Cut-off Value for Thyroglobulin Washout Concentration in the Detection of Cervical Lymph Node Metastases in Patients after Thyroidectomy Due to Differentiated Thyroid Cancer.

The aim of this study was to establish the cut-off value for the thyroglobulin (Tg) concentration in washout fluid from fine needle aspiration biopsy (FNA-Tg) in the detection of cervical lymph node metastases of differentiated thyroid cancer (DTC). We evaluated the validity and clinical utility of fine needle aspiration biopsy cytology (FNAB-C), FNA-Tg, and the combined method in detecting DTC recurrences. The study included 82 patients after the total thyroidectomy and elective and, in some cases, also selective cervical lymphadenectomy. The majority of patients also underwent subsequent 131I ablative therapy. The patients presented with 1-6 enlarged and/or ultrasonographically suspicious cervical lymph nodes. One to four aspirates of each lymph node were taken, with a total of 297 samples. An FNA-Tg of 4.34 ng/mL was established as the cut-off value for detecting cervical lymph node DTC metastases for the IRMA Brahms DYNO test, Tg-S. FNAB-C is highly specific (91-99%) but not sensitive enough (53-69%) to be used as a standalone method in the detection of cervical lymph node metastases. FNA-Tg is more sensitive (91%), but caution should be taken when selecting patients for surgery with an FNA-Tg higher than the established cut-off value but lower than the serum Tg concentration. To select patients for lymphadenectomy, we recommend using the combined method (FNAB-C and FNA-Tg) with a sensitivity of 96% and specificity of up to 97%. More than one sample should be taken with each fine needle aspiration biopsy (FNAB) to obtain a representative set of samples.

Calcitonin and procalcitonin in patients with medullary thyroid cancer or bacterial infection.

OBJECTIVES: To evaluate procalcitonin (PCT) utility as a marker of medullary thyroid cancer (MTC). MATERIAL AND METHODS: Calcitonin (CT) and PCT levels were measured in MTC patients and patients with serious bacterial infections. 70 patients were enrolled in the study: 6 MTC active patients: 4 with disseminated, unreoperable disease and 2 re-operated patients, in whom markers were checked before and after surgery; 23 MTC patients in remission after radical surgery; 11 non-toxic nodular goiter (NTNG) patients; 30 patients with severe, bacterial infection or sepsis. RESULTS: All MTC active patients had greatly elevated CT and PCT levels. In two re-operated patients, marker levels decreased but were still above the reference range. In 15 MTC patients in remission, the levels of either marker were not increased. Both markers were slightly increased in 3 patients in this group, while CT was elevated in 5 patients. In all but 1 patient in the NTNG group, both marker levels were not elevated. Among patients with bacterial infection, PCT and CT levels showed no increase in 8 patients, both markers were elevated in 10 patients, and an increase of PCT levels was seen in 10 patients while of CT only in 2 patients. Correlations between CT and PCT values were very strong in MTC patients (r = 0.95; p = 0.004 for active MTC, r = 0.60; p = 0.002 for MTC patients in remission) and in patients with NTNG (r = 0.77; p = 0.02). In patients with infection, both parameters were completely independent (r = 0.002; p = 0.99). CONCLUSIONS: PCT measurement could be an alternative to CT measurement for evaluation of MTC status.

Can procalcitonin be useful for medullary thyroid cancer?

INTRODUCTION: Calcitonin, the best known marker for medullary thyroid cancer (MTC), has several laboratory limitations which limit its use in the routines of non-specialized laboratories. Procalcitonin, the precursor of calcitonin, is free from these drawbacks. The aim of this study was to compare calcitonin and procalcitonin levels in MTC patients with active disease or in remission, and in patients with non-toxic nodular goiter (NTNG). MATERIAL AND METHODS: Forty-three serum samples, obtained from 40 patients (6 MTC active disease patients, 23 MTC patients in remission, and 11 NTNG patients), were tested for calcitonin and procalcitonin levels. The levels of both markers were measured in 2 MTC patients with active disease before and after surgery. One was re-operated due to neck relapse, the other one due to liver metastases. RESULTS: Both procalcitonin and calcitonin levels were considerably higher in all MTC patients with the active disease. In two re-operated patients, the levels of both markers decreased after surgery but remained above the reference range. In the remission group of MTC patients, 18 had both markers within the reference range, 2 had slightly elevated calcitonin, and 3 patients exhibited both markers slightly increased. In the NTNG group, all but one patient had normal procalcitonin and calcitonin levels. Analysis revealed a significant correlation between procalcitonin and calcitonin levels (r = 0.7383; p < 0.0001). CONCLUSIONS: Procalcitonin has a similar distribution of values as calcitonin and may be used for evaluation of MTC status in some situations when accurate CT estimation is not achievable.

An evaluation of the value of first thyroglobulin determination in the diagnostics of metastases immediately following differentiated thyroid carcinoma surgery.

INTRODUCTION: Evaluation of the differential value of the first thyroglobulin (Tg) concentration, measured after thyroidectomy (Tx) but before thyroid remnant ablation, in patients with differentiated thyroid carcinoma (DTC) as a marker of either metastases or residual cancer (M). MATERIAL AND METHODS: Data from 517 patients with DTC after Tx, with follow-up > 1.5 year were analysed retrospectively. Patients in whom either the course of the disease was unclear or interference in the Tg test was possible (a-TgAb [+], Tg recovery < 80%) were excluded from the study. Finally, the data from 247 patients were evaluated (age: 14-79 years; 223 women, 24 men). The results of TSH, thyroid radioiodine uptake (T(up24)), thyroid remnant volume (V) and Tg in patients with diagnosed M (group M1; n = 35) were compared with the same parameters in patients with remission > 1.5 year (group M0; n = 212). The area under the ROC curve was calculated. The clinical decision limit of Tg level to be suggestive of metastases was determined by means of efficiency curve. RESULTS: Groups M0 and M1 did not differ from each other with respect to TSH concentration (median 49.7 mIU/l vs 44.3; p = 0.16) or thyroid remnant volume (1.4 vs 1.1 ml; p = 0.79). However, they did differ with respect to T(up24) (7.6 vs 3.2%; p = 0.01) and Tg (4.5 vs 96.7 ng/ml; p = 0.000000). Area under ROC for Tg was 0.78 +/- 0.05 (mean +/- s.e.m.). The decision limit of Tg for suspected M was determined at 38.1 ng/ml, Tg sensitivity was 0.57 (95%CI 0.39-0.74) and specificity 0.96 (95%CI 0.92-0.98). CONCLUSIONS: First thyroglobulin concentration, determined after thyroidectomy but before other treatment, is higher in patients with metastatic DTC than in patients without such metastases. This indicates that Tg level may be used as an early marker of either residual or metastatic DTC (even if thyroid remnants are present).

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer.

INTRODUCTION: Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. MATERIAL AND METHODS: The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and (131)I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15-711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94-100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. RESULTS: Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. CONCLUSIONS: 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes in patients with differentiated thyroid cancer.

[Application of 13-cis-retinoic acid in patients with 131I scintigraphically-negative metastases of differentiated thyroid carcinoma]. / Zastosowanie kwasu 13-cis-retinowego u pacjentów z nieniejodochwytnymi przerzutami zrózcowanego raka tarczycy.

INTRODUCTION: The loss of iodine uptake by differentiated thyroid carcinoma (DTC) cells is a major therapeutic problem especially in patients with nonsurgical metastatic foci or local recurrence. Using 13-cis-retinoic acid, it was attempted to retain iodine uptake as a result of redifferentiation (influence by retinoic acid receptors present in DTC cells). MATERIAL AND METHODS: Between 1999 and 2005, 13-cis-retinoic acid was used in 11 patients with disseminated PTC and high serum level of thyroglobulin (Tg) before (131)I treatment (2 patients were treated twice - 13 treatment cycles in total). Side effects in skin and mucous membranes were observed in all the patients, however, their intensity did not require termination of the therapy. RESULTS: Increase of iodine uptake was observed in 5 patients (45%). Decreased Tg concentration was observed in 9 patients. In that group, increased (131)I uptake was observed in 4 patients with distant metastases. All determinations of Tg concentrations were carried out under TSH stimulation. CONCLUSIONS: 13-cis-retinoic acid causes an increase of radioiodine uptake in around half of treated patients, however, the follow-up of these patients indicates that this increase does not result in either full remission or even stabilisation of neoplastic disease. The possibility should be considered to use cis-retinoic acid as an independent therapeutic approach in patients with radioiodine non-avid foci of thyroid carcinoma especially those showing high expression of RARb and RXRg receptors.