Disclosures. Learning objectives. Case 1A. Autoimmune Thyroid Disease: Medical and Surgical Issues. I have nothing to disclose.

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1 Disclosures Autoimmune Thyroid Disease: Medical and Surgical Issues I have nothing to disclose. Chrysoula Dosiou, MD, MS Clinical Assistant Professor Division of Endocrinology Stanford University School of Medicine November 9, 202 Learning objectives Review some of the pitfalls in the evaluation and treatment of thyroid nodules and thyroid cancer in patients with Hashimoto s disease Hürthle cells on FNA Risk of hypothyroidism after hemithyroidectomy Follow-up of thyroid cancer in the presence of TG Abs Discuss surgical considerations in the management of Graves disease, with input from recent clinical guidelines When is surgery the preferred option Preoperative preparation, type of surgery and surgeon Risk of malignancy and prognosis of concomitant thyroid cancer; role of ultrasound Case A 63 yro woman seen for a second opinion for evaluation of an abnormal thyroid FNA result. Pt has a 2.5 cm R solid hypoechoic thyroid nodule, detected on neck ultrasound that was obtained to evaluate a mild goiter. TSH normal. US-guided FNA: a few Hürthle cells in a background of lymphocytes, scant colloid. Pt referred for hemithyroidectomy; wants second opinion.

2 Case A: Question Would you recommend hemithyroidectomy in this patient? A. Yes B. No C. Need more data to decide 2/3 /3 Hürthle cells in thyroid nodules Differential Diagnosis Hürthle cell adenoma Hürthle cell carcinoma need resection Autoimmune thyroid disease (Hashimoto s or Graves ) Multinodular goiter with Hürthle cell metaplasia Thyroid changes after head and neck irradiation do NOT need resection Question: How to distinguish above? Hürthle cells in thyroid nodules Back to our patient Case A Features that distinguish Hürthle cell neoplasm from benign Hürthle cell lesion : Nonmacrofollicular architecture Absence of colloid Absence of inflammation Presence of transgressing blood vessels Combination identified HCN 86% of the time Typically Hürthle cell neoplasms have a separate population of monotonous Hürthle cells devoid of lymphocytic infiltrate Pathology reviewed at our institution: most consistent with chronic lymphocytic thyroiditis Patient s labs: TSH.5 anti-tpo antibodies: 880 Repeat US in year: no change in size of thyroid nodule; patient asymptomatic and euthyroid Elliott et al., Cancer Cytopathology

3 Case B Same presentation Pathology reviewed: findings consistent with Hürthle cell neoplasm Patient s labs: TSH.5 anti-tpo antibodies: 880 Risk of malignancy ( 30%); referred for hemithyroidectomy Case B: Question The patient wants to know her risk of developing hypothyroidism after her surgery, if the pathology is benign and she does not need completion thyroidectomy. What do you advise her? Risk is about: A. 0% B. 25% C. 50% D. 80% Risk of hypothyroidism after hemithyroidectomy Risk of hypothyroidism after hemithyroidectomy Recent meta-analysis of 32 studies, including 4,899 patients Risk of hypothyroidism after hemithyroidectomy: 22% (95% CI 9-27%) Four studies distinguished risk of overt hypothyroidism (4%) vs subclinical hypothyroidism (2%) Risk factors identified: Presence of anti-tpo antibodies (48% vs 9%) Higher TSH levels preoperatively (even within normal range) High degree of inflammation in the resected lobe (49% vs 0%) Conflicting results for: Age Presence of thyroglobulin antibodies (Tg Abs) Verloop et al., JCEM 202 Verloop et al., JCEM 202 3

4 Case C Case C: Question Pathology reviewed at our institution: papillary thyroid carcinoma Patient s labs: TSH.5 anti-tpo antibodies: 880 How does the presence of Tg Abs affect your follow-up of this patient? A few weeks after surgery, Thyrogen stimulated WBS shows only uptake in the thyroid bed. Stimulated TG undetectable Tg Abs: 452 Patient treated with I3, 50mCi; post-treatment scan with similar findings to pre-treatment WBS Prevalence of thyroid autoantibodies (anti-tpo or TgAb alone or in combination) in the general population compared with that in patients with differentiated thyroid cancer 40% Thyroglobulin antibodies (Tg Abs) in thyroid cancer 20-25% of patients with differentiated thyroid cancer have Tg Abs ; these interfere with immunometric TG assays causing falsely low results Titer of Tg Abs can be used as a surrogate tumor marker; falling titers indicate decreased burden of disease 2 4% Tg Ab levels reported by different methods can vary 00-fold on the same specimen; critical to use the same lab and same assay to follow In adequately treated patients Tg Ab titers fall by 50% at 6-2 months and disappear at a median time of 3 years by Endocrine Society Spencer C A et al. JCEM 998;83:2-27 Greater role of imaging in patients with Tg Abs Spencer et al., JCEM 20 3 Görges et al., Eur J Endocrinol Chiovato et al., Ann Intern Med Kim et al., JCEM

5 Prevalence of Tg Abs in DTC patients after initial treatment Tg Abs and Tg RIA after initial thyroid surgery according to patient disease status in follow-up Görges R et al. Eur J Endocrinol 2005;53:49-55 Spencer C A et al. JCEM 998;83: Society of the European Journal of Endocrinology 998 by Endocrine Society Take home points - I Hashimoto s and thyroid nodules / thyroid cancer:. Beware of Hürthle cells on FNA 2. Increased risk of hypothyroidism after hemithyroidectomy 3. In patients who have Tg Abs, use Tg Ab titer (same assay) for f/u Case 2A 25 yro woman seeking consultation for management of Graves disease. Has had symptoms of hyperthyroidism for 2 months and eye irritation/pain for 3 weeks. PE: BP 25/79, HR 2, Temp Thyrotoxic-appearing, has bilateral periorbital edema, moderate conjunctival injection and severe proptosis, diffuse moderate goiter with bruit, hand tremor. Labs: TSH < 0.0, Free T4 3.2 (0.6-.6), Free T3 8 (normal ), TSI 4% 5

6 Case 2A: Question What would you recommend as the preferred treatment in this patient: A. Thyroidectomy B. Antithyroid medication C. Radioiodine with steroids Hyperthyroidism Management Guidelines, 20 How should overt hyperthyroidism due to GD be managed? RECOMMENDATION 4 Patients with overt Graves hyperthyroidism should be treated with any of the following modalities: 3I therapy, antithyroid medication, or thyroidectomy. /++0 Technical remarks: Once the diagnosis has been made, the treating physician and patient should discuss each of the treatment options, including the logistics, benefits, expected speed of recovery, drawbacks, potential side effects, and cost. This sets the stage for the physician to make recommendations based on best clinical judgment and allows the final decision to incorporate the personal values and preferences of the patient. Long-term QoL similar in patients treated with the 3 modalities. 2 Bahn et al., Thyroid 20 2 Abraham-Nordling et al., Thyroid 2005 Hyperthyroidism Management Guidelines, 20 Hyperthyroidism Management Guidelines, 20 Factors that favor choice of surgery as treatment: Symptomatic compression or large goiters (> 80g) Relatively low uptake of radioactive iodine Documented thyroid malignancy Suspected thyroid malignancy (suspicious or indeterminate cytology) Large hypofunctioning nodule Coexisting hyperparathyroidism requiring surgery Females planning pregnancy in < 4-6 months, especially if TRAb levels are particularly high Patients with moderate to severe active Graves ophthalmopathy Contraindications to surgery as treatment: Substantial comorbidity (cardiopulmonary dz, end-stage cancer, etc) Pregnancy is a relative contraindication; operate at the end of second trimester if pt cannot be treated with antithyroid medications Bahn et al., Thyroid 20 Preparation for surgery: Whenever possible, patient should be rendered euthyroid with Methimazole preoperatively to decrease risk of thyroid storm Potassium iodide in the immediate preop period (0 days); decreases vascularity and intraop blood loss 2,3 If pt needs to be operated urgently or is intolerant of antithyroid medication, treat with beta blockade and potassium iodide preoperatively Corticosteroids may also be used for emergent surgery 4 Bahn et al., Thyroid 20 2 Erbil et al., JCEM Ansaldo et al., J Am Coll Surg Baeza et al., Clin Endocrinol 99 6

7 Hyperthyroidism Management Guidelines, 20 Type of surgery and surgeon: Distribution of thyroid surgeons and cases according to surgeon volume groups Near-total or total thyroidectomy is the procedure of choice (0% risk of relapse vs 8% risk of relapse at 5 years in subtotal thyroidectomy) Refer to high-volume thyroid surgeon High volume surgeons have significantly better outcomes 2,3 Risk of complications in hands of high-volume surgeons: < 2% permanent hypoparathyroidism, < % RLN injury 4 Palit et al., J Surg Res Sosa et al., Ann Surg Sosa et al., J Am Coll Surg Röher et al., Chirurg 999 Sosa et al., Ann Surg 998 Case 2B Patient elects to proceed with thyroidectomy. Case 2B: Questions What is her risk of malignancy? If she has concomitant thyroid cancer, is her prognosis different from patients without Graves? Should you get a preoperative thyroid ultrasound? 7

8 Graves disease (GD) and risk of thyroid cancer Prospective study of 245 Graves patients 35% had nodules by US; nodules 5 mm (80%) had FNA Prevalence of thyroid cancer 3.3% (all papillary).6% of patients with nodules 0.5 cm had cancer Prevalence of nodules and thyroid cancer in GD similar to that in the Korean general population Mean size of tumor 0 mm; 75% micropapillary Risk of cancer higher in patients 45 yrs old (6.7% vs.3 %); older patients also had higher risk of locally advanced cancer (5.6% vs 0%) Kim et al., Clin Endocrinol 2004 GD and thyroid cancer Prognosis Patients with GD and micropapillary carcinoma who undergo thyroidectomy have excellent prognosis; 99% disease-free survival at 20 yrs Data controversial for patients with thyroid cancer > cm, with some studies supporting more aggressive behavior of papillary thyroid cancer in GD patients, 2,3 while others not 4,5 Kikuchi et al., Br J Surg Hales et al., JCEM Belfiore et al., JCEM Yano et al., Eur J Endocrinol Pellegriti et al., JCEM 998 Hyperthyroidism Management Guidelines, 20 GD and thyroid ultrasound The use of thyroid ultrasonography in all patients with GD has been shown to identify more nodules and cancer than does palpation and 23I scintigraphy. However, since most of these cancers are papillary microcarcinomas with minimal clinical impact, further study is required before routine ultrasound (and therefore surgery) can be recommended. If a thyroid nodule is discovered in a patient with GD, the nodule should be evaluated and managed according to the guidelines published for nodules in euthyroid individuals. Bahn et al., Thyroid 20 Take home points - II Hashimoto s and thyroid nodules / thyroid cancer:. Beware of Hürthle cells on FNA 2. Increased risk of hypothyroidism after hemithyroidectomy 3. Use TG Ab titer (same assay) for f/u Graves disease management:. Expanded role of surgery in recent clinical guidelines 2. Near-total or total thyroidectomy by a high volume surgeon 3. Render patient euthyroid first with methimazole; treat also with beta blockers and potassium iodide preoperatively 4. Routine preoperative ultrasound not yet recommended 8

9 Thank you for your attention! 9