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A difficult case of mediastinal parathyroid adenoma: theoretical and clinical considerations
S. Luncã, C. Stãnescu, G. Bouras, M. Vix, J. Marescaux (Chirurgia, 99 (6): 563-566)
Bilateral neck exploration is successful in more than 95% of patients with primary hyperpara- thyroidism (HPT) when performed by an experienced endocrine surgeon (1). Failure to remove hyperfunctioning tissue results in persistent or recurrent HPT and the need for reoperation.
Persistent HPT occurs in 3.2% of cases (2). This can result from the surgeon's inexperience leading to inadequate exploration and incomplete excision, or be associated with supranumerary and ectopic parathyroid glandular tissue. The presence of a pathological parathyroid gland in an ectopic position is responsible for 50% of failures of surgical treatment for primary HPT (3). It is estimated that about 11 to 25% of patients with primary HPT have ectopic mediastinal parathyroid tissue (2). Most of these mediastinal ectopic glands are accessible by the cervical approach and only a minority (2%) require a thoracic approach (2, 3). Here we present a difficult case of persistent HPT secondary to an ectopic middle mediastinal parathyroid adenoma, which was eventually successfully managed in a specialist unit.
Case report
A 44 year-old female patient was diagnosed with primary HPT. Presenting symptoms included lethargy, osteoarticular pain, gastrointestinal colic and renal colic. Biochemical analysis revealed a blood calcium level of 3.2mmol/l, raised parathyroid hormone level (88ng/l) and hypophosphataemia (0.48 mmol/l). The patient had a past medical history of bilateral pyelo-tomy and urostomy for nephrolithiasis and a double left kidney. Initial surgical treatment involved bilateral neck exploration during which three normal parathyroid glands were found. A biopsy was taken from the right inferior gland for frozen section while both inferior and superior left glands were macroscopically assessed to be normal. The exploration was extending deep into the neck and into the superior mediastinum in search for the 4th superior right parathyroid gland, which was not found. The patient had persistent hyperparathyroidaemia and hypercalcaemia post-operatively as well as persistent symptoms. Computed tomography (CT) at this point showed a suspicious 5 mm mass between the right brachiocephalic arterial trunk and superior vena cava. Radioisotope scan revealed a solitary focus of abnormal tracer uptake in the superior right mediastinum. A second cervical exploration with partial median sternotomy was performed, however, no adenoma was found. A decision was made to excise the thymus gland together with pre-tracheal fascia. Despite this extensive excision, the hyperparathyroidism persisted and the patient was therefore referred to our tertiary referral centre.
Further investigations were performed in order to localize the lesion more precisely. Cervicothoracic CT scan and magnetic resonance imaging (MRI) (fig.1) revealed a small mass in the right middle mediastinum, which was interpreted as a possible adenoma.
Tc-99 sestamibi scintigraphy (fig. 2) similarly localized the causative lesion in the mediastinum.
Parathyroid hormone venous sampling revealed high levels of PTH (902.2ng/l) at the junction between the right internal jugular and subclavian vein near the internal mammary vein. Arteriography showed a hypervascularised mass in the right superior mediastinum at the level of a thymic branch which emerged from the right internal mammary artery.
The patient then received further exploratory surgery with a complete median sternotomy. On this occasion, a small adenoma measuring 16x15x10mm was discovered in the middle mediastinum posterior and inferior to the right subclavicular artery. Intra-operative PTH measurement was used to determine adequacy of parathyroidectomy. This showed normal PTH levels which confirmed the complete excision of pathological tissue. Intraoperative frozen section revealed parathyroid tissue. The patient made a good post-operative recovery with normalization of biochemical indices and subsidence of symptoms.
Histopathological analysis revealed a parathyroid adenoma weighing 450 mg having a normal heterogenic aspect without necrosis or capsular invasion.
Figura 1a
Figura 1b
Figura 2
Parathyroid tissue in the middle mediastinum is a rare occurrence that presents several challenges to the surgeon both in terms of diagnosis and surgical approach (4). The identification and removal of such an adenoma is difficult due to the small size and soft consistency. Bilateral neck exploration without preoperative localisation can lead to failure due to an ectopic parathyroid gland such as a mediastinal adenoma which is inaccessible at initial cervical exploration.
If such a pathological gland is not found at initial exploration, as with our patient, a second-look re-exploration is made more difficult due to the distortion of anatomy caused by scarring from the first exploration. This leads to the loss of normal anatomical features such colour and shape which are particularly important in this type of surgery. This can lower the success rate and increase the operative risk making complications such as recurrent nerve damage and hypoparathyroidism more likely. The threshold for re-operation in persistent HPT must be raised due to the potential difficulties which can be encountered. If the biochemical and clinical HPT is severe, then re-exploration is mandatory, in particular if the abnormalities are sustained after a period of observation. In the present case, persistence of pre-operative symptoms with no improvement over several months indicated re-exploratory surgery. Prior to second-look surgery, pre-operative localization is essential in order to facilitate the surgeon in an otherwise difficult situation. In the absence of pre-operative localization, there is a 33-40% chance of failure of operative tumour identification with a sternotomy and a complication rate of 21% (5). CT and MRI accurately localize adenomas greater than 1.5 cm in 75-80% of cases. Technetium-99 sestamibi scintigraphy offers the best results with a specificity of 99.8% and a sensitivity of 90.7% (6). If the parathyroid gland is greater than 1 gram in weight, the success rate for radioisotope scan is 86%, for lesions greater than 2 grams it is close to 100%. Lesions less than 500 mg in size can also be detected by this technique. Combination of scintigraphy with CT or MRI increases the success rate for localization of persistent parathyroid adenomas to 90% (7). However interpretation can be difficult, misleading, and unsuccessful in the previously operated patient. For our patient, the mediastinal adenoma was identified by initial CT more anteriorly than in reality, however the surgery proved difficult due to fibrotic reaction in the superior mediastinum, the small size of the adenoma and its position in the middle mediastinum. The tumour was therefore not identified during the first re-exploration. Apart from such non-invasive diagnostic modalities, there are invasive tests such as PTH venous sampling and arteriography which were also performed for our patient and confirmed the presence of the adenoma in the mediastinum further facilitating the pre-operative localization (PTH level 902.2 ng/l). Arteriography may be performed in conjunction with embolization of any vascular lesions and this can be used for ablation of any ectopic glands. However, 40% of ectopic lesions can be missed by arteriography and embolization has a failure rate of 40% (8). In recent years, the rapid intraoperative determination of blood PTH level has been used to determine the adequacy of excision of the hypersecreting parathyroid gland. The adequate resection is considered accomplished if the level decreases by at least 50% compared to values prior to excision and at this point the operation can be regarded as complete. In cases when two adenomas are present, intraoperative blood sampling accurately determines complete excision only in 50% of patients (9).
In the present case, combining various investigations and a wide exploration including a median sternotomy with the experience of the surgeon enabled the identification of a small adenoma (16 x 15 x 10mm, 450mg) in the middle mediastinum. The adequacy of resection was confirmed by decreased PTH levels after 20 minutes (less than 70% from the initial value). When intraoperative localization proves difficult, intraoperative ultrasound can increase the detection rate of adenomas from 36% to 76% and decrease the operative time by 50%. In addition, radio-guided intra-operative detection by immediate preoperative injection of technetium-99-sestamibi radioisotope can be used (7).
This case illustrates the failure of bilateral neck exploration in the identification of an ectopic adenoma. Although this is an uncommon situation, it has to be born in mind in every case of HPT as inadequate excision of the hypersecreting tissue puts the patient at risk from a second more challenging operation. If the pathological gland is not identified, it is mandatory to perform accurate preoperative localization by at least two methods in order to reliably detect the lesion at second look. Currently, radioisotope scan offers the best sensitivity and specificity and combination of this with CT or MRI increases the chance for detection. During re-operation, mediastinal exploration must be thorough, especially if a superior parathyroid gland was not identified at initial exploration. Median sterno-tomy is the best approach in re-explorations because it permits a complete exploration of the anterior mediastinum and excision of the thymus. Compared to thoracotomy, median sternotomy also provides better access to the middle mediastinum.
Intraoperative PTH levels offer a precise way of confirming successful excision of adenomas especially at re-operation. Such cases must be managed by experienced surgeons at specialist units, which have the means for preoperative and intraoperative detection.

1. Jaskowiak, N., Norton, J.A., Alexander, R., Doppman, J.L., Shawker, T, Skarulis, M., et al. - A prospective trial evaluating a standard approach to reoperation for missed parathyroid adenoma. Ann Surg 1996, 224:308.
2. Peeler, B.B., Martin, W.H., Sandler, M.P., Goldstein, R.E. - Sestamibi parathyroid scanning and preoperative localization studies for patients with recurrent/persistent hyperparathyroidism or significant comorbid conditions: development of an optimal strategy. Am Surg., 1997, 63:37.
3. Shen, W., Duren, M., Morita, E., Higgins, C., Duh, Q.Y. - Siperstein AE, et al. Reoperation for persistent or recurrent primary hyperparathyroidism. Arch. Surg., 1996, 131:861.
4. Curley, I.R., Wheeler, M.H., Thompson, N.W., Grant, C.S. - The challenge of the middle mediastinal parathyroid. World J Surg., 1988, 12:818.
5. Conn, J.M., Goncalves, M.A., Mansour, K.A., McGarity, W.C. - The mediastinal para- thyroid. Am Surg., 1991, 57:62.
6. Denham, D.W., Norman, J. - Cost-effectiveness of preoperative sestamibi scan for primary hyperparathyroi-dism is dependent solely upon the surgeon's choice of preoperative procedure. J Am Coll Surg., 1998, 186:293.
7. Rossi, H.L., Ali, A., Prinz, R.A. - Intraoperative sestamibi scanning in reoperative parathyroidectomy. Surgery, 2000, 128:744.
8. Doherty, G.M., Doppman, J.L., Miller, D.I. et al. - Results of multidisciplinary strategy for management of mediastinal parathyroid adenoma as a cause of persistent primary hyperparathyroidism. Ann Surg., 1992, 215:101.
9. Gauger, P.G., Agarwal, G., England, B.G., et al. - Intraoperative parathyroid hormone monitoring fails to detect double parathyroid adenomas: a 2-institution experience. Surgery, 2001, 130:1005.

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