BRIEF REPORT
Embolization of Bronchial Artery–supplied Ectopic Parathyroid Adenomas Located in the Aortopulmonary Window Mujtaba Ali, MD, and David A. Kumpe, MD
ABSTRACT Ectopic parathyroid adenomas in the aortopulmonary window (APW) are extremely rare, constituting only 1% of ectopic mediastinal adenomas and 0.24% of all parathyroid adenomas. The authors have encountered three patients with ectopic adenomas in the APW. In each case, the primary arterial supply to the APW adenoma arose from the bronchial artery. In addition, there was a small anastomotic arterial channel connecting the bronchial artery supplying the adenoma to the left inferior thyroid. All three adenomas were treated with transcatheter embolization, with control of hyperparathyroidism in two of three patients. One patient required thoracoscopic removal of the adenoma. It is critical that the interventionalist be aware of this arterial supply pattern to allow successful embolization of an APW ectopic adenoma.
ABBREVIATIONS APW = aortopulmonary window, PTH = parathyroid hormone
Ectopic parathyroid adenomas are rare but are a common cause of failed surgery for hyperparathyroidism, which occurs in 3%–5% of standard open surgical neck explorations (1,2). In 20%–50% of patients with recurrent or persistent hyperparathyroidism after surgical exploration, the ectopic adenoma is located in the mediastinum (3). A mediastinal adenoma is present in 2.3% of patients undergoing neck exploration (4). Mediastinal parathyroid adenomas are most often located in the anterior mediastinum, in the region of the thymus. Only 1% of ectopic mediastinal adenomas are located in the aortopulmonary window (APW) in the middle mediastinum (4), accounting for 0.24% of all patients undergoing surgery for hyperparathyroidism. The usual arterial supply to a mediastinal adenoma arises from a descending branch of the inferior thyroid artery, an arteria thyroidea ima, or the thymic branch of the internal mammary artery (3,5). Rarely, adenomas have been reported to be supplied by small branches arising from From the Department of Radiology, University of Colorado Anschutz Medical Campus, 12401 East 17th Avenue, Leprino Building, Room 527, Aurora, CO 80045. Received July 5, 2013; final revision received October 2, 2013; accepted October 3, 2013. Address correspondence to D.A.K.; E-mail: [email protected] Neither of the authors has identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; 25:138–143 http://dx.doi.org/10.1016/j.jvir.2013.10.008
the superior thyroid or brachiocephalic artery (6). We have treated three patients using transcatheter embolization in whom an ectopic parathyroid adenoma was located in the APW and supplied by the bronchial artery. This pattern of arterial supply to APW adenomas has been reported once previously (7).
CASE REPORTS We reviewed these cases after approval by the Colorado Multiple Institutional Review Board, the institutional review board for the University of Colorado. Three patients with suspected APW adenomas were referred for parathyroid venous sampling, parathyroid diagnostic arteriography, and transcatheter embolization.
Case 1 A 35-year-old man with persistent hyperparathyroidism presented with fatigue, joint pain, and a history of left renal calculi. A surgical neck exploration was performed with a left superior parathyroidectomy, but this failed to resolve his symptoms and hypercalcemia. A chest computed tomography (CT) scan was initially read as negative. Parathyroid venous sampling showed markedly elevated parathyroid hormone (PTH) levels in a left mediastinal vein, 18,679 pg/mL (baseline values from other samples, 101–460 pg/mL) (Fig 1a). Review of the chest CT scan demonstrated a 6-mm soft tissue nodule in the APW
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Figure 1. Case 1. A 35-year-old man with persistent hyperparathyroidism. (a) Parathyroid venous sampling yielded marked elevation of PTH (18,679 ng/mL) from a left mediastinal vein. In comparison, 22 other samples had values of 101–460 ng/mL. This suggests the presence of a parathyroid adenoma in the left mediastinum. The draining veins include the region of the APW. (b) After positive venous sampling, a chest CT scan, in retrospect, shows a 6-mm soft tissue nodule in the APW adjacent to the left lower trachea, consistent with parathyroid adenoma (arrow). (c) Selective injection of the common trunk of the right and left bronchial arteries shows the primary arterial supply to the APW adenoma (arrows) arising from the right bronchial branch. (d) Superselective injection of the feeding artery to the adenoma shows the anastomotic branch to the left inferior thyroid artery (arrow). (e) Superselective arteriography via the bronchial artery obtained 3 weeks after the first embolization with polyvinyl alcohol and Ethiodol. The microcatheter tip has been advanced into the anastomotic branch to the left inferior thyroid artery, cranial to the adenoma (small arrow). Reperfusion of the adenoma has occurred (large arrow). (f) Arteriography of the bronchial artery after protective embolization of the anastomotic branch to the inferior thyroid with microcoils (small arrow), followed by injection of 0.3 mL of 95% ethyl alcohol and then N-butyl cyanoacrylate glue. No opacification of the adenoma is seen (large arrow). Compare with (e).
adjacent to the left lower trachea (Fig 1b). The patient was referred for transcatheter localization and ablation. Selective arteriography of the left inferior thyroid artery demonstrated multiple small arterial branches descending into the mediastinum to opacify a 10 mm 6 mm lesion on the superior surface of the confluence of the left side of the trachea and the left main stem bronchus. The inferior thyroid arterial branches supplying the adenoma were too small to be catheterized with a microcatheter. Selective arteriography of a common bronchial artery demonstrated that its right bronchial branch gave rise to a branch extended superiorly to
supply the mediastinal adenoma (Fig 1c). This branch was the primary arterial supply to the adenoma. There was reflux into a small, tortuous arterial branch communicating with the inferior thyroid arterial plexus (Fig 1d). Using a Mikaelsson 5-F catheter (Cook, Inc, Bloomington, Indiana) as a guide, a PROWLER 10 microcatheter (Codman Neurovascular, Inc, Raynham, Massachusetts) was used to perform embolization of the feeding branch supplying the adenoma with a dilute suspension of polyvinyl alcohol particles, 50–150 μm in diameter, followed by a small amount of ethiodized oil (Ethiodol; Guerbet, Bloomington, Indiana) to increase
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the ischemic effect. Films obtained after embolization demonstrated no opacification of the adenoma or the communicating arteries of the inferior thyroid arterial plexus noted previously. The patient reported no change in his symptoms 3 weeks after the procedure. He had elevated levels of serum calcium (11.6 mg/dL) and PTH (103 pg/dL). The patient agreed to undergo a second embolization attempt. Selective bronchial arteriography demonstrated recanalization of the right bronchial artery and the arterial supply to the mediastinal adenoma and retrograde filling of the communicating branch to the left inferior thyroid artery. A 1.2-F MAGIC microcatheter (Balt Extrusion, Montmorency, France) was advanced into a communicating branch just distal to the adenoma (Fig 1e). Protective embolization of this arterial segment was performed using two 1.5-cm Berenstein Liquid Coils (Boston Scientific, Natick, Massachusetts). The 1.2-F MAGIC microcatheter was repositioned proximal to the liquid metal coils. Provocative testing of this arterial branch using intraarterial cardiac lidocaine 40 mg and amobarbital sodium (Amytal Sodium) 50 mg resulted in no change in the patient’s voice quality or pitch modulation. Embolization of the artery was performed with a slow injection of 0.3 mL of 95% ethanol, followed by N-butyl cyanoacrylate glue, 2.5:1 dilution (Codman Neurovascular). Subsequent arteriography demonstrated no opacification of the adenoma or distal arterial branches (Fig 1f). The patient’s serum calcium and PTH-related peptide levels normalized after the second embolization and were normal 6 months later. Despite apparent successful ablation of his parathyroid adenoma, he continued to experience symptoms of fatigue and pain related to new renal calculi. He was subsequently lost to follow-up.
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hypervascular, crescent-shaped, 5 mm 17 mm blush immediately superior to the left main stem bronchus, compatible with an adenoma. An arterial branch continued superiorly past the adenoma into the upper mediastinum, retrogradely filling the left inferior thyroid artery (Fig 2). Using a 5-F Mikaelsson catheter as a guide, a PROWLER microcatheter was used to perform embolization of the feeding artery with a dilute solution of polyvinyl alcohol particles, 45–150 μm in diameter, preserving the patency of the connecting branch between the inferior thyroid and the bronchial arteries. An arteriogram obtained after embolization showed no filling of the arteries supplying the adenoma or parenchymal blush. The patient’s serum calcium and PTH levels normalized within days of the embolization, indicating that the adenoma had been treated. However, several weeks after the procedure, the patient again complained of easy fatigability, and her serum calcium was again elevated. The patient returned for repeat embolization approximately 12 weeks after the initial ablation procedure. Selective arteriography of the left bronchial artery demonstrated a recurrent hypervascular blush in the region of the parathyroid adenoma. Numerous attempts were made
Case 2 A 41-year-old woman with persistent hyperparathyroidism presented with limb weakness and fatigue. A surgical neck exploration failed to reveal a parathyroid adenoma. A subsequent CT scan of the thorax demonstrated a round, 1.5-cm lesion against the outer APW, anterior to the left main stem bronchus. Selective venous sampling demonstrated a markedly elevated PTH level of 7,529 pg/mL (baseline values from other samples, 100–350 pg/mL) in a left lateral mediastinal vein, which drained the APW region, confirming that the APW lesion identified on CT scan represented a mediastinal parathyroid adenoma. The patient underwent diagnostic arteriography and embolization 3 weeks after the venous sampling procedure. Selective arteriography of the left internal mammary artery and left costocervical trunk was normal. The left thyrocervical trunk could not be located. Selective arteriography of the left bronchial artery demonstrated a superiorly directed branch supplying a
Figure 2. Case 2. A 41-year-old woman with persistent hyperparathyroidism. Superselective injection of the artery arising from the left bronchial artery supplying the adenoma (thick black arrow) shows a communicating branch (thin black arrows) that anastomoses with the descending branch of the left inferior thyroid (curved white arrow).
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to perform superselective catheterization of the feeder to the adenoma using various microwire and microcatheter combinations plus intraarterial nitroglycerin. This superselective catheterization could not be accomplished because the bronchial artery was dissected at its origin. Attempts to access the adenoma through the anastomosing branch arising from the inferior thyroid artery were also unsuccessful. The procedure was abandoned. The adenoma was subsequently removed by video-assisted thoracoscopy.
Case 3 A 19-year-old woman with large renal calculi, hydronephrosis, and pyelonephritis and a diagnosis of primary hyperparathyroidism was referred for management of a suspected mediastinal parathyroid adenoma. A sestamibi nuclear medicine scan demonstrated a focus of activity in the left mediastinum. A chest CT scan demonstrated an enhancing 11 mm 10 mm soft tissue nodule in the APW. Selective venous sampling demonstrated elevated PTH levels in a left mediastinal vein, 11,017 pg/mL (baseline values from other samples, 314–573 pg/mL), confirming that the lesion was an APW adenoma. The patient chose endovascular ablation over thoracic surgery.
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The patient underwent transcatheter ablation of the adenoma 6 weeks after venous sampling. Selective arteriography of the left thyrocervical trunk and left internal mammary arteries did not show the adenoma. Selective arteriography of the common trunk of the lower lobe left and right bronchial arteries using a Mikaelsson catheter demonstrated a densely blushing, bowl-shaped lesion closely apposed to the inferior surface of the thoracic aorta supplied by the right bronchial branch (Fig 3a). A PROWLER 14 microcatheter was advanced through the Mikaelsson catheter into the specific arterial branch supplying the adenoma (Fig 3b). Embolization of this branch was performed with 0.3 mL of 95% ethanol. Arteriography performed 5 minutes later demonstrated pruning of the arteries within the adenoma but continued perfusion. Embolization of the branch was then performed with N-butyl cyanoacrylate glue mixed with tantalum powder in a 2:1 mixture with Ethiodol. Subsequent arteriography demonstrated no perfusion of the adenoma. The patient’s symptoms were resolved 4 weeks after the procedure. Her serum calcium and PTH levels had normalized and remained normal 19 months after the embolization.
Figure 3. Case 3. A 19-year-old woman with primary hyperparathyroidism. (a) Selective arteriography of the common trunk of the bronchial artery shows the supply to the APW adenoma (curved white arrow) from a branch arising from the right bronchial artery and opacification of a small communicating artery extending toward the left inferior thyroid artery (small black arrows). (b) Superselective microcatheterization of the arterial branch supplying the adenoma. The lack of reflux of contrast material into the parent artery makes the dual arterial supply to the adenoma irrelevant as a possible source of failure of transcatheter ablation.
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DISCUSSION Ectopic parathyroid adenomas are rarely encountered in the APW. In one compilation of 7,869 patients (4) who underwent an operation for hyperparathyroidism, there were 181 patients (2.3%) with mediastinal adenomas. Among 181 patients with mediastinal adenomas, 19 APW parathyroid tumors were identified, accounting for 1% of mediastinal adenomas and 0.24% of all patients undergoing surgery for hyperparathyroidism. There are two reported series of patients with APW parathyroid adenomas comprising 10 (7) and 19 (4) patients. Doppman et al (7) also gathered another 15 cases from the literature. A more recent report documented seven cases of APW adenomas among 33 patients with mediastinal parathyroid lesions who were treated with minimally invasive procedures (8). The total number of patients with hyperparathyroidism in this series was not noted. In our three cases, the arterial supply pattern was the same. In each case, the primary arterial supply to the APW adenoma arose from the bronchial artery; in two cases, the supply was from the right bronchial branch of a common right and left bronchial artery trunk. In one case, the arterial supply arose from a separate left bronchial artery. In all three cases, there was also a small anastomotic arterial channel connecting the bronchial artery supplying the adenoma to the left inferior thyroid artery. The APW adenoma was opacified by injection of the left thyrocervical trunk in only one of three patients; no injections of either internal mammary artery showed the adenoma. Doppman et al (7) noted that among four patients with APW adenomas, arteriography was negative when only the thyrocervical trunk and internal mammary arteries were studied. Reference is made to two cases (4,9) in which injection of the internal mammary artery opacified the adenoma. To our knowledge, only two images of bronchial artery supply to an ectopic parathyroid adenoma in the APW have been published (7), and the anastomotic connection between the bronchial artery and the inferior thyroid artery when an APW adenoma is present has not been described. Treatment of mediastinal adenomas with transcatheter embolization, sclerosis, or staining has been reported (6,10–12). Doppman et al (7) attempted treatment in four patients with APW adenomas, without success. Although diagnostic venous sampling, diagnostic arteriography, and transcatheter ablation are usually reserved only for patients with persistent hyperparathyroidism after unsuccessful neck exploration, if a mediastinal adenoma is detected in a patient with primary hyperparathyroidism, these modalities can also be applied, as in our case 3. Most data reporting successful ablation of mediastinal parathyroid adenomas include the use of hypertonic ionic contrast material as described by Doppman et al
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(13–16). Hypertonic contrast material would still be our material of choice, but we have been unable to obtain this for many years. It has been suggested that absolute alcohol is a reasonable alternative to contrast medium because of greater ablative potency and the need for smaller doses with greater effect (10,12). In our experience in these three cases, embolization of the adenoma with small particles, including the injection of Ethiodol after particulate embolization in one case, produced only transient decrease in PTH production with recurrent function of the adenoma. We achieved permanent ablation with a combination of absolute alcohol followed by N-butyl cyanoacrylate embolization. It is possible that the dual arterial supply from the communicating artery and from the inferior thyroid artery played a role in the initial failure of particles with or without Ethiodol in cases 1 and 2. Even in the case when embolization ultimately fails, as in case 2, the transient decrease in PTH and serum calcium levels in response to embolization serves two useful purposes: (a) It definitely establishes that the lesion treated by embolization is the ectopic adenoma, and (b) angiographic images from the procedure, which are usually obtained in orthogonal projections, definitely localize the adenoma anatomically, which is helpful to the surgeon. The literature reports short-term success rates of endovascular ablation of mediastinal parathyroid adenomas of 73%–83% and long-term success rates of 63%–71% (6,11,17). Reported complications of endovascular parathyroid ablation attempts include chest pain, bradycardia, respiratory arrest, hiccups, hoarseness, hypocalcemia, hand weakness, slurred speech, acute thyroiditis, and acute renal failure (6,16). None of our patients experienced significant complications during or after the procedure. Nonetheless, regarding ectopic adenomas in the APW, Doppman et al (7) cautioned of potential damage to the pulmonary artery and vein, aorta, vagus, recurrent laryngeal and phrenic nerves, and bronchial and esophageal walls. Provocative neurologic testing using intraarterial preservative-free lidocaine and Amytal Sodium was performed in case 1. The utility of neurologic testing immediately before embolization of the bronchial artery has been reported (18). Pharmacologic provocative testing and neurophysiologic monitoring has been demonstrated to have a high negative predictive value in identifying potential neurologic deficits before ablation of spinal cord arteriovenous malformations as well as various intracranial and extracranial lesions (19–22). It has been reported that following unsuccessful attempts at ablation, surgical excision of parathyroid adenomas via median sternotomy can achieve up to 100% short-term resolution of symptoms and long-term cure (14). Nevertheless, the surgical cure of APW parathyroid adenomas is a formidable challenge. In a contemporary series (4), to cure 18 of 19 patients with
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APW parathyroid tumors, the following 40 operations were performed: 18 neck explorations, 12 cervicosternotomies, 5 median sternotomies, 1 anterior and 2 left thoracotomies, and 2 thoracoscopies. In this series, second operations (after failed neck exploration) were successful in 60%, whereas 40% of patients required another reoperation for cure. It is well known that sternotomy is associated with longer hospital stay, greater pain, and a more difficult recuperation period (16). Minimally invasive treatment of mediastinal adenomas has been reported to have similar morbidity and mortality to open surgery with a shorter hospital stay (8). In conclusion, given its minimally invasive nature and generally high success rates, we believe endovascular ablation remains a viable and reasonable modality in carefully selected patients for the treatment of APW parathyroid adenomas supplied by the bronchial artery. We now believe that other patients with mediastinal adenomas outside the APW that do not derive their arterial supply from the inferior thyroid artery, internal mammary artery, or arteria thyroidea ima should undergo bronchial arteriography as well, but we have not yet encountered such a case.
REFERENCES 1. Udelsman R. Six hundred fifty-six consecutive explorations for primary hyperparathyroidism. Ann Surg 2002; 235:665–670; discussion 670–672. 2. Zarebczan B, Chen H. Influence of surgical volume on operative failures for hyperparathyroidism. Adv Surg 2011; 45:237–248. 3. Conn JM, Goncalves MA, Mansour KA, McGarity WC. The mediastinal parathyroid. Am Surg 1991; 57:62–66. 4. Arnault V, Beaulieu A, Lifante JC, et al. Multicenter study of 19 aortopulmonary window parathyroid tumors: the challenge of embryologic origin. World J Surg 2010; 34:2211–2216. 5. Krudy AG, Doppman JL, Brennan MF. The significance of the thyroidea ima artery in arteriographic localization of parathyroid adenomas. Radiology 1980; 136:51–55. 6. Miller DL, Doppman JL, Chang R, et al. Angiographic ablation of parathyroid adenomas: lessons from a 10-year experience. Radiology 1987; 165:601–607.
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7. Doppman JL, Skarulis MC, Chen CC, et al. Parathyroid adenomas in the aortopulmonary window. Radiology 1996; 201:456–462. 8. Said SM, Cassivi SD, Allen MS, et al. Minimally invasive resection for mediastinal ectopic parathyroid glands. Ann Thorac Surg 2013; pii:S00034975(13)01171-5. 9. Curley IR, Wheeler MH, Thompson NW, Grant CS. The challenge of the middle mediastinal parathyroid. World J Surg 1988; 12:818–824. 10. Cook GJ, Fogelman I, Reidy JF. Successful repeat transcatheter ablation of a mediastinal parathyroid adenoma 6 years after alcohol embolization. Cardiovasc Intervent Radiol 1997; 20: 314–316. 11. McIntyre RC Jr, Kumpe DA, Liechty RD. Reexploration and angiographic ablation for hyperparathyroidism. Arch Surg 1994; 129: 499–503; discussion 504–505. 12. Reidy JF, Ryan PJ, Fogelman I, Lewis JL. Ablation of mediastinal parathyroid adenomas by superselective embolization of the internal mammary artery with alcohol. Clin Radiol 1993; 47:170–173. 13. Doppman JL, Marx SJ, Spiegel AM, et al. Treatment of hyperparathyroidism by percutaneous embolization of a mediastinal adenoma. Radiology 1975; 115:37–42. 14. Krudy AG, Doppman JL, Marx SJ, Spiegel AM, Aurbach G, Brennan MF. Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining. Radiology 1981; 140:63–65. 15. Marx SJ, Doppman JL, Spiegel AM, Wolfe D, Aurbach GD. Embolization of a mediastinal parathyroid adenoma. J Clin Endocrinol Metab 1974; 39:1110–1114. 16. Heller HJ, Miller GL, Erdman WA, Snyder WH 3rd, Breslau NA. Angiographic ablation of mediastinal parathyroid adenomas: local experience and review of the literature. Am J Med 1994; 97:529–534. 17. Doherty GM, Doppman JL, Miller DL, et al. Results of a multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism. Ann Surg 1992; 215: 101–106. 18. Schrodt JF, Becker GJ, Scott JA, Warren CH, Benenati SV. Bronchial artery embolization: monitoring with somatosensory evoked potentials. Work in progress. Radiology 1987; 164:135–139. 19. Deveikis JP. Sequential injections of amobarbital sodium and lidocaine for provocative neurologic testing in the external carotid circulation. AJNR Am J Neuroradiol 1996; 17:1143–1147. 20. Lefkowitz M, Giannotta SL, Hieshima G, et al. Embolization of neurosurgical lesions involving the ophthalmic artery. Neurosurgery 1998; 43: 1298–1303. 21. Niimi Y, Sala F, Deletis V, Setton A, de Camargo AB, Berenstein A. Neurophysiologic monitoring and pharmacologic provocative testing for embolization of spinal cord arteriovenous malformations. AJNR Am J Neuroradiol 2004; 25:1131–1138. 22. Tawk RG, Tummala RP, Memon MZ, Siddiqui AH, Hopkins LN, Levy EI. Utility of pharmacologic provocative neurological testing before embolization of occipital lobe arteriovenous malformations. World Neurosurg 2011; 76:276–281.
Embolization of Bronchial Artery–supplied Ectopic Parathyroid Adenomas Located in the Aortopulmonary Window Mujtaba Ali, MD, and David A. Kumpe, MD
ABSTRACT Ectopic parathyroid adenomas in the aortopulmonary window (APW) are extremely rare, constituting only 1% of ectopic mediastinal adenomas and 0.24% of all parathyroid adenomas. The authors have encountered three patients with ectopic adenomas in the APW. In each case, the primary arterial supply to the APW adenoma arose from the bronchial artery. In addition, there was a small anastomotic arterial channel connecting the bronchial artery supplying the adenoma to the left inferior thyroid. All three adenomas were treated with transcatheter embolization, with control of hyperparathyroidism in two of three patients. One patient required thoracoscopic removal of the adenoma. It is critical that the interventionalist be aware of this arterial supply pattern to allow successful embolization of an APW ectopic adenoma.
ABBREVIATIONS APW = aortopulmonary window, PTH = parathyroid hormone
Ectopic parathyroid adenomas are rare but are a common cause of failed surgery for hyperparathyroidism, which occurs in 3%–5% of standard open surgical neck explorations (1,2). In 20%–50% of patients with recurrent or persistent hyperparathyroidism after surgical exploration, the ectopic adenoma is located in the mediastinum (3). A mediastinal adenoma is present in 2.3% of patients undergoing neck exploration (4). Mediastinal parathyroid adenomas are most often located in the anterior mediastinum, in the region of the thymus. Only 1% of ectopic mediastinal adenomas are located in the aortopulmonary window (APW) in the middle mediastinum (4), accounting for 0.24% of all patients undergoing surgery for hyperparathyroidism. The usual arterial supply to a mediastinal adenoma arises from a descending branch of the inferior thyroid artery, an arteria thyroidea ima, or the thymic branch of the internal mammary artery (3,5). Rarely, adenomas have been reported to be supplied by small branches arising from From the Department of Radiology, University of Colorado Anschutz Medical Campus, 12401 East 17th Avenue, Leprino Building, Room 527, Aurora, CO 80045. Received July 5, 2013; final revision received October 2, 2013; accepted October 3, 2013. Address correspondence to D.A.K.; E-mail: [email protected] Neither of the authors has identified a conflict of interest. & SIR, 2014 J Vasc Interv Radiol 2014; 25:138–143 http://dx.doi.org/10.1016/j.jvir.2013.10.008
the superior thyroid or brachiocephalic artery (6). We have treated three patients using transcatheter embolization in whom an ectopic parathyroid adenoma was located in the APW and supplied by the bronchial artery. This pattern of arterial supply to APW adenomas has been reported once previously (7).
CASE REPORTS We reviewed these cases after approval by the Colorado Multiple Institutional Review Board, the institutional review board for the University of Colorado. Three patients with suspected APW adenomas were referred for parathyroid venous sampling, parathyroid diagnostic arteriography, and transcatheter embolization.
Case 1 A 35-year-old man with persistent hyperparathyroidism presented with fatigue, joint pain, and a history of left renal calculi. A surgical neck exploration was performed with a left superior parathyroidectomy, but this failed to resolve his symptoms and hypercalcemia. A chest computed tomography (CT) scan was initially read as negative. Parathyroid venous sampling showed markedly elevated parathyroid hormone (PTH) levels in a left mediastinal vein, 18,679 pg/mL (baseline values from other samples, 101–460 pg/mL) (Fig 1a). Review of the chest CT scan demonstrated a 6-mm soft tissue nodule in the APW
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Figure 1. Case 1. A 35-year-old man with persistent hyperparathyroidism. (a) Parathyroid venous sampling yielded marked elevation of PTH (18,679 ng/mL) from a left mediastinal vein. In comparison, 22 other samples had values of 101–460 ng/mL. This suggests the presence of a parathyroid adenoma in the left mediastinum. The draining veins include the region of the APW. (b) After positive venous sampling, a chest CT scan, in retrospect, shows a 6-mm soft tissue nodule in the APW adjacent to the left lower trachea, consistent with parathyroid adenoma (arrow). (c) Selective injection of the common trunk of the right and left bronchial arteries shows the primary arterial supply to the APW adenoma (arrows) arising from the right bronchial branch. (d) Superselective injection of the feeding artery to the adenoma shows the anastomotic branch to the left inferior thyroid artery (arrow). (e) Superselective arteriography via the bronchial artery obtained 3 weeks after the first embolization with polyvinyl alcohol and Ethiodol. The microcatheter tip has been advanced into the anastomotic branch to the left inferior thyroid artery, cranial to the adenoma (small arrow). Reperfusion of the adenoma has occurred (large arrow). (f) Arteriography of the bronchial artery after protective embolization of the anastomotic branch to the inferior thyroid with microcoils (small arrow), followed by injection of 0.3 mL of 95% ethyl alcohol and then N-butyl cyanoacrylate glue. No opacification of the adenoma is seen (large arrow). Compare with (e).
adjacent to the left lower trachea (Fig 1b). The patient was referred for transcatheter localization and ablation. Selective arteriography of the left inferior thyroid artery demonstrated multiple small arterial branches descending into the mediastinum to opacify a 10 mm 6 mm lesion on the superior surface of the confluence of the left side of the trachea and the left main stem bronchus. The inferior thyroid arterial branches supplying the adenoma were too small to be catheterized with a microcatheter. Selective arteriography of a common bronchial artery demonstrated that its right bronchial branch gave rise to a branch extended superiorly to
supply the mediastinal adenoma (Fig 1c). This branch was the primary arterial supply to the adenoma. There was reflux into a small, tortuous arterial branch communicating with the inferior thyroid arterial plexus (Fig 1d). Using a Mikaelsson 5-F catheter (Cook, Inc, Bloomington, Indiana) as a guide, a PROWLER 10 microcatheter (Codman Neurovascular, Inc, Raynham, Massachusetts) was used to perform embolization of the feeding branch supplying the adenoma with a dilute suspension of polyvinyl alcohol particles, 50–150 μm in diameter, followed by a small amount of ethiodized oil (Ethiodol; Guerbet, Bloomington, Indiana) to increase
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the ischemic effect. Films obtained after embolization demonstrated no opacification of the adenoma or the communicating arteries of the inferior thyroid arterial plexus noted previously. The patient reported no change in his symptoms 3 weeks after the procedure. He had elevated levels of serum calcium (11.6 mg/dL) and PTH (103 pg/dL). The patient agreed to undergo a second embolization attempt. Selective bronchial arteriography demonstrated recanalization of the right bronchial artery and the arterial supply to the mediastinal adenoma and retrograde filling of the communicating branch to the left inferior thyroid artery. A 1.2-F MAGIC microcatheter (Balt Extrusion, Montmorency, France) was advanced into a communicating branch just distal to the adenoma (Fig 1e). Protective embolization of this arterial segment was performed using two 1.5-cm Berenstein Liquid Coils (Boston Scientific, Natick, Massachusetts). The 1.2-F MAGIC microcatheter was repositioned proximal to the liquid metal coils. Provocative testing of this arterial branch using intraarterial cardiac lidocaine 40 mg and amobarbital sodium (Amytal Sodium) 50 mg resulted in no change in the patient’s voice quality or pitch modulation. Embolization of the artery was performed with a slow injection of 0.3 mL of 95% ethanol, followed by N-butyl cyanoacrylate glue, 2.5:1 dilution (Codman Neurovascular). Subsequent arteriography demonstrated no opacification of the adenoma or distal arterial branches (Fig 1f). The patient’s serum calcium and PTH-related peptide levels normalized after the second embolization and were normal 6 months later. Despite apparent successful ablation of his parathyroid adenoma, he continued to experience symptoms of fatigue and pain related to new renal calculi. He was subsequently lost to follow-up.
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hypervascular, crescent-shaped, 5 mm 17 mm blush immediately superior to the left main stem bronchus, compatible with an adenoma. An arterial branch continued superiorly past the adenoma into the upper mediastinum, retrogradely filling the left inferior thyroid artery (Fig 2). Using a 5-F Mikaelsson catheter as a guide, a PROWLER microcatheter was used to perform embolization of the feeding artery with a dilute solution of polyvinyl alcohol particles, 45–150 μm in diameter, preserving the patency of the connecting branch between the inferior thyroid and the bronchial arteries. An arteriogram obtained after embolization showed no filling of the arteries supplying the adenoma or parenchymal blush. The patient’s serum calcium and PTH levels normalized within days of the embolization, indicating that the adenoma had been treated. However, several weeks after the procedure, the patient again complained of easy fatigability, and her serum calcium was again elevated. The patient returned for repeat embolization approximately 12 weeks after the initial ablation procedure. Selective arteriography of the left bronchial artery demonstrated a recurrent hypervascular blush in the region of the parathyroid adenoma. Numerous attempts were made
Case 2 A 41-year-old woman with persistent hyperparathyroidism presented with limb weakness and fatigue. A surgical neck exploration failed to reveal a parathyroid adenoma. A subsequent CT scan of the thorax demonstrated a round, 1.5-cm lesion against the outer APW, anterior to the left main stem bronchus. Selective venous sampling demonstrated a markedly elevated PTH level of 7,529 pg/mL (baseline values from other samples, 100–350 pg/mL) in a left lateral mediastinal vein, which drained the APW region, confirming that the APW lesion identified on CT scan represented a mediastinal parathyroid adenoma. The patient underwent diagnostic arteriography and embolization 3 weeks after the venous sampling procedure. Selective arteriography of the left internal mammary artery and left costocervical trunk was normal. The left thyrocervical trunk could not be located. Selective arteriography of the left bronchial artery demonstrated a superiorly directed branch supplying a
Figure 2. Case 2. A 41-year-old woman with persistent hyperparathyroidism. Superselective injection of the artery arising from the left bronchial artery supplying the adenoma (thick black arrow) shows a communicating branch (thin black arrows) that anastomoses with the descending branch of the left inferior thyroid (curved white arrow).
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to perform superselective catheterization of the feeder to the adenoma using various microwire and microcatheter combinations plus intraarterial nitroglycerin. This superselective catheterization could not be accomplished because the bronchial artery was dissected at its origin. Attempts to access the adenoma through the anastomosing branch arising from the inferior thyroid artery were also unsuccessful. The procedure was abandoned. The adenoma was subsequently removed by video-assisted thoracoscopy.
Case 3 A 19-year-old woman with large renal calculi, hydronephrosis, and pyelonephritis and a diagnosis of primary hyperparathyroidism was referred for management of a suspected mediastinal parathyroid adenoma. A sestamibi nuclear medicine scan demonstrated a focus of activity in the left mediastinum. A chest CT scan demonstrated an enhancing 11 mm 10 mm soft tissue nodule in the APW. Selective venous sampling demonstrated elevated PTH levels in a left mediastinal vein, 11,017 pg/mL (baseline values from other samples, 314–573 pg/mL), confirming that the lesion was an APW adenoma. The patient chose endovascular ablation over thoracic surgery.
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The patient underwent transcatheter ablation of the adenoma 6 weeks after venous sampling. Selective arteriography of the left thyrocervical trunk and left internal mammary arteries did not show the adenoma. Selective arteriography of the common trunk of the lower lobe left and right bronchial arteries using a Mikaelsson catheter demonstrated a densely blushing, bowl-shaped lesion closely apposed to the inferior surface of the thoracic aorta supplied by the right bronchial branch (Fig 3a). A PROWLER 14 microcatheter was advanced through the Mikaelsson catheter into the specific arterial branch supplying the adenoma (Fig 3b). Embolization of this branch was performed with 0.3 mL of 95% ethanol. Arteriography performed 5 minutes later demonstrated pruning of the arteries within the adenoma but continued perfusion. Embolization of the branch was then performed with N-butyl cyanoacrylate glue mixed with tantalum powder in a 2:1 mixture with Ethiodol. Subsequent arteriography demonstrated no perfusion of the adenoma. The patient’s symptoms were resolved 4 weeks after the procedure. Her serum calcium and PTH levels had normalized and remained normal 19 months after the embolization.
Figure 3. Case 3. A 19-year-old woman with primary hyperparathyroidism. (a) Selective arteriography of the common trunk of the bronchial artery shows the supply to the APW adenoma (curved white arrow) from a branch arising from the right bronchial artery and opacification of a small communicating artery extending toward the left inferior thyroid artery (small black arrows). (b) Superselective microcatheterization of the arterial branch supplying the adenoma. The lack of reflux of contrast material into the parent artery makes the dual arterial supply to the adenoma irrelevant as a possible source of failure of transcatheter ablation.
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Embolization of Ectopic Parathyroid Adenomas in the APW
DISCUSSION Ectopic parathyroid adenomas are rarely encountered in the APW. In one compilation of 7,869 patients (4) who underwent an operation for hyperparathyroidism, there were 181 patients (2.3%) with mediastinal adenomas. Among 181 patients with mediastinal adenomas, 19 APW parathyroid tumors were identified, accounting for 1% of mediastinal adenomas and 0.24% of all patients undergoing surgery for hyperparathyroidism. There are two reported series of patients with APW parathyroid adenomas comprising 10 (7) and 19 (4) patients. Doppman et al (7) also gathered another 15 cases from the literature. A more recent report documented seven cases of APW adenomas among 33 patients with mediastinal parathyroid lesions who were treated with minimally invasive procedures (8). The total number of patients with hyperparathyroidism in this series was not noted. In our three cases, the arterial supply pattern was the same. In each case, the primary arterial supply to the APW adenoma arose from the bronchial artery; in two cases, the supply was from the right bronchial branch of a common right and left bronchial artery trunk. In one case, the arterial supply arose from a separate left bronchial artery. In all three cases, there was also a small anastomotic arterial channel connecting the bronchial artery supplying the adenoma to the left inferior thyroid artery. The APW adenoma was opacified by injection of the left thyrocervical trunk in only one of three patients; no injections of either internal mammary artery showed the adenoma. Doppman et al (7) noted that among four patients with APW adenomas, arteriography was negative when only the thyrocervical trunk and internal mammary arteries were studied. Reference is made to two cases (4,9) in which injection of the internal mammary artery opacified the adenoma. To our knowledge, only two images of bronchial artery supply to an ectopic parathyroid adenoma in the APW have been published (7), and the anastomotic connection between the bronchial artery and the inferior thyroid artery when an APW adenoma is present has not been described. Treatment of mediastinal adenomas with transcatheter embolization, sclerosis, or staining has been reported (6,10–12). Doppman et al (7) attempted treatment in four patients with APW adenomas, without success. Although diagnostic venous sampling, diagnostic arteriography, and transcatheter ablation are usually reserved only for patients with persistent hyperparathyroidism after unsuccessful neck exploration, if a mediastinal adenoma is detected in a patient with primary hyperparathyroidism, these modalities can also be applied, as in our case 3. Most data reporting successful ablation of mediastinal parathyroid adenomas include the use of hypertonic ionic contrast material as described by Doppman et al
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(13–16). Hypertonic contrast material would still be our material of choice, but we have been unable to obtain this for many years. It has been suggested that absolute alcohol is a reasonable alternative to contrast medium because of greater ablative potency and the need for smaller doses with greater effect (10,12). In our experience in these three cases, embolization of the adenoma with small particles, including the injection of Ethiodol after particulate embolization in one case, produced only transient decrease in PTH production with recurrent function of the adenoma. We achieved permanent ablation with a combination of absolute alcohol followed by N-butyl cyanoacrylate embolization. It is possible that the dual arterial supply from the communicating artery and from the inferior thyroid artery played a role in the initial failure of particles with or without Ethiodol in cases 1 and 2. Even in the case when embolization ultimately fails, as in case 2, the transient decrease in PTH and serum calcium levels in response to embolization serves two useful purposes: (a) It definitely establishes that the lesion treated by embolization is the ectopic adenoma, and (b) angiographic images from the procedure, which are usually obtained in orthogonal projections, definitely localize the adenoma anatomically, which is helpful to the surgeon. The literature reports short-term success rates of endovascular ablation of mediastinal parathyroid adenomas of 73%–83% and long-term success rates of 63%–71% (6,11,17). Reported complications of endovascular parathyroid ablation attempts include chest pain, bradycardia, respiratory arrest, hiccups, hoarseness, hypocalcemia, hand weakness, slurred speech, acute thyroiditis, and acute renal failure (6,16). None of our patients experienced significant complications during or after the procedure. Nonetheless, regarding ectopic adenomas in the APW, Doppman et al (7) cautioned of potential damage to the pulmonary artery and vein, aorta, vagus, recurrent laryngeal and phrenic nerves, and bronchial and esophageal walls. Provocative neurologic testing using intraarterial preservative-free lidocaine and Amytal Sodium was performed in case 1. The utility of neurologic testing immediately before embolization of the bronchial artery has been reported (18). Pharmacologic provocative testing and neurophysiologic monitoring has been demonstrated to have a high negative predictive value in identifying potential neurologic deficits before ablation of spinal cord arteriovenous malformations as well as various intracranial and extracranial lesions (19–22). It has been reported that following unsuccessful attempts at ablation, surgical excision of parathyroid adenomas via median sternotomy can achieve up to 100% short-term resolution of symptoms and long-term cure (14). Nevertheless, the surgical cure of APW parathyroid adenomas is a formidable challenge. In a contemporary series (4), to cure 18 of 19 patients with
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APW parathyroid tumors, the following 40 operations were performed: 18 neck explorations, 12 cervicosternotomies, 5 median sternotomies, 1 anterior and 2 left thoracotomies, and 2 thoracoscopies. In this series, second operations (after failed neck exploration) were successful in 60%, whereas 40% of patients required another reoperation for cure. It is well known that sternotomy is associated with longer hospital stay, greater pain, and a more difficult recuperation period (16). Minimally invasive treatment of mediastinal adenomas has been reported to have similar morbidity and mortality to open surgery with a shorter hospital stay (8). In conclusion, given its minimally invasive nature and generally high success rates, we believe endovascular ablation remains a viable and reasonable modality in carefully selected patients for the treatment of APW parathyroid adenomas supplied by the bronchial artery. We now believe that other patients with mediastinal adenomas outside the APW that do not derive their arterial supply from the inferior thyroid artery, internal mammary artery, or arteria thyroidea ima should undergo bronchial arteriography as well, but we have not yet encountered such a case.
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