1. Thyroid Nodules ENDOCRINOLOGY DIVISION Dr. HAKIMI, SpAK Dr. MELDA DELIANA, SpAK Dr. SISKA MAYASARI LUBIS, SpA

2. Anatomical Considerations

3. The Thyroid Nodule Congenital anomalies  Thyroglossal duct cyst Inflammatory lesions  Inflammatory foci  Compensatory regenerative nodules (TSH,TGI) Hyperplasia Neoplasia  Benign  Malignant

4. Follicular epithelial neoplasms  Follicular adenoma  Differentiated: Papillary, Follicular Poorly Differentiated (Insular) Anaplastic Parafollicular epithelial neoplasms  Medullary carcinoma  Mixed/composite carcinoma Other primary epithelial neoplasms Primary non-epithelial neoplasms Secondary tumors

5. Incidence  Occur in only 0,05-1,8% of children  The most common form of cancer is papilary thyroid carcinoma  Folicular adenomas & colloid cysts is majority of benign tyhroid nodules

6. The Approach to Investigation of the Thyroid Nodule  Clinical examination  Thyroid function tests  Ultrasound  Cytology of fine needle aspirate (FNAB)  Thyroid scan  MRI

7. Clinical examination  Painless nodules  Firm or hard consistency  Fixed to surrounding tissue  Rapid growth  Cervical adenopathy, hoarseness, dysphagia  Exposed to irradiation  Family history of thyroid cancer or pheochromocytoma  Other syndromes associated with nodular thyroid disease

8. Thyroid function tests  Anti TPO & anti Tg Abs Abs (+)  underlying CLT, doesn’t exclude thyroid cancer  TSH, T4, T3 elevation T4 or/and T3  functioning nodules  Serum calcitonin for familial case of thyroid cancer  Genetic screening for mutation of RET proto- oncogen  suspected multiple endocrine neoplasia type 2

9. Methods of Ret/PTC Analysis DNA  PCR analysis of ret/PTC gene rearrangements has been difficult due to variable break-point sites leading to heterogeneous tumor profiles RNA  RT-PCR for ret/PTC mRNA is the “gold standard”  Variability of expression; not “all or none” Protein  Immunohistochemistry

10. Ret/PTC Gene Rearrangements

11. Ultrasonography  Non invasive method  Confirm & evaluate the morphological characteristic of thyroid nodules  Cystic or homogeneously hyperechoic  lower risk of malignancy  Solid hypoechoic, calcifications, irreguler shape & absence of a halo  malignant nodules

12. The limitation :  No reliably predict of malignancy  Depend on individual experiences

13. Ultrasonography YROID ASS

14. Cytology of fine needle aspirate & biopsy (FNA)  20% of FNAB are insufficient or non diagnostic  Repeat aspiration is ussually successful  Identifiable on cytology by the presence of characteristic cell abnormalities  In very young children, open excisional biopsy is suitable alternative

15. Fine Needle Aspiration Biopsy

16. Computed Tomography  Distinguish cystic from solid  Extent of lesion  Vascularity (with contrast)  Detection of unknown primary (metastatic)  Pathologic node (lucent, >1.5cm, loss of shape)  Avoid contrast in thyroid lesions

17. Computed Tomography

18. Magnetic Resonance Imaging  Similar information as CT  Better for upper neck and skull base  Vascular delineation with infusion

19. Magnetic Resonance Imaging

20. Differential Diagnosis

21. Therapy Excision for benign tumors & cysts Malignant thyroid tumors   Total or near total thyroidectomy  Radioiodine ablation  Monitoring for recurrence & disease progression  Thyroid nodules < 1 cm or with benign cytology  follow by serial ultrasound every 6-12 months  Significant interval growth  repeated FNAB

22. Treatment of Thyroid Cancer  Papillary and follicular thyroid cancer Generally excellent prognosis Risk for recurrence for as long as 30 years  Initial management Surgery and radioactive iodine LT 4 suppressive therapy  Follow-up Physical examination Radioactive iodine scans Serum Tg TSH and T 4

23. Standard Treatment of Thyroid Cancer Whole Body Scan Tg Assay Suppression Therapy Total Thyroidectomy 1 Year RAI Ablation Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2003;88:1433-1441. Sherman SI. Lancet. 2003;361:501-511. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463. Mazzaferri EL, et al. Endocr Relat Cancer. 2002;9(4):227-247.

24. RAI Ablation Physical Exam Ultrasound Thyroid Cancer Initial Treatment Strategy Surgery Total Thyroidectomy Lobectomy Isthmusectomy Intermediate and High Risk Low Risk Diagnosis of Thyroid Cancer Kinder BK. Curr Opin Oncol. 2003;15):71-77. Sherman SI. Lancet. 2003;361:501-511. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463.

25. Radioactive Iodine  Destroys remnants of normal thyroid tissue  Destroys thyroid cancer cells  Identifies distant metastases  Maximizes sensitivity and specificity of serum thyroglobulin Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463. Cohen EG, et al. Otolaryngol Clin North Am. 2003;36:129-157.

26. TSH Suppression Pituitary TSH Thyroid T 4 - + Pituitary TSH Thyroid T 4 - + Normal Thyroid Cancer Patients Minimum LT 4 to suppress TSH without thyrotoxicosis Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000. Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463. Sherman SI. Lancet. 2003;361:501-511.

27. Target TSH Suppression <0.10.1 to 0.40.5 to 1 Low to Undetectable Suppressed but Detectable Low Normal Most patients with no evidence of disease Persistent or recurrent disease High-risk patients Very low-risk patients Long-term survivors TSH, mIU/L Patients Optimal TSH Mazzaferri EL, et al. J Clin Endocrinol Metab. 2001;86:1447-1463. Sherman SI. Lancet. 2003;361:501-511. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000.