Ectopic intravagal parathyroid adenoma
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1 CASE REPORT Jonathan Irish, MD, FRCSC, Section Editor Ectopic intravagal parathyroid adenoma Jurstine Daruwalla, MBBS, PhD, 1 Nirupa Sachithanandan, MBBS, FRACP, PhD, 2 David Andrews, MBBS, FANZCA, DDU, PhD, 3,4 Julie A. Miller, BA, MD, FRACS 5,6,7 * 1 Department of Surgery, University of Melbourne, Austin Health, Victoria, Australia, 2 Department of Endocrinology, St. Vincent s Hospital, Victoria, Australia, 3 Department of Anesthesia and Pain Management, Royal Melbourne Hospital, Parkville, Australia, 4 Department of Anesthesia, Perioperative and Pain Medicine Unit, The University of Melbourne, Parkville, Australia, 5 Endocrine Surgery Unit, Royal Melbourne Hospital, Victoria, Australia, 6 Epworth Freemasons Hospital, Victoria, Australia, 7 University of Melbourne, Department of Surgery, Victoria, Australia. Accepted 10 April 2015 Published online 15 July 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI /hed ABSTRACT: Background. Intraneural parathyroid adenomas are rare, with only 9 cases of intravagal adenomas reported. All but one of the reported cases was found after multiple neck explorations. To the best of our knowledge, we report the first case of nonsupernumerary ectopic intravagal parathyroid identified at primary exploration. Methods and Results. A 17-year-old girl with primary hyperparathyroidism and nephrolithiasis was referred with a sestamibi scan reporting a left lower parathyroid adenoma. eutopic parathyroid tissue was identified during full exploration of the left side of the neck. Exploration of the carotid sheath revealed a fusiform swelling of the vagus nerve at the level of the carotid. Longitudinal incision of the vagal perineurium revealed a 7-mm parathyroid adenoma, which was enucleated. The patient recovered uneventfully, with normalization of serum calcium, parathyroid hormone (PTH), and normal vocal cord function. Conclusion. We believe that this is the first reported case of nonsupernumerary intravagal parathyroid adenoma resected at initial exploration. The vagus nerve is a rare location for a parathyroid adenoma, but one that should be considered, even during primary exploration. VC 2015 Wiley Periodicals, Inc. Head Neck 37: E200 E204, 2015 KEY WORDS: parathyroid adenoma, primary hyperparathyroidism, vagus nerve INTRODUCTION Primary hyperparathyroidism develops in 20 to 30 per 100,000 people per year, with most cases caused by a parathyroid adenoma. 1,2 Common presentations of primary hyperparathyroidism include asymptomatic hypercalcemia, nephrolithiasis, and reduced bone mineral density. 3 Other patients experience bone pain, constipation, or severe fatigue. 4 In patients with primary hyperparathyroidism, cure rates after initial surgery are up to 90% to 95%. 5 8 For the remaining 5% to 10%, persistent hyperparathyroidism may be the result of unrecognized multiglandular disease, 5,7 9 or the inability to identify a parathyroid adenoma, which may be located in an ectopic position, in individuals with single gland disease. Reoperation for persistent primary hyperparathyroidism is associated with increased morbidity because of difficulty identifying parathyroid tissue and other cervical structures, particularly the recurrent laryngeal nerve. 5,7,8 Identifying adenomas, particularly at reexploration, is incumbent upon an understanding of the potential location of the ectopic parathyroid glands. Parathyroid glands typically migrate during embryogenesis from the third and fourth pharyngeal pouches to their respective inferior and superior locations on the dorsal *Corresponding author: J. Miller, Suite 12, Level 2, 20 Flemington Rd, Parkville, Victoria, 3052, Australia. Julie.Miller@mh.org.au surface of the thyroid. 10 Ectopic parathyroid glands may be located anywhere along the path of their embryological descent. The inferior parathyroid has a longer embryological migration tract and is therefore more likely to descend to an abnormal or ectopic location, or to descend incompletely. 10 rmal ectopic parathyroid tissue has been identified in pharyngeal structures of the neck, including the carotid sheath, 7,11 as well as the hypoglossal 12 and vagus nerves. 10,13 True intravagal parathyroids are exceedingly rare, with only 9 documented cases (Table 1). In all but 1 report, intravagal parathyroid adenomas were found after 1 to 4 14 previous failed explorations. 11,15,16 Some patients underwent a median sternotomy, 7 thyroidectomy, reexploration of the carotid sheath, 4 and even mediastinoscopy 7 as part of their reexploration. In all scenarios, further imaging was sought before reexploration, which correctly localized the intravagal parathyroid adenoma. Although repeat imaging facilitated successful surgery, some patients required invasive preoperative localizing studies, including angiography and venous sampling. 5,7 In this study, we report an intravagal parathyroid adenoma found at initial parathyroid exploration in the absence of any other parathyroid tissue identified in the ipsilateral neck. CASE REPORT A 17-year-old girl presented with her first episode of nephrolithiasis and associated fatigue. Investigation E200 HEAD & NECK DOI /HED DECEMBER 2015
2 INTRAVAGAL PARATHYROID ADENOMA AND REVIEW OF THE LITERATURE TABLE 1. Ectopic intravagal parathyroid adenoma in primary hyperparathyroidism. Author year. of cases. of previous explorations Operations performed. of other parathyroid glands seen Imaging performed Location adenoma Supernumerary Reiling et al Total thyroidectomy 2 Ultrasound, CT, scintigraphy At level of right carotid Takimoto et al Subtotal parathyroidectomy 2 left 2 right Repeat ultrasound, CT, and scintigraphy Doppman et al Right hemithyroidectomy, thymectomy, mediastinal exploration Buell et al Right hemithyroidectomy, thymectomy, median sternotomy Pawlik et al Subtotal parathyroidectomy, right hemithyroidectomy and thymectomy Chan et al Thymectomy, total thyroidectomy, 2 previous carotid sheath explorations Daruwalla et al 2014 (this study) 1 0 Left neck exploration with cervical thymectomy 2 left 1 right Repeat ultrasound, MR, CT, scintigraphy, venous sampling, arteriography injection of right external carotid 2 left 1 right Angiography, chest MRI, venous sampling, repeat ultrasound, CT, MRI, and scintigraphy, venous sampling 4 Repeat venous sampling and ultrasound * Repeat ultrasound, SPECT, sestamibi, CT and MRI, angiography and venous sampling 0 (right side not explored) Initial ultrasound and scintigraphy Below left carotid Yes Above right carotid Above right carotid Below left carotid Yes 3 above carotid (2 left, 1 right) 1 below right carotid At level of carotid 3 yes, 1 unclear Abbreviations: SPECT, single photon emission CT. * Patients referred from other institutions and studies were unable to clarify from operative notes and path slides how many parathyroids were previously identified or inadvertently removed. HEAD & NECK DOI /HED DECEMBER 2015 E201
3 DARUWALLA ET AL. FIGURE 1. (A) Suspected parathyroid adenoma high in the left carotid sheath at preoperative assessment (arrow), although the formal radiology report suggests left inferior adenoma. Intraoperative exploration revealed a fusiform swelling of the left vagus nerve at the level of the carotid. (B) Of note, no other parathyroid tissue was found in the left side of the neck, including the thymus or in any other part of the operative field (including the gray shaded area). (C) The perineurium was incised revealing a small mass consistent with parathyroid tissue on frozen section biopsy (arrow). revealed primary hyperparathyroidism, with elevated serum corrected calcium of 2.81 mmol/l (normal range, mmol/l) and parathyroid hormone (PTH) of 12.1 pmol/l (normal range, pmol/l). Twenty-four hour urinary calcium was normal, at 5.3 mmol/24 h (normal, <6.2 mmol/24 h). The patient denied other symptoms, but had a flat effect on examination. There were no palpable neck masses. Surgeon-performed ultrasound showed a normal thyroid with no evidence of parathyroid adenoma. A 99m Tc sestamibi scan was reported as suspicious for a left inferior parathyroid adenoma. However, the surgeon reviewed the images and suspected a parathyroid adenoma high in the left carotid sheath (Figure 1A). The patient underwent left-sided parathyroid exploration. The carotid sheath was explored up to the, but only lymph nodes were identified. The thyroid was then mobilized and explored, but no eutopic parathyroid glands were discovered. A left cervical thymectomy was performed, and the paratracheal groove, upper mediastinum, and retropharyngeal space were cleared. The left recurrent laryngeal nerve was identified and preserved. Given the patient s young age, the fat in the neck was predominantly brown fat, making identification of parathyroid tissue more challenging. However, no parathyroid tissue was found. Attention was then turned back to the carotid sheath, where a fusiform swelling was identified in the vagus nerve at the level of the carotid. A longitudinal incision was made in the perineurium, and a soft, tancolored nodule was identified and enucleated from the vagus nerve (Figure 1C, arrow). This did not give rise to any intraoperative hemodynamic changes, such as bradycardia; as experienced in a previous report. 17 Frozen section biopsy confirmed parathyroid tissue. Rapid intraoperative PTH level is not available in our institution. However, because of consistency between imaging and operative findings, a decision was made not to explore the right side of the neck. The field was checked for hemostasis, and the incision was closed. Total operative time was 100 minutes. The operative diagram is shown Figure 1B. On postoperative day 1, serum-corrected calcium and PTH had dropped to 2.31 mmol/l and 1.3 pmol/l, respectively. The patient s voice was normal, she had no dysphagia, was tolerating a normal diet, and was discharged home. The patient s mood and fatigue improved E202 HEAD & NECK DOI /HED DECEMBER 2015
4 INTRAVAGAL PARATHYROID ADENOMA AND REVIEW OF THE LITERATURE after surgery. She became more interactive and reported increased energy. Three months later, she remained eucalcemic (corrected calcium, 2.31 mmol/l) with a normal PTH of 2.3 mmol/l. DISCUSSION Parathyroid glands have been previously identified anywhere from the parapharyngeal skull base to the middle mediastinum. They may be intrathyroidal, 7,10 intrathymic, 18 within the carotid sheath, in the lateral neck, adjacent to the hyoid bone, adjacent to the submandibular gland 11 in the paranasopharyngeal space, or intravagal. 4 This is only the second reported case of an intravagal parathyroid adenoma identified at initial parathyroid exploration. Part of the vagus nerve is derived from the fourth pharyngeal arch, bordered on either side by the third and fourth pharyngeal pouches. The close proximity may explain the presence of intravagal parathyroid tissue. 19,20 To date, there have been only 9 reported cases of supernumerary intravagal parathyroids in the English literature. 16,20,21 However, these case reports may not reflect the true incidence, as intravagal parathyroid tissue has been documented in autopsy reports with a frequency of up to 6%. 20 Chan et al 4 reported a series of 8 ectopic parathyroid adenomas, including 4 glands identified and excised from within the epineurium of the vagus nerve. Previously reported cases suggest that these intravagal neoplasms are commonly situated at or cranial to the carotid, just as ours was. 22 It is worth noting that except for one early account, 23 all previously reported cases of intravagal parathyroid adenomas were discovered at reoperation (Table 1). 16,17,22,24 It is not clear, however, whether the parathyroids identified at initial operation were enlarged, and the persistent hyperparathyroidism was a result of multigland disease. In some cases, patients have previously undergone 2 to 4 neck explorations involving thymectomy and total thyroidectomy, as well as bilateral carotid sheath explorations. Multiple explorations are associated with increased complications, including damage to the recurrent laryngeal nerve, 17 bleeding, 7 and longer operative time up to a median of 240 minutes. 4 We report an operative time of 100 minutes, which included time for histological frozen section biopsies during the exploration. 7 Imaging has also played a major role before repeat exploration. Single photon emission CT (SPECT) offers low-dose radiation but lends itself to lower resolution images that does not necessarily give the anatomic detail provided by high-resolution dedicated CT. There is some evidence to suggest that ultrasound plus SPECT offers an incremental value in localizing adenomas over either technique alone. However, there is no reported benefit of SPECT when the adenoma is localized on sestamibi but not on ultrasound. Postoperatively, the patient was cured of her primary hyperparathyroidism. Enucleation of the gland from the vagus nerve did not result in alteration of the voice postoperatively. Indeed this has been the experience of our colleagues who describe a similar gentle and meticulous technique of separating the adenoma from the nerve fibers; except in 1 case in which the nerve fibers were sacrificed in the setting of malignancy. 16 Our colleagues do describe cases of transient recurrent laryngeal nerve paresis giving rise to difficulty swallowing and a hoarse voice, which did not occur in our patient. The perceived difference in our case was that no eutopic parathyroid tissue was found and, therefore, the intravagal adenoma was not supernumerary. Two of the 9 reported cases have had similar findings, but only after multiple re-explorations. 22,24 Furthermore, adenoma sizes vary from 0.5 cm up to 2.5 cm. 17,22,23,25 In our case, once the perineurium was incised, the initially observed fusiform swelling was reduced revealing only a small amount of tissue, roughly mm. CONCLUSION Intravagal parathyroid tissue may be the sole cause of hyperparathyroidism and this rare location must be considered among other ectopic sites as part of the intraoperative exploration. This case also illustrates the importance of the surgeon reviewing all imaging before parathyroid surgery. The initial sestamibi report was erroneous, and the surgeon s review of the images led to recognition of a rare ectopic site of a parathyroid adenoma, resulting in a successful primary exploration. REFERENCES 1. Mundy GR, Cove DH, Fisken R. Primary hyperparathyroidism: changes in the pattern of clinical presentation. 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5 DARUWALLA ET AL. 20. Lack EE, Delay S, Linnoila RI. Ectopic parathyroid tissue within the vagus nerve. Incidence and possible clinical significance. Arch Pathol Lab Med 1988;112: Hung CJ, Lin PW, Lee PC, Chen HH, Chen FF. Supernumerary intravagal parathyroid hyperplasia. Surgery 2002;131: Doppman JL, Shawker TH, Fraker DL, et al. Parathyroid adenoma within the vagus nerve. AJR Am J Roentgenol 1994;163: Takimoto T, Okabe Y, Ito M, Umeda R. Intravagal parathyroid adenoma. J Laryngol Otol 1989;103: Buell JF, Fraker DL, Doppman JL, et al. High cervical intravagal hypercellular parathyroid gland as the etiology of severe persistent primary hyperparathyroidism. Am Surg 1995;61: Pawlik TM, Thompson N. Supernumerary intravagal parathyroid hyperplasia. Surgery 2002;132: E204 HEAD & NECK DOI /HED DECEMBER 2015
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