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Partial thyroid arterial embolization for the treatment of hyperthyroidism
European Journal of Radiology 81 (2012) 1192–1196
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Partial thyroid arterial embolization for the treatment of hyperthyroidism a ˛ Krzysztof Brzozowski a,∗ , Piotr Piasecki a , Piotr Ziecina , Emilia Frankowska b , Andrzej Jaroszuk c , c b ´ Grzegorz Kaminski , Romana Bogusławska-Walecka a Department of Interventional Radiology, Military Institute of Health Service, Central Teaching Hospital of the Ministry of National Defence, Szaserów 128 Str., 04-141 Warsaw, Poland b Department of Radiology, Military Institute of Health Service, Central Teaching Hospital of the Ministry of National Defence, Warsaw, Poland c Department of Endocrinology and Isotope Therapy, Military Institute of Health Service, Central Teaching Hospital of the Ministry of National Defence, Warsaw, Poland
a r t i c l e
i n f o
Article history: Received 25 January 2011 Received in revised form 17 March 2011 Accepted 23 March 2011 Keywords: Arterial embolization Thyroid Toxic nodular goiter Graves’ disease
a b s t r a c t Background: Hyperactive thyroid gland in patients that are unable to tolerate or accept standard therapy is a common clinical problem. Aim of the study was to evaluate effectiveness of partial thyroid arterial embolization in patients with hyperthyroidism. Material/methods: From May 2004 to November 2005 partial thyroid gland embolization was performed in 15 patients. Mean thyroid gland volume was 162 ml. Embolization of one to three thyriod arteries was performed with the mixture of Histoacryl and Lipiodol. Selective angiography was performed after embolization to ensure that the targeted arteries were completely occluded. Follow-up study covered 12 patients. Results: The embolization procedure was well tolerated by all patients. Three days after embolization fT3 and fT4 levels were higher than before the procedure. Further laboratory tests showed quick reversal to near-normal or normal levels of thyroid hormones. 12 weeks follow-up showed: normal serum levels of fT3, fT4 and TSH in 9 of 12 patients (75%), hyperthyroidism in 3 of 12 patients (25%), goiter volume reduction of approximately 32% of its original volume (from 13 to 76.3%), mean thyroid gland volume of 94 ml. One year after embolization 7 of 12 patients required thyreostatic drugs. At two and four years follow-up thyreostatics doses were significantly lower and thyroid tissue was fibrotic. Conclusions: Based on our results the treatment of the thyroid gland goiters using arterial thyroid gland partial embolization may be offered as an effective alternative for patients who will not or cannot accept standard therapy. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Treatment of patients with hyperactive thyroid gland goiter is a significant clinical problem. Despite the availability of effective treatment strategies for thyroid gland goiter there are some patients who are unable to tolerate or accept standard therapy. There are three options of standard therapy in case of hyperactive thyroid gland goiter: thyreostatic drugs, radioiodine and surgical treatment [1,2]. Sometimes none of these therapeutic methods can be used. It happens in patients who failed to respond to radioactive iodine therapy, patients who cannot tolerate the thyreostatic drugs and patients who are poor surgical candidates (especially the elderly with severe cardiac problems or with large mediastinal goiter). Moreover, standard therapy may not always be used in young women of the child bearing age [2].
∗ Corresponding author. Tel.: +48 22 6816127; fax: +48 22 6816854. E-mail address: [email protected] (K. Brzozowski). 0720-048X/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2011.03.071
Endovascular embolization of the thyroid arteries was first described in 1984 by Gunther and co-authors [3]. They performed embolization in three patients with parathyroid gland tumors using transcatheter injection of alcohol, all in cases with high surgical risk. Later, in 1999, Isozaki described percutaneous ethanol injection into a lesion in the thyroid gland in 54-year-old man with medullary thyroid carcinoma [4]. A larger study was published in 2002 by Xiao and co-authors [5]. They described 22 cases of Graves’ disease with hyperthyroidism. They performed embolization of two or three thyroid arteries using PVA (polyvinyl alcohol) particles followed by placement of an embolization coil in the main artery trunk to obtain complete artery occlusion. After the procedure they observed that the size of the thyroid gland had decreased by one third to one half of its original volume and majority of patients became euthyroid. Embolization of thyroid arteries is also mandatory in iatrogenic lesions, for example after biopsy [6]. Investigations described above inspired us to perform our own studies. Considering limitations of existing therapies in selected cases of hyperthyroidism we wanted to evaluate effectiveness of thyroid gland embolization techniques.
K. Brzozowski et al. / European Journal of Radiology 81 (2012) 1192–1196
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2. Materials and methods From May 2004 to November 2005 we performed partial thyroid gland embolization in 15 patients (12 females, 3 males; mean age 57 years; age range from 31 to 83 years). Patients presented with: toxic nodular goiter with compression of the local structures (7 patients), Graves’ disease (5 patients), amiodarone-induced thyrotoxicosis (2 patients) and recurrent toxic nodular goiter with compression symptoms (1 patient). In our study we included patients who failed to respond to standard therapy (were unable to tolerate or accept it). Inclusion criteria were: refusal of surgical treatment (6 patients), contraindications for surgical treatment (severe cardiac problems, 5 patients), noncompliance with or having serious side effects to antithyroid drugs (1 patient), failure to respond to radioactive iodine therapy (3 patients). 4 out of 15 patients were medically fit to surgery but they were offered partial thyriod embolization as less invasive alternative. All patients required thyreostatic therapy: 12 out of 15 patients were in the state of euthyreosis, 3 out of 15 patients had hyperthyroidism (1 patient with toxic nodular goiter, 1 patient with amiodarone-induced thyrotoxicosis and one patient with Graves’ disease). Patients with toxic nodular goiter (7 cases) and patient with recurrent toxic nodular goiter (1 case) complained of mild respiratory distress and dysphagia from compression of the trachea and esophagus caused by large goiter. Mean thyroid gland volume measured in CT was 162 ml, with main part of thyroid in the mediastinum (Fig. 1). All patients were informed about the procedure, its risk and potential side effects. The study protocol was approved by the internal ethics committee of our hospital. The procedures started with the puncture of femoral artery using the Seldinger technique under local anesthesia, followed by selective angiography of thyroid arteries. The catheter was advanced sequentially to both superior and both inferior thyroid arteries. DSA with iodinated contrast media (Omnipaque 350) was performed as a treatment planning for visualization of the arteries and regions of the thyroid gland supplied by them (Fig. 2). In normal condition the major blood supply to the thyroid gland comes from the left and right superior thyroid arteries. According to Xiao et al.
Fig. 1. Contrast-enhanced CT (MPR). Left brachiocephalic vein (arrowhead) strained by large mediastinum goiter (arrows).
bilateral superior thyroid arteries account for nearly 70% of the total blood supply in the majority of patients [5]. The angiograms helped us to evaluate the pathological thyroid blood supply [5,12]. Based on this evaluation we decided on how many and which arteries should be embolized. We chose the arteries that provided most of the blood supply to pathologically changed thyroid tissue based on angiographic appearance of the vessels, the flow and the contrast uptake of the thyroid gland. At least one thyroid artery was saved to ensure blood flow to parathyroid glands. The occlusion of one to three of four thyroid arteries seemed sufficient to block the majority of the blood supply to the gland. In most cases (67%) we embolized two arteries – right and left inferior thyriod artery. After selective catheterization by guiding catheter (Cordis Envoy 5F) we coaxially introduced the microcatheter (Cook Microferret 1.8F) into the artery lumen (Fig. 3). Embolization was performed with the mixture (3:1 solution) of Histoacryl (monomeric n-butyl-2-cyanoacrylate, B. Braun Medical AG, Switzerland) and Lipiodol (Guebert GmbH, France) until we achieved total occlusion of the main artery trunk.
Fig. 2. Digital subtraction angiography (DSA). Selective angiogram of left inferior thyroid artery (arrow) shows large goiter in mediastinum with hypervascularity – arterial (a) and parenchymal phase (b).
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K. Brzozowski et al. / European Journal of Radiology 81 (2012) 1192–1196
Fig. 3. DSA. Selective catherization of left inferior thyroid artery with microcatheter (arrow).
This way we accomplished simultaneous occlusion of small vessels and the main artery trunk. Selective angiography was performed after embolization to ensure that the targeted arteries were completely occluded (Figs. 4–6). To evaluate the clinical effectiveness the serum levels of free T3 (fT3 ), free T4 (fT4 ), TSH and calcium were measured before the procedure and on the 3rd day and 1st, 2nd, 4th and 12th week after embolization. A follow-up contrast enhanced CT examination was performed 1, 3 and 12 months after the procedure to establish correlation between decreasing free T4 level and volume of thyroid gland. In three cases (2 patients with Graves’ disease and one patient with nodular goiter after thyroidectomy) follow-up period was less
Fig. 4. DSA. Control angiogram after embolization of left inferior thyroid artery shows complete target vessel occlusion (arrow).
Fig. 5. Conventional chest X-ray. Opacifying Histacryl and Lipiodol mixture visible in the vessels lumen after embolization (arrows).
than 3 months for reasons not related to the study (patients lost to follow-up). In remaining 12 patients group (10 females, 2 males; age range of 44–83 years; mean age 63 years) follow-up lasted: 13–18 months in 5 cases and 4–9 months in 7 cases. 3. Results Control angiogram performed after embolization showed that the majority of the blood supply to the thyroid gland was affected. The embolization procedure was well tolerated by all patients. Minor complications included: tension feeling in the neck and mild neck pain which spontaneously subsided, fever that lasted no longer than 3 days and in one patient asymptomatic transient hypocalcemia. We did not experience any angiography-related complications such as non target embolization or gluing of the catheter. Three or four days after the procedure patients were released from the hospital. Three days after embolization fT3 and fT4 levels were higher than before embolization. Laboratory tests (1st, 2nd, 4th and 12th week after embolization) showed quick reversal to near-normal or normal levels of thyroid hormones (Fig. 7). Twelve weeks after the procedure serum levels of fT3 , fT4 and TSH were normal in 9 of 12 patients (75%). Hyperthyroidism was found in 3 of 12 patients (25%) – two with toxic nodular goiter, one with Graves’ disease. Most of patients required antithyroid drugs to maintain euthyreosis. Levothyroxine LT4 supplementation was required in 2 cases. CT examination performed 3 months after embolization showed: goiter volume reduction of approximately 32% of its original volume (from 13 to 76.3%), mean thyroid gland volume was 94 ml. At one year follow-up 7 patients required antithyroid therapy. Two and four years after embolization procedure thyreostatics doses were significantly lower and thyroid tissue was evidently fibrotic in imaging studies. Sonography demonstrated hypoechoic thyroid tissue. CT scans showed hypodense thyroid tissue with decreased enhancement after administration of
K. Brzozowski et al. / European Journal of Radiology 81 (2012) 1192–1196
1195
Fig. 6. DSA. Selective catherization of left superior thyroid artery (long arrow) before (a) and after the embolization (b). Embolization material (mixture of Histoacryl and Lipiodol) is seen in distal part of superior thyroid artery (short arrows) and in inferior thyroid artery (arrowheads).
Fig. 7. Median baseline serum free T4 levels before endovascular treatment (BT) and in follow-up tests performed during 12 weeks after embolization (free T4 normal range: 9–22 pmol/l).
contrast medium caused by fibrosis and extremely diminished vascularity. In 7 patients with toxic nodular goiter compression symptoms resolved. Two of five patients with Graves’ disease had orbitopathy with 5/6 points in Clinical Activity Score (CAS). The embolization improved the course of associated orbitopathy to 3/4 points in CAS. Decreased volume of the functioning thyroid tissue shortened the time required to obtain euthyreotic state and led to reduction of antithyroid drugs doses. Before thyriod gland embolization 3 of 15 patients required thiamazole (5–7.5 mg per day), after the procedure only one of these patients required thiamazole (5 mg per day) in order to obtain euthyreosis. 4. Discussion Thyroid arterial embolization is a procedure without established protocols. Therefore, before performing embolization it was necessary to define the targeted arteries. Selective angiography of bilateral superior and inferior thyroid arteries was performed
before embolization. In each case we chose 2 or 3 arteries that provided the majority of the blood supply to the thyroid gland. Performing post treatment angiograms was necessary to ensure the blockage of chosen vessels and the effect of the embolization. As embolization material we used a mixture of Histoacryl and Lipiodol that ensures the total occlusion of small vessels and the main artery trunk simultaneously. The experience gained from our study has shown minor disadvantages of Histoacryl embolization. The usage of Histoacryl requires simultaneous administration of Lipiodol that has high concentration of iodine, what might have contributed to persisting or recurring hyperthyroidism, especially in patients with nodular goiter. PVA does not have this side effect, reduces the possibility of revascularization and can be successfully used in thyroid embolization. Therefore nowdays in our practice we also use PVA-100 or PVA-200 particles. Three days after embolization fT3 and fT4 levels were higher than before embolization what did not affect clinical condition of patients. The presumptive mechanism of this finding can be the release of thyroid hormones due to the necrosis and ischemia of thyroid tissue after embolization. One of the goals of the thyroid embolization was to reduce the goiter size. It allowed elimination or resolving of compression symptoms (7 patients with toxic nodular goiter and 1 patient with recurrent toxic nodular goiter). Decreased volume was associated with a reduction in antithyroid doses. In patients with Graves’ disease (2 cases) the embolization improved the course of associated orbitopathy. Selective embolization of the thyroid gland has an outcome similar to the surgical subtotal thyroidectomy. Embolization of the majority of the thyroid gland arteries is associated with good therapeutic effect. We suggest that the number of embolized arteries should depend on arterial supply of goiter and should be evaluated by selective arteriography. The post-treatment study confirmed the success of the procedure – we observed the normalization of the levels of thyroid hormones and decreased volume of the goiter. Although at one year follow-up 7 out of 12 patients required thyreostatic drugs to obtain euthyreosis the doses of these drugs were significantly lower.
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Latest publications show that embolization procedure may be used for quick preparation to thyroidectomy [7,8]. Dedecjus et al. [9] performed preresective selective embolization of thyroid arteries in 10 patients. The procedure decreased operating time and blood flow through the thyroid, minimalizing blood loss during and after thyroidectomy. Selective embolization of thyroid arteries can also effectively palliate the tumour-related symptoms in inoperable anaplastic thyroid cancer patients [10]. In study published by Zhao in 2009 [11] thyroid arterial embolization enhances the positive expression of pro-apoptotic genes in Graves’ disease. It results in apoptosis of thyroid cells and helps restore the thyroid size and function. Our report confirms and completes results of previous trials. In our opinion, endovascular embolization techniques are valuable alternative of treatment in selected cases of hyperthyroidism, especially considering limitations of existing therapies. More patients should be evaluated and preferably in multiple clinical centers. The future challenge will be making thyroid embolization acceptable alternative treatment of hyperthyroidism. References [1] Nauman A, Nauman J. Thyroid diseases. In: Wojtczak A, editor. Internal diseases. Warszawa: PZWL; 1995. p. 27–58, t. III. [2] Singer PA, Cooper DS, Levy EG, et al. Treatment guidelines for patients with hyperthyroidism and hypothyroidism, Standards of Care Committee American Thyroid Association. JAMA 1995;273(10):808–12.
[3] Gunther R, Beyer J, Hesch H, et al. Percutaneous transcatheter ablation of parathyroid gland tumors by alcohol injection and contrast media infusion. ROFO Fortschr Geb Rontgenstr Nuklearmed 1984;140(1):27– 30. [4] Isozaki T, Kiba T, Numata K, et al. Medullary thyroid carcinoma with multiple hepatic metastases: treatment with transcatheter arterial embolization and percutaneous ethanol injection. Intern Med 1999;38(1):17– 21. [5] Xiao H, Zhuang W, Wang S, et al. Arterial embolization: a novel approach to thyroid ablative therapy for Graves’ disease. J Clin Endocrinol Metab 2002;87(8):3583–9. [6] Perona F, Barile A, Oliveri M, et al. Superior thyroid artery lesion after US-guided chemical parathyroidectomy: angiographic diagnosis and treatment by embolization. Cardiovasc Interbent Radiol 1999;22(3):249– 50. [7] Tartaglia F, Salvatori FM, Pichelli D, et al. Preoperative embolization of thyroid arteries in a patient with a large cervicomediastinal hyperfunctioning goiter. Thyroid 2007;17(8):787–92. [8] Ramos HE, Braga-Basaria M, Haquin C, et al. Preoperative embolization of thyroid arteries in a patient with large multinodular goiter and papillary carcinoma. Thyroid 2004;14(11):967–70. [9] Dedecjus M, Tazbir J, Kaurzel Z, et al. Evaluation of selective embolization of thyroid arteries (SETA) as a preresective treatment in selected cases of toxic goiter. Thyroid Res 2009;2(1):7. [10] Dedecjus M, Tazbir J, Kaurzel Z, et al. Selective embolization of thyroid arteries as a preresective and palliative treatment of thyroid cancer. Endocr Relat Cancer 2007;14(3):847–52. [11] Zhao W, Gao BL, Yi GF, et al. Apoptotic study in Graves disease treated with thyroid arterial embolization. Endocr J 2009;56(2):201– 11. [12] Marache P. Vascular interventional radiology. Bull Acad Natl Med 1991;175:1113–20.
Contents lists available at ScienceDirect
European Journal of Radiology journal homepage: www.elsevier.com/locate/ejrad
Partial thyroid arterial embolization for the treatment of hyperthyroidism a ˛ Krzysztof Brzozowski a,∗ , Piotr Piasecki a , Piotr Ziecina , Emilia Frankowska b , Andrzej Jaroszuk c , c b ´ Grzegorz Kaminski , Romana Bogusławska-Walecka a Department of Interventional Radiology, Military Institute of Health Service, Central Teaching Hospital of the Ministry of National Defence, Szaserów 128 Str., 04-141 Warsaw, Poland b Department of Radiology, Military Institute of Health Service, Central Teaching Hospital of the Ministry of National Defence, Warsaw, Poland c Department of Endocrinology and Isotope Therapy, Military Institute of Health Service, Central Teaching Hospital of the Ministry of National Defence, Warsaw, Poland
a r t i c l e
i n f o
Article history: Received 25 January 2011 Received in revised form 17 March 2011 Accepted 23 March 2011 Keywords: Arterial embolization Thyroid Toxic nodular goiter Graves’ disease
a b s t r a c t Background: Hyperactive thyroid gland in patients that are unable to tolerate or accept standard therapy is a common clinical problem. Aim of the study was to evaluate effectiveness of partial thyroid arterial embolization in patients with hyperthyroidism. Material/methods: From May 2004 to November 2005 partial thyroid gland embolization was performed in 15 patients. Mean thyroid gland volume was 162 ml. Embolization of one to three thyriod arteries was performed with the mixture of Histoacryl and Lipiodol. Selective angiography was performed after embolization to ensure that the targeted arteries were completely occluded. Follow-up study covered 12 patients. Results: The embolization procedure was well tolerated by all patients. Three days after embolization fT3 and fT4 levels were higher than before the procedure. Further laboratory tests showed quick reversal to near-normal or normal levels of thyroid hormones. 12 weeks follow-up showed: normal serum levels of fT3, fT4 and TSH in 9 of 12 patients (75%), hyperthyroidism in 3 of 12 patients (25%), goiter volume reduction of approximately 32% of its original volume (from 13 to 76.3%), mean thyroid gland volume of 94 ml. One year after embolization 7 of 12 patients required thyreostatic drugs. At two and four years follow-up thyreostatics doses were significantly lower and thyroid tissue was fibrotic. Conclusions: Based on our results the treatment of the thyroid gland goiters using arterial thyroid gland partial embolization may be offered as an effective alternative for patients who will not or cannot accept standard therapy. © 2011 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Treatment of patients with hyperactive thyroid gland goiter is a significant clinical problem. Despite the availability of effective treatment strategies for thyroid gland goiter there are some patients who are unable to tolerate or accept standard therapy. There are three options of standard therapy in case of hyperactive thyroid gland goiter: thyreostatic drugs, radioiodine and surgical treatment [1,2]. Sometimes none of these therapeutic methods can be used. It happens in patients who failed to respond to radioactive iodine therapy, patients who cannot tolerate the thyreostatic drugs and patients who are poor surgical candidates (especially the elderly with severe cardiac problems or with large mediastinal goiter). Moreover, standard therapy may not always be used in young women of the child bearing age [2].
∗ Corresponding author. Tel.: +48 22 6816127; fax: +48 22 6816854. E-mail address: [email protected] (K. Brzozowski). 0720-048X/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ejrad.2011.03.071
Endovascular embolization of the thyroid arteries was first described in 1984 by Gunther and co-authors [3]. They performed embolization in three patients with parathyroid gland tumors using transcatheter injection of alcohol, all in cases with high surgical risk. Later, in 1999, Isozaki described percutaneous ethanol injection into a lesion in the thyroid gland in 54-year-old man with medullary thyroid carcinoma [4]. A larger study was published in 2002 by Xiao and co-authors [5]. They described 22 cases of Graves’ disease with hyperthyroidism. They performed embolization of two or three thyroid arteries using PVA (polyvinyl alcohol) particles followed by placement of an embolization coil in the main artery trunk to obtain complete artery occlusion. After the procedure they observed that the size of the thyroid gland had decreased by one third to one half of its original volume and majority of patients became euthyroid. Embolization of thyroid arteries is also mandatory in iatrogenic lesions, for example after biopsy [6]. Investigations described above inspired us to perform our own studies. Considering limitations of existing therapies in selected cases of hyperthyroidism we wanted to evaluate effectiveness of thyroid gland embolization techniques.
K. Brzozowski et al. / European Journal of Radiology 81 (2012) 1192–1196
1193
2. Materials and methods From May 2004 to November 2005 we performed partial thyroid gland embolization in 15 patients (12 females, 3 males; mean age 57 years; age range from 31 to 83 years). Patients presented with: toxic nodular goiter with compression of the local structures (7 patients), Graves’ disease (5 patients), amiodarone-induced thyrotoxicosis (2 patients) and recurrent toxic nodular goiter with compression symptoms (1 patient). In our study we included patients who failed to respond to standard therapy (were unable to tolerate or accept it). Inclusion criteria were: refusal of surgical treatment (6 patients), contraindications for surgical treatment (severe cardiac problems, 5 patients), noncompliance with or having serious side effects to antithyroid drugs (1 patient), failure to respond to radioactive iodine therapy (3 patients). 4 out of 15 patients were medically fit to surgery but they were offered partial thyriod embolization as less invasive alternative. All patients required thyreostatic therapy: 12 out of 15 patients were in the state of euthyreosis, 3 out of 15 patients had hyperthyroidism (1 patient with toxic nodular goiter, 1 patient with amiodarone-induced thyrotoxicosis and one patient with Graves’ disease). Patients with toxic nodular goiter (7 cases) and patient with recurrent toxic nodular goiter (1 case) complained of mild respiratory distress and dysphagia from compression of the trachea and esophagus caused by large goiter. Mean thyroid gland volume measured in CT was 162 ml, with main part of thyroid in the mediastinum (Fig. 1). All patients were informed about the procedure, its risk and potential side effects. The study protocol was approved by the internal ethics committee of our hospital. The procedures started with the puncture of femoral artery using the Seldinger technique under local anesthesia, followed by selective angiography of thyroid arteries. The catheter was advanced sequentially to both superior and both inferior thyroid arteries. DSA with iodinated contrast media (Omnipaque 350) was performed as a treatment planning for visualization of the arteries and regions of the thyroid gland supplied by them (Fig. 2). In normal condition the major blood supply to the thyroid gland comes from the left and right superior thyroid arteries. According to Xiao et al.
Fig. 1. Contrast-enhanced CT (MPR). Left brachiocephalic vein (arrowhead) strained by large mediastinum goiter (arrows).
bilateral superior thyroid arteries account for nearly 70% of the total blood supply in the majority of patients [5]. The angiograms helped us to evaluate the pathological thyroid blood supply [5,12]. Based on this evaluation we decided on how many and which arteries should be embolized. We chose the arteries that provided most of the blood supply to pathologically changed thyroid tissue based on angiographic appearance of the vessels, the flow and the contrast uptake of the thyroid gland. At least one thyroid artery was saved to ensure blood flow to parathyroid glands. The occlusion of one to three of four thyroid arteries seemed sufficient to block the majority of the blood supply to the gland. In most cases (67%) we embolized two arteries – right and left inferior thyriod artery. After selective catheterization by guiding catheter (Cordis Envoy 5F) we coaxially introduced the microcatheter (Cook Microferret 1.8F) into the artery lumen (Fig. 3). Embolization was performed with the mixture (3:1 solution) of Histoacryl (monomeric n-butyl-2-cyanoacrylate, B. Braun Medical AG, Switzerland) and Lipiodol (Guebert GmbH, France) until we achieved total occlusion of the main artery trunk.
Fig. 2. Digital subtraction angiography (DSA). Selective angiogram of left inferior thyroid artery (arrow) shows large goiter in mediastinum with hypervascularity – arterial (a) and parenchymal phase (b).
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K. Brzozowski et al. / European Journal of Radiology 81 (2012) 1192–1196
Fig. 3. DSA. Selective catherization of left inferior thyroid artery with microcatheter (arrow).
This way we accomplished simultaneous occlusion of small vessels and the main artery trunk. Selective angiography was performed after embolization to ensure that the targeted arteries were completely occluded (Figs. 4–6). To evaluate the clinical effectiveness the serum levels of free T3 (fT3 ), free T4 (fT4 ), TSH and calcium were measured before the procedure and on the 3rd day and 1st, 2nd, 4th and 12th week after embolization. A follow-up contrast enhanced CT examination was performed 1, 3 and 12 months after the procedure to establish correlation between decreasing free T4 level and volume of thyroid gland. In three cases (2 patients with Graves’ disease and one patient with nodular goiter after thyroidectomy) follow-up period was less
Fig. 4. DSA. Control angiogram after embolization of left inferior thyroid artery shows complete target vessel occlusion (arrow).
Fig. 5. Conventional chest X-ray. Opacifying Histacryl and Lipiodol mixture visible in the vessels lumen after embolization (arrows).
than 3 months for reasons not related to the study (patients lost to follow-up). In remaining 12 patients group (10 females, 2 males; age range of 44–83 years; mean age 63 years) follow-up lasted: 13–18 months in 5 cases and 4–9 months in 7 cases. 3. Results Control angiogram performed after embolization showed that the majority of the blood supply to the thyroid gland was affected. The embolization procedure was well tolerated by all patients. Minor complications included: tension feeling in the neck and mild neck pain which spontaneously subsided, fever that lasted no longer than 3 days and in one patient asymptomatic transient hypocalcemia. We did not experience any angiography-related complications such as non target embolization or gluing of the catheter. Three or four days after the procedure patients were released from the hospital. Three days after embolization fT3 and fT4 levels were higher than before embolization. Laboratory tests (1st, 2nd, 4th and 12th week after embolization) showed quick reversal to near-normal or normal levels of thyroid hormones (Fig. 7). Twelve weeks after the procedure serum levels of fT3 , fT4 and TSH were normal in 9 of 12 patients (75%). Hyperthyroidism was found in 3 of 12 patients (25%) – two with toxic nodular goiter, one with Graves’ disease. Most of patients required antithyroid drugs to maintain euthyreosis. Levothyroxine LT4 supplementation was required in 2 cases. CT examination performed 3 months after embolization showed: goiter volume reduction of approximately 32% of its original volume (from 13 to 76.3%), mean thyroid gland volume was 94 ml. At one year follow-up 7 patients required antithyroid therapy. Two and four years after embolization procedure thyreostatics doses were significantly lower and thyroid tissue was evidently fibrotic in imaging studies. Sonography demonstrated hypoechoic thyroid tissue. CT scans showed hypodense thyroid tissue with decreased enhancement after administration of
K. Brzozowski et al. / European Journal of Radiology 81 (2012) 1192–1196
1195
Fig. 6. DSA. Selective catherization of left superior thyroid artery (long arrow) before (a) and after the embolization (b). Embolization material (mixture of Histoacryl and Lipiodol) is seen in distal part of superior thyroid artery (short arrows) and in inferior thyroid artery (arrowheads).
Fig. 7. Median baseline serum free T4 levels before endovascular treatment (BT) and in follow-up tests performed during 12 weeks after embolization (free T4 normal range: 9–22 pmol/l).
contrast medium caused by fibrosis and extremely diminished vascularity. In 7 patients with toxic nodular goiter compression symptoms resolved. Two of five patients with Graves’ disease had orbitopathy with 5/6 points in Clinical Activity Score (CAS). The embolization improved the course of associated orbitopathy to 3/4 points in CAS. Decreased volume of the functioning thyroid tissue shortened the time required to obtain euthyreotic state and led to reduction of antithyroid drugs doses. Before thyriod gland embolization 3 of 15 patients required thiamazole (5–7.5 mg per day), after the procedure only one of these patients required thiamazole (5 mg per day) in order to obtain euthyreosis. 4. Discussion Thyroid arterial embolization is a procedure without established protocols. Therefore, before performing embolization it was necessary to define the targeted arteries. Selective angiography of bilateral superior and inferior thyroid arteries was performed
before embolization. In each case we chose 2 or 3 arteries that provided the majority of the blood supply to the thyroid gland. Performing post treatment angiograms was necessary to ensure the blockage of chosen vessels and the effect of the embolization. As embolization material we used a mixture of Histoacryl and Lipiodol that ensures the total occlusion of small vessels and the main artery trunk simultaneously. The experience gained from our study has shown minor disadvantages of Histoacryl embolization. The usage of Histoacryl requires simultaneous administration of Lipiodol that has high concentration of iodine, what might have contributed to persisting or recurring hyperthyroidism, especially in patients with nodular goiter. PVA does not have this side effect, reduces the possibility of revascularization and can be successfully used in thyroid embolization. Therefore nowdays in our practice we also use PVA-100 or PVA-200 particles. Three days after embolization fT3 and fT4 levels were higher than before embolization what did not affect clinical condition of patients. The presumptive mechanism of this finding can be the release of thyroid hormones due to the necrosis and ischemia of thyroid tissue after embolization. One of the goals of the thyroid embolization was to reduce the goiter size. It allowed elimination or resolving of compression symptoms (7 patients with toxic nodular goiter and 1 patient with recurrent toxic nodular goiter). Decreased volume was associated with a reduction in antithyroid doses. In patients with Graves’ disease (2 cases) the embolization improved the course of associated orbitopathy. Selective embolization of the thyroid gland has an outcome similar to the surgical subtotal thyroidectomy. Embolization of the majority of the thyroid gland arteries is associated with good therapeutic effect. We suggest that the number of embolized arteries should depend on arterial supply of goiter and should be evaluated by selective arteriography. The post-treatment study confirmed the success of the procedure – we observed the normalization of the levels of thyroid hormones and decreased volume of the goiter. Although at one year follow-up 7 out of 12 patients required thyreostatic drugs to obtain euthyreosis the doses of these drugs were significantly lower.
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Latest publications show that embolization procedure may be used for quick preparation to thyroidectomy [7,8]. Dedecjus et al. [9] performed preresective selective embolization of thyroid arteries in 10 patients. The procedure decreased operating time and blood flow through the thyroid, minimalizing blood loss during and after thyroidectomy. Selective embolization of thyroid arteries can also effectively palliate the tumour-related symptoms in inoperable anaplastic thyroid cancer patients [10]. In study published by Zhao in 2009 [11] thyroid arterial embolization enhances the positive expression of pro-apoptotic genes in Graves’ disease. It results in apoptosis of thyroid cells and helps restore the thyroid size and function. Our report confirms and completes results of previous trials. In our opinion, endovascular embolization techniques are valuable alternative of treatment in selected cases of hyperthyroidism, especially considering limitations of existing therapies. More patients should be evaluated and preferably in multiple clinical centers. The future challenge will be making thyroid embolization acceptable alternative treatment of hyperthyroidism. References [1] Nauman A, Nauman J. Thyroid diseases. In: Wojtczak A, editor. Internal diseases. Warszawa: PZWL; 1995. p. 27–58, t. III. [2] Singer PA, Cooper DS, Levy EG, et al. Treatment guidelines for patients with hyperthyroidism and hypothyroidism, Standards of Care Committee American Thyroid Association. JAMA 1995;273(10):808–12.
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