Thyroid Nodules. Hossein Gharib, MD, MACP, MACE

Transcription

1 Thyroid Nodules Hossein Gharib, MD, MACP, MACE Professor of Medicine Mayo Clinic College of Medicine President Elect, American College of Endocrinology University Course January 2008 CP

2 Thyroid Nodule Usually discovered during careful neck exam Palpation is easiest but least sensitive method of nodule detection More common in women, I deficiency, and radiation exposure Most common endocrine disorder; worldwide 750 million people with goiter CP

3 Prevalence and Clinical Relevance Nodules are palpable in 5% Incidence 0.1% per year = 300,000 new nodules in U.S. Present in 50% by US = 100 million people in U.S. Importance: A common clinical problem Gharib H and Papini E: Endocrinol Metab Clin N Am 36:707, 2007 CP

4 Prevalence of Thyroid Nodules by Palpation ( ) or by Ultrasonography or Autopsy ( ) in Patients Without Radiation Exposure or Known Thyroid Disease Prevalence (%) Mazzaferri EL: NEJM 328:553, 1993 Age (years) CP

5 Initial Nodule Evaluation Should include Serum TSH measurement Thyroid FNA Thyroid US AACE Guidelines: Endocr Pract 12:63, 2006 CP

6 Increased Risk or Malignancy in Thyroid Nodule History of childhood head/neck radiation Family history of PTC, MTC or MEN2 Age <20 or >60 years Male sex Hard, fixed or enlarging nodule Cervical adenopathy CP

7 Calculation of Probability of Malignancy on Clinical Parameters and TSH Calculated Age Clinical TSH risk of Gender (yr) goiter type (mµ/l) malignancy (%) Female 40 Solitary nodule Female 40 Solitary nodule Female 40 Solitary nodule Female 40 Solitary nodule Female 40 Solitary nodule Female 40 Solitary nodule JCEM 91:4295, 2006 CP

8 Cancer Risk and Nodule Size 402 pt Non-palpable nodules US-FNA Nodule 10 mm 9.1% Malignant Nodule >10 mm 7.0% Papini E et al: JCEM 87:1941, 2002 CP

9 FNA Results Results Cytology (%) Benign (negative) 65 Malignant (positive) 5 Nondiagnostic 20 (unsatisfactory) Suspicious 10 (indeterminate) Probability of malignancy (%) <1 >99 <3 20 Gharib H and Papini E: Endocrinol Metabol Clin N Am 36:707, 2007 CP

10 Benign and Malignant Thyroid Cytology Colloid nodule PTC CP

11 Predictive Value of US Hypoechogenicity Microcalcifications Irregular margins Inc vascularity (CDF) Specificity Sensitivity Papini E: JCEM 87:1941, 2002 Mandel S: Endocr Pract 10:246, % CP

12 Suspicious Cytology Which is benign? CP

13 Suspicious FNA Reaspiration does not help and may be confusing Mayo Clin Proc, 1993 Immunohistochemical markers (tolemerase, HBME-1, galectin-3) have failed to regularly and reliably help Ann Intern Med, 2005 Radioisotope scan frequently shows a non- or hypofunctioning nodule Mayo Clin Proc, 1994 CP

14 Guidelines Suspicious FNA AACE, 2006 Repeat biopsy not recommended Currently, we recommend surgical excision of all indeterminate thyroid nodules ATA, 2006 At the present time, the use of specific molecular markers to improve the diagnostic accuracy of indeterminate nodules is not recommended If cytology is indeterminate or suspicious for neoplasm, a radioiodine thyroid scan should be considered ETA, 2006 Immunocytochemistry is neither sensitive nor specific enough and such techniques should be validated before routine use Correct Dx can be obtained only at histology CP

15 Surgical Treatment for FN AACE, 2006 Pt with suspicious nodules should be treated with lobectomy and isthmectomy or total thyroidectomy Frozen section should be performed but it is not useful in distinguishing benign from malignant nodules ATA, 2006 For follicular lesion lobectomy or total thyroidectomy should be considered ETA, 2006 The surgical procedure for FN should consist of lobectomy for a solitary nodule or NTTx for a MNG Many authors do not perform FS because of the high frequency of false-negative results; those authors suggest NTTx rather than the risk of 2-stage surgery of cancer found at postop histology CP

16 Conventional Wisdom Because hot or hyperfunctioning thyroid nodules are cellular tumors, FNA results in smears that usually are suspicious for follicular neoplasm (FN) CP

17 Cytology in Hot Nodule Among 22 pt with hot nodule 21 had benign FNA; 1 suspicious Liel Y: Acta Cytol, 1987 Among 50 pt with hot nodule, FNA was consistent with a colloid nodule in 90% Gharib H, unpublished data CP

18 Hot Nodule 3.0 cm right lobe nodule TSH 0.01 FNA necessary? CP

19 Is FNA Necessary in Hot Nodule? Single thyroid nodule or MNG and suppressed TSH; FNA not necessary AACE, 2006 I firmly believe that any palpable nodule should be aspirated Oertel Y: Endocr Pract, 2007.hyperfunctioning thyroid nodules are rarely if ever malignant Gharib H: Endocr Pract, 2007 CP

20 Unsuspected Thyroid Nodules Autopsy* Clinical** Normal thyroid palpation (821) Solitary palpable nodule (151) Nodular 49.5% US Single 12.2% MNG 37.3% Multiple nodules 48% Malignancy 4.8% 3 3 nodules 33% *Mortenson JD: JCEM,1955 **Tan B and Gharib H: Arch Intern Med, 1995 CP

21 When to Perform US AACE, 2006 Any pt with a palpable nodule; history of neck radiation; family history of PTC, MTC, or MEN2 Evaluation of unexplained cervical adenopathy ATA, 2006 Thyroid US should be performed in all patients with one or more thyroid nodules ETA, 2006 Currently, thyroid US is mandatory when a nodule is discovered at palpation CP

22 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 (1986 U.S.) Cochand-Priollet et al 132 Scan/US US (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 (2006 U.S.) CP

23 When to Consider US-FNA? For any size nodule with H/O radiation, FMTC or MEN2 For any size nodule with suspicious US features For nodule exhibiting extracapsular growth or cervical nodes irrespective of size AACE, 2006 CP

24 Author, yr CT in NTD Country Pt (no.) Tx (no.) MTC No. % Pacini, 1994 Italy 1, Rieu, 1995 France Vierhapper, 1997 Austria 1, Niccoli, 1997 France 1,167 1, Ham, 2001 Korea 1,448? CP

25 Would you measure serum CT in pt with NTD? ATA 3.6% Aust Endos 1% LATS 5.4% ETA 32% JCEM, 2005 BJS, 2003 CP

26 Expert Opinion on CT Measurement Based on our assumption, plasma CT determination in the assessment of thyroid nodule pt would appear to be highly favorable compared with a number of other accepted health interventions. Borget I et al: JCEM, 2007 The issue of CT testing in pt with thyroid disease remains, in our minds, controversial. It does not seem to us that the use of basal CT levels in the routine screening of pt with nodular thyroid disease is warranted without the ability to use gastrin stimulation as a confirmatory test. Hodall SP & Burman KD: JCEM, 2004 CP

27 When to Measure Serum CT AACE, 2006 Only if FNA or FHx suggests MTC ATA, 2000 No recommendation either for or against routine CT measurement ETA, 2006 Serum CT measurement is recommended in the initial diagnostic evaluation of thyroid nodules CP

28 T4 Suppressive Therapy Why Should It Work? Because TSH stimulates and maintains normal thyroid follicular cell function and growth, therefore its suppression should shrink nodules CP

29 T4 Suppressive Therapy 9 studies (596 pt) Changes in T4 and TSH after T4 indicated good compliance Nodule volume decreased significantly in only <20% of treated group T4 suppressive therapy led to a nonsignificant improvement in the rate of response to therapy (defined as 50% nodule volume reduction by US) (pooled RR 1.83, 95% CI ) Richter B et al: Endo Metab Clin N Am 31:699, 2002 CP

30 Expert Opinion We conclude that there is no certain proof that suppression of nodular thyroid with T4 is beneficial in most patients and its continued use should be discouraged Nodule shrinkage for its own sake, is a surrogate outcome that may not be of clinical value to patient or physician Gharib H and Mazzaferri EL: Ann Intern Med 128:386, 1998 CP

31 Guidelines AACE, 2006 Currently, routine T4 therapy in pt with thyroid nodules is not recommended Consider T4 therapy for pt in iodine deficiency, young pt with small nodule, nodular goiter without autonomy Avoid T4 therapy in most cases especially for large nodules, clinically suspicious lesions, postmenopausal women, pt with cardiac or systemic disease ATA, 2006 The panel does not recommend suppression therapy of benign thyroid nodules CP

32 Reaspiration of Cytologically- Benign Nodule is Not Necessary 116 pt with benign FNA Rebiopsy an all in one 16 had 3 FNAs Repeat FNA Identical in 105 (90%) Identical after 2 repeat FNA Changed colloid to cyst in 11 (9.5%) Eur J Endo 132:677, 1995 CP

33 Reaspiration of Cytologically- Benign Nodule is Necessary 235 pt with benign FNA Followed for average 2.9 yr Repeat FNA Benign in 204 (86%) Non-dx in 19 (8%) Suspicious in 11 (5%) Malignant in 1 (0.4%) Rebiopsy reduces false-negative rates Endocr Pract 7:237, 2001 CP

34 Follow-Up of Benign Nodules Wiersinga Wm, 1995 One might opt for repeat palpation and FNAC 1 yr after a benign FNA result ATA, 2000 Use US in follow-up (35%) AACE, 2006 Follow benign nodules ATA, 2006 Easily palpable benign nodules do not require US monitoring, but pt should be followed clinically at 6-18 mo intervals CP

35 Large Symptomatic MNG Treatment: T4, surgery or RAI? CP

36 Indications for Treatment of MNG Hyperthyroidism Goiter growth or suspicion of malignancy Local compressive symptoms Cosmetic concerns CP

37 Expert Opinion Rx LATS ATA ETA (%) (%) (%) No Rx T I Surgery JCEM 90:117, year-old woman gm asymptomatic nontoxic MNG CP

38 Treatment of MNG Thyroidectomy is preferred for most pt especially if prompt resolution of local symptoms or hyperthyroidism is necessary RAI is gaining popularity as alternative Rx to surgery RAI is safe, effective and can be used to treat small MNG (volume <100 ml) in pt high risk for surgery T4 Rx not effective in iodine-sufficient areas CP