Nodular Thyroid Disease

Transcription

1 1 Nodular Thyroid Disease Michael T. McDermott MD Director, Endocrinology and Diabetes Practice University of Colorado Hospital Objectives Review the differential diagnosis of thyroid nodules Discuss current evaluation strategies for thyroid nodules Explain management approaches to benign, indeterminate and malignant thyroid nodules

2 2 Case History A 26 year old woman recently noted a lump in her neck. She has had no neck pain, dysphagia, hoarseness or dyspnea. PE: BP 112/68 P 68 Ht 5 9 Wt 132 lb. Thyroid: 1.5 cm nodule in left lobe; non-tender and freely movable Neck: no cervical lymph nodes Lab: TSH 0.9 mu/l (nl: ) Thyroid Nodules Prevalence Palpation: 4-7% Ultrasound: 13-40% Autopsy: 50%

3 3 Benign Colloid nodule Thyroid adenoma Thyroid cyst Thyroiditis Lymph node Parathyroid adenoma Thyroid Nodules Differential Diagnosis Malignant Papillary carcinoma Follicular carcinoma Anaplastic carcinoma Medullary carcinoma Thyroid lymphoma Metastatic carcinoma Thyroid Nodules History - Increased Cancer Risk Gender: Male > Female Age: Young > Old Family History: Papillary, Medullary Radiation Therapy: Head and Neck Symptoms: Dysphagia or Hoarseness

4 4 Thyroid Nodules Physical Exam - Increased Cancer Risk Nodule Size: > 3 cm Nodule Consistency: Firm, Fixed Lymph Nodes: Present in Neck Thyroid Nodules Lab Testing Serum TSH: <.01 g Likely Benign Thyroid Ultrasound Size and Features Fine Needle Aspiration (FNA) False Negative: 5-10% False Positive: Rare

5 5 1. Measure serum TSH in the initial evaluation of a patient with a thyroid nodule. If the serum TSH is low, a radionuclide thyroid scan should be performed using either technitium pertechnetate or I-123. Recommendation Rating: A 2. Thyroid ultrasound should be performed in all patients with known or suspected thyroid nodules. Recommendation Rating: A

6 6 5. a) FNA is the procedure of choice in the evaluation of thyroid nodules. Recommendation Rating: A b) US Guided FNA is recommended for nodules that are non-palpable, predominantly cystic, or located posteriorly in the thyroid lobe. Recommendation Rating: B 12. a) If two or more thyroid nodules > 1 cm are present, those with a suspicious sonographic appearance should be aspirated preferentially. Recommendation Rating: B b) If none have a suspicious sonographic appearance and multiple sonographically similar coalescent nodules with no intervening normal parenchyma are present, the likelihood of malignancy is low and it is reasonable to aspirate the largest nodules only and observe the others with serial US examinations. Recommendation Rating: C

7 Thyroid Nodules Ultrasound: Cancer Prediction Sensitivity Specificity Microcalcifications 40% 90% Absence of halo 66% 46% Irregular margins 64% 84% Hypoechoic 83% 49% Increased blood flow 70% 65% MicroCa + Irreg marg 30% 95% MicroCa + Hypoechoic 28% 95% FNA 92% 84% Thyroid Nodules FNA Cytology: Cancer Prediction Malignant: Very High Risk of Cancer Benign: Very Low Risk of Cancer Indeterminate: 20-30% Risk of Cancer 7

8 8 7. Surgery is recommended if a cytology result is diagnostic of papillary thyroid cancer. Recommendation Rating: A 8. a) Molecular markers (BRAF, RAS, RET/PTC, PAX3-PPAR, Galectin-3) may be considered for patients with indeterminate FNA cytology to help guide management. Recommendation Rating: C

9 9 Malignancy Panel BRAF Ras Ret/PTC PAX8 - PPARg Thyroid Nodules Molecular Diagnosis Benignancy Panel Exon Array High PPV Inform (Asuragen) High NPV Affirma (Veracyte) 8. b) The use of FDG-PET to improve diagnostic accuracy of indeterminate nodules cannot be recommended for or against. Recommendation Rating: I

10 A low or low normal serum TSH concentration may suggest the presence of autonomous nodule(s). A technitium pertechnetate or I-123 scan should be performed and directly compared to the US images to determine functionality of each nodule > cm. FNA should then be considered only for those isofunctioning or nonfunctioning nodules, among which those with suspicious sonographic features should be aspirated preferentially. Recommendation Rating: B 9. If the cytology reading reports a follicular neoplasm, a I-123 thyroid scan may be considered, if not already done, especially if the serum TSH is in the low normal range. If a concordant autonomously functioning nodule is not seen, lobectomy or total thyroidectomy should be considered. Recommendation Rating: C

11 11 Thyroid Nodules Thyroid Scan Hot Nodule Almost Never Cancer Thyroid Nodules Thyroid Scan Cold Nodule 80% Benign 20% Malignant

12 If nodule cytology is benign, further immediate diagnostic studies or treatment are not required routinely. Recommendation Rating: A 14. a) It is recommended that all benign thyroid nodules be followed with serial US examinations 6-18 months after the initial FNA. If nodule size is stable (no more than a 50% change in volume or < 20% increase in at least two nodule dimensions in solid nodules or in the solid portion of mixed cystic-solid nodules), the interval before the next follow-up clinical exam or US may be longer, e.g., every 3-5 years. Recommendation Rating: C

13 b) If there is evidence for nodule growth either by palpation or sonographically (more than a 50% change in volume or a 20% increase in at least two nodule dimensions with a minimal increase of 2 mm in solid nodules or in the solid portion of mixed cysticsolid nodules), the US guided FNA should be repeated Recommendation Rating: B 16. Routine levothyroxine suppression therapy of benign thyroid nodules is not recommended in iodine sufficient populations. Recommendation Rating: F

14 Child: the diagnostic and therapeutic approach to thyroid nodules should be the same as in an adult (clinical evaluation, serum TSH, US, FNA). Recommendation Rating: A 19. Pregnant Women: with thyroid nodules, if euthyroid or hypothyroid, perform an FNA. If TSH levels are low and persist after the first trimester, FNA may be deferred until after pregnancy and cessation of lactation, when a radionuclide scan can be performed to evaluate nodule function. Recommendation Rating: A

15 a) A nodule with cytology indicating PTC discovered early in pregnancy should be monitored by US. If it grows substantially (as defined above) by 24 weeks gestation, surgery should be performed at that point. However, if it remains stable by midgestation or is diagnosed in the second half of pregnancy, surgery may be performed after delivery. In patients with more advanced disease, surgery in the second trimester is reasonable. Recommendation Rating: C 20. b) In pregnant women with FNA that is suspicious for or diagnostic of PTC, consideration should be given to administration of LT4 therapy to keep the TSH in the range of mu/l. Recommendation Rating: C

16 Thyroid Nodules Management Scheme Summary Measure Serum TSH TSH Normal g Ultrasound + FNA Biopsy TSH Low g Thyroid Scan FNA Biopsy (Usually with Ultrasound) Malignant g Surgery Benign g Observe Indeterminate g Molecular Analysis / Surgery Case History A 40 year old woman presents with a constricting sensation in her neck and progressive dysphagia for solid foods. PE: BP 144/90 P 82 Ht 5 4 Wt 192 lb. Thyroid: enlarged (4 x nl), nodular Neck: no JVD, + Pemberton s sign Lab: TSH: 0.9 mu/l (nl: ) 16

17 17 Nontoxic Goiter Classification Diffuse Nontoxic Goiter Multinodular Goiter Multinodular Goiter

18 Iodine Deficiency Nontoxic Goiter Etiology/Pathogenesis Inefficient Thyroid Hormone Secretion Goitrogen Ingestion Iodine excess Lithium use Amiodarone use Thyroid Hormone Synthesis Disorder Nontoxic Goiter Clinical Features Symptoms Mass Sensation Dysphagia Hoarseness Signs Multinodular Goiter SVC Obstruction Pemberton s Sign 18

19 19 Nontoxic Goiter Management Options Observation Surgery Radioactive Iodine (I-131) Levothyroxine Suppression Surgery for Nontoxic Goiter Considerations Immediate Relief of Symptoms Discovery of Unexpected Cancer Hypothyroidism (common) Hypoparathyroidism (uncommon) Recurrent Laryngeal Nerve Damage

20 20 Radioiodine for Nontoxic Goiter Considerations Size Reduction (~ 30%) Hypothyroidism (~ 50%) Graves Disease (~ 5%) Failure to Find Underlying Cancer LT4 Suppression for Nontoxic Goiter Considerations Low Efficacy Bone Loss Cardiac Dysrhythmias

21 Case History A 66 year old woman presents with 5 day history of dyspnea and palpitations. PE: BP 140/78 P 120 Ht 5 8 Wt 140 lb. Thyroid: enlarged, multiple nodules EKG: atrial fibrillation Lab: TSH < 0.03 mu/l (nl: ) Free T4 5.5 ng/dl (nl: ) RAIU: 4 hr. = 34% 24 hr. = 48% Thyroid Scan: patchy uptake Hyperthyroidism Hypothalamus TRH Overt Hyperthyroidism i TSH h Free T4 h Total T3 T3 + T4 TSH Subclinical Hyperthyroidism i TSH nl Free T4 nl Total T3 21

22 Thyrotoxicosis Differential Diagnosis - RAIU High RAIU Graves Disease Toxic MNG Toxic Nodule HCG Secreting Tumor Central Thyrotoxicosis Low RAIU Postpartum Thyroiditis Silent Thyroiditis Subacute Thyroiditis Factitious Thyrotoxicosis Iodine Induced Amiodarone Induced Order Thyroid Scan Toxic Multinodular Goiter Patchy Uptake Mutation of TSH Receptor or a Subunit Causing Autonomous Nodule Function 22

23 Toxic Thyroid Nodule Solitary Uptake Mutation of TSH Receptor or a Subunit Causing Autonomous Nodule Function Toxic MNG and Toxic Nodule Treatment Anti-Thyroid Drugs for 4-6 Weeks (prior to other Rx) Methimazole: 30 mg QD; i in 1-2 months Propylthiouracil: 100 mg TID; i in 1-2 months Beta Blocker: Atenolol 50 mg QD until euthyroid Goal: Rapid Symptom Relief; Remission will not Occur Liver Disease: PTU (AST, ALT, Liver Failure) Agranulocytosis: ~1/200 (Check CBC when Febrile) Radioiodine (I-131) Therapy Hypothyroidism occurs in ~ 50% (Avg: 3-12 Months) Surgical Therapy Hypothyroidism occurs in ~ 50% (1-2 Weeks) 23