Keywords

Mediastinal Parathyroid Glands

Mediastinal parathyroid glands are the result of abnormal migration of the parathyroids during embryogenesis. The parathyroid glands develop from the dorsal wing of the third and fourth pharyngeal pouches [1]. The superior parathyroids derive from the fourth pharyngeal pouch, while the inferior develop from the third one. The ventral wing of the third pharyngeal pouch gives rise to the thymus, which descends to its final position in the mediastinum. The inferior parathyroid glands follow the descending route of the thymus; this explains their ectopic location into the mediastinum [1, 2]. Due to their more extensive migration, inferior parathyroids are more often ectopic than the superior ones.

The prevalence of ectopic parathyroid glands is reported to range from 6.3 to 16% in surgical series [3,4,5,6,7], but a rate of 28–42% is reported in autopsy series [8, 9]. Ectopic parathyroids have been reported in up to 45% of patients with persistent/recurrent primary hyperparathyroidism [7].

About 60–80% of the ectopic mediastinal parathyroid can be found in the superior mediastinum within the thymus or at the origin of the great vessels. The remaining mediastinal parathyroids are located in the middle and posterior mediastinum in variable percentages [10].

A supernumerary or fifth parathyroid gland is reported in 2.5–22% of the ectopic mediastinal parathyroid gland. Supernumerary glands are usually located in the upper anterior mediastinum within the thymus or perithymic fat [6, 7, 10].

Mediastinal parathyroid glands become of concern when hyperparathyroidism (primary or secondary) occurs. Parathyroid adenomas are the most common cause of primary hyperparathyroidism, accounting for about 85% of cases. They are usually solitary, but a double adenoma can be found in 2–4% of cases. Multiglandular hyperplasia is found in 15% to 20% of cases [2, 11]. Parathyroid carcinoma accounts for about 1% of the case. Rare cases of parathyroid carcinoma in mediastinal parathyroid glands have been described; there are a few reports on giant parathyroid carcinomas mimicking substernal goiter [12].

The actual prevalence of mediastinal parathyroid adenoma (MPA) is unknown but has been reported to range from 6 to 30% [13, 14]. The ectopic mediastinal parathyroid gland is the most common cause for unsuccessful operation for either primary or secondary hyperparathyroidism by experienced surgeon [15,16,17].

The clinical manifestation of primary hyperparathyroidism from MPA has been reported to be more severe than in eutopic parathyroid adenomas. Patients with MPA are more likely to present with higher calcium levels and more severe bone impairment. This may be due either to the prolonged, persistent hypercalcemia or the often delayed localisation of the mediastinal parathyroid adenomas [4].

Preoperative Localisation

Preoperative localization is essential for a successful mediastinal exploration for parathyroid adenomas. Although a variety of preoperative imaging techniques are available, the optimal preoperative localization study for MPA has not yet been determined.

Technetium-99m (Tc-99m) sestamibi scintigraphy has proven to be the single best imaging modality for preoperative localisation of parathyroid adenomas, with a reported sensitivity of 80–90%. For mediastinal parathyroid adenoma, the Tc-99m sestamibi scan sensitivity and specificity are reported to be lower than for the cervical parathyroid adenomas. Tc-99m sestamibi single-photon emission computed tomography (SPECT) is reported to be superior to planar imaging and in combination with computed tomography (SPECT/CT) can improve both sensitivity and specificity compared to planar scan [18, 19].

Computed tomography (CT) and magnetic resonance imaging (MRI) is useful to identify the mediastinal parathyroid tumour and provide relevant information about its anatomical location and relationship with the other structures. Four-dimensional CT is frequently employed in the preoperative workup for localisation of ectopic parathyroid adenomas [20].

The latest preoperative imaging techniques including dual-energy CT and positron emission tomography (PET) MRI have been reported to be useful in detecting parathyroid adenomas in cases of failure of conventional imaging [21]. Simultaneous PET-MRI is a new hybrid technique of imaging that allows exact fusion of molecular and anatomical imaging providing excellent soft-tissue analysis [22].

Surgical Approaches

Most of the MPAs can be excised through a cervical approach, by removing the anterior mediastinal fat and the thymus either during the first exploration or in the setting of remedial operations [10]. Only 1–2% of ectopic MPAs require a thoracic approach to be resected [15].

For MPAs that cannot be removed through a cervical approach, a variety of thoracic approaches can be employed including open surgery techniques (sternotomy, thoracotomy) and minimally invasive techniques as thoracoscopy (including robotic-assisted), mediastinotomy , and mediastinoscopy [10]. The selection of the appropriate surgical approach depends on the location of the ectopic parathyroid tumour and is critical for successful mediastinal parathyroid tumour identification and excision.

The sternotomy was the preferred approach for surgical excision in the past. This approach allows an excellent operative view and an accurate tumour identification. In the majority of the cases, it is not necessary to perform a total sternotomy as a partial sternotomy is adequate to provide good access to the anterior mediastinum [23]. These surgical approaches have been reported to be associated with significant complications including phrenic and recurrent laryngeal nerve injuries, pleural effusion, innominate vein laceration, wound infections, mediastinitis, and death in up to 12–29% of cases [10, 24, 25].

Recently the minimally invasive approaches have gained popularity, and thoracoscopic surgery has replaced conventional sternotomy or thoracotomy for resection of deep ectopic MPAs. These minimally invasive surgical techniques have been reported to be feasible and safe with a low rate of complications even in the setting of reoperative procedures [26, 27]. Accurate preoperative localisation is necessary to establish the appropriate surgical approach. Some authors have suggested the level of the aortic arch as a landmark for guiding the proper surgical approach. Based on their experience, they assumed that MPAs located in the superior mediastinum above the level of the aortic arch could be removed successfully through a transcervical approach, while for those found below the aortic arch in the middle or posterior mediastinum, a transthoracic procedure should be employed [14]. Lastly, the robotic approach has recently been described for mediastinal ectopic parathyroid glands [28, 29]. Only a few series have been reported in the literature, describing this technique as a promising surgical approach for mediastinal parathyroid adenomas, in selected cases [29]. Intraoperative PTH monitoring is used to confirm parathyroid adenoma resection and cure of hyperparathyroidism. A PTH level decline of >50% and into the normal range 10 min after adenoma excision is used as a predictor of cure [30].