1. Update in Evaluation & Management of Thyroid Nodules & Cancer BY PROF/ GOUDA ELLABBAN 2. 29 y.o. woman with thyroid nodule Palpable nodules in 6% women & 2% men Sonographic nodules in ~1/3 women 3. 29 y.o. woman with thyroid nodule Clinical Issues Is it too large? Is it too active? Is it malignant? 4. Evaluation of the Thyroid Nodule Patient History Patient gender Patient age 5. Evaluation of the Thyroid Nodule Patient History Patient gender Patient age Boelaert, et al. J Clin Endocrinol Metab. 2006 Jul 25; [Epub ahead of print] CancerPrevalence(%) Age (yrs) 6. Evaluation of the Thyroid Nodule Patient History Growth pattern Local neck symptoms Persistent hoarseness or cough Hemoptysis [Pain, dysphagia, dyspnea] Symptoms of thyroid dysfunction Hyperthyroid = ? Toxic adenoma Hypothyroid = ? Autoimmune thyroiditis 7. Evaluation of the Thyroid Nodule Patient History Symptoms of metastatic disease Other cervical masses Chest pain or dyspnea Bone pain Neurological symptoms 8. Evaluation of the Thyroid Nodule Patient History Symptoms of metastatic disease Symptoms of hypercalcitoninemia Flushing Diarrhea Pruritus 9. Evaluation of the Thyroid Nodule Patient History Symptoms of metastatic disease Symptoms of hypercalcitoninemia Features of MEN IIa or IIb Pheochromocytoma (or severe HBP, paroxysmal symptoms, adrenal tumor) Hyperparathyroidism (or hypercalcemia or renal stones) 10. Evaluation of the Thyroid Nodule Patient History Symptoms of metastatic disease Symptoms of hypercalcitoninemia Features of MEN IIa or IIb Symptoms of primary extrathyroidal cancer Lung Breast Renal cell 11. Evaluation of the Thyroid Nodule Patient Other Relevant History Therapeutic cervical irradiation Childhood tonsils, adenoids, thymic enlargement. hemangiomas Adolescent acne Young adult lymphoma 12. Evaluation of the Thyroid Nodule Patient Other Relevant History Therapeutic cervical irradiation Family history Benign nodules Medullary cancer Other MEN II features Social history Place of birth: iodine deficient? 13. Evaluation of the Thyroid Nodule Patient Physical Exam Nodule characteristics Size Consistency Tenderness 14. Evaluation of the Thyroid Nodule Patient Physical Exam Nodule characteristics Size Consistency Tenderness Fixation Cervical adenopathy 15. Evaluation of the Thyroid Nodule Patient Physical Exam Nodule characteristics Thyroid status: or Features of MEN IIb Submucosal neuromas Marfanoid body habitus Sign of primary extrathyroidal cancer 16. Evaluation of the Thyroid Nodule Patient Laboratory Testing TSH Excludes hyperthyroidism Potentially due to autonomous nodule Identifies hypothyroidism Potentially due to autoimmune thyroiditis 17. Evaluation of the Thyroid Nodule Patient Laboratory Testing Boelaert, et al. J Clin Endocrinol Metab. 2006 Jul 25; [Epub ahead of print] CancerPrevalence(%) Serum TSH (mU/L) 18. Evaluation of the Thyroid Nodule Patient Laboratory Testing Universal use: TSH Selective use: Calcitonin Antithyroid antibodies Not helpful: Thyroglobulin Future Blood Tests for Thyroid Cancer mRNA for TSH receptor and Tg BRAF mutant thyroid cells Thyroid-specific methylated genes 19. Evaluation of the Thyroid Nodule Patient Radionuclide Imaging 20. Evaluation of Thyroid Nodule Patient Radionuclide Scan Possibilities Cold 21. Evaluation of Thyroid Nodule Patient Radionuclide Scan Possibilities Cold Hot TSH receptor structure Activating mutation 22. Evaluation of Thyroid Nodule Patient Radionuclide Scan Possibilities Cold Warm Hot 23. Cold nodules usually benign... but could be cancer Hot nodules never cancer and revealed by low TSH Warm nodules treated as cold Usually delay, inconvenience, & cost for minimal diagnostic information Evaluation of Thyroid Nodule Patient Limitations of Radionuclide Scan 24. Evaluation of the Thyroid Nodule Patient Sonographic Imaging 25. Confirms the mass is thyroidal May identify features suspicious for cancer Irregular border Calcifications Regional adenopathy Often reveals additional nodules Guidance for fine needle aspiration Evaluation of Thyroid Nodule Patient Value of Sonography 26. Solid lesions are usually benign... but could be cancer Complex cysts are usually benign... but could be cancer Small simple cysts are almost always benign Delay, inconvenience, & cost for minimal diagnostic information Evaluation of Thyroid Nodule Patient Limitations of Sonography 27. Evaluation of the Thyroid Nodule Patient Fine Needle Aspiration 28. Cytologic Evaluation of Thyroid Nodules Benign Nodules 97-98% sensitivity for cancer detection Justifies initial observation in virtually all patients 29. Cytologic Evaluation of Thyroid Nodules Malignant Nodules 95% true positives Justifies surgery in virtually all patients 30. Comparison of Diagnostic Approaches Costs 0 58 115 173 230 288 FNA First TSH First Radionuclide Scan First MedianCost($) * p < 0.0001 for all comparisons 31. 0 5 9 14 18 FNA First TSH First RNS First MedianTimeto Diagnosis(days) * p < 0.0001 for all comparisons Comparison of Diagnostic Approaches Time to Diagnosis 32. Thyroid Nodule Management TSH Suppression Therapy 33. Thyroid Nodule Management TSH Suppression Therapy 34. 64 y.o. man with thyroid nodule Referred for thyroid nodule Mild discomfort with swallowing, but no other local symptoms or evident thyroid dysfunction. PE: Clinically euthyroid man with 3.5 cm firm smooth mobile nodule with no regional adenopathy FNA performed elsewhere 35. 64 y.o. man with thyroid nodule Previous FNA: hemosiderin-laden macrophages, no malignant cells seen Previous FNA cytology slides requested. No malignant cells seen = no thyroid epithelium seen 36. Evaluation of Thyroid Nodules Cystic Nodules 37. Evaluation of Thyroid Nodules Cystic Nodules 38. 64 y.o. man with thyroid nodule Previous FNA: hemosiderin-laden macrophages, no malignant cells seen Previous FNA cytology slides requested. No malignant cells seen = no thyroid epithelium seen Repeat FNA with sonographic guidance Cytology: papillary thyroid cancer. 39. Evaluation of Thyroid Nodules Cystic Nodules FNA cytology is more often inadequate. Sonographically guided FNA may improve yield in some cases. Fluid reaccumulation is common, and unpredictable. Surgical indications: No benign cytological diagnosis in complex cyst Nodule size and/or associated symptoms 40. Indeterminate Nodule Surgery Surgery for Thyroid Nodules Approach to Management Observation (on L-T4) Growth 41. Indeterminate Nodule Surgery Bilateral Tx Unilateral lobectomy Surgery Surgery for Thyroid Nodules Approach to Management Observation (on L-T4) Growth ? 42. Indeterminate Nodule Surgery Bilateral Tx Unilateral lobectomy Surgery Cytologic Evaluation of Thyroid Nodules Approach to Management Observation (on L-T4) Growth Less risk of RLN and parathyroid injury Avoids thyroxine requirement if nodule is benign 43. Indeterminate Nodule Surgery Bilateral Tx Unilateral lobectomy Surgery Cytologic Evaluation of Thyroid Nodules Approach to Management Observation (on L-T4) Growth Optimal procedure for thyroid cancer, avoiding potential 2-stage thyroidectomy Greater assurance there will be no future nodule recurrence 44. Cytologically Indeterminate Thyroid Nodules Clinical Criteria for Decision-Making Worrisome features larger nodules fixation younger patients males Schlinkert RT, et al. Mayo Clin Proc 1997;72:913-6; and others. Reassuring features females multinodularity 45. What operation should the patient have? Considerations Clinical probability of cancer Cytological nuances Contralateral nodularity Patient preference* Not intraoperative frozen section 46. Otherwise asymptomatic No known risk factors for cerebrovascular, neurological, or ophthalmologic disease. PE: Neurologically normal woman with no carotid bruit. Carotid ultrasound requested. 56 y.o. woman with intermittent blurred vision 47. Normal carotids 1.4 x 1.2 cm left lobe nodule, mainly solid, with four more cystic lesions, all 1.5 cm. TSH Sonographically-guided FNA Thyroid Incidentalomas Diagnostic Assessment 50. Conclusions Evaluation of Thyroid Nodules Palpable thyroid nodules are common (2-6%) and sonographic nodules are even more common (~30+%), but only 5-10% are cancers. Clinical evaluation of nodule patients is seldom diagnostic. Cytological evaluation of FNA material is most cost- effective approach to differential diagnosis. Surgery remains the court of last resort for a minority of patients. 51. 1.7 cm papillary thyroid cancer, with two additional 3 mm foci Tumor extending to resection margin 1 of 4 resected nodes positive Remnant ablation considered 32 y.o. NY attorney 52. Thyroid Cancer Approach to Diagnosis & Management Thyroid nodules Thyroid cancersBenign lesions Thyroidectomy T4 Therapy & Monitoring 131I Remnant Ablation ? 53. Thyroid Cancer Management Arguments for Remnant Ablation Lower risk of recurrent cancer Retrospective studies Nonrandomized prospective trials Ablation of residual thyroid tissue to increase the specificity of future TSH-stimulated monitoring with radioiodine scanning and serum thyroglobulin 54. Thyroid Cancer Management Monitoring for Recurrence TPO I- I-Na+ I - I- Na + NIS TSH-R AC G K + Na+ Na+ K + Tg 55. Extrathyroidal invasion Nodal and extracervical metastases Aggressive histologies PTC: Columnar and Tall Cell, and Insular Variants FTC: Angioinvasive Multifocality ? Thyroid Remnant Radioablation Criteria 56. Thyroid Cancer Management TSH Suppression Therapy 57. Thyroid Cancer Management TSH Suppression Therapy 58. Impact of TSH Score on Overall Survival of High-Risk Stage III & IV Patients Jonklaas et al. In press, 2006 Mean TSH 0.1 mU/L* P=0.01 *Extrapolation to typical TSH assay 59. Impact of TSH Score on Overall Survival of Stage II Patients Jonklaas et al. In press, 2006 P0.5 mU/L* Mean TSH