1. 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

2. “..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

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

4. 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

5. 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

6. 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

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

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

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

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

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

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

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

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

15. 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

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

17. 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)

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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.

24. Acknowledgement
Dr. Brian Lang

25. Thank you!