Thyroid Nodule Evaluation and Management Judith N. Green, M.D. Clinical Associate Professor
Evaluation and Management of Thyroid Nodules Epidemiology of Thyroid Nodules Evaluation of Thyroid Nodules Clinical evaluation Lab and Radiographic analysis Fine needle aspiration Management of Thyroid Nodules Algorithm
Prevalence of Thyroid Nodules Increases with age More common in women 4.3 to 1 versus 1.2 to 1 Palpation 6.4% of women and 1.5% of men in Framingham study had nodules in 30-59 year age range Ultrasound 30-50% of patients in several series Usually multiple
Thyroid Nodule Detection: Ultrasound versus Palpation 55% of nodules >/= 1.5 cm not palpable Schneider, et al JCEM 1997:82:4020 33% of patients with thyroid cancer nodule not palpable Thyroid nodule found fortuitously on ultrasound, surgery or autopsy < 40 years old: age 10 = % detected i.e., at age 30, 20% detected 40 60 years old: age 15 = % detected i.e., at age 50, 35% detected > 60 years old: age 20 = % detected i.e., at age 70, 50% detected NEJM 1993:328-553
Ultrasound in Nodular Thyroid Disease Cancer found in 7% of solitary nodules Cancer found in 9% of multinodular goiters Unclear if long term outcome affected by early detection Ultrasound should be considered for all patients with suspected nodules Marquisee et al. Ann Int Med 2000;133:696
Frequency of Cancer in Nodules based on Ultrasound Characteristics 3483 nodules found in 1985 patients FNA if nodule > 1.0 cm in at least 2 dimensions 14.8% rate of cancer Higher rate of cancer in men with nodules Composition of nodule Size did not predict malignancy Frates M, eta. J Clin Endocrinol Metab: 2006: 91:3411-3417
Epidemiology Nodules removed surgically 42-77 % Colloid nodules 15-40% Adenomas 8-17% Carcinomas
Prevalence by Carcinoma Type Papillary - 70% Follicular - 15% Medullary - 5-10% Anaplastic - 5% Lymphoma - 5% Metastatic rare Breast, lung, renal, GI, melanoma
Why Evaluate Thyroid Nodules Thyroid cancer Proper treatment Hyperthyroidism Treat hyperthyroidism to avoid cardiac, bone or other complications TSH < 0.1 mu/l Local symptoms Compression of trachea or esophagus
Clinical Evaluation High risk factors for thyroid cancer Head and neck irradiation (including XRT for breast) Family history of thyroid cancer (Medullary, Gardner s, Cowden Syndrome) Dysphonia or dysphagia Rapid growth Associated neck masses 71% of these patients with one or more risk factor had thyroid cancer Hamming, et al. Arch Intern Med. 1990;150:113-116
Physical exam Complete head and neck exam Bimanual palpation of thyroid gland and cervical chain of lymph nodes Laryngoscope: Evaluate for vocal cord mobility and symmetry
Anatomy Thyroid gland includes 2 lobes and isthmus. Isthmus: conical or pyramidal shape
Laboratory Evaluation Obtain serum TSH in all patients with nodules If TSH is low, measure free T4 and T3 May be an autonomous nodule or toxic multinodular goiter May be a cold nodule in the setting of hyperthyroidism High TSH would suggest Hashimoto s or other thyroiditis (thyroid antibody may be useful)
Initial Radiographic Evaluation: Ultrasound If TSH is normal or elevated then ultrasound is next step Identifies multiple nodules Used to improve accuracy of FNA Characterizes nodules to stratify FNA
Other Thyroid Imaging CT or MRI of Neck Not useful for evaluation of intrathryoidal nodules Useful for evaluation of local compressive symptoms
Nuclear medicine thyroid scanning Performed to evaluate nodule function Technetium-99 versus Iodine 5% of nodules that trap Tech-99 are cold on iodine scan Most useful in patients with hyperthyroidism Before routine use of FNA Scan + U/S were tests of choice for evaluation of nodules
Thyroid Radionuclide Scans 99m Tc Cold Nodule Normal Thyroid Uptake
Solitary Autonomous Hot Nodules Hot Nodules Suppression of remaining Gland Very low risk of malignancy FNA generally not required Treatment: Radioiodine or Surgical Lobectomy
Indications for FNA Nodules greater than 1 cm Nodules with suspicious characteristics on ultrasound Irregular margins Calcifications Intranodular hypervascularity
FNA: Cytopathology of Nodules Clinical utility of FNA Easy to perform, cost effective and welltolerated Accurately identifies papillary carcinoma in most cases Accurate for benign diagnoses False positive rate - 1% False negative rate - 5% Grant CS, et al. Surgery. 1989:106:980-986.
FNA: Cytopathology of Thyroid Nodules Bethesda Classification Insufficient Benign (~1% malignant) Atypical/Follicular Lesion of Undetermined Significance (AFLUS) (5-20% malignant) Follicular Neoplasm (20-30% malignant) Suspicious for Malignancy (~70% malignant) Malignant (>90% malignant) Baloch Z, et al. Cytojournal. 7; 2008.5-6
FNA: Cytopathology of Nodules Limitations of FNA Insufficient or indeterminate in 21-31% Unable to distinguish follicular carcinoma from adenoma Hashimoto s versus lymphoma Somewhat dependent on skill Sampling error if < 1cm or > 4 cm Difficult in predominately cystic lesions Gharib H. Thyroid Today. 1997;XX(1). Burch HB, et al. Acta Cytologica. 1996;40:1176-1183.
Follicular Carcinoma Vascular invasion must be present FNA is inadequate to make this diagnosis
Future Directions for FNA Molecular testing Oncogene amplification BRAF, RAS, RET/PTC
Therapies for Thyroid Nodules Surgery Hemithyroidectomy (risk recurrence in multinodular goiter) Subtotal or total thyroidectomy L-thyroxine Considered for nodules in hypothyroid and euthyroid patients I-131 Considered for nodules in hyperthyroid and euthyroid patients
Treatment of Diffuse or Multinodular Goiter Suppressive Therapy Antithyroid Medications: Propylthiouracil and Methimazole I-131 Surgical Therapy
Multinodular Goiter FNA of Dominant Cold Nodules Carries same risk of cancer as solitary cold nodule Surgery indicated for abnormal or indeterminate FNA and local compressive symptoms Radioiodine - if hyperthyroid, iodine uptake is high or if poor surgical risk Belfiore, et al. Am. J. Med. 1992;93:363-369.
Use of I-131 for Goiter Non Toxic Goiter Reduced 36% after 3 months Reduced 72% after 3 years 36% hypothyroid by 3 years Bonnema et al. Eur J Endocrinol 2004;150:439 Euthyroid and hyperthyroid patients Thyroid volume reduced 34-40%, tracheal deviation reduced 20% and narrowest lumen increased 36% at 1 year 14% hypothyroid after 2 years Huysmans, et al. Ann Intern Med 1994;121:757 De Klerk, et al. J Nucl Med 1997;38:372
Surgery for Multinodular Goiter Subtotal Thyroidectomy Recurrence rates 10+% per decade Maurer et al. J Nucl Med 1999;40:1313 Thus, total thyroidectomy by experienced surgeon for any patients with bilateral nodules or bilaterally enlarged thyroid is treatment of choice No prospective data demonstrates that TSH suppression decreases goiter or nodule recurrence rate after subtotal thyroidectomy except in radiated population Mandel, et al. Ann Intern Med 1993;119;492 Maurer et al. J Nucl Med 1999;40:1313
Management of Functioning Thyroid Nodules Solitary Autonomous Nodules Treatment for patients with TSH <0.1 mu/l Radioactive Iodine No surgical risk Nodule may remain Incidence of hypothyroidism Hemithyroidectomy Surgical risk Nodule is gone Low incidence of hypothyroidism
Management of Benign Euthyroid Nodules Thyroxine suppression By reducing TSH levels, nodule growth will be inhibited or even shrink Problems: Not all nodules are alike and may respond differently Well-differentiated cancers express TSH receptors Long-term therapy may have significant side effects
Thyroxine Suppression Side-effects Bone loss in post menopausal women Arrhythmia including Atrial Fibrillation Cardiac hypertrophy Not shown in all studies but may be improved by Beta blockers Uzzan B, et al. J Clin Endocrinol Metab. 1996;81:4278-4289
Management of Thyroid Carcinoma Surgical options Total thyroidectomy Thyroid lobectomy benign or inconclusive frozen section Near total thyroidectomy Preserve minimal thyroid tissue, RLN, parathyroid glands. +/- Neck dissection N0 Elective neck dissection is not indicated for WDTC N+ - Level II-V and VI neck dissection Level I if clinically + nodes - rare
Intraoperative Anatomy
Complications of Total Thyroidectomy Total Thyroidectomy Laryngeal nerve injury: 3% Hypoparathyroidism: 2.6% Sosa et al. Ann Surg 228:320;1998 Subtotal Thyroidectomy Laryngeal Nerve injury: 1.9% Hypoparathyroidism: 0.2% Udelsman et al. World J Surg 20:88;1996. Higher rates with re-operation Maurer et al. J Nucl Med 1999;40:1313 Surgeons performing >100 thyroidectomies had a 4 fold lower complication rate than those performing <10 cases annually
Special Circumstances Pregnancy Pregnancy increases risk of nodules 9.4% in nulliparous women 25% in women who have been pregnant Attributed to increased renal iodide excretion and basal metabolic rate Nodules presenting during pregnancy 30 patients, 43% cancerous HCG may be growth promoter
Special Circumstances Recommendations: Pregnancy Surgery done for cancer before end of 2 nd trimester or post-partum Women with a history of thyroid cancer need to be counseled about the increased risk
Special Circumstances Children Nodules more likely to be cancer than in adults 10% malignant in ages <21 years More likely to present with neck metastases
Thyroid FNA: Key Points Accurate for Benign Lesions Accurate for Papillary Thyroid Cancer Unable to distinguish Benign Follicular adenoma from carcinoma
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