Clinical and Surgical Year in Review

ThyroidVol. 34, No. 1 Editorial and CommentariesFree AccessClinical and Surgical Year in ReviewWhitney Goldner and Catherine SinclairWhitney GoldnerAddress correspondence to: Whitney Goldner, MD, Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Nebraska Medical Center, 984120 Nebraska Medical Center, Omaha, NE 68198-4120, USA E-mail Address: [email protected]Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Nebraska Medical Center, Omaha, Nebraska, USA.Search for more papers by this author and Catherine SinclairAddress correspondence to: Catherine Sinclair, MD, Department of Surgery, Monash University, Melbourne Thyroid Surgery, 159 Wattletree Road, Clayton 3144, Australia E-mail Address: [email protected]Department of Surgery, Monash University, Clayton, Australia.Icahn School of Medicine at Mount Sinai, New York, New York, USA.Search for more papers by this authorPublished Online:16 Jan 2024https://doi.org/10.1089/thy.2023.0601AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail BackgroundFor the American Thyroid Association's (ATA) Centennial Annual Meeting, we presented the Clinical and Surgical Years in Review. The most clinically impactful articles or topics published in the realm of clinical and surgical thyroidology since the previous ATA meeting were highlighted.MethodsA literature search was conducted using PubMed from September 1, 2022, through September 1, 2023. Articles were original research, human studies, and published in the English language. Search terms and MeSH terms for all thyroid diagnoses were used.In addition, articles reviewed in Clinical Thyroidology from October 2022 to September 2023 and the most cited and downloaded articles from multiple endocrine and surgical journals were evaluated. Consensus statements, guidelines, opinion papers, or commentaries were excluded. The ATA members were queried for opinions regarding impactful articles in the field. Ultimately, articles were chosen by the speakers based on novelty of the topic, ability to address common clinical questions and/or challenge current management paradigms, or potential to impact patient care (Tables 1 and 2).Table 1. Clinical Year in Review Summary Take-Home PointsQOL in hypothyroidism is complex and may be tied to provider relationship and preexisting/concurrent somatic symptom disorder.1,2Disparities exist in thyroid cancer care, and it is critical we find ways to improve access to guideline concordant care.6–10Environmental exposures are common and can be associated with thyroid cancer.11Implementation of AI assist when evaluating thyroid nodules can improve provider workflow, efficiency, and accuracy of diagnosis.12Methimazole is a reasonable option for long-term therapy of hyperthyroidism from TMNG.13It is important to repeat thyroid function tests in euthyroid TPO+ women while trying to conceive since many may develop dysfunction before conception.14Long-term follow-up of thyroid nodules can be individualized based on three-year trend of nodule growth rate.16Preoperative molecular results may predict overall risk of recurrence in thyroid cancer.17More research needs to be done regarding the role of GLP-1 receptor agonists and association with non-medullary thyroid cancer.18Postoperative risk of recurrence prediction may be enhanced by including additional (non-histological) features.24Progressive metastatic radioiodine-resistant DTC has increasingly more options for treatment and targeted therapy.25–28AI, artificial intelligence; DTC, differentiated thyroid carcinoma; GLP-1, Glucagon like peptide-1 receptor agonists; QOL, quality of life; TMNG, toxic multinodular goiter; TPO+, thyroid peroxidase antibody positive.Table 2. Surgical Year in Review Summary Take-Home PointsThermal ablative techniques for benign thyroid nodules achieve similar cosmetic and symptomatic improvement to conventional surgery with less risk of thyroid hormone disturbance.15The indications for thermal ablation of papillary thyroid microcarcinoma are currently being explored. Tumor multifocality and BRAF mutations alone may not be contraindications to ablation.19,20Large (>4 cm), intrathyroidal, encapsulated, well-differentiated follicular cell-derived carcinoma without vascular invasion follows an indolent clinical course. They have negligible risk of locoregional recurrence or distant metastases and could potentially be treated by lobectomy alone, although larger scale studies are needed for validation.22Patients with cN1b T1/T2 papillary thyroid carcinoma who undergo lobectomy may exhibit similar recurrence-free survival to those undergoing total thyroidectomy after controlling for major prognostic factors.23Patients enrolled in an active surveillance protocol who subsequently go on to have delayed surgery do not have increased rates of surgical morbidity or mortality.21The combination of neoadjuvant therapy (BRAF/MEK inhibition) followed by surgery can convert inoperable to operable disease, reducing surgical morbidity and increasing overall and progression-free survival, independent of AJCC stage (IVB vs. IVC).29Performance of a central neck dissection, but not patient age or body mass index, is a major risk factor for incidental parathyroidectomy following pediatric thyroidectomy.4Significant improvements in disease-specific QOL and psychosocial functioning are achieved following total thyroidectomy in adolescents with Graves' disease.3Long-term rates of clinical hypothyroidism following thyroid lobectomy are likely higher than previously reported. Annual TSH testing for at least five years post-lobectomy should be considered.5AJCC, The American Joint Committee on Cancer; TSH, thyrotropin.Quality of LifeHypothyroidismOptimization of health-related quality of life (QOL) is an important component of long-term management of various thyroid disorders, especially hypothyroidism. Perros et al. conducted a cross-sectional, multinational online survey of 3915 persons with self-reported hypothyroidism from 68 different countries.1 They reported that satisfaction with care and treatment of hypothyroidism was not associated with the type of treatment for hypothyroidism, which is in contrast to other recent studies showing improved QOL with triiodothyronine (T3) + thyroxine (T4) therapy when compared with T4 monotherapy.They also reported that the lack of confidence and trust in health care professionals was strongly associated with dissatisfaction with treatment of hypothyroidism. In a separate article, the same group administered the validated PHQ-15 survey to assess for somatization, and 58.6% of hypothyroid participants met the criteria for somatization disorder (SSD).2 There were significant associations between SSD and young age, female sex, unemployment, household income, type of treatment (specifically T4 monotherapy), number of comorbidities, and the view that thyroid medications did not control symptoms was also reported (p < 0.001). Overall, these two studies highlight the potential additional factors that may also contribute to QOL in patients with hypothyroidism in addition to the type of thyroid hormone replacement.Surgery for pediatric Graves' diseaseThis prospective longitudinal study investigated disease-specific QOL and psychosocial functioning in adolescents (aged 12–19 years) undergoing total thyroidectomy (TT) definitive surgery for Grave's disease.3 Five validated surveys were administered to patients and parents preoperatively and 6 months postoperatively—there were 37 patient–parent dyads at baseline and 20 dyads postoperatively. Significant improvements in disease-specific QOL and psychosocial functioning were noted after TT on the Questionnaire for Patients with Thyroid Disease (ThyPRO) and Pediatric QOL Scales (PedsQL). Thyroid eye disease symptoms and scar appearance concerns were minimal, although 20–25% of patients–parents reported intermediate or high irregularities and dissatisfaction with scar appearance. These results will help counsel and set appropriate preoperative expectations for adolescent patients (and families) undergoing TT for Grave's disease. Future studies comparing treatment options (e.g., TT to radioactive iodine [RAI]) in this patient population would be beneficial.Incidental parathyroidectomy and postoperative hypocalcemiaRemaining in the pediatric realm, the next article investigated the occurrence of incidental parathyroidectomy (IP) among pediatric patients undergoing thyroid surgery.4 In this retrospective case–control study, IP was defined as the presence of parathyroid tissue in the surgical specimen. Overall rate of IP was 35%. Univariable risk factors for IP included a preoperative diagnosis of thyroid malignancy, suspicious lymphadenopathy, TT, central compartment dissection, and parathyroid reimplantation. The only multivariable association with IP was performance of central neck dissection—child age and body mass index (BMI) did not impact on rates of IP. Patients with IP were more likely to require postoperative calcium and/or vitamin D supplementation (44% vs. 16%, p < 0.001). Awareness of these risk factors is important for patient counseling regarding short- and long-term outcomes following thyroid surgery.Thyroid hormone replacement following lobectomyThis article challenges how patients are counseled before partial thyroid surgery with respect to thyroid hormone replacement therapy (THRT). This retrospective case series analyzed the rate of long-term thyroid replacement hormone after lobectomy in 235 patients—thyroid hormone therapy was initiated in 46.8%.5 On multivariate analysis, only the presence of Hashimoto's thyroiditis was independently associated with THRT use after lobectomy (odds ratio [OR] 3.02 [CI 1.39–6.97]; p = 0.006). However, notably, the timing of initiation of hormone replacement from the date of surgery (available in 81 patients) was 647 ± 109 days (1.7 ± 0.3 years), with 25% having initiation of hormone >2 years after surgery. The median time to hormone initiation was 0.56 years. These findings suggest that long-term rates of clinical hypothyroidism following thyroid lobectomy may be higher than previously reported. This has significant implications for accurate preoperative patient counseling and timing of postoperative biochemistry and suggests that annual thyrotropin (TSH) testing should be performed at least five years after lobectomy.Health DisparityDisparity in access to care and guideline concordant care is an important area that needs to be recognized and addressed. Multiple studies were published in the last year, in both pediatric and adult populations, reporting non-White, uninsured or government insured (Medicare and Medicaid), and those who live at an increased distance from a treating facility were associated with delays in care, larger primary tumors, distant metastatic disease, and higher stage at diagnosis.6–10 Racial and ethnic minorities were also less likely to receive guideline concordant care before the 2015 ATA guidelines, but here has been improvement with implementation of the newer guidelines, but those with Medicaid continue to have lower rates of guideline concordant care for both surgery and RAI.9,10 This emphasizes the critical need to identify barriers as well as solutions to providing equal, guideline-concordant care for all.Environmental ExposuresThe recognition of the role of environmental exposures and thyroid health continues to be an emerging area of focus. Many substances have endocrine-disrupting abilities, are ubiquitous, and have long lag times before causing disease, making them silent risk factors for many diseases including thyroid dysfunction and cancer. Polychlorinated biphenyls (PCBs) are man-made organic chemicals that are present in electrical, heat transfer, and hydraulic equipment as well as plasticizers in paints, plastics, and rubber. In a nested case–control study evaluating 742 persons with papillary thyroid carcinoma and 742 age-matched controls in the U.S. military between 2000 and 2013, PCB congeners were analyzed in specimens collected on average nine years before the development of papillary thyroid cancer in the cases. Significant associations between serum levels of four PCBs and development of thyroid cancer were found (p = 0.001).11 Research needs to continue in this arena, with ongoing vigilance about exposures in our environment that may play a role in increasing rates of thyroid disease and cancer.Artificial IntelligenceThe use of artificial intelligence (AI) in all aspects of medicine is on the rise, but only a minority reach adoption. This study focuses on the human–machine interaction and the adoption of AI specifically for radiologists reading thyroid ultrasounds.12 For the retrospective portion of the study, >1700 images were used to build the algorithm. Both junior and senior radiologists identified significant features that were associated with AI effectiveness in reading thyroid nodule ultrasound images. They optimized the AI by implementing AI assist only for significant features found to be helpful for AI effectiveness in the retrospective analysis. For the prospective portion of the study, junior and senior radiologists evaluated 300 images first with an entire AI platform and then with the assistance of optimized AI. AI reduced evaluation time and increased diagnostic accuracy. Junior radiologists were better with all AI, and senior radiologists were better with optimized AI. This study provides one example of how AI may be integrated into our clinical workflow to optimize diagnostic accuracy as well as enhance efficiency.Thyroid DysfunctionHyperthyroidism and toxic nodulesPersonalized therapy for hyperthyroidism is necessary to facilitate shared decision-making with patients to determine the most appropriate treatment. Options for both Grave's disease and toxic multinodular goiter (TMNG) are RAI therapy, surgical removal, and antithyroid drug (ATD) therapy. Long-term ATD therapy for TMNG was evaluated in a prospective, randomized controlled trial of 130 patients with TMNG randomized to RAI therapy or methimazole (MMI).13 After 12 years, 46% of the RAI group was euthyroid compared with 96% of the MMI group. In addition, in the MMI group, only two (4%) were hypothyroid and none had subclinical hyperthyroidism compared with the RAI group, where 46% were hypothyroid and 8% had subclinical hyperthyroidism. The median time to euthyroidism was also significantly different between groups with MMI of 4.3 ± 1.3 months compared with RAI at 16.3 ± 15 months (p < 0.001). MMI may be superior to RAI when considering nonsurgical therapies for TMNG when considering time to achieve and maintain euthyroidism.Thyroid and pregnancyAdequate maternal thyroid hormone levels are essential to maternal and fetal health. The TABLET trial was an observational trial evaluating whether low-dose levothyroxine reduced infertility and miscarriage rates in thyroid peroxidase antibody (TPO)-positive women.14 In a secondary analysis of TABLET trial participants, post-enrolment labs in the TABLET trial, euthyroid TPO-positive women were evaluated.14 Eighty-nine (9.5%) participants developed thyroid dysfunction after initially being euthyroid at enrolment. Eighty-four percent of these women had abnormal labs before achieving pregnancy, and 69% were within 3 months of enrolment, before conception. Pregnancy and live birth rates were significantly lower for women who were randomized to placebo who had untreated subclinical hypothyroidism. This study is important as it highlights the importance of repeat TSH testing in TPO-positive women who are trying to conceive, even if labs were normal within the previous three months.Thyroid NodulesThermal ablation of benign nodulesOver the past decade, there has been a significant increase in use of thermal ablation for treatment of thyroid nodular disease, and this article evaluated short-term outcomes of thermal ablation techniques for the treatment of benign thyroid nodules.15 This systematic review and Bayesian network analysis of 16 articles included 4112 patients who were followed for a mean of 11.9 months. Primary endpoints were volume reduction ratio (VRR) and symptom and cosmetic improvement. Secondary endpoints included voice disturbances, recurrent laryngeal nerve palsy, hypothyroidism, and nodule regrowth.There were no significant differences in primary outcomes on meta-analyses between any of conventional surgery (CS), radiofrequency ablation (RFA), microwave ablation (MWA), laser ablation (LA), and high-intensity focused ultrasound. On surface under the cumulative ranking area ranking for VRR, CS (98.49) ranked highest, followed by RFA (62.81) and LA (58.41). There were no significant differences on sensitivity analyses between any of the ablation arms with regard to symptom and cosmetic scores. For the vocal complications network, CS had an increased risk of complications compared with MWA (relative risk [RR] 3.68 [CI 1.38–11.89]) and RFA (RR 5.14 [CI: 1.74–19.32]). Overall, this study adds to the literature on ablation for benign thyroid nodules, also demonstrating that there remains a paucity of randomized controlled trials and prospective data.Follow-up of benign nodulesXiang et al. published a prospective observational study of 389 consecutive patients with solitary, solid, cytologically benign (Bethesda II) thyroid nodules ≥1 cm with at least 4 years of follow-up.16 They identified three distinct nodule growth patterns: (1) stagnant with growth rate of <0.2 mm/year, (2) slow with growth rate of 0.2–1.0 mm/year, and (3) fast with growth rate of >1 mm/year. Odds of fast growth was increased in persons with younger age <50 (OR 2.2) and larger nodules: OR 3.5 in nodules 2–2.9 cm and OR 4.4 in nodules ≥3 cm. Nodules without any growth in 3 years did not have further growth, and only 5% of stagnant nodules with <0.2 mm/year had growth. In multiple regression analysis adjusting for age, TSH, sex, and nodule diameter at baseline, the three-year growth pattern was the strongest independent predictor of long-term growth. Hence, the authors conclude that the three-year growth rate pattern can assist in predicting long-term growth and help determine long-term benign nodule follow-up recommendations.Preoperative molecular testingThe role of molecular testing of thyroid nodules preoperatively to inform aggressiveness of thyroid cancer and potentially guide therapy remains a hot topic this year. This retrospective cohort study evaluated 945 thyroid cancer patients who had preoperative molecular testing and had undergone thyroidectomy.17 Recurrences occurred in 17 (2.9%) patients of low risk, 20 (6.7%) patients of intermediate risk, and 13 (22.8%) patients of high risk of recurrence tumors (p < 0.001). They categorized all molecular mutations into molecular risk groups (MRG). The preoperative risk based on molecular test results (MRG) was compared with postoperative ATA risk of recurrence based on histopathology results. They found that the MRG in addition to tumor size was statistically equivalent to postoperative ATA risk of recurrence, suggesting that overall risk of recurrence may be able to be determined preoperatively, which could in turn affect surgical treatment decision-making. This is one of many studies evaluating the role of preoperative molecular testing in the evaluation and treatment of thyroid nodules and thyroid malignancies.Thyroid CancerGlucagon-like peptide-1 receptor agonist and thyroid cancerGlucagon-like peptide-1 receptor agonist (GLP-1RA) usage has dramatically increased in recent years for not only diabetes and cardiovascular disease but also weight loss, and providers from multiple specialties are now routinely prescribing these medications. GLP-1RA usage is contraindicated in those with a personal or family history of medullary thyroid carcinoma, and previous studies including meta-analyses have not shown an association between GLP-1RA usage and non-medullary thyroid carcinoma. This study is a nested case–control analysis using the French health care insurance system database evaluating persons with type 2 diabetes who had received second-line agents between 2006 and 2018 who also developed thyroid cancer.18Time of exposure to GLP-1RA factored in a 6-month lag time, and thyroid cancer cases were matched with up to 20 controls for age, sex, diabetes duration, and adjusted for confounders. Increased rates of non-medullary thyroid carcinoma were reported with 1–3 years of GLP-1RA usage (adjusted hazard ratio of 1.58). This database association study alone is not enough to change current thyroid nodule or cancer workup but given a significant percentage of the population are now using these drugs, this article highlights the importance of further research in this area.Thermal ablation for thyroid cancerIn addition to the rapid expansion of the literature on benign nodule ablation, clinical studies on ablation for papillary microcarcinoma are also becoming more widespread. Most of these studies evaluate the role of ablation for unifocal, low-risk papillary thyroid microcarcinoma (PTMC) and conclude that it may be a safe and effective alternative to active surveillance or surgery. However, two recent studies evaluated the use of RFA in (1) the treatment of multifocal PTMC compared with surgery (n = 97, 44 in the RFA group and 53 in the surgery group); and (2) the treatment of BRAF-positive PTMC (n = 60), concluding that it may be a valid management approach in these settings.19,20 Although these studies are retrospective and relatively small, they challenge our thinking and start to explore the role of molecular features in patient selection for ablation of PTMC.Active surveillanceActive surveillance (AS) protocols are well established in many parts of the world and provide an alternative management option to surgical intervention for patients with carefully selected PTMC. One criticism of AS is that patients who choose to observe may have higher surgical complication rates should surgical salvage be necessary for disease progression. The next article was designed to assess whether delaying surgery due to an AS protocol worsens postoperative outcomes compared with upfront surgery on the basis of more advanced disease.21 This comparative analysis of unfavorable events after immediate surgery (IS) versus delayed (conversion) surgery (CS) in patients with cT1aN0M0 PTMC included 1739 patients undergoing IS versus 242 (8.4%) undergoing CS. Significantly more patients in the IS group had coincident Grave's disease, whereas the mean tumor size was significantly larger in the CS group (9 mm vs. 8 mm, p < 0.001).Significantly more patients in the CS group had lateral neck dissection (5.8% vs. 0.5%, p < 0.001), whereas the converse was true for central neck dissection (94.2% vs. 99.5%, p < 0.001). There were no significant differences between groups in terms of postoperative complications (hypoparathyroidism, vocal cord paralysis, hematoma, or postoperative hormone supplementation). On intention-to-treat analysis, AS patients (n = 2896) overall had significantly fewer complications than IS patients in all domains analyzed, and death from thyroid cancer was 0% in both cohorts. Taken together, these results demonstrate that AS protocols do not increase subsequent surgical morbidity should salvage surgery be required and provide support for AS as a valid alternative management option to surgery for carefully selected PTMC.Surgical treatment de-escalation for well-differentiated thyroid carcinomaThis next group of articles focus on surgical treatment de-escalation in well-differentiated thyroid carcinoma (WDTC). The first article was a retrospective cohort study evaluating the use of thyroid lobectomy (TL) over TT in the treatment of large (>4 cm) well-differentiated follicular cell-derived carcinomas without vascular invasion.22 In this study, 56 patients underwent TT and 32 underwent lobectomy. Patients with high-risk histology including tall cell variant, extrathyroidal extension, vascular invasion, high-grade histology, infiltrative tumors, and positive resection margins were excluded. Demographics were similar between lobectomy and TT groups, with the exception of significantly more patients having additional foci of carcinoma in the TT group (46% vs. 9%, p < 0.001) and significantly more patients receiving radioactive iodine postoperatively in the TT group (59% vs. 0%, p < 0.001).Of note, 37% of the lobectomy cohort were follicular or oncocytic neoplasms. The median tumor size was 5 cm, and the median follow-up was 4.8 years. No recurrence—local, regional, or distant—was observed in the entire cohort with disease-specific survival and disease-free survival (both 100%). These results suggest that encapsulated WDTC (follicular thyroid carcinoma, oncocyticthyroid carcinoma, papillary thyroid carcinoma [PTC]) without other risk factors follows an indolent clinical course with negligible risk of recurrence regardless of tumor size. These results need validation in multicenter prospective trials that can also assess the impact of factors such as focal vascular invasion, microscopic positive margins, and molecular markers.Should cN1b disease alone be a deciding factor for TT? Our answer would frequently be “yes” to facilitate the administration of postoperative radioactive iodine. However, the next article evaluates the use of TL over TT in patients with unilateral clinical lateral (cN1b) neck metastases.23 This retrospective study from China used propensity matching to compare outcomes for patients having TL versus TT for unilateral T1 or T2 PTC over 17 years. Exclusion criteria included lymph node yield <20 or primary tumor >4 cm, aggressive histological variants, gross extra-thyroidal extension, metastatic node size of >3 cm, and distant metastases.There were 530 patients (265 propensity-matched pairs) included in final analysis. Structural recurrence occurred in 21 (7.9%) patients in the TL group and 17 (6.4%) patients in the TT group. Five-year recurrence-free survival (RFS) was 92.3% versus 93.7% for TL versus TT groups, respectively. On multivariate analysis, risk factors for reduced RFS were age ≥65 years and number of metastatic nodes. Of note, postoperative radioactive iodine use was low in this study (29% in TT group)—whether RFS in the TT group would have been lower had the postoperative iodine rate been higher is not clear. In addition, the role of molecular testing and histological features such as extranodal extension remain to be explored in future studies.Postoperative risk of recurrence assessmentCurrently, the ATA risk of recurrence is based on histopathologic variables determined postoperatively. Grani et al. performed a prospective cohort analysis using the Italian Thyroid Cancer Observatory database.24 They included 4773 patients: 52% low risk, 39% intermediate risk, and 8.6% high risk. They built a decision tree for risk index based on their response to therapy and developed models of prediction of risk. Features that significantly influenced the risk of recurrence included factors that are not currently in the ATA risk of recurrence criteria including age, sex, BMI, and other circumstances around diagnosis. Overall, higher age at diagnosis was associated with higher risk, and BMI also influenced outcome. This study emphasizes that patient factors likely contribute to the biologic behavior of tumors and need to be considered when determining overall risk of recurrence.Advanced and metastatic thyroid cancerThere have been multiple phase II and III trials in the last year for metastatic radiorefractory (RAIR) thyroid cancer. The Cosmic-311 trial showed that cabozantinib was effective in those with metastatic RAIR thyroid cancer who had progressed on lenvatinib or sorafenib and had a progression-free survival (PFS) of 11 months.25 In addition, in a phase II trial of patients with BRAF-mutated RAIR thyroid cancer, Busaidy et al. reported that the combination of a BRAF and MEK inhibitor (dabrafenib and trametinib) was not superior in efficacy to a BRAF inhibitor alone (dabrafenib).26 Leboulleux et al. published two phase II studies last year. The first was in BRAF-mutated RAIR thyroid cancer. They treated 24 patients with dabrafenib/trametinib, which resulted in an improvement in RAI uptake from 5% baseline to 95% post-treatment scan.The 12-month PFS was 82%, and the 24-month PFS was 68%.27 In contrast, redifferentiation therapy was not as robust in those with RAS mutations. The second study was a phase II study that evaluated trametinib for redifferentiation therapy in 11 patients with RAS-mutated RAIR thyroid cancer. RAI uptake increased from 30% at baseline to 60% post-treatment, but the overall response rate was 20% at 6 months.28 These articles highlight the promise of new therapies for patients with RAIR metastatic thyroid cancer. They also emphasize the need to personalize therapy to each patient as all RAIR patients do not respond equally to the available therapies. In addition, neoadjuvant BRAF-directed therapy for anaplastic thyroid carcinoma was shown to reduce morbidity and prolong survival.29 These results give hope of longer term survival to patients with a disease that was previously rapidly fatal, and it will be very interesting to see where this research leads over the next century.ConclusionsOver the past century, our knowledge and research in all realms of thyroidology have expanded dramatically. With this expansion has come challenges to long-held beliefs and alterations in management strategies that, 100 years ago, would have been difficult to envisage. As we move into this second century of the ATA, we carry with us both the wisdom of