What to do when the parathyroid gland is not found during a transcervical exploration?

Abstract

The most frequent cause of suboptimal results in a parathyroid adenoma resection is an ectopic location, mainly in the anterior mediastinum. These cases may not always be resected through a traditional cervical access. We present 2 cases of primary hyperparathyroidism who underwent an unsuccessful bilateral cervical exploration due to parathyroid tissue located inside the thymic gland. A video-assisted thoracoscopic surgery thymectomy with intraoperative determination of blood parathormone levels was performed. A 50% reduction of intraoperatory parathyroid hormone blood from the highest basal level at 5 and 10 min after resection was obtained. Final pathological results showed an intra-thymic parathyroid adenoma in the first patient and an intra-thymic focus of parathyroid hyperplasia in the second patient. In conclusion, video-assisted thoracoscopic surgery thymectomy could be the optimal approach to resect ectopic parathyroid adenomas located in the anterior mediastinum.

INTRODUCTION

Primary hyperparathyroidism (PHPT) is caused by excessive secretion of parathyroid hormone (PTH) inducing hypercalcemia. The main cause of PHPT is parathyroid adenomas. Around 10% of these adenomas have an ectopic location, being the most common inside the thymic gland in the anterior mediastinum [1]. This is due to a common embryological origin of thymus and inferior parathyroid glands from third pharyngeal sac [2]. The presence of ectopic parathyroid tissue is the most acceptable explanation of unsuccessful bilateral cervical exploration [3]. Nowadays, there is no standard approach to resect an ectopic parathyroid adenoma (EPA) located in the mediastinum. In this paper, we describe a video-assisted thoracoscopic surgery (VATS) approach adopted in 2 cases of PHPT.

PATIENTS AND METHODS

This study was approved by the institutional review board, and written informed consent from patients was obtained.

The first patient was a 42-year-old women diagnosed of nephrolithiasis resulting from PHPT with a 99mTc-sestamibi scintigraphy (99mTC-MIBI) that did not show any hyperfunctional structure. In 2010, a bilateral cervical exploration was performed, and the left inferior parathyroid gland was not found.

The second patient was a 25-year-old women, also with nephrolithiasis secondary to PHPT studied in a private practice centre in 2015. After a negative 99mTC-MIBI, a bilateral cervical examination failed to identify the right lower parathyroid gland. Due to the persistence of hyperparathyroidism, both patients were referred to our institution for a re-evaluation in 2018.

Following our protocol, a Fluorocholine positron emission tomography combined with computed tomography (CT) was done after a negative 99mTC-MIBI. In the second patient, a hypermetabolic lesion in the anterior mediastinum was detected (Fig. 1A). A chest CT showed a 5 mm × 5 mm lesion located anterior to the innominate vein in the first patient and a 6 mm × 3.5 mm pre-aortic lesion in the second patient (Fig. 1B).

Figure 1:

(A) Fluorocholine positron emission tomography–computed tomography shows a hypermetabolic lesion in the anterior mediastinum. (B) Chest computed tomography reveals a lesion anterior to the innominate vein. (C) The patient is positioned in a 45° left lateral decubitus with a 30° abduction of the right arm. (D) Thymic veins must be clamped to avoid an important bleeding. The black arrow shows a thymic vein.

A right VATS thymectomy combined with intraoperatory monitoring of PTH levels was performed in both cases in 2019. The patients were placed in a 45° left lateral decubitus position with a 30° abduction of the right arm (Fig. 1C). A single-lung ventilation helped to improve the exploration of mediastinum. One 5-mm port was placed on the right fifth intercostal space of the median axillary line for the video-thoracoscope, and the other 2 trocars were placed under direct vision. Carbon dioxide insufflation was used to facilitate the dissection.

The resection started by the lower poles of the thymic gland. It followed the limits of both phrenic nerves and the surface of the parietal pericardium until the innominate vein was identified. Both superior thymus poles and the innominate vein were carefully dissected. Between 2 and 4 thymic veins are normally present and they must be carefully clamped to avoid an important bleeding (Fig. 1D).

Intraoperative monitoring of PTH blood levels at baseline and 5–10 min after excision of the sample was performed. After discarding air leaks and ensuring correct hemostasis, a pleural drainage was placed through one of the incisions.

RESULTS

A decrease of >50% from PTH baseline levels at 5 and 10 min after resection and the return to normal values (below 5 pg/dl) was achieved, demonstrating that the resection was complete (Table 1). Both patients had a rapid postoperative recovery, being discharged at the first postoperative day after removing the pleural drainage. Hypercalcemia was solved in both cases, although they needed treatment with calcium supplements at discharge (Table 1). Pathological results showed an intra-thymic parathyroid adenoma in the first patient and an intra-thymic focus of parathyroid hyperplasia in the second one. During 1 year of postoperative follow-up no complications were registered. Further endocrine follow-up was made in their reference centre.

Table 1:

Patient information about location of ectopic parathyroid tissue by chest computed tomography, intraoperative parathyroid hormone values and serum calcium levels corrected for albumin at discharge

	Location of ectopic parathyroid tissue	Size (mm)	Baseline PTH (pg/dl)	5′ PTH (pg/dl)	10′ PTH (pg/dl)	Corrected calcium levels at discharge (mg/dl)
Patient 1	Anterior to the innominate vein	5 × 5	15.7	3.29	2.81	7.62
Patient 2	Pre-aortic	6 × 3.5	20	2	1.6	8.36

PTH: parathyroid hormone.

DISCUSSION

In 1991, Doppman and Miller said that the best method for preoperative location of parathyroid adenomas was to find an expert surgeon. Almost 30 years after the paradigm has changed. In the minimally invasive approach era, the importance of exploit all image recourses available is extremely high.

Nowadays, the gold standard imaging technique to locate parathyroid adenomas is the 99TC-MIBI, due to its high sensitivity [3]. Fluorocholine positron emission tomography–CT is a good choice when no hyperfunctional tissue is detected on 99mTC-MIBI [4]. Chest CT scan is useful in order to define the anatomic characteristics of the tumour. Four-dimensional CT has recently demonstrated a higher sensitivity than 99TC-MIBI alone and in combination [5]. The correct use of all these imaging techniques deserves further discussion.

Surgery remains the best treatment option; however, the location of the adenoma is basic to choose the best approach: a transcervical approach if the tumour is superior to the innominate vein; a sternotomy or a thoracotomy if the tumour is below the vein; and an anterior mediastinotomy if the tumour is in the aortopulmonary window [6].

The development of minimally invasive techniques in thoracic surgery offers an improvement over the described approaches. The National Institute for Health and Care Excellence published in 2007 a clinical guideline for thoracoscopic excision of mediastinal parathyroid tumours that emphasizes the use of VATS as the most recommended approach [7]. Robotic thymectomy has demonstrated that is superior to open surgery and comparable to VATS approach but further randomized controlled studies are required to make definitive conclusions [8].

It is relevant to know that a complete thymectomy is not essential to resect an EPA, but there are some cases that it could be necessary:

1. When the EPA is near the innominate vein/thymic veins. Anatomical resection of the thymic gland warrants less risk of bleeding.

2. Parathyroid hyperplasy because a microscopic focus could remain in the thymic tissue left behind.

3. Risk of capsule rupture and spread of parathyroid tissue (parathyromatosis) in case of difficult intraoperative localization of the lesion, as it is not visible in most cases.

The intraoperative identification of the EPA in the anterior mediastinum is the most important limitation. Intraoperative 99mTC-MIBI in the operative field has been used to locate MIBI-avid parathyroid adenomas, but its application in mediastinal EPA is still unknown [9]. The use of anatomical markers such as methylene blue could facilitate the intraoperative identification of the EPA, although its specificity is not 100%, mainly due to its ability to spread through adipose tissue [6, 7]. Indocyanine green angiography has demonstrated a high sensitivity for the intraoperative identification of pathologic parathyroid glands leading to a resection rate of 95.16%, being especially useful in cases of ectopic parathyroid glands [10]. However, it is worth to mention that intraoperative PTH monitoring offers a physiological information about the resolution of PHPT.

In the 2 cases presented, the evidence of a complete resection has been based on the intraoperative decrease of PTH values and the complete dissection of the thymus following the established landmarks described. We consider that intraoperative monitoring of PTH blood levels at 5 and 10 min after resection is mandatory since it has shown a decrease in the surgical failure rate from 21.2% to 3% [6].

CONCLUSION

VATS thymectomy should be considered as the optimal approach to resect mediastinal EPA, as it provides the benefits of minimally invasive surgery. To improve the effectiveness of surgery we recommend intraoperative monitoring of PTH blood levels to demonstrate at least a 50% reduction from the highest basal level at 5 and 10 min after resection.

 

Conflict of interest: none declared.

Reviewer information

Interactive CardioVascular and Thoracic Surgery thanks Rui Haddad and the other, anonymous reviewer(s) for their contribution to the peer review process of this article

 

The present work has been presented in the Spanish National Surgery Congress by the Spanish Surgery Association (CNC-AEC), and is going to be presented in the next International Joint Meeting in Thoracic Surgery and the next Spanish Society of Thoracic Surgery (SECT) Congress in 2021.