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Measurement of the AST to LD Ratio in Parathyroid Tissue Suspension Can Precisely Differentiate a Hyperfunctioning Parathyroid

Kikumori, Toyone Ichikawa, Takahiro Inaishi, Takahiro Miyajima, Noriyuki Shibata, Masahiro Takeuchi, Dai 名古屋大学

2020.08

概要

Background: Frozen section of excised tissue is used to confirm removal of the etiology of primary hyperparathyroidism in the current era of intraoperative parathyroid hormone measurement and provides safeguards for surgeons. We recently reported that the aspartate aminotransferase (AST)/lactate dehydrogenase (LD) ratio in tissue suspension can accurately distinguish normal parathyroid tissue from other tissues. Therefore, we hypothesized that this ratio may also be applied to distinguish hyperfunctioning parathyroid tissue (HPT) from other tissues. Methods: We prospectively analyzed 22 patients who underwent parathyroidectomy for primary hyperparathyroidism (benign, 21; malignant, 1) from July 2018 to October 2019. In total, 27 specimens were examined. Approximately 1 mm3 of minced HPT as confirmed by frozen sections was suspended in 1 mL of normal saline and AST and LD levels were measured. The AST/LD ratios of other tissues (normal parathyroid tissue, thyroid gland, adipose tissue, and others; n = 94) were obtained from our previous report. Results: The AST/LD ratio of benign HPT was consistently higher than that of other tissues (P < 0.001). The optimal cut-off value was 0.36 according to the receiver operating characteristic curve, with 100% sensitivity and specificity. The AST/LD ratio in malignant HPT was also markedly lower than that in benign HPT. Conclusion: This method might be a new adjunct for intraoperative differentiation of HPT with an accuracy and turnaround time comparable with those of frozen sections, minimal cost, and no need for dedicated pathological staff. Additionally, this method might increase the treatment success rate in settings with limited medical resources.

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Figure legends

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Figure 1

242

Box plot showing logarithmically transformed AST/LD ratios in suspensions of various

243

tissues. The box plot shows upper and lower quartiles. The median is represented by a bold

244

line within the boxes. The whiskers extend from each quartile to the minimum or maximum,

245

and outliers are indicated by dots. The median for each of the tissue types is indicated at the

246

bottom of the figure. Thyroid cancer: local recurrence, metastatic lymph nodes, and primary

247

tumor; miscellaneous tissues: median cervical cyst, connective tissue, and thymus. The bold

248

horizontal broken line indicates the optimal threshold value for distinguishing HPT from

249

other tissues (0.36).

250

Figure 2

251

Scatter plot showing the correlation between the AST/LD ratio and intact PTH in suspensions

252

of HPT. The data were logarithmically transformed. The closed square indicates a malignant

253

case. The closed circle in parentheses indicates a case that was off the scale. The bold vertical

254

line indicates the optimal threshold value for distinguishing HPT from other tissues (0.36).

255

The correlation coefficient (r) is indicated in the graph. ns: not significant.

Table 1

Table 1

Table 1

Patients’ characteristics, surgical indications, and specimen information.

Sex (M : F )

Age (mean, (range))

6:16

57y, (32-83)

Surgical indication

Primary hyperparathyroidism due to single adenoma

Primary hyperparathyroidism due to double adenomas

Multiple endocrine neoplasia type 1

Parathyroid carcinoma

Total

14

22

Analyzed specimens of hyperfunctioning parathyroid tissue

Adenoma

Hyperplasia

Carcinoma

Total

16

10

27

Previously reported specimens (for comparison)

Normal parathyroid gland

Thyroid cancer

Normal lymph node

Normal thyroid

Adipose tissue

43

19

13

10

Miscellaneous

Total

Median cervical cyst

Connective tissue

Thymus

94

Table 2

Table 2

Hyperfuctioning parathyroid tissue (hyperplasia)

age sex

37 F

66 F

43 F

44 M

54 F*

32 M**

Surgical Indication

MEN1

MEN1

MEN1

MEN1

MEN1

MEN1

Surgical procedure

total

total

total

total

total

subtotal

AST (IU/L)

99

360

138

81

566

168

559

236

107

107

LD (IU/L)

238

342

239

155

511

251

675

250

168

97

15,395

320,625

152,125

33,975

49,550

130,300

53,460

120,975

43,725

19,090

0.42

1.05

0.58

0.52

1.11

0.67

0.83

0.94

0.64

1.1

intact PTH (pg/mL)

AST/LD

Hyperfuctioning parathyroid tissue (adenoma)

age sex

63 F

63 M

53 M

67 F

40 M

39 F

50 F

66 F

73 F

50 F

Surgical Indication

SA

SA

SA

SA

SA

SA

SA

SA

SA

DA

AST (IU/L)

114

704

95

71

223

42

243

25

198

215

425

LD (IU/L)

180

1,982

78

375

108

221

48

299

273

366

23,190

***

13,760

13,125

102,825

56,988

160,875

38,412

78,850

205,875

390,500

0.63

0.36

1.22

14.2

0.59

0.39

1.1

0.52

0.66

0.79

1.16

intact PTH (pg/mL)

AST/LD

Hyperfuctioning parathyroid tissue (adenoma)

age sex

Hyperfuctioning parathyroid tissue (carcinoma)

75 F

60 M

72 F

75 F

83F

40 F

Surgical Indication

SA

SA

SA

SA

SA

ParaCa

AST (IU/L)

69

215

139

41

21

126

LD (IU/L)

81

265

105

49

46

583

60,875

14,975

157,500

61,013

25,700

30,850

0.85

0.81

1.32

0.84

0.46

0.22

intact PTH (pg/mL)

AST/LD

Table 2

Table 2.

Patients’ age, sex, surgical indications, surgical procedures, AST levels, LD levels, intact PTH values, and the AST/LD ratio.

Data are shown for each final pathological diagnosis.

MEN1: multiple endocrine neoplasia type 1; SA: single adenoma; DA: double adenoma; ParaCa: parathyroid cancer.

Total: total parathyroidectomy followed by autotransplantation; subtotal: subtotal parathyroidectomy.

*This patient had multiple enlarged parathyroid glands. Therefore, multiple specimens were available for analysis using a remnant of

autotransplantation.

**Subtotal parathyroidectomy was performed because of multiple liver metastases of a pancreatic neuroendocrine tumor.

*** off-scale high.

figure 1

10

0.36

AST/LD

0.1

0.01

Hyperfunctioning Normal

parathyroid

parathyroid

tissue (benign)

tissue

median

0.8

0.43

Parathyroid

carcinoma

Normal

thyroid

Adipose

tissue

Normal

lymph node

Thyroid

cancer

Miscellaneous

0.22

0.12

0.1

0.07

0.07

0.06

Figure 1

figure 2

()

intact

PTH

(pg/mL)

100,000

r=-0.13, ns

10,000

0.1

0.36

AST/LD

10

Figure 2

...

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