FNA-TG of Neck Nodes in the Patients with PTC is Affected by Serum Concentration of TSH And Thyroglobulin

JH Moon1, YI Kim2, JA Lim3, HS Choi3, SW Cho3, KW

Kim4, JC Paeng2, YJ Park3, KH Yi5, DJ Park3, J-K Chung2

1Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul

National University College of Medicine2Department of Nuclear Medicine, Seoul National University College of Medicine3Department of Internal Medicine, Seoul National University Hospital, Seoul National

University College of Medicine4Seoul National University Healthcare System Kangnam Center, Seoul National

University College of Medicine5SMG-SNU Boramae Medical Center, Seoul National University College of Medicine

Statement of interest: None

• Measuring the concentration of thyroglobulin directly in the washout of the needle used in FNAC

FNA-Tg

• Factors affecting FNA-Tg and resulting in the discrepancy between the final diagnosis and FNA-Tg

Various cut-off value (0.93-50 ng/ml)

•To suggest an optimal cut-off value of FNA-Tg to determine malignant LN with a large number of cases from PTC patients

•To find out parameters affecting FNA-Tg and the diagnosis using FNA-Tg

- Evaluation of discrepant results

Study objectives

Subjects and Methods

Patient characteristics and FNA-Tg according to the final diagnosis

　 Final diagnosisp-value

　 Malignancy Benign

Lymph nodes (n) 190 338 　

Patients 　 　 　

Sex (male/female, %) 30.5/69.5 24.3/75.7 0.228*

Age (year) 52.6 ± 15.0 49.5 ± 12.4 0.017†

Primary tumor 　 　 　

Size (mm) 18.0 ± 10.9 13.5 ± 11.4 < 0.001†

Multiplicity (yes/no, %) 69.5/30.5 63.1/36.9 0.203* Lymph nodes metastasis (yes/no, %) 87.0/13.0 59.3/40.7 < 0.001*

Lymphatic invasion (yes/no, %) 51.0/49.0 27.2/72.8 < 0.001*

Vascular invasion (yes/no, %) 32.3/67.7 15.7/84.3 < 0.001* Extrathyroid extension (yes/no, %) 90.3/9.7 71.6/28.4 < 0.001*

FNA-Tg (ng/ml) 521.2 (3676.8) 0.1 (0.2) < 0.001‡

Serum Tg (ng/ml) 1.4 (9.5) 0.2 (0.4) < 0.001‡

FNA-Tg - Serum Tg (ng/ml) 333.3 (2397.7) 0.0 (0.3) < 0.001‡

Data are expressed as mean ± SD or median (interquatile range).

FNA-Tg, thyroglobulin in the needle washout fluid of fine-needle aspiration cytology

*Derived from a Chi-square test.

†Derived from a Student's T test.

‡Derived from a Mann-Whitney U test.

Validation of Cut-off value(FNA-Tg vs. FNA-Tg – serum Tg)

Included lymph nodes

Cut-off valueSensitivity

(%)Specificity

(%)FNA-Tg(ng/ml)

FNA-Tg - serum Tg

(ng/ml)

Surgically resected LNs only (n =165)1.11 　 93.8 88.9

0.15 87.4 89.7

Surgically resected LNs and LNs F/U for 36 months or more (n = 255)

1.11 　 94.1 95.0

0.40 87.3 95.3

Surgically resected lymph nodes and LNs F/U for 24 months or more (n = 377)

0.99 　 94.2 95.5

0.40 87.7 96.1

Surgically resected lymph nodes and LNs F/U for 12 months or more (n = 528, all cases)

1.0 　 93.2 95.9

　 0.48 85.7 96.7

Diagnostic performance

ROC of FNA-Tg for Dx of malig. LN. in all casesOptimal cut-off value: 1.0 ng/ml AUC: 0.967 (95% CI 0.949-0.984)

Diagnosis modality Sensitivity (%) Specificity (%)

FNAC 83.6* 98.2*

FNA-Tg (cut off value, 1.0 ng/ml) 93.2* 95.9*

FNA-Tg (1.0 ng/ml) + FNAC 98.4 94.4

*p < 0.05 vs. FNA-Tg + FNAC, derived from a McNemar test.

The cut-off value of FNA-Tg according to the presence of thyroid gland

Prior to thyroidectomy

After thyroidectomy

2.24 ng/ml (95.0%, 96.3%)AUC: 0.987 (95% CI 0.975-0.999)

1.09 ng/ml (90.8%,

96.5%)AUC: 0.956 (95% CI 0.932-0.980)

FNA-Tg, serum Tg and TSH according to the presence of thyroid gland

FNA-Tg

201.0 (3884.77)

0.1 (2.90)

All cases Malignant cases Benign cases

Serum TgCorrelated

ρ = 0.383p < 0.001

Correlatedρ = 0.228p = 0.004

Correlatedρ = 0.210p < 0.001

Serum TSHCorrelated

ρ = 0.210p < 0.001

Correlatedρ = 0.335p < 0.001

Not correlatedρ = 0.075p = 0.183

Correlation of FNA-Tg with serum Tg or TSH

Correlation of FNA-Tg with TgAb

TgAb - TgAb +

0.1 (7.15)

0.3 (71.46)

Serum TSH and Tg on the diagnosis from FNA-Tg

Logistic regression analysis of serum TSH and Tg with the diagnosis using FNA-Tg cut-off value 1.0 ng/ml

　Odd ratio

95% confidence interval for odds ratio p-value

　 Lower Upper

Serum TSH 1.171 1.038 1.321 0.01

Serum Tg 1.035 1.012 1.059 0.003

The dependent variable was the diagnosis using ENA-Tg cut off value 1.0 ng/ml, and the independent vari-ables

were serum TSH and Tg levels.

　Odd ratio

95% confidence interval for odds ratio p-value

　 Lower Upper

No serum TSH suppres-sion 2.871 1.794 4.595 < 0.001

Serum Tg presence 1.980 1.261 3.109 0.003

The dependent variable was the diagnosis using ENA-Tg cut off value 1.0 ng/ml, and the independent vari-ables

were no serum TSH suppression (serum TSH ≥ 0.4 mU/l) and serum Tg presence (serum Tg ≥ 0.2 ng/ml).

Logistic regression analysis of serum TSH suppression and serum Tg presence with the diagnosis using FNA-Tg cut-off value 1.0 ng/ml

Clinical implications

•Optimal cut-off value of FNA-Tg was 1.0 ng/ml

•FNA-Tg + FNAC showed better diagnostic rate than FNAC or FNA-Tg alone.

•FNA-Tg was correlated with serum Tg and TSH, not with TgAb.

•The diagnosis using FNA-Tg can be affected by serum TSH and Tg levels.

Summary

• The combination of FNAC and FNA-Tg can complement the low sensitivity of FNAC alone.

• TSH suppression and the presence of serum Tg should be considered for accurate FNA-Tg-based diagnosis of metastatic malignant LNs in PTC patients.

Conclusion