Evaluation and Management of the Thyroid Nodule Oh, I get it, the TSH goes up and down UCSF Head and Neck Conference October 24, 2008 Peter A. Singer, M.D. Professor and Chief Clinical Endocrinology University of Southern California Thyroid? Big deal--you ve got one test (TSH), and one pill (L-T4) Jon Singer Thyroid Nodule Facts in the U.S. Prevalence (of palpable lesions) 5% = ~10,000,000 Incidence 0.1% = ~300,000 new palpable nodules per year Nodules on ultrasound 40% = ~112,000,000 Prevalence of cancer in nodules 5% = ~560,000 Incidence of cancer 0.004% = ~34,000 new cases per year 1
Thyroid Nodules Thyroid Cancer Incidence & Mortality 1973-2002 60 9 8 Incidence % prevalence 40 20 ultrasound palpation Rate per 100,000 7 6 5 4 3 2 1 Mortality 0 10 20 30 40 50 60 70 80 90 Age (years) Mazzaferri, NEJM, 1993 0 1973 1976 1979 1982 1985 1988 1991 1994 1997 2000 Year Davies, L. and Welch, H. G. : Increasing incidence of thyroid cancer in the United States, 1973-2002. Journal of the American Medical Association 295(18), 2164-2167. 2167. 5-10-2006 Types of Thyroid Nodules Benign (90+ %) Colloid, hyperplastic Hashimoto s Cysts Follicular adenoma Hurthle cell lesion Malignant (< 10%) Papillary cancer Follicular cancer Medullary cancer Anaplastic cancer Thyroid lymphoma Metastatic 60 Year Old Man with Thyroid Nodule History: Healthy man noticed non-tender swelling right side of neck while shaving. Feels mild increase in pressure with swallowing for the past 6 months; no change in voice; no XRT or FH thyroid ca. Symptomatically euthyroid. PMH: HTN Exam: 4 cm oblong, firm, mobile right thyroid nodule. What is the likelihood of Ca? 2
Degree of Clinical Concern for Carcinoma in a Thyroid Nodule Based on History and Physical Exam Less Concern Chronic stable exam Evidence of a functional disorder (eg Hashimoto s toxic nodule) Multinodular gland without dominant nodule? More Concern Age <20, >60 years Males Rapid growth, pain History of radiation therapy Family history thyroid ca Hard, fixed lesion Lymphadenopathy Vocal cord paralysis Size > 4 cm Tracheo-esophageal esophageal pressure (eg stridor, dysphagia) Cancer Risk in Solitary or Multiple Thyroid Nodules Cancer rate (%) Individuals Definition FNA 1 Multiple Study (yr, location) (no.) of nodularity technique nodule nodules McCall et al 442 Scan/Hx Palpation 17 13 (1986 U.S.) Cochand-Priollet et al 132 Scan/US US 13 14 (1994 France) Sachmechi et al 443 Scan Palpation 8 10 (2000 U.S.) Marqusee et al 156 US US 7 9 (2000 U.S.) Papini et al 494 US US 9 6 (2002 Italy) Deandrea et al 420 US US 6 7 (2002 Italy) Frates et al 1,985 US US 14.8 14.9 (2006 U.S.) CP1268220-37 60 year old man with nodule workup? EVALUATION OF THE THYROID NODULE THE EXPERTS OPINIONS Blood tests? -TSH 2.6 miu/ml -TPO not done -Tg not indicated Imaging? -nuclear scan? -US? *ATA Membership Survey (%) FNAB 96 Scan 56 US 28 TSH 93 Antibodies 31 Tg 14 CBC 12 Chem Panel 10 *Solomon B, et al JCEM 1996;81:333 (39 y/o with 2 cm nodule) ** ATA Standards of Care Committee Yes It all depends Yes It all depends No Not mentioned Not mentioned Singer PA, et al Arch Int Med 1996;156:2165 3
IMAGING OF THE THYROID NODULE THE EXPERTS OPINIONS (%) ATA 1996 ATA 2000 ETA 2000 ATA 2006 Scan 56 23 66 prn US 28 34 80 yes Scan + US -- 13 58 -- JCEM 81:333, 1996 JCEM 85:2493, 2000 Thyroid 18: 2006 Adenomatous goiter Initially uniform hypertrophy and hyperplasia Focal areas of colloid accumulation 4
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Advantages of Ultrasound in Evaluation of Nodules Delineates lesion with unclear findings on palpation Detects nonpalpable lesions (esp with XRT) More accurate follow-up More accurate FNA, esp with cystic lesions US Characteristics of Thyroid Nodules Echogenicity (hypo*-, hyper-, iso-) Calcifications (micro*-, dense, eggshell-b9) Margins (infiltrative, spiculated, irregular*, well- defined) Halo (absent*, irregular*, present and regular) Colloid (comet tails) Vascularity (intranodular*, peripheral, absent, spoke and wheel) Shape (taller than wide*) *associated with thyroid cancer Ajuga et al, JCU 1996;24:139 Papillary CA 6
Papillary CA Cystic Papillary CA Papillary Carcinoma Comet Tail Artifact = Colloid 7
Spoke & Wheel = Follicular Lesion? 60 Year Old Man with Thyroid Nodule FNA (by palpation) done FNA Classification and Results Results Cytology (%) Benign (negative) 65 Malignant (positive) 5 Nondiagnostic 20 (unsatisfactory) Suspicious 10 (indeterminate) Probability of malignancy (%) <1 >99 <3 20 FNAB Imperatives Must have adequate material if if inadequate, repeat. Must have experienced cytopathologist Examine all of your slides with the cytopathologist! Gharib H and Papini E: Endocrinol Metabol Clin N Am, 2007 CP1268220-17 8
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Nondiagnostic Rates of Palpation FNA and US FNA Palpation FNA USGFNA Takashima, 1994 19% (12/62) 4% (10/256) Carmeci, 1998 16% (60/370) 7% (9/127) Danese, 1998 9% (433/4986) 4% (167/4697) 60 year old man with thyroid nodule FNA result follicular lesion now what s the likelihood of Ca? Hatada, 1998 30% (28/94) 17% (12/72) Takashima, J Clin Ultrasound1994; Carmeci, Thyroid, 1998; Danese, Thyroid 1998; Hatada, Am J Surg, 1998 10
60 year old man with thyroid nodule 60 Year Old Man with Thyroid Nodule So, what do you advise? lobectomy? total tdx? Because of high degree of suspicion of Ca, total thyroidectomy recommended. He opted for lobectomy Right lobectomy = minimally invasive follicular CA; foci of papillary CA 11
60 year old man with thyroid nodule Now what? Completion surgery no tumor Papillary Thyroid Cancer Tumor Size in USA Rate per 100,000 4.0 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0 1988 1990 1992 1994 1996 1998 2000 2002 Year Davies, L JAMA295(18), 2164-2167. 2167. 5-10-2006 0-1.0 cm 1.1-2.0 cm 2.1-5.0 cm >5.0 cm 49% 1cm 87% 2cm What About The Thyroid Incidentaloma? PTC found in 7/119 (6%) of USG FNA for incidentally detected lesions > 1 cm (Hagag, et al. Thyroid 1998; 8:989) PTC in 23/450 (5%) of non-palpable nodules, most <1.5 cm. Non-diagnostic FNA in 30% of lesions <1 cm (Leenhardt, et al. J Clin Endocrinol Metab 1999; 84:24) 162 pts with PTC dx by USG FNA; avg nodule size 6.9 mm; half had f/u for 3-4 yrs. -70 % stable or reduced in size -1.2 % developed LN mets (Ito, et al. Thyroid 2003; 13:381) 12
Proposed 2008 ATA Guidelines for FNA <1 cm: high risk Hx, or abnormal Cx nodes >1 cm: hypoechoic and solid, or microca++ 1.5-2 cm: solid and iso/hyperechoic >2cm: predominantly cystic or spongiform without suspicious US findings Pure cystic: not indicated Spongiform nodule: may defer Multiple nodules: Prioritize based on above If multiple similar on US, coalescent nodules w/o suspicious US features, FNA the largest. Here s What s New--Is Serum TSH a Predictor for Malignancy? Prospective study (1984-2002) of 1500 pts (1304 female, 196 male, mean age 47.8 yrs) with thyroid enlargement, evaluated with TSH, FNAB, histology. Clinical exam: diffuse goiter (12 %), single nodule (57 %), MNG (31 %). Open bx or surgery (for FNA malignant, suspicious, or obstructive sxs) in 553 pts (37 %). Boelaert K, et al. JCEM 2006; 91:4295 Risk Factors for Malignancy Serum TSH - a new risk factor for thyroid cancer in nodules Boelaert J et al JCEM 91:4295, 2006 Sensitivity and specificity of FNA to predict malignancy 88 % and 84 %. Independent risk factors were younger and older age, males, and solitary nodules by palpation. Risk for malignancy higher with baseline TSH (> 0.9 mu/l) Boelaert K, et al. JCEM 2006; 91:4295 Prevalence (%) of malignancy 35 30 25 20 15 10 5 0 * ** *** p < 0.05 p < 0.01 P < 0.001 * n=27 < 0.4 0.4-0.9 1.0-1.7 1.8-5.5 > 5.5 TSH ** n=182 n=322 n=336 n=316 *** 13
Frequency of Cancer According to Age Prevalence of Malignancy/TSH 25 50 45 20 40 Prevalence (%) 15 10 5 Malignancy (%) 35 30 25 20 15 10 0 <20 20-29 30-39 40-49 50-59 60-69 70-79 >80 Age (years) 5 0 <0.06 0.06-0.39 0.40-1.39 1.40-2.4 2.50-4.99 >5.00 Boelaert K, et al. JCEM 2006; 91:4295 Serum TSH (miu/l) Haymart MR, et al. JCEM 2008; 93: 809 Finally, when are US and FNA not indicated? 14
OK, I get it now can we discuss $$? 15