ORIGINAL ARTICLE
Effect of Recent Contrast-Enhanced CT and Patient Age on Image Quality of Thyroid Scintigraphy Trine Borup Andersen, PhD, MD,* Ramune Aleksyniene, PhD, MD,* Lars Christian Gormsen, PhD, MD,† Lars Jødal, MSc,* and Lars J. Petersen, DMSc, MD*‡ Purpose of the Report: When thyroid scintigraphy (TS) is performed after contrast-enhanced CT (CE-CT), tracer uptake of 99mTcO4 in the thyroid gland can be inhibited by free iodide. Currently, it is recommended to postpone TS until 4 to 8 weeks after CE-CT, but few data exist to support this recommendation. The purpose was to investigate the effect of CE-CT and other variables for the diagnostic quality of TS. Patients and Methods: This retrospective study included 196 patients subjected to TS less than 3 months after a CE-CT (median, 66 days). Patients with elevated thyroid-stimulating hormone (>4.5 mIU/L) or suspected thyroiditis were excluded. Logistic regression was used to calculate the probability of a TS of diagnostic quality with the variables days since CE-CT, age, thyroid-stimulating hormone, and kidney function (eGFR). Results: Days since CT and age were highly significant (P < 0.001) predictors for diagnostic TS. The probability of diagnostic quality TS after CE-CT increased with time and reached approximately 70% to 80% 6 to 8 weeks after CE-CT. Analysis of age-specific populations showed age to be a strong independent factor. Conclusions: Our findings are in consensus with the currently recommended interval of 6 to 8 weeks between CE-CT and TS. However, our results indicate that patient age should be taken into account, and we suggest the following delay from CE-CT to TS: 4 weeks for patients aged younger than 50 years, 6 weeks for patients aged 50 to 60 years, and 8 weeks for patients aged older than 60 years. Key Words: contrast media, thyroid scintigraphy, iodide, CE-CT, image quality, CT (Clin Nucl Med 2015;40: 297–302)
T
hyroid scintigraphy (TS) is a key imaging modality in the management of thyroid disorders. In adults, the most common indications are the evaluation of a palpable nodule or enlarged gland or the visualization of the uptake pattern in the hyperthyroid patient to plan a treatment strategy. Today, an increasing number of patients are referred to TS shortly after a previous contrast-enhanced CT (CE-CT). This is in part due to the more widespread availability of CT in general and in part to the presence of more incidental thyroid findings on the CT. Thyroid scintigraphy is most commonly performed with 99m TcO4. However, the uptake of 99mTcO4 may be impaired by excess inorganic free iodide from recently injected contrast media blocking the thyroid iodide trap, which in turn reduces intrathyroidal iodide concentration by decreasing the sodium-iodide symporter expression.1 99m TcO4 avidity in the thyroid is also reduced because it is transported by the same sodium-iodide symporter. A period should thus be allowed between CE-CT and subsequent TS. Textbook recommendations, as well as guidelines from the European Society of Urogenital Radiology1 and the Society of Nuclear Medicine, recommend 4 to 8 weeks between an iodide CE-CT and a TS.2–5 However, the duration of this period Received for publication September 16, 2014; revision accepted December 10, 2014. From the *Department of Nuclear Medicine, Aalborg University Hospital, Aalborg; †Department of Nuclear Medicine, Aarhus University Hospital, Aarhus N; and ‡Department of Clinical Medicine, University of Aalborg, Aalborg, Denmark. Conflicts of interest and sources of funding: none declared. Reprints: Trine Borup Andersen, PhD, MD, Department of Nuclear Medicine, Aalborg University Hospital, Hobrovej 18-22, DK-9000, Aalborg, Denmark. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/15/4004–0297
between imaging modalities has not been supported by larger clinical original studies. A recent small study tends to support these prevailing recommendations. Padovani et al6 showed that the urine levels of iodine were normalized within 1 month after CE-CT in thyrectomized patients. However, we have not been able to identify studies that have pointedly studied the impact of a recent CE-CT on subsequent TS image quality. The purpose of this study was therefore to investigate the image quality of TS among patients subjected to a recent CE-CT performed within 3 months before TS and to investigate the influence of age, renal function, and hyperthyroidism on the probability of the TS being diagnostic. To address these aims, we estimated the probability of diagnostic image quality of TS at different time points between CE-CT and scintigraphy.
PATIENTS AND METHODS Patient Population and Study Design The study was carried out as a retrospective review of patients referred for TS between January 1, 2010 and November 31, 2012. No ethical approval was required by the national legislation in Denmark, which was confirmed by the local ethical committee. Inclusion criteria were as follows: age 18 years and older, CE-CT performed within 1 day and up to 3 months before TS, and planar TS performed in accordance with institutional practices (see below). Patients with serum/plasma concentrations of thyroid-stimulating hormone (TSH) greater than 4.5 mIU/L or suspected thyroiditis were excluded to avoid other causes of low tracer uptake. Furthermore, poor quality scintigraphies due to patient movement were excluded. If patients had a repeat scintigraphy within 3 months after the CE-CT, only the first TS was included in the study (Fig. 1). The small subset of patients with more than 1 TS was assessed separately. The prevalence of nondiagnostic TS was also investigated in a control group of patients with no history of a previous CE-CTwithin 10 years. Two hundred consecutive patients fulfilling the eligibility criteria for the test population, except for a history of no previous CE-CT within 10 years, were identified by computer search. To sex-match the test group, additional men were added to the control group. The control group was added to the protocol after the assessment of the primary study population with CE-CT to allow for comparisons with a CE-CT–naive group.
Thyroid Scintigraphy The TS was performed according to institutional practices and was largely in accordance with the European Association of Nuclear Medicine procedure guidelines.5 The patient was placed in a supine position with the neck comfortably extended and was then injected intravenously with 99mTcO4. A maximal distance of 8 cm between the collimator and patient was targeted, except in presence of a very large goiter, when adaptations to the required distance were made. Imaging in the anterior projection started within 5 minutes after the injection. The initial protocol was an activity of 74 MBq (2 mCi) and an image acquisition with small FOV γ-camera (Thyrus, Philips ADAC A/S, Eindhoven, the Netherlands) equipped with a 6-mm pinhole collimator. During the study, the injected activity was changed to 150 MBq (4 mCi), and the imaging camera to the Orbiter Scintron γ-camera (MiE, Seth, Germany) with a 4-mm pinhole collimator. Both protocols
Clinical Nuclear Medicine • Volume 40, Number 4, April 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.nuclearmed.com
297
Clinical Nuclear Medicine • Volume 40, Number 4, April 2015
Andersen et al
FIGURE 1. Illustration of patient selection.
required image registration for 10 minutes or 150,000 counts. A radioactive point source was used to identify anatomical landmarks and palpable nodules.
Assessment of Thyroid Scintigraphy Assessment of the TS of those patients with a prior CE-CT was performed by 2 consultants in nuclear medicine (R.A. with 7 years and L.C.G. with 6 years of training). To mimic the clinical situation, observers had access to the relevant clinical and demographic information, as well as to the laboratory data and days elapsed between CT and TS. The observers reported yes or no to the following question: “Is the quality of the scintigraphy sufficient to evaluate the uptake pattern (presence/absence of a cold nodule; diffuse/multinodular/adenoma)?” In addition, the activity uptake in the thyroid versus the salivary glands was evaluated on a 4-grade scale: 1, no or very faint uptake compared
TABLE 2. Models Considered for Logistic Regression and P Values for the Coefficients
TABLE 1. Patient Characteristics
Patients included Female Male Age, mean (SD), y Days between CT and TS, median (range) Reasons for referral, % Hyperthyreosis Goiter Palpable nodule Incidental finding on CT Intrathoracic goiter on CT PET incidentaloma Other
298
www.nuclearmed.com
with the salivary glands; 2, low uptake compared with the salivary glands; 3, similar uptake compared with the salivary glands; or 4, increased uptake compared with the salivary glands. Finally, the consultants were asked to rate the overall visual activity in the thyroid versus the background activity (not salivary glands): 1, none or very faint uptake; 2, decreased uptake; 3, normal uptake; or 4, increased uptake. The grading of image quality was performed during the same session by the 2 observers, independently. No discussion was allowed during the assessment. In case of a disagreement on diagnostic quality, consensus was obtained at a later session. If a consensus could not be reached, a third observer made the final decision. Based on the results (see later), a control group of patients without
Test Group
Control Group
196 71% 29% 64 (12) 44 (1–90)
200 69% 31% 54 (13)
19 15 5 38 11 3 6
29.5 32 21.5
0.5 16.5
Model parameters Individual parameters Days after CT Patient age eGFR* Hyperthyroid Combination: age and eGFR Patient age eGFR* Combination: days and age Days after CT Patient age
P
Effect of Recent Contrast-Enhanced CT and Patient Age on Image Quality of Thyroid Scintigraphy Trine Borup Andersen, PhD, MD,* Ramune Aleksyniene, PhD, MD,* Lars Christian Gormsen, PhD, MD,† Lars Jødal, MSc,* and Lars J. Petersen, DMSc, MD*‡ Purpose of the Report: When thyroid scintigraphy (TS) is performed after contrast-enhanced CT (CE-CT), tracer uptake of 99mTcO4 in the thyroid gland can be inhibited by free iodide. Currently, it is recommended to postpone TS until 4 to 8 weeks after CE-CT, but few data exist to support this recommendation. The purpose was to investigate the effect of CE-CT and other variables for the diagnostic quality of TS. Patients and Methods: This retrospective study included 196 patients subjected to TS less than 3 months after a CE-CT (median, 66 days). Patients with elevated thyroid-stimulating hormone (>4.5 mIU/L) or suspected thyroiditis were excluded. Logistic regression was used to calculate the probability of a TS of diagnostic quality with the variables days since CE-CT, age, thyroid-stimulating hormone, and kidney function (eGFR). Results: Days since CT and age were highly significant (P < 0.001) predictors for diagnostic TS. The probability of diagnostic quality TS after CE-CT increased with time and reached approximately 70% to 80% 6 to 8 weeks after CE-CT. Analysis of age-specific populations showed age to be a strong independent factor. Conclusions: Our findings are in consensus with the currently recommended interval of 6 to 8 weeks between CE-CT and TS. However, our results indicate that patient age should be taken into account, and we suggest the following delay from CE-CT to TS: 4 weeks for patients aged younger than 50 years, 6 weeks for patients aged 50 to 60 years, and 8 weeks for patients aged older than 60 years. Key Words: contrast media, thyroid scintigraphy, iodide, CE-CT, image quality, CT (Clin Nucl Med 2015;40: 297–302)
T
hyroid scintigraphy (TS) is a key imaging modality in the management of thyroid disorders. In adults, the most common indications are the evaluation of a palpable nodule or enlarged gland or the visualization of the uptake pattern in the hyperthyroid patient to plan a treatment strategy. Today, an increasing number of patients are referred to TS shortly after a previous contrast-enhanced CT (CE-CT). This is in part due to the more widespread availability of CT in general and in part to the presence of more incidental thyroid findings on the CT. Thyroid scintigraphy is most commonly performed with 99m TcO4. However, the uptake of 99mTcO4 may be impaired by excess inorganic free iodide from recently injected contrast media blocking the thyroid iodide trap, which in turn reduces intrathyroidal iodide concentration by decreasing the sodium-iodide symporter expression.1 99m TcO4 avidity in the thyroid is also reduced because it is transported by the same sodium-iodide symporter. A period should thus be allowed between CE-CT and subsequent TS. Textbook recommendations, as well as guidelines from the European Society of Urogenital Radiology1 and the Society of Nuclear Medicine, recommend 4 to 8 weeks between an iodide CE-CT and a TS.2–5 However, the duration of this period Received for publication September 16, 2014; revision accepted December 10, 2014. From the *Department of Nuclear Medicine, Aalborg University Hospital, Aalborg; †Department of Nuclear Medicine, Aarhus University Hospital, Aarhus N; and ‡Department of Clinical Medicine, University of Aalborg, Aalborg, Denmark. Conflicts of interest and sources of funding: none declared. Reprints: Trine Borup Andersen, PhD, MD, Department of Nuclear Medicine, Aalborg University Hospital, Hobrovej 18-22, DK-9000, Aalborg, Denmark. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. ISSN: 0363-9762/15/4004–0297
between imaging modalities has not been supported by larger clinical original studies. A recent small study tends to support these prevailing recommendations. Padovani et al6 showed that the urine levels of iodine were normalized within 1 month after CE-CT in thyrectomized patients. However, we have not been able to identify studies that have pointedly studied the impact of a recent CE-CT on subsequent TS image quality. The purpose of this study was therefore to investigate the image quality of TS among patients subjected to a recent CE-CT performed within 3 months before TS and to investigate the influence of age, renal function, and hyperthyroidism on the probability of the TS being diagnostic. To address these aims, we estimated the probability of diagnostic image quality of TS at different time points between CE-CT and scintigraphy.
PATIENTS AND METHODS Patient Population and Study Design The study was carried out as a retrospective review of patients referred for TS between January 1, 2010 and November 31, 2012. No ethical approval was required by the national legislation in Denmark, which was confirmed by the local ethical committee. Inclusion criteria were as follows: age 18 years and older, CE-CT performed within 1 day and up to 3 months before TS, and planar TS performed in accordance with institutional practices (see below). Patients with serum/plasma concentrations of thyroid-stimulating hormone (TSH) greater than 4.5 mIU/L or suspected thyroiditis were excluded to avoid other causes of low tracer uptake. Furthermore, poor quality scintigraphies due to patient movement were excluded. If patients had a repeat scintigraphy within 3 months after the CE-CT, only the first TS was included in the study (Fig. 1). The small subset of patients with more than 1 TS was assessed separately. The prevalence of nondiagnostic TS was also investigated in a control group of patients with no history of a previous CE-CTwithin 10 years. Two hundred consecutive patients fulfilling the eligibility criteria for the test population, except for a history of no previous CE-CT within 10 years, were identified by computer search. To sex-match the test group, additional men were added to the control group. The control group was added to the protocol after the assessment of the primary study population with CE-CT to allow for comparisons with a CE-CT–naive group.
Thyroid Scintigraphy The TS was performed according to institutional practices and was largely in accordance with the European Association of Nuclear Medicine procedure guidelines.5 The patient was placed in a supine position with the neck comfortably extended and was then injected intravenously with 99mTcO4. A maximal distance of 8 cm between the collimator and patient was targeted, except in presence of a very large goiter, when adaptations to the required distance were made. Imaging in the anterior projection started within 5 minutes after the injection. The initial protocol was an activity of 74 MBq (2 mCi) and an image acquisition with small FOV γ-camera (Thyrus, Philips ADAC A/S, Eindhoven, the Netherlands) equipped with a 6-mm pinhole collimator. During the study, the injected activity was changed to 150 MBq (4 mCi), and the imaging camera to the Orbiter Scintron γ-camera (MiE, Seth, Germany) with a 4-mm pinhole collimator. Both protocols
Clinical Nuclear Medicine • Volume 40, Number 4, April 2015 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.nuclearmed.com
297
Clinical Nuclear Medicine • Volume 40, Number 4, April 2015
Andersen et al
FIGURE 1. Illustration of patient selection.
required image registration for 10 minutes or 150,000 counts. A radioactive point source was used to identify anatomical landmarks and palpable nodules.
Assessment of Thyroid Scintigraphy Assessment of the TS of those patients with a prior CE-CT was performed by 2 consultants in nuclear medicine (R.A. with 7 years and L.C.G. with 6 years of training). To mimic the clinical situation, observers had access to the relevant clinical and demographic information, as well as to the laboratory data and days elapsed between CT and TS. The observers reported yes or no to the following question: “Is the quality of the scintigraphy sufficient to evaluate the uptake pattern (presence/absence of a cold nodule; diffuse/multinodular/adenoma)?” In addition, the activity uptake in the thyroid versus the salivary glands was evaluated on a 4-grade scale: 1, no or very faint uptake compared
TABLE 2. Models Considered for Logistic Regression and P Values for the Coefficients
TABLE 1. Patient Characteristics
Patients included Female Male Age, mean (SD), y Days between CT and TS, median (range) Reasons for referral, % Hyperthyreosis Goiter Palpable nodule Incidental finding on CT Intrathoracic goiter on CT PET incidentaloma Other
298
www.nuclearmed.com
with the salivary glands; 2, low uptake compared with the salivary glands; 3, similar uptake compared with the salivary glands; or 4, increased uptake compared with the salivary glands. Finally, the consultants were asked to rate the overall visual activity in the thyroid versus the background activity (not salivary glands): 1, none or very faint uptake; 2, decreased uptake; 3, normal uptake; or 4, increased uptake. The grading of image quality was performed during the same session by the 2 observers, independently. No discussion was allowed during the assessment. In case of a disagreement on diagnostic quality, consensus was obtained at a later session. If a consensus could not be reached, a third observer made the final decision. Based on the results (see later), a control group of patients without
Test Group
Control Group
196 71% 29% 64 (12) 44 (1–90)
200 69% 31% 54 (13)
19 15 5 38 11 3 6
29.5 32 21.5
0.5 16.5
Model parameters Individual parameters Days after CT Patient age eGFR* Hyperthyroid Combination: age and eGFR Patient age eGFR* Combination: days and age Days after CT Patient age
P
