Electronic Letters to:

Endocrine Care: Christine L. H. Snozek, Eugene P. Chambers, Carl C. Reading, Thomas J. Sebo, J. Woody Sistrunk, Ravinder J. Singh, and Stefan K. G. Grebe Serum Thyroglobulin, High-Resolution Ultrasound, and Lymph Node Thyroglobulin in Diagnosis of Differentiated Thyroid Carcinoma Nodal Metastases J Clin Endocrinol Metab 2007; 92: 4278-4281 [Abstract] [Full text] [PDF]

eLetters: Submit a response to this article

Electronic letters published:

Response to Chabre et al's letter: Lymph node thyroglobulin is a quantity, not a concentration

Stefan Grebe   (28 February 2008)

Lymph node thyroglobulin is a quantity, not a concentration

Olivier CHABRE, Patrice Faure, Anne-Laure Borel, Robert Boizel   (13 February 2008)

Response to Chabre et al's letter: Lymph node thyroglobulin is a quantity, not a concentration 28 February 2008
Stefan Grebe Mayo Clinic Send letter to journal: Re: Response to Chabre et al's letter: Lymph node thyroglobulin is a quantity, not a concentration grebs{at}mayo.edu Stefan Grebe	We share the concern of Drs. Chabre, Faure, Borel and Boizel that variability in needle wash volume will impact the measured concentration of thyroglobulin. We were therefore careful to point out in our paper that our data were generated using total needle wash volumes of 0.5-1 mL and that we consider this the preferred approach. When these guidelines are followed, then reporting of thyroglobulin concentrations works well and results in excellent clinical test performance, when using a 1 ng/mL cut-off, as we demonstrate clearly in the paper. Whether reporting thyroglobulin in ng/FNA basis would be able to further improve test performance is unlikely, given the outstanding test performance we observed in our study. It also remains doubtful that reporting thyroglobulin in ng/FNA instead of ng/mL would be advantageous when there is greater variability in needle wash volume than in our study. While superficially appealing, such an approach has many serious real-life drawbacks. First, it introduces another source of variability into the measurement process, as the collected needle wash volume would have to be measured accurately in order to back-calculate the measured thyroglobulin concentrations (laboratory tests use concentration-based calibration curves) to ng/FNA. Typically, the coefficient of variation (CV) of such volume measurements might be expected to be in the order of 5% under real-life conditions. As independent measurement errors are multiplicative, adding this on top of a 5% analytical CV would increase the assay’s total CV to about 25%. Second, reporting thyroglobulin in ng/FNA rather than ng/mL would introduce several additional sources of potential laboratory error. There would be a manipulation of the sample when its volume is measured, allowing for potential loss of sample, contamination of sample, or sample mix-up. There would also be the possibility of transcription error when documenting the measured total sample volume. Further potential for sample misidentification or transcription error would be introduced when the instrument-generated thyroglobulin concentration is transferred to the ng/FNA calculation. The calculation itself would have to be performed off-line, and calculation errors could occur. Finally, the result of the calculation would have to be entered into result sheets or the laboratory information system, again with the potential for patient/sample mix-up or transcription error. In balance, we feel that using standard ng/mL reporting for thyroglobulin in FNA needle washes is probably preferable to reporting in ng/FNA under most circumstances and will yield reliable results. It remains important, however, to give the clinicians who collect the samples some guidelines about recommended total needle wash sample volumes.
Lymph node thyroglobulin is a quantity, not a concentration 13 February 2008
Olivier CHABRE, Professor of Endocrinology, MD PhD Université Joseph Fourier and Centre Hospitalier Grenoble, FRANCEUniversitaire Albert Michallon, Patrice Faure, Anne-Laure Borel, Robert Boizel Send letter to journal: Re: Lymph node thyroglobulin is a quantity, not a concentration OlivierChabre{at}chu-grenoble.fr Olivier CHABRE, et al.	We would like to point out what we believe is an error in the way Snozek et al. (1) present their data in their study of the diagnostic value of measuring the quantity of thyroglobulin remaining inside the needle after fine needle aspiration biopsy of a lymph node suspected contain a metastasis of differentiated thyroid cancer. To measure thyroglobulin quantity, the authors use 3 to 6 punctures of the same lymph node with different needles, rinse each needle with a variable volume of saline serum, and pool the material into a sample in which the concentration of thyroglobulin is then measured. As a result, the data that they report depend not only on the patient’s lymph node, but also on the variations in the method. Imagine, for instance, that a lymph node is punctured 3 times with 3 different needles, each retaining 1 ng thyroglobulin. If each needles is then washed with 0.33 ml, the total amount of thyroglobulin will be 3 ng, diluted in a total volume of 1 ml, so the measured thyroglobulin concentration will be 3ng/ml. However, if the same lymph node is punctured 6 times with 6 needles, each of them rinsed with 0.1 ml, the concentration becomes 10 ng/ml (6 ng/ 0.6 ml). Consequently, variations in the procedure reported by the authors could induce a 3.3 fold difference in the final result. This casts some doubts on the meaning of the 1 ng/ml cut off level that the authors use for diagnosis of DTC lymph node metastasis. We believe it is important to recognize that what is should be measured is the total quantity of thyroglobulin extracted from a lymph node, which can be easily calculated from the concentration of thyroglobulin in the sample, multiplied by the volume of the sample. In 1992, Pacini, who first described FNA thyroglobulin assessment, recognized this problem and expressed the result in ng/FNA, not in ng/ml (2). References 1. Snozek C, Chambers EP, Reading CC, Sebo TJ, Sistrunk W, Singh RJ, Grebe KJ 2007 Serum Thyroglobulin, High-Resolution Ultrasound, and Lymph Node Thyroglobulin in Diagnosis of Differentiated Thyroid Carcinoma Nodal Metastases. J Clin Endocrinol Metab 92:4278-4281 2. Pacini F, Fugazzola L, Lippi F, Ceccarelli C, Centoni R, Miccoli P, Elisei R, Pinchera A 1992 Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. J Clin Endocrinol Metab 74:1401-1404