J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 12, Number 8, August 2020, pages 499-507

Examination of Malignant Findings of Thyroid Nodules Using Thyroid Ultrasonography

Figure 1. Flow chart of the enrollment process for the malignant and benign nodule groups. *Undetermined significance, falling under “III. Atypia of undetermined significance or follicular lesion of undetermined significance” in the diagnostic category of the Bethesda System. ^†Follicular neoplasm, falling under “IV. Follicular neoplasm or suspicious for a follicular neoplasm” in the diagnostic category of the Bethesda System.

Figure 3. Difference in the value of serum thyroglobulin (Tg)/nodule volume ratios between the malignant and benign nodule groups. IQR: interquartile range.

**Table 1.** Characteristics of Thyroid Nodules on Ultrasonography
Characteristics of thyroid nodules
Shape	An integer indicates a circle or an ellipse. Irregularity indicates an irregular shape.
Boundary property	Edge of the lesion is linear (smooth) versus serrated (coarse).
Boundary clarity	Clear versus unclear boundary.
Internal echo property	Echo properties with uniform internal echo (homogeneous) versus uneven internal echo (heterogeneous).
Internal echo level	The solid part of the thyroid is evaluated by comparing it to the surrounding thyroid tissue.
Internal coarse calcification	Lesion contains coarse (≥ 1 mm) high echo findings.
Microcalcifications	Lesion contains fine (< 1 mm) high echo findings.
Internal blood flow	The internal blood flow on color Doppler imaging is visible.
Boundary hypoechoic zone	A low echo band is visible at the boundary.
Nodule type	Solid (no cystic areas) versus mixed (solid and cystic areas).

Table 1. Characteristics of Thyroid Nodules on Ultrasonography

Characteristics of thyroid nodules

Shape

An integer indicates a circle or an ellipse. Irregularity indicates an irregular shape.

Boundary property

Edge of the lesion is linear (smooth) versus serrated (coarse).

Boundary clarity

Clear versus unclear boundary.

Internal echo property

Echo properties with uniform internal echo (homogeneous) versus uneven internal echo (heterogeneous).

Internal echo level

The solid part of the thyroid is evaluated by comparing it to the surrounding thyroid tissue.

Internal coarse calcification

Lesion contains coarse (≥ 1 mm) high echo findings.

Microcalcifications

Lesion contains fine (< 1 mm) high echo findings.

Internal blood flow

The internal blood flow on color Doppler imaging is visible.

Boundary hypoechoic zone

A low echo band is visible at the boundary.

Nodule type

Solid (no cystic areas) versus mixed (solid and cystic areas).

**Table 2.** Profiles of Patients With Thyroid Nodules
	Total (331 nodules, 236 patients)	Malignant nodules (33 nodules, 26 patients)	Benign nodules (298 nodules, 210 patients)	P-value*
Values are expressed as mean ± standard deviation, count or median (interquartile range). *Malignant nodules versus benign nodules according to Welch’s t-test, Fisher’s exact test, or Wilcoxon’s test. ^†Welch’s t-test. ^‡Fisher’s exact test. ^§Wilcoxon’s test. BMI: body mass index; Tg: thyroglobulin; TgAb: anti-thyroglobulin antibody; TPOAb: anti-thyroid peroxidase antibody.
Age, years	59.4 ± 13.9	52.8 ± 16.7	60.2 ± 13.4	< 0.05^†
Sex, n (male/female)	57/179	11/15	46/164	< 0.05^†
BMI, kg/m²	23.6 ± 4.2	24.2 ± 4.1	23.5 ± 4.2	0.45^†
History of thyroid disease, n (yes/no/unknown)	18/215/3	0/25/1	18/190/2	0.12^‡
Family history of thyroid disease, n (yes/no/unknown)	42/173/21	6/15/5	36/158/16	0.08^‡
Laboratory parameters
Tg, ng/mL	55.3 (20.8 - 115.6)	91.6 (17.7 - 138.0)	52.4 (20.8 - 114.6)	0.42^§
TgAb, IU/mL	15.0 (10.0 - 35.0)	17.5 (10.8 - 80.0)	15.0 (10.0 - 34.0)	0.44^§
TPOAb, IU/mL	8.0 (6.0 - 11.0)	7.5 (5.8 - 11.0)	8.0 (6.0 - 11.0)	0.99^§

Table 2. Profiles of Patients With Thyroid Nodules

Total (331 nodules, 236 patients)

Malignant nodules (33 nodules, 26 patients)

Benign nodules (298 nodules, 210 patients)

P-value*

Values are expressed as mean ± standard deviation, count or median (interquartile range). *Malignant nodules versus benign nodules according to Welch’s t-test, Fisher’s exact test, or Wilcoxon’s test. ^†Welch’s t-test. ^‡Fisher’s exact test. ^§Wilcoxon’s test. BMI: body mass index; Tg: thyroglobulin; TgAb: anti-thyroglobulin antibody; TPOAb: anti-thyroid peroxidase antibody.

Age, years

59.4 ± 13.9

52.8 ± 16.7

60.2 ± 13.4

< 0.05^†

Sex, n (male/female)

57/179

11/15

46/164

< 0.05^†

BMI, kg/m²

23.6 ± 4.2

24.2 ± 4.1

23.5 ± 4.2

0.45^†

History of thyroid disease, n (yes/no/unknown)

18/215/3

0/25/1

18/190/2

0.12^‡

Family history of thyroid disease, n (yes/no/unknown)

42/173/21

6/15/5

36/158/16

0.08^‡

Laboratory parameters

Tg, ng/mL

55.3 (20.8 - 115.6)

91.6 (17.7 - 138.0)

52.4 (20.8 - 114.6)

0.42^§

TgAb, IU/mL

15.0 (10.0 - 35.0)

17.5 (10.8 - 80.0)

15.0 (10.0 - 34.0)

0.44^§

TPOAb, IU/mL

8.0 (6.0 - 11.0)

7.5 (5.8 - 11.0)

8.0 (6.0 - 11.0)

0.99^§

**Table 3.** Comparison of Ultrasonography Results Between Benign and Malignant Nodules
	Benign nodule	Malignant nodule	P value
Values of the thyroid gland and nodule are expressed as mean ± standard deviation. *Welch’s t-test. ^†Pearson’s χ² test. ^‡Fisher’s exact test.
Volume of the thyroid gland, mL (n)	37.3 ± 27.3 (181)	25.5 ± 11.0 (22)	< 0.01*
Volume of thyroid nodule, mL (n)	11.7 ± 7.1 (283)	3.9 ± 2.4 (31)	< 0.01*
Shape, % (n)			0.10^†
Arranged	53.9% (159)	38.7% (12)
Irregular	46.1% (136)	61.3% (19)
Boundary properties, % (n)			0.29^†
Smooth	56.7% (166)	46.9% (15)
Coarse	43.3% (127)	53.1% (17)
Boundary clarity, % (n)			0.51^†
Clear	62.2% (184)	56.3% (18)
Unclear	37.8% (112)	43.8% (14)
Internal properties, % (n)			0.74^†
Uniform	31.5% (93)	34.4% (11)
Non-uniform	68.5% (202)	65.6% (21)
Internal echo level, % (n)			< 0.01^†
Isoechoic	68.1% (201)	46.9% (15)
Hypoechoic	31.9% (94)	53.1% (17)
Coarse internal calcification, % (n)			0.09^‡
Presence	12.5% (37)	3.1% (1)
Absence	37.5% (259)	96.9% (31)
Microcalcifications, % (n)			< 0.01^†
Presence	24.1% (71)	62.5% (20)
Absence	75.9% (224)	37.5% (12)
Internal blood flow, % (n), [Adjusted standardized value]			< 0.05^†
Abundant	27.1% (79) [-2.0]	43.8% (14) [+2.0]
Small amount	49.8% (145) [0]	50% (16) [0]
None	23% (67) [+2.2]	6.23% (2) [-2.2]
Boundary hypoechoic zone, % (n)			0.28^‡
Regular	14.0% (41)	9.4% (3)
Irregular	12.3% (36)	21.9% (7)
None	73.6% (215)	68.8% (22)
Nodule type, % (n)			< 0.01^‡
Solid	59.1% (176)	97.0% (32)
Mixed	40.9% (122)	3.0% (1)

Table 3. Comparison of Ultrasonography Results Between Benign and Malignant Nodules

Benign nodule

Malignant nodule

P value

Values of the thyroid gland and nodule are expressed as mean ± standard deviation. *Welch’s t-test. ^†Pearson’s χ² test. ^‡Fisher’s exact test.

Volume of the thyroid gland, mL (n)

37.3 ± 27.3 (181)

25.5 ± 11.0 (22)

< 0.01*

Volume of thyroid nodule, mL (n)

11.7 ± 7.1 (283)

3.9 ± 2.4 (31)

< 0.01*

Shape, % (n)

0.10^†

Arranged

53.9% (159)

38.7% (12)

Irregular

46.1% (136)

61.3% (19)

Boundary properties, % (n)

0.29^†

Smooth

56.7% (166)

46.9% (15)

Coarse

43.3% (127)

53.1% (17)

Boundary clarity, % (n)

0.51^†

Clear

62.2% (184)

56.3% (18)

Unclear

37.8% (112)

43.8% (14)

Internal properties, % (n)

0.74^†

Uniform

31.5% (93)

34.4% (11)

Non-uniform

68.5% (202)

65.6% (21)

Internal echo level, % (n)

< 0.01^†

Isoechoic

68.1% (201)

46.9% (15)

Hypoechoic

31.9% (94)

53.1% (17)

Coarse internal calcification, % (n)

0.09^‡

Presence

12.5% (37)

3.1% (1)

Absence

37.5% (259)

96.9% (31)

Microcalcifications, % (n)

< 0.01^†

Presence

24.1% (71)

62.5% (20)

Absence

75.9% (224)

37.5% (12)

Internal blood flow, % (n), [Adjusted standardized value]

< 0.05^†

Abundant

27.1% (79) [-2.0]

43.8% (14) [+2.0]

Small amount

49.8% (145) [0]

50% (16) [0]

None

23% (67) [+2.2]

6.23% (2) [-2.2]

Boundary hypoechoic zone, % (n)

0.28^‡

Regular

14.0% (41)

9.4% (3)

Irregular

12.3% (36)

21.9% (7)

None

73.6% (215)

68.8% (22)

Nodule type, % (n)

< 0.01^‡

Solid

59.1% (176)

97.0% (32)

Mixed

40.9% (122)

3.0% (1)

**Table 4.** Diagnostic Accuracy of the Ultrasonographic Findings
	Sensitivity (%)	Specificity (%)	Positive likelihood ratio
Internal echo level (hypoechoic)	53.1	68.1	1.67
Microcalcifications (presence)	62.5	75.9	2.6
Internal blood flow (abundant)	43.8	72.9	1.61
Nodule type (solid)	96.9	41.4	1.65

Table 4. Diagnostic Accuracy of the Ultrasonographic Findings

Sensitivity (%)

Specificity (%)

Positive likelihood ratio

Internal echo level (hypoechoic)

53.1

68.1

1.67

Microcalcifications (presence)

62.5

75.9

2.6

Internal blood flow (abundant)

43.8

72.9

1.61

Nodule type (solid)

96.9

41.4

1.65