTC (72) 20 (27.8) 5 (6.9) 14 (19.4) Compressive symptoms are common in thyroid dis- Follicular adenoma (32) 15 (46.9) 4 (12.5) 10 (31.3) ease. In a series of over 3,000 thyroidectomies, Lacoste Thyroiditis (29) 21 (72.4) 4 (18.8) 12 (41.4) et al. found that 11% of patients complained of compressive symptoms.1 Multinodular goiter, one of the more FTC (11) 5 (45.5) 0 (0.0) 1 (9.1) common indications for thyroidectomy, is associated with Graves (11) 4 (36.4) 1 (9.1) 1 (9.1) compressive symptoms. In a 7-year series, 33% of patients diagnosed with benign goiter had compressive ATC (7) 5 (71.4) 0 (0.0) 5 (71.4) symptomatology.4 A separate study focusing on marked MTC (2) 1 (50.0) 0 (0.0) 2 (100.0) thyroid gland enlargement reported an incidence of 86%.8 In our series, the overall incidence of compressive Other (17) 9 (52.9) 2 (11.8) 4 (23.5) symptoms was 52%, with 61% of patients with benign PTC ¼ papillary thyroid carcinoma; FTC ¼ follicular thyroid carci- multinodular goiter having symptoms of compression. noma; ATC ¼ anaplastic thyroid carcinoma; MTC ¼ medullary thyroid On average, patients with dysphagia and/or shortness of carcinoma. breath had a larger volume of thyroid gland when compared to asymptomatic patients (75.5 mL vs. 37.1 mL) volume >40 mL for a unilateral lobe and 80 mL for (P < .001). bilateral lobes, were identified. Thirty-one percent (n ¼ Despite the relationship between gland size and 50) of patients with compressive symptoms had marked compressive symptoms, not all patients with an enlarged enlargement of the thyroid gland, compared to 17% (n ¼ thyroid gland develop compressive symptoms. Shaha 26) of patients without compressive symptoms (P ¼ found that 15% of patients with large goiters were .009). There was not a significant relationship between asymptomatic.5 Similarly, in a study of patients with compressive symptoms and the presence of inflammation benign goiter, one third of patients with radiologic evi- (Spearman rank order correlation). dence of marked tracheal deviation were asymptomatic.4 Postoperatively, 11% (n ¼ 35) of patients com- The present study demonstrates that among patients plained of compressive symptoms. Of the 172 patients with marked thyroid enlargement, 34% were asymptom- who presented with compressive symptoms, only 25 (8%) atic with regard to compression. The above data suggest continued to have compressive symptoms following thy- that there are factors in addition to size, such as pattern roidectomy, indicating a significant relief of these of growth, that are involved in the development of com- symptoms with surgery (P < .001). Ten patients (3%) pressive symptoms. without presenting complaints of compression developed Patients with thyroiditis have a high incidence of compressive symptoms after surgery. Patients who con- tracheoesophageal compression, and evidence suggests tinued to have symptoms had an average age of 56 years that inflammation of the thyroid gland is related to com- (SD ¼ 14.4), and 80% were female. These demographic pressive symptoms.,2 In a prospective series of thyroid data were not statistically different when compared to pathology and globus sensation, Burns and Timon deter- the group of patients with resolution of symptoms, who mined that histological features of inflammation were had a mean age of 52 years (SD ¼ 15, P ¼ .572) and correlated with the greatest improvement in symptoms were 84% female (P ¼ .582). Pathologic diagnosis was after thyroidectomy.3 In our study, the presence of also similar between the two groups. Sixty-four percent inflammation among patients with compressive symp- of patients with continued symptoms and 52% of toms was not significantly different than the presence patients with resolved symptoms were diagnosed with of inflammation in patients without compressive symp- benign goiter (P ¼ .254). toms. Seventy-two percent of patients with the Four patients in this series developed postoperative inflammatory condition of lymphocytic thyroiditis, how- hematoma, and three of these four patients continued to ever, complained of dysphagia or shortness of breath. have postoperative compressive symptoms. This was These data suggest that inflammation may play a role in statistically significant compared to the group of the development of compressive symptoms. patients who no longer had symptoms after surgery (P < Multiple studies have demonstrated improvement .005). Two of the patients who continued to have symp- or resolution of compressive symptoms after thyroid sur- toms were diagnosed with ATC, and one patient with gery.2,9,16 In a two-year prospective study, 80% of globus continued symptoms had a longstanding history of sub- symptoms were alleviated postoperatively.3 Similarly, in glottic stenosis. our study, 85% of patients with preoperative compressive The average volume of gland in patients who had symptoms had resolution of compressive symptoms after resolution of symptoms was 72.5 mL (SD ¼ 81; range, thyroidectomy. The average volume of the gland was not 0.4–479 mL). In patients who continued to have symp- significantly different in patients who continued to have toms after surgery, the average volume of gland was symptoms compared to patients who had resolution of

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