Management of Toxic Multinodular Goiter - Role of surgery Joint Hospital Surgical Grandround Management of Toxic Multinodular Goiter - Role of surgery Shi LAM Queen Mary Hospital

“..two distinct types of thyroid intoxication…” – H.S Plummer 1913 Hyperplastic (Grave’s) Non-hyperplastic (Plummer’s) Solitary toxic nodule Toxic multinodular goiter Two major causes (> 80%) of hyperthyroidism worldwide

Multinodular Goiters (MNG) Commonly adopted definition thyroid volume > 20ml nodular lesions > 5 – 10mm Prevalence determined by iodine intake palpation: 3 – 5% USG screening: 10 - 50% endemic in regions of low iodine intake risk factors: age, female, parity, smoking, obesity

Hong Kong is a region of borderline iodine deficiency Chinese Nutrition Society Recommendation adolescent / adult : 150 ug / day pregnant / lactating women: 250 ug / day upper limit 1000 ug/day Center for food safety report 2011 median daily food iodine content 44 ug/day 59% of population has iodine intake < 50 ug / day iodine rich food: seaweed > crustaceans > eggs > milk > fish iodine scarce food: grains, meat, vegetable, tea / coffee

Natural history – nodule growth Alexander et al. Ann Intern Med 2003 USG follow-up of 330 benign nodules 39% nodules increase volume by 15% in 35 months cystic nodules tend to remain static age, gender and TSH level were not predictive of nodule growth Papini et al. J Clin Endocrinol Metab. 1998 45% increase volume, 25% in nodule number in 5 years

Natural history - thyrotoxicosis Prospective cohorts Elte et al. Postgrad Med J 1990 Wiener et al. Clin Nucl Med. 1979 158 euthyroid MNG patients with autonomous functioning thyroid mean follow-up 4 – 12.2 years 10% patients develop thyrotoxicosis Factors associated with hyperthyroidism older age hyperfunctional nodules size > 3cm autonomously functioning thyroid volume > 16ml

Spectrum & course of Plummer’s disease Age Goiter/ nodularity

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity Thyrotoxicosis

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity Thyrotoxicosis adolescent + non-autonomous euthyroid

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity Thyrotoxicosis adolescent + non-autonomous euthyroid  40 ++ autonomous

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity Thyrotoxicosis adolescent + non-autonomous euthyroid  40 ++ autonomous Plummer’s disease

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity Thyrotoxicosis adolescent + non-autonomous euthyroid  40 ++ autonomous 60 +++  autonomous subclinical hyperthyroidism

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity Thyrotoxicosis adolescent + non-autonomous euthyroid  40 ++ autonomous 60 +++  autonomous subclinical hyperthyroidism Toxic multinodular goiter

Spectrum & course of Plummer’s disease Age Goiter/ nodularity  Automaticity Thyrotoxicosis adolescent + non-autonomous euthyroid  40 ++ autonomous 60 +++  autonomous subclinical hyperthyroidism > 60 mass effect   autonomous overt hyperthyroidism Iodine exposure

Management of toxic MNG Goals correct dysfunction – mass / thyrotoxicosis exclude / treat malignancy Options medical radio-active iodine surgery percutaneous ablations

Overt thyrotoxicosis in toxic MNG Preferred treatment options surgery total / near-total thyroidectomy immediate restoration of euthyroidism retrosternal goiters, weight > 90g <1% retreatment rate <2% permanent recurrent laryngeal nerve injury <2% permanent hypoparathyroidism contraindications: pregnancy (1st and 3rd trimester)

Overt thyrotoxicosis in toxic MNG Preferred treatment options 131I avoids surgical / anaesthetic risk euthyroidism: 3 months – 60%, 6 months – 80% hypothyroidism: 1 year – 3%, 24 years – 64%; 40% size reduction contraindications: lactating pregnant / planning pregnant in 6 months

Overt thyrotoxicosis in toxic MNG Other treatment options Anti-thyroid medications does not induce remission for patients not fit for surgery, limitted life expectancy Percutaneous ablation (ethanol / radio-frequency / high intensity focused ultrasound ) lack of long-term experience

Subclinical thyrotoxicosis Common in toxic multinodular goiter Porterfield et al. World J Surg 2008 438 / 586 (82%) patients with toxic nodular goiter Long-term consequence Sawin et al. NEJM 1994 prospective cohort of 2007 subjects > 60 years old follow-up: 10 years subjects with subclinical hyperthyroidism (TSH < 0.1 mU/L) have 3-fold increased risk in developing atrial fibrillation

Risk of malignancy Incidental carcinoma in toxic multinodular goiter: Review by Pazaitou et al. Horm Metab Res 2012 7 retrospective cohorts of toxic nodular goiter 1611 subjects Cancer in 1.6 – 8.8% Microcarcinoma (<10mm): 35 – 88% of tumors Excellent prognosis compared with euthyroid patients QMH (unpublished) Toxic multinodular goiter operated for non-suspicious causes Excluded FNAC confirmed or suspicious nodules 16/178 (9%) found to have carcinoma 15 papillary carcinoma, 1 Hurthle cell carcinoma Mean diameter 12mm

Risk of malignancy ? Clinical significance higher reported prevalence due to more detailed pathological examination ? hyperthyroidism not previously identified as risk factors for manifesting carcinoma of thyroid ? Pre-operative risk stratification cold nodules on scintigraphy family history exposure to neck irradiation USG findings > 50% carcinomas found outside of “dominant” / “cold” nodules

Summary Toxic multinodular goiter is the manifesting stage of a chronic process of hyperplasia and acquisition of automaticity in the thyroid gland. Hyperthyroidism, overt or subclinical, is an indication for definitive interventions, in the form of thyroidectomy or radio-active iodine ablation. In the absence of suspicion of malignancy, surgery is probably still a “safer offer” in younger patients in view of the accumulated life-time risk for an incidental carcinoma to progress into a manifesting cancer.

Acknowledgement Dr. Brian Lang

Thank you!