Giant Parathyroid Adenoma Associated With Aberrant Subclavian Artery and Nonrecurrent Laryngeal Nerve

Abstract

Parathyroid adenomas are responsible for 80% to 85% of cases of primary hyperparathyroidism. Giant parathyroid adenomas are a rare type of parathyroid adenoma defined as weighing >3.5 grams. Although giant parathyroid adenomas are rare entities whose clinical presentation may not be atypical, their surgical management can be challenging, especially in the setting of anatomical variants. We present here a case of a 29-year-old female with a 37-gram giant adenoma which was diagnosed after presentation with recurrent severe headaches. The presentation was also unique in that it was associated with a right aberrant subclavian artery and nonrecurrent laryngeal nerve.

Introduction

Primary hyperparathyroidism has an average incidence of approximately 25 and 66 cases per 100 000 person-years for men and women, respectively. ¹ Of all causes of primary hyperparathyroidism, parathyroid adenoma is most common, constituting 80% to 85% of the cases. ² Parathyroid adenomas are benign neoplasms of the parathyroid glands leading to autonomous secretion of parathyroid hormone outside the control of the normal negative feedback mechanism. This, in turn, leads to hypercalcemia and potentially related signs and symptoms. Adenomas are typically <1 gram; however, adenomas weighing ≥95th percentile or 3.5 grams are defined as “giant adenomas.” ³ As surgical excision serves as the definitive treatment for parathyroid adenomas, it is vital that surgeons be familiar with not only normal neck and thoracic inlet anatomy but also anatomical variants. Moreover, surgeons must be able to recognize these anatomical variants in the context of an abnormally giant adenoma. Here, we present a case of a right-sided giant parathyroid adenoma in a 29-year-old female with an aberrant subclavian artery (ASA) and a nonrecurrent laryngeal nerve (NRLN).

Case Report

A 29-year-old female was referred to our institution for hyperparathyroidism. Six months prior, the patient was incidentally found to have a mildly elevated calcium level while undergoing routine testing as part of her preoperative evaluation for umbilical hernia repair. Subsequently, the patient developed severe headaches prompting multiple emergency department visits, one of which leading to a computed tomography (CT) scan of the head which was normal. Further laboratory testing confirmed persistent hypercalcemia (serum ionized calcium level 1.47 mmol/L; upper range of normal 1.33), elevated intact PTH (148 pg/mL; upper range of normal 88), and a normal 25-hydroxy vitamin D level (42 ng/mL), suggesting primary hyperparathyroidism. A sestamibi scan demonstrated a large mass with intense focal uptake inferior to the right thyroid lobe. Computed tomography with contrast of the neck confirmed a well-circumscribed 5.2-cm mass with heterogeneous enhancement arising from the inferior pole of the right thyroid gland and extending inferiorly into the mediastinum (Figure 1A). There was no associated adenopathy in the neck or thorax; however, there was dilation of the right internal jugular vein from outflow obstruction at the thoracic inlet (Figure 1B). Imaging also revealed a right ASA arising from the common carotid and traversing posteriorly to the esophagus (Figure 1C). The risks of operative intervention were discussed with the patient with special attention applied to discussing the presence of a right NRLN secondary to her right ASA, given the uncertain location of the nerve within the surgical field. On the day of surgery, preoperative intact-PTH was 167 pg/mL. Ultrasonography at the surgical bed was performed after positioning for surgery, and the mass was identified lying posterior to the right inferior thyroid pole filling the space between the trachea and the right carotid artery while extending inferiorly into the mediastinum. During the dissection in the right tracheoesophageal groove, the right NRLN was identified. The NRLN emerged laterally 1.5 cm inferior to the right inferior thyroid pole from behind the carotid artery. Intraoperative electromyographic (EMG) neuromonitoring verified the identity of the NRLN. The nerve coursed medially and then superiorly while giving off multiple branches. The nerve trunk and its branches were positioned directly on the ventral surface of the adenoma. The mass was first bluntly dissected and delivered from the mediastinum before carefully dissecting the NRLN and its branches to allow mobilization of the adenoma, whose last attachment superiorly was posterior to the inferior thyroid lobe (Figure 2A). Frozen section diagnosis for surgical margin clearance confirmed no remaining parathyroid tissue. Intraoperative intact PTH sampled 10 minutes after delivery of the surgical specimen was 29 pg/mL, an 83% drop. The NRLN and its branches remained structurally intact and without any change in the size of the evoked-EMG potentials at the end of the procedure. Final histopathology of the gland reported a nodule weighing 37 grams with histologic features consistent with a parathyroid adenoma. On postoperative day 1, the patient’s ionized calcium level was 1.25 mmol/L and her voice remained strong and intact. After the surgery, the patient had an uneventful course and the headaches resolved without any recurrences.

Figure 1.

Coronal section of contrast-enhanced computed tomography (CT) scan of neck illustrating: (A) heterogeneously enhancing oblong giant parathyroid adenoma at the thoracic inlet (arrow) supplied by a branch of the inferior thyroid artery (arrow head); (B) dilation of right internal jugular vein (arrow) from outflow obstruction at the thoracic inlet and origin of the parathyroid adenoma from the right inferior thyroid pole (arrow head); and (C) right aberrant subclavian artery (arrow).

Figure 2.

(A) Intraoperative photograph of giant parathyroid adenoma in situ with the inferior aspect of the adenoma delivered from the thoracic inlet showing attachment to the lower lobe of the thyroid gland (arrow); (B) excised giant parathyroid adenoma.

Discussion

Giant parathyroid adenomas (>3.5 grams) make up about 5% of all parathyroid adenomas. ³ Although the average size of a giant parathyroid adenoma is 5.65 grams, they rarely exceed 30 grams in weight with very few reports describing weights up to 110 grams. ^3,4 Thus, our 37-gram adenoma is likely >99th percentile in size and weight. More interestingly, our giant adenoma was associated with a right ASA and NRLN and one of the presenting symptoms was severe headaches. To our knowledge, this is the first case report with such a combination in the literature.

Most parathyroid adenomas are diagnosed in the asymptomatic stage following an incidental finding of hypercalcemia on routine blood work. Although it was initially believed that giant parathyroid adenomas followed a similar asymptomatic path, a recent review of case reports published between 2009 and 2019 discovered that most giant parathyroid adenomas presented with symptoms of varying severity including bone/abdominal pain, chronic depression, and recurrent kidney stones. ⁴ Our patient’s giant adenoma was associated with severe headaches. The severe headaches could have been caused by jugular distension due to venous compression at the junction of the right jugular and brachiocephalic veins (Figure 1B).

Although giant parathyroid adenomas are infrequently encountered, they can present a challenge for the surgeon. Due to their large sizes, these tumors can extend inferiorly into the thoracic inlet and mediastinum. Their proximity and large size also pose an increased risk of injury to the recurrent laryngeal nerve. Our case added an extra layer of complexity because of a branching NRLN in association with a right ASA. In normal embryonic development, the recurrent laryngeal nerve, which is derivative of the sixth branchial arch, descends into the mediastinum being hooked and dragged by the fourth branchial arch vessels, the right subclavian artery, and the aorta. Whereas the normal right recurrent laryngeal nerve loops around the right subclavian artery and ascends superiorly, a NRLN arises directly from the vagus nerve at or near the level of the thyroid gland, extending directly from the cervical vagus nerve.

In patients undergoing thyroid surgery, ASA and NRLN are present in about 0.6% to 1.3%. ^5,6 Four anatomical subtypes of NRLN have been described. ⁷ Adopting this classification, the NRLN in the present case arose below the inferior thyroid artery, consistent with a type IIB. Current research indicates that identification of the ASA and protection of NRLN can be facilitated by preoperative ultrasonography and intraoperative nerve monitoring, respectively. ^8,9 When faced with a giant parathyroid adenoma, CT imaging should also be employed given its superior anatomic detail to ultrasonography. ¹⁰ Our case illustrates achievement of optimal surgical outcome through adoption of both recommendations.

Conclusion

Parathyroid adenomas represent the most common cause of primary hyperparathyroidism and are definitively treated with surgical excision. Our patient highlights several uncommon findings in parathyroid surgery: symptom of severe headaches, a giant adenoma, a right ASA, and NRLN. Although the presence of these entities can contribute to a challenging surgery with significant potential for complications, risks can be minimized and surgical outcome can be optimized by adoption of an evidence-based approach to preoperative recognition via various imaging modalities and intraoperative nerve monitoring.