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Original Studies |
Division and Research Unit of Endocrinology (M.Z., D.C., M.R.G., V.T.) and Department of Pathology (V.N.), Scientific Institute, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 Italy
Address all correspondence and requests for reprints to: Matteo Zingrillo, M.D., Divisione ed Unità di Ricerca di Endocrinologia, Ospedale Casa Sollievo della Sofferenza, Istituto di Ricovero e Cura a Carattere Scientifico, San Giovanni Rotondo (Fg), 71013, Italy.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Symptom score was significantly reduced (P < 0.01) after 6 months and at the end of the follow-up (2.1 ± 0.3 vs. 0.2 ± 0.5 and vs. 0.2 ± 0.4). A significant (P < 0.01) nodule volume reduction was observed, without differences between solid or mixed CBNs; the reduction was 50% or more in 92.7% of patients. Neither clinical parameters nor pretreatment nodule ultrasonographic features were related to nodule reduction.
Disappearance or significant reduction (>0.5 cm) of tracheal displacement was obtained in 61% and in 39% of patients, respectively.
One patient experienced prethyroid region edema, pain, and mild fewer, which reversed within 1 week; and one patient had dysphonia, caused by vocal cord palsy, which reversed spontaneously within 1 month.
At the end of the follow-up, nodules with just necrotic material at cytology showed a greater (P < 0.05) volume reduction than nodules with residual benign thyroid cells.
Our data suggest that PEI is a safe and effective treatment of large CBNs, although sometimes serious side effects do occur.
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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In patients with CBNs who either refuse surgery or are at poor surgical risk, percutaneous ethanol injection (PEI), which is an established treatment in other thyroid nodular disease (4, 5, 6, 7, 8, 9, 10), may play a role (11, 12, 13).
The present study was undertaken to assess the feasibility of PEI treatment in patients affected by large (>10 mL) CBNs. The end-point of our study was to evaluate the efficacy of PEI on: 1) symptoms of local compression; and 2) nodule volume and tracheal displacement at ultrasound.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Forty-one patients affected by CBN were enrolled from January 1993 to October 1996.
Inclusion criteria were as follows: 1) clinical finding of a single
thyroid palpable nodule; 2) ultrasonographic evidence of a
well-delimited solid or prevalently solid (cystic component lower than
40%), large (
10 mL) nodule; 3) the presence of a cold area,
corresponding to the palpable nodule, at 99mTc
scintigraphy; 4) at least two benign (colloid nodular goiter with
various degrees of cellular hyperplasia) cytological examinations,
performed by ultrasound guided fine-needle biopsy (FNAB), within a
12-month interval; 5) normal values of plasma free thyroid hormones,
TSH and calcitonin; 6) the presence of at least one of the following
indications for surgery: neck discomfort, dysphagia, tracheal
displacement, estethic complaint; and 7) stability of nodule
volume (volume change < 1 mL), free of treatment in the 6 months
before starting PEI.
All patients either had poor surgical risk or refused surgery. Exclusion criteria were as follows: 1) age under 16 and over 60 yr; 2) previous neck irradiation; 3) history of familial thyroid cancer; 4) ultrasonographic evidence of calcifications or fibrosis within the nodule; 5) uncertain nodule border (risk of ethanol seepage into the surrounding normal thyroid parenchyma, during the injection); and 6) substernal nodule (incomplete access to the nodule).
Clinical characteristics of the 41 patients studied are shown in
Table 1
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Patients entered the study after giving informed consent, according to the Declaration of Helsinki.
Methods
Symptoms evaluation. The following symptoms were considered: 1) pressure symptoms in the neck; 2) difficulty in swallowing (dysphagia); and 3) estethic complaint. An arbitrary score (0 = absent; 1 = moderate; 2 = severe) was attributed to each symptom. The sum of these single scores was indicated as the symptom score (SYS).
Ultrasound examination and PEI procedure. Ultrasound examination and PEI procedure were carried out by the same operator using a real-time scanner (Toshiba Tosbee, Otawara-shi, Tochigi-Ken, Japan) with a 7.5-MHz probe. Nodule volume was calculated by a previously validated algorithm (14). Tracheal displacement was evaluated by performing transversal scans at different levels of thyroid lobes: tracheal longitudinal axis variation of more than 1 cm was considered as positive. To exclude lumen reduction, tracheal displacement at ultrasound was confirmed by an upper-mediastinum x-ray.
PEI was performed by injecting, with a 20-G needle, sterile 95% ethanol (Salf, Bergamo, Italy) into the nodule, under sonographic guidance. To optimize the effect of PEI, the needle was repositioned when the diffusion of ethanol during the injection was inhomogeneous. We pursued the administration of approximately 1 mL ethanol/mL nodule volume. The mean ethanol volume/nodule volume ratio was 0.8 ± 0.2 mL. The ethanol was injected at weekly intervals, divided into 2–7 mL doses, with a mean of 5 ± 2 (range 2–8) sessions per patient.
The variability of the amount of ethanol injected for each session was caused by both total nodule volume and individual tolerance (i.e. injection on larger nodules was better tolerated).
PEI was well tolerated by most patients, and none of them refused to continue the ongoing treatment. All patients experienced local pain, but analgesics were rarely required. One patient experienced prethyroid region edema, pain and mild fewer, which reversed within 1 week during prednisone treatment. Finally, dysphonia appeared in a patient soon after the first PEI session; an ipsilateral vocal cord palsy was identified, which reversed spontaneously within 1 month. No treatment interruption was needed in this subject.
Follow-up. Assessments of SYS and ultrasonography were performed by the same observer 3, 6, 12, 24, and 36 months after the last PEI session. Mean follow-up after the last PEI sessions was 21 ± 9 months (range 12–36).
At the end of the follow-up, in all patients having the residual nodule volume more than 1 mL (40 out of 41), an ultrasonographically guided FNAB was performed; a second aspiration, in a different site, was carried out if ultrasound showed inhomogeneity within the treated nodule.
The percentage of nodular volume reduction was defined as follows: nodule volume (mL) after PEI/nodule volume (mL) before PEI x 100.
Unpaired or paired Student’s t tests were used to compare mean values. Pearson (if data were distributed normally) or Spearman (if data were not distributed normally) analyses were used to look for numerical correlation between variables. Stepwise regression analysis was used to look for multiple correlations. Data are expressed as mean ± SD.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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SYS was significantly (P < 0.01) reduced after 6 months (2.1 ± 0.3 vs. 0.2 ± 0.5) and at the end of the follow-up period (0.2 ± 0.4). Disappearance or a significant reduction (>0.5 cm) of tracheal displacement was observed 6–12 months after PEI in 22 of 36 (61%) and in 14 of 36 (39%) patients, respectively.
Nodule size
A progressive and significant (P < 0.01) nodule
size reduction was observed, reaching the plateau between 3 and 6
months after the last PEI session (Fig. 1). A percentage of volume reduction of
69.0 ± 12.2 (range 42.2–89.0, median 68.4) was observed 6 months
after PEI. A similar result was observed at the end of the follow-up
period (70.9 ± 14.6% volume reduction, range 41–94, median
73.1) with no difference observed between solid or mixed CBNs
(70.1 ± 14.1 vs. 69.4 ± 19.3%,
respectively).
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Neither patient parameters (i.e. sex and age), nor pretreatment nodule ultrasonographic features (i.e. basal volume, solid or mixed, solitary or prominent) were able to predict, by both single- and multiple-regression analysis, efficacy of PEI on nodule volume reduction.
In 31 of the 40 patients (77.5%) who performed FNAB, residual cytologically benign thyroid cells were observed at the end of the follow-up. In contrast, just necrotic follicular cells, cell debris, ghost eosinophilic follicles, and blood cells were observed in the remaining 9 patients (22.5%), who had a volume reduction greater (P < 0.05) than that observed in the former 32 patients (79.2 ± 8.9 vs. 65 ± 19%).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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10 mL) CBNs in
most patients. Maximal mean reduction was obtained within 6 months and
remained unchanged during the entire follow-up period. Moreover, a
significant reduction or disappearance of symptoms and tracheal
displacement was obtained in most patients. As a consequence, surgery,
which was initially indicated in all patients, was no longer necessary
in any of them. The efficacy of PEI treatment, in terms of nodule volume reduction, was not predictable by any of the patient characteristic and nodule features taken into account in this study.
The efficacy of PEI treatment in CBNs has been recently reported in two studies (12, 13).
At variance with a recent report on PEI treatment in CBNs (12), we carried out a limited number of PEI sessions, just enough to avoid surgery, without necessarily pursuing a total destruction of the nodule.
In a prospective randomized trial (13), the effect of a single PEI session vs. suppressive doses of LT4 was compared in euthyroid patients with a single solid colloid thyroid nodule with median nodule volume, at baseline, less than 10 mL: after 12 months the median nodule reduction in the PEI group was higher than in the LT4 group (47% vs. 9%, respectively, P < 0.0001), indicating that a single PEI session may be considered for the treatment of relatively small nodules.
Further studies, with longer follow-up, are needed to define which approach is the most convenient one, to prevent nodule regrowth.
Our data support PEI in the treatment of CBNs, when surgery cannot be performed. In iodine-deficient areas, where thyroid cold nodules are larger and more common (4.3 vs. 1.7%) than in iodine-sufficient areas (16), there is a stronger need for alternative treatments of symptomatic, large CBNs, not eligible for surgery; and PEI may turn out to be such an alternative.
Although the false-negative rate of FNAB in cold thyroid nodules is less than 2% (3), caution is suggested in the selection of CBNs before PEI treatment and during the subsequent follow-up.
In conclusion, our data suggest that PEI is a safe and effective treatment of symptomatic large CBNs. This treatment might be proposed to patients who either refuse surgery or are at poor surgical risk.
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Acknowledgments |
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Received February 20, 1998.
Revised April 29, 1998.
Revised July 1, 1998.
Accepted July 31, 1998.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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