Natural History of Thyroid Nodule

Natural History of Thyroid Nodule

Xiaohong Wu Department of Endocrinology, First Affiliated Hospital,

Nanjing Medical University, Nanjing, China

Thyroid Nodules: the scope of the problem

• Palpation: 3% ~ 7%• Ultrasonography: 20% ~76%• More common in:

elderly persons;

women;

those with iodine deficiency;

those with a history of radiation

exposure.

Endocr Pract. 2010;16(Suppl 1)

Prevalence of Thyroid Incidentalomas in health check-up

ages(year) male/female male(%) female (%) total (%)

10 ~ 22/14 9.1 7.1 8.3

30 ~ 69/61 17.4 23.0 20.0

50 ~ 86/59 39.51) 52.53) 44.82)

≥70 19/10 73.71) 60.03) 69.02)

total 196/144 31.6 36.1 33.5

Note: compared with other ages, 1) P < 0.01, 2) P <0.05, compared with group A、 B, 3) P < 0.05

Wu X, Liu C, et al. Chinese Journal of Practical Internal Medicine， 2005; 25(9):823-824

Prevalence of Thyroid Nodules in Jiangsu Province

ages (year) male female

sample size

cases prevalence sample size

cases prevalence

20-29 242 12 4.96 273 23 8.42

30-39 386 30 7.77 716 109 15.22

40-49 567 63 11.11 1056 196 18.56

50-59 617 105 17.02 1061 328 30.91

60- 552 134 24.28 658 294 44.68

total 2364 344 14.55 3764 950 25.24

Feng C, Liu C, et al. Chinese Journal of Endocrinology and Metabolism. 2011, 27: 492-494

In China, according to a recent community survey in ten cities, thyroid nodules have a prevalence of approximately 18.6%.

Etiology of Thyroid Nodules

Endocr Rev. 2003;24(1):102-32.

Endocr Pract. 2010;16(Suppl 1)

Pat. P.M. Nodular Volume After 6 Years3.1 ml 4.3 ml

6.3 ml

Course of Thyroid Nodules

• What is the long-term course of thyroid nodules?

• What influences growth and function of thyroid nodules?

Questions

Long-Term Follow-up of Thyroid Nodule Growth

109 euthyroid patients with benign thyroid nodules95 women, 14 men; 46,2 ± 12,7 (14 - 73) years

Follow-up of at least 3 years3 - 13 years (median 4,9 years)

Quadbeck B, et al. Exp Clin Endocrinol Diabetes. 2002;110:348-354

Development of Thyroid Nodules


Evaluation of Factors affecting Thyroid Nodules Growth


Evaluation of Factors affecting Thyroid Nodules Growth


Determinants of Nodular Growth

According to the Cox Proportional Harzards Model

There was no significant influence on the growth pattern of thyroid nodules of:

– Age and sex of the patient,– Initial size of the nodule, – Scintigraphic behaviour of the nodule,– TSH-suppression by therapy


Conclusions• The majority of benign thyroid nodules exhibits a slow

growth rate during long-term observation.– After 3 yeras only half of the nodules have significantly increased

in size.

• Thyroid nodules do grow more rapidly than the whole goitre of the same patient.

• The growth rate of thyroid nodules is mainly determined endogeneously rather than by exogenous factors, which show little, if any, infleunce.


How about Thyroid Incidentalomas

Health check-up

Thyroid ultrasonography

Incidentalomas

Clinical evaluation

d>1cm, US-FNA

FT3,FT4,TSH,Tg,Nodule volumes Follow-up

n=323, M/F=196/144

n=144,M/F=62/52

Wu X, Liu C, et al. Chinese Journal of Practical Internal Medicine,2005;25(9):823-824

Four-year Follow-up of Thyroid Incidentalomas

10

36

4014

25

0 10 20 30 40 (%)

di sappeared

decreased

unchanged

i ncreased

Sol i tary tomul ti pl e


Changes of Thyroid Incidentalomas after Four-year Follow-up

- 1

- 0. 53

- 0. 05

0. 29

- 1

- 0. 8

- 0. 6

- 0. 4

- 0. 2

0

0. 2

0. 4

nodule volume

di sappeared decreased unchanged i ncreased


Characteristics of 20 included publicationsStudyname Publication year Study design Follow-up Nodule n Criteria of change Change of nodules at endpoint

(percentage change)

Increase No change DecreaseCheung 1989 Cohort 1.5ys 37 NA 19 - -Kuma 1994 Cohort 15ys 134 Not defined 13.5 33.6 52.9

Knudsen 2000 Cohort 2ys 45 Nodule diameter≥ 5mm

2.2 91.1 6.7

Buadbeck 2000 Cohort 5ys 57 Not defined 35 31 24Rago 2001 Cohort 3ys 27 Nodule volume≥30% 11.1 - -

Quadbeck 2002 Cohort 3ys 139 Nodule volume≥30% 61.2 15.8 23

Alexander 2003 Cohort 20m 330 Nodule volume≥15% 39 - -

Wu 2005 Cohort 4ys 100 Nodule volume≥20% 14 40 46

Murat 2006 Cohort 39m 531 Nodule volume≥15% 32 34.9 33.1

Gharib 1987 Case-control 0.5y 25 Failure of any reduction

40 60

Reverter 1992 Case-control 1y 20 Nodule is not reduced or reduced to

50%

85 15

Papini 1993 Case-control 1y 50 Failure of any reduction

74 26

La Rosa 1995 Case-control 1y 22 Nodule is not reduced or reduced to

50%

100 0

Mainini 1995 Case-control 2ys 10 Nodule is not reduced or reduced to

50%

100 0

Lima 1997 Case-control 1y 20 Nodule is not reduced or reduced to

20%

80 20

Papini 1998 Case-control 5ys 41 Nodule is not reduced or reduced to

11.7%

53.7 46.3

Zelmanovitz 1998 Case-control 1y 24 Nodule is not reduced or reduced to

50%

91.7 8.3

Larijani 1999 Case-control 1y 30 Failure of any reduction

60 40

Sakalauskiene 2002 Case-control 0.5y 25 Failure of any reduction

84 16

Wemeau 2002 Case-control 1.5ys 59 Nodule is not reduced or reduced to

20%

69.5 30.5

Forest plot of 9 studies providing the percentage of volume increase for benign thyroid nodules

NOTE: Weights are from random effects analysis

Overall (I-squared = 96.9%, p = 0.000)

Wu 2005

ID

Kuma 1994

Quadbeck 2002

Alexander 2003

Buadbeck 2000

Rago 2001

Knudsen 2000

Cheung 1989

Murat 2006

Study

25.21 (13.12, 37.31)

14.00 (7.20, 20.80)

percentage (95% CI)

13.50 (7.71, 19.29)

61.20 (53.10, 69.30)

39.00 (33.74, 44.26)

35.00 (22.62, 47.38)

11.10 (-0.75, 22.95)

2.20 (-2.09, 6.49)

19.00 (6.36, 31.64)

32.00 (28.03, 35.97)

100.00

11.32

Weight

11.44

11.16

11.49

10.46

10.55

11.57

10.41

11.60

%

25.21 (13.12, 37.31)

14.00 (7.20, 20.80)

percentage (95% CI)

13.50 (7.71, 19.29)

61.20 (53.10, 69.30)

39.00 (33.74, 44.26)

35.00 (22.62, 47.38)

11.10 (-0.75, 22.95)

2.20 (-2.09, 6.49)

19.00 (6.36, 31.64)

32.00 (28.03, 35.97)

100.00

11.32

Weight

11.44

11.16

11.49

10.46

10.55

11.57

10.41

11.60

%

0-69.3 0 69.3

Forest plot of 6 studies providing rate of no-change of the volume for benign thyroid nodules



Knudsen 2000

Murat 2006

Kuma 1994

Quadbeck 2002

Buadbeck 2000

ID

Wu 2005

Study

41.03 (22.01, 60.06)

91.10 (82.78, 99.42)

34.90 (30.85, 38.95)

33.60 (25.60, 41.60)

15.80 (9.74, 21.86)

31.00 (18.99, 43.01)

percentage (95% CI)

40.00 (30.40, 49.60)

100.00

16.67

17.09

16.71

16.92

16.11

Weight

16.50

%

41.03 (22.01, 60.06)

91.10 (82.78, 99.42)

34.90 (30.85, 38.95)

33.60 (25.60, 41.60)

15.80 (9.74, 21.86)

31.00 (18.99, 43.01)

percentage (95% CI)

40.00 (30.40, 49.60)

100.00

16.67

17.09

16.71

16.92

16.11

Weight

16.50

%

0-99.4 0 99.4

Forest plot of 17 publications providing rate of volume decrease for benign thyroid nodules



Lima 1997

Larijani 1999

Quadbeck 2002

Buadbeck 2000

Zelmanovitz 1998

Wu 2005

Sakalauskiene 2002

Mainini 1995

Reverter 1992

La Rosa 1995

Papini 1998

Wemeau 2002

Knudsen 2000

ID

Papini 1993

Gharib 1987

Murat 2006

Kuma 1994

Study

25.58 (17.57, 33.60)

20.00 (2.47, 37.53)

40.00 (22.47, 57.53)

23.00 (16.00, 30.00)

24.00 (12.91, 35.09)

8.30 (-2.74, 19.34)

46.00 (36.23, 55.77)

16.00 (1.63, 30.37)

0.10 (-1.86, 2.06)

15.00 (-0.65, 30.65)

0.10 (-1.22, 1.42)

46.30 (31.04, 61.56)

30.50 (18.75, 42.25)

6.70 (-0.60, 14.00)

percentage (95% CI)

26.00 (13.84, 38.16)

60.00 (40.80, 79.20)

33.10 (29.10, 37.10)

52.90 (44.45, 61.35)

100.00

5.08

5.08

6.39

5.95

5.96

6.11

5.52

6.69

5.35

6.70

5.40

5.87

6.36

Weight

5.82

4.85

6.61

6.25

%

25.58 (17.57, 33.60)

20.00 (2.47, 37.53)

40.00 (22.47, 57.53)

23.00 (16.00, 30.00)

24.00 (12.91, 35.09)

8.30 (-2.74, 19.34)

46.00 (36.23, 55.77)

16.00 (1.63, 30.37)

0.10 (-1.86, 2.06)

15.00 (-0.65, 30.65)

0.10 (-1.22, 1.42)

46.30 (31.04, 61.56)

30.50 (18.75, 42.25)

6.70 (-0.60, 14.00)

percentage (95% CI)

26.00 (13.84, 38.16)

60.00 (40.80, 79.20)

33.10 (29.10, 37.10)

52.90 (44.45, 61.35)

100.00

5.08

5.08

6.39

5.95

5.96

6.11

5.52

6.69

5.35

6.70

5.40

5.87

6.36

Weight

5.82

4.85

6.61

6.25

%

0-79.2 0 79.2

How about nodular goiter?• On the basis of cross-sectional data and ultrasonic scanning,

an average annual growth rate of 4.5% in multinodular goiter has been reported---Am J Med 1990;89:602–608

• In the Whickham survey, 20% of the women and 5% of the men who had goiters in the initial survey had no goiter in the follow-up survey, whereas only 4% of the women and none of the men acquired a goiter between the two surveys.

---Clin Endocrinol (Oxf) 1995;43:55–68

• In a 20-yr follow-up study of 11- to 18-yr-old subjects in the southwestern United States, 60% of the 92 subjects who had diffuse goiters initially had spontaneous regression by the age of 30 yr. ---Am J Med 1991;91:363–370

Decreasing frequency of goiter with age

• A fall in lean body mass with age, known to be related to thyroid volume

• A fall with age in IGF-I and GH

• At least in women, the loss of estradiol-mediated increase in proliferation and down-regulation of the NIS gene

Clin Endocrinol (Oxf) 1998;48:701–706J Am Geriatr Soc 1999;47:1238–1243Endocrinology 1999;140:5705–5711

Follow-up of Nontoxic AutonomouslyFunctioning Thyroid Nodules

J Clin Endocrinol Metab 1980;50:1089–1093

Correlation of change in nodule size and function and duration of follow up for nontoxic AFTN


Increase: 15/159=9.4%No change: 138/159=86.8%

Decrease: 6/159=3.8%

Toxic: 14/159=8.8%

Correlation of function of untreated AFTN with age after varying follow-up periods


Nodules greater than 3 cm in size at diagnosis carried a 20% risk of developing hyperthyroidism, whereas nodules less than 2.5 cm in size had only a 2-5% risk of developing hyperthyroidism within the same time frame

Correlation of changes in nodule size and function andduration of follow up for nontoxic AFTN from iodine-sufficient

(control) and iodine-deficient (endemic) areas


Nontoxic Nodular Goiter

• An incidence of 8-10% of overt hyperthyroidism during a 6- to 12-yr follow-up period corresponding to 0-6% per year. .

• In part, this progression depends on genetic predisposition, somatic mutations in individual nodules, and extrinsic factors such as iodine intake.

Postgrad Med J 1990;66:186–190Clin Nucl Med 1979;4:181–190

J Clin Endocrinol Metab 1980;50:1089–1093J Clin Endocrinol Metab 1983;56:283–287

Acta Endocrinol (Copenh) 1993;128:51–55

• The natural history of thyroid nodule with respect to

growth and function varies and is difficult to predict

in a given patient.

• Most patients need no treatment after malignancy is

ruled out.

• New molecular genetic techniques applied on FNAB

should lead to an increasing understanding of the

pathogenesis of nodular thyroid disease and a better

characterization of phenotypes.

Summary

Acknowledgements

Yingyue Lv

Yili Xu

Xiaojing Wang

Jiayu Zhu

Xiaoyun Liu

Huanhuan Chen

Kuangfeng Xu

Tao Yang

Collaborators:

Yu Duan

Xinhua Ye

Hongjun Lin

Meiping Shen

Wei Liu

Supervisor:

Chao LiuGrants: NSFC(30971404/C140406 and 81070621/H0704) Jiangsu Province key medical personnel project (RC2011068) International Science and technology cooperation (BZ2011042)

Thank you!

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Natural History of Thyroid Nodule