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Original Studies |
Departments of Medicine (D.L.G), Radiology (M.F.), and Obstetrics and Gynecology (S.G.F.), Loyola University of Chicago, Maywood, Illinois 60153
Address correspondence and requests for reprints to: Donald L. Gordon, M.D., FACP, Division of Endocrinology and Metabolism, Loyola University Medical Center, 2160 South First Avenue, Maywood, Illinois 60153. E-mail: DGORDON{at}luc.edu
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Abstract |
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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All studies evaluating the effect of L-T4 therapy on thyroid nodule volume measured by US have used the FNAB technique to verify a nonneoplastic cytology before therapy was initiated. The traumatic characteristics of a FNAB have been amply demonstrated by changes in serum thyroglobulin levels (15, 16, 17, 18), thyroid scan (19), histology (20), and the size of the thyroid nodule (20, 21) after the procedure. Repetitive thrusting of a needle into the thyroid nodule as part of the FNAB technique as a factor affecting nodule volume has never been evaluated. Therefore, we assessed changes in nodule volume caused by a FNAB in patients with a colloid goiter by comparing US measurements before the biopsy with volume measurements immediately after, as well as 1 month and 6 months later, in euthyroid patients who have not been treated with thyroid hormone.
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Subjects and Methods |
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The study consisted of patients with clinical solitary thyroid nodules who were found to be euthyroid by a TSH determination, had a colloid goiter by cytologic examination, and in whom the nodule was solid. Twenty-three patients were enrolled in the study, but complete data was lacking in 6 patients. Data at all 4 time points on the remaining 17 patients form the basis of this report. US measurements of thyroid nodule volume were made within 1 month before the FNAB, the same day after the biopsy, and approximately 1 month and 6 months later; and the results at different time points were compared. No patient received thyroid hormone therapy. Informed consent was obtained from all patients before their enrollment in the study. The study was approved by the institutional review board at Loyola University Medical Center.
Ultrasonography
Thyroid nodule volume was measured using a high-resolution US with a 7-MHZ phased-array US probe (Acuson, Mountainview, CO) employing a linear or sector format. Standard images were obtained in both axial and sagittal planes. Each nodule was measured in 3 dimensions (AP, transverse, and sagittal) using electronic calipers. Nodule volume was calculated using the formula for the volume of a prolate ellipse (L x W x D x 0.523). All images and measurements were recorded on film so that size could be compared for the study. The inherent variation of the US procedure was evaluated by the measurement of thyroid nodules in 12 nonbiopsied patients, by 2 different experienced technologists, on the same day, with each technologist blinded to the results of the other’s measurements.
Biopsy
The FNAB technique was similar to that described elsewhere, except that 2–4 passes into the thyroid nodule were performed under US guidance using a 22-gauge needle without local anesthesia (19, 20). Aspirated tissue was smeared on slides, stained, and the smears interpreted for adequacy of material, usually after 2 passes. Additional passes were made when necessary. The criteria of Kini et al. (22) were used for final cytologic assessment. Other than minor discomfort from the procedure, there were no major complaints by patients or complications.
Statistical analysis
Given that the distribution of nodule volumes for the 17
evaluable subjects at 4 time intervals was not normally distributed,
the analysis was conducted using both parametric and nonparametric
approaches. In all cases, the statistical conclusions were similar.
With the exception of the inclusion of both sample means and medians
for descriptive purposes, all statistical results presented are based
on parametric testing. Changes in nodule volume, across time, were
examined using techniques for ANOVA with repeated measures.
Nondirectional variability in the changes in nodule size between
specific time points was assessed using paired t tests on
the absolute value of the change in nodule measurements; no adjustment
was made to the 
level for multiple comparisons. For all testing, a
two-sided level of 0.05 was considered statistically
significant.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Seventeen patients not included in the interrater reliability
assessment completed the study. The mean thyroid nodule volume was
measured before the FNAB and at 3 time intervals after the biopsy
(Table 1
). There was no statistically
significant change over time in either the mean or median thyroid
nodule volume. Volumes expressed as a percent change from the previous
measurements also demonstrated no significant differences over time.
Although the median volume of the thyroid nodule at each period of
assessment was less than the sample mean caused by a skewed
distribution, the trends over time were similar. There was a trend
toward a decrease in nodule volume over time when compared with the
immediate post-FNAB volume. Although not statistically significant,
these data suggest that the nodule size decreases during follow-up
after a FNAB.
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),
i.e. nodules increased and decreased at different intervals
during follow-up. Statistically significant variation in nodule volume
occurred at each period of measurement after the FNAB. Analysis of
differences in nodule volume variability between time intervals
(pre-FNAB to immediate post-FNAB, immediate post-FNAB to 1-month
post-FNAB, and 1-month post-FNAB to 6-month post-FNAB) demonstrated
statistically significant differences across time (P =
0.0032). The variability in mean change of nodule volume was greatest
between the 1-month post-FNAB and the immediate post-FNAB periods, when
compared with either the immediate post-FNAB and the pre-FNAB periods
(P = 0.006) or the 6-month post-FNAB and the 1-month
post-FNAB periods (P = 0.008).
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). Most changes of more than 50%
were caused by enlargement of nodules, despite the tendency of the mean
thyroid nodule volume to decrease. At 1 month, there were 5 of 17
subjects in whom nodular volume changed by more than 50% when compared
with nodule volume immediately post biopsy and 6 of 17 subjects when
compared with pre-FNAB nodule volume. At 6 months post FNAB, there were
2 of 17 subjects whose nodular volume changed by more than 50% when
compared with the respective thyroid nodule volume immediately post
biopsy and 1 of 17 when compared with pre-FNAB volume. The number of
subjects whose nodular volume decreased by more than 50% when compared
with pre-FNAB measurements were 0, 1, and 0 for the immediate
post-FNAB, 1-month, and 6-month periods, respectively.
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Discussion |
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Any study that evaluates a therapeutic intervention that could potentially change thyroid nodule size must initially define the nonneoplastic nature of the nodule by FNAB. In this type of experimental design, an assumption is made that the biopsy procedure does not affect thyroid nodule size. However, no data has been published to analyze this effect. We evaluated the assumption that the FNAB does not affect thyroid nodule size. The interrater reliability of the US procedure for thyroid volume measurements in our study accounted for only 5.5% of the total variance among nodules, suggesting that 95% of the variation observed in nodule measurements represents true change in nodule volume over the course of follow-up. Because the potential for a delay in the diagnosis of a malignancy exists if a FNAB is deferred, changes in thyroid nodule volume over time, as a reflection of the natural history of the disease, were not evaluated.
We measured thyroid nodule volume, by US, before a FNAB, as well as immediately after, 1 month and 6 months later. There was no statistically significant difference in thyroid nodule size at any point measured after the FNAB, whether the volume was expressed in absolute numbers or as percentage changes. However, there was marked variation in the changes in both directions for individual subject’s thyroid nodule volumes, some being quite dramatic. These dichotomous changes tended to cancel out any significant change in mean nodule volume. This variability was significant for all changes in thyroid nodule size after the FNAB, with the greatest variation occurring 1 month post FNAB. It is possible that the variations in nodule size are part of the natural history of a colloid goiter observed over time; however, some of the changes in volume after FNAB were quite dramatic. The significantly greater variability of changes in nodule volume at 1 month post-FNAB than at 6 months after the biopsy suggests that the biopsy procedure may have been the major factor in these changes. Unfortunately, there are no US studies describing volumetric changes of thyroid nodules occurring without diagnostic (FNAB) and therapeutic (TSH suppression) intervention.
Most previous studies fail to define whether the FNAB has been performed before or after the initial US (6, 7, 8, 9, 10, 11, 12, 13, 14, 25, 26, 27). The only reference that describes whether the initial procedure was an FNAB or an US, in studies evaluating the effect of TSH suppression on thyroid nodule size, was a letter to the editor by Gharib et al. (29) clarifying that, in their experimental design, the US was usually performed at a variable period of time after the biopsy (5). Our study suggests that conclusions based on comparisons of thyroid nodule size will vary, depending on the time of measurement. Modification of results caused by the FNAB must be taken into account. Comparisons should probably be determined upon the prebiopsied thyroid nodule volume. Although we did not perform any histologic examination after the FNAB, it is likely that tissue changes exist that explain the alterations in nodule size that differed so markedly between patients. Initial changes might include edema, hemorrhage, necrosis, or infarction; however, because we excluded patients with nodules containing cystic degeneration, removal of fluid as part of the FNAB would not be a consideration. Variation in thyroid nodule volume occurring 1 or more months after the FNAB might be caused by hemorrhage, necrosis, infarction, or fibrosis (20). The changes in thyroid nodule volume after FNAB may be influenced by the vascularity of the nodule, the histology of the nodule, the number of biopsy passes, the number of thrusts per pass, rotation of the needle on insertion, other mechanical factors introduced by the person performing the biopsy, and the use of iodine as an antiseptic for the US probe in patients with varying degrees of iodine consumption. Changes in nodule size caused by the biopsy procedure will affect both arms of an experimental design consisting of a treatment and a control group in which a comparison is sought after a therapeutic intervention. Because there is marked individual variability in changes of thyroid nodule volume and a trend toward decreasing nodule size after the FNAB, it may be necessary to delay any study of therapeutic effects until a change attributable to the biopsy procedure can no longer be demonstrated.
An arbitrary change of more than 50% has been used as a clinically meaningful decrease in thyroid nodule volume when evaluating the effect of TSH suppression (5, 7, 10, 11, 12, 13, 14, 23, 25, 27). We show that, at 1 month post-FNAB, 6 of 17 (35%) patients have a more than 50% change in thyroid nodule size, when compared with the prebiopsy volume; although, in only 1 patient, was the nodule smaller. By 6 months post FNAB, there was still 1 of 17 (6%) patients whose thyroid nodule size was larger than its prebiopsy size. Clearly, these changes attributable to the FNAB procedure could interfere with the interpretation of the effectiveness of any therapeutic intervention that measures shrinkage of thyroid nodules, when the criterion used is a more-than 50% reduction in thyroid nodule volume.
In conclusion, we have demonstrated individual marked variability in thyroid nodule volume after a FNAB. The variability was significant and ,at times, quite dramatic, making it difficult to have attributed changes in nodule size to any potential therapeutic intervention, at least for the period studied. A multicenter study may be necessary to define the time required to eliminate the changes in thyroid nodule volume attributable to the biopsy procedure. Only then can studies be designed that can adequately evaluate the effects of TSH suppression on thyroid nodule volume.
Received July 2, 1999.
Revised August 19, 1999.
Accepted August 26, 1999.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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