Seminars in Roentgenology
Volume 45, Issue 1 , Pages 53-56, January 2010

Case of the Season: Ectopic Parathyroid Adenoma in the Pericardium: A Report of Robotically Assisted Minimally Invasive Parathyroidectomy

  • Ruchi Yadav, MD

      Affiliations

    • Section of Thoracic Imaging, Division of Radiology, Imaging Institute, Cleveland Clinic, Cleveland, OH
    • ,
  • Tan-Lucien H. Mohammed, MD, FCCP

      Affiliations

    • Section of Thoracic Imaging, Division of Radiology, Imaging Institute, Cleveland Clinic, Cleveland, OH
    • Corresponding Author InformationAddress reprint requests to Tan-Lucien H. Mohammed, MD, FCCP, Section of Thoracic Imaging, Division of Radiology, Imaging Institute Cleveland Clinic, 9500 Euclid Avenue, Mailcode: Hb6, Cleveland, OH 44195
    • ,
  • Donald R. Neumann, MD, PhD

      Affiliations

    • Section of Molecular and Functional Imaging, Division of Radiology, Imaging Institute, Cleveland Clinic, Cleveland, OH
    • ,
  • Tomislav Mihaljevic, MD

      Affiliations

    • Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, OH
    • ,
  • Aaron Hoschar, MD

      Affiliations

    • Department of Pathology, Cleveland Clinic, Cleveland, OH

Article Outline

 

Primary hyperparathyroidism (PHPT) is an endocrine disorder caused by abnormal secretion of parathyroid hormone (PTH) from one or more of the parathyroid glands, resulting in hypercalcemia. In more than 80% of cases, a single solitary parathyroid adenoma is the cause of PHPT.1, 2, 3, 4, 5 The Position Statement of the American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons Task Force on PHPT6 along with nearly a hundred scientific data support parathyroidectomy as the only curative safe and cost-effective therapy for PHPT.3, 7, 8, 9, 10, 11, 12, 13, 14 Despite successful curative rates (>90% with parathyroidectomy6), advances in preoperative imaging, along with adjunctive intraoperative tools (assays and equipment), persistent and recurrent hyperparathyroidism remain challenges for radiologists, clinical endocrinologists, cardiothoracic surgeons, and endocrine surgeons.3 It has been estimated that abnormal supernumerary (fifth)15 and ectopic parathyroid glands are the cause of PHPT and secondary hyperparathyroidism in up to 20% of cases.8

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Case Presentation 

A 23-year-old Caucasian woman presented to an outside hospital for evaluation for nephrolithiasis and was subsequently diagnosed with primary hyperparathyroidism (PHPT). Preoperative delayed 99mTc sestamibi imaging revealed uptake in the right aspect of the thyroid gland. She underwent an unsuccessful unilateral right neck exploration at which time a right thyroidectomy and a right parathyroidectomy were performed. The right thyroid gland and parathyroid glands were normal on frozen section biopsy. During the right neck exploration, the biopsy of the right thymus gland revealed no significant findings. Her serum PTH level failed to normalize postoperatively (167 ng/dL-236 ng/dL; normal: 28-61 ng/dL). For that reason, the patient presented to our institution for further evaluation.

Ultrasound of the neck was unremarkable except for right thyroidectomy. Selected venous PTH sampling did not demonstrate activity in the neck, thus excluding the possibility of an adenoma in the neck. Clinical decision was made to perform 123I/99mTc iodine-sestamibi subtraction imaging with single-photon emission computed tomography (SPECT) of the neck and chest. Contrast-enhanced computed tomography (CT) of the same region was performed for attenuation correction and anatomic localization purposes. Subtraction imaging detected an area of intense uptake in the mediastinum. SPECT localized this small focus of abnormal uptake to the anterior mediastinum, left of midline (Fig. 1). Coregistration of the SPECT with contrast-enhanced CT images (Fig. 2) demonstrated that the abnormal activity corresponded to an 8 × 6 mm rounded, enhancing lesion within the anterior pericardium adjacent to the right ventricular outflow tract (Fig. 3).

  • View full-size image.
  • Figure 3. 

    Coregistration of the transverse SPECT and CT images demonstrates correspondence of the focal sestamibi accumulation and the enhancing pericardial lesion (arrow). (Color version of figure is available onlline.)

The patient had a preoperative sestamibi injection for radioisotope-guided surgery. She underwent minimally invasive robotic-assisted removal of the ectopic parathyroid gland via a left hemithorax approach. There was a significant decrease in her intraoperative parathyroid hormone (iPTH) levels from 158 to 21 pg/mL after surgery. Neo-gamma probe measurements of radioactivity levels of the excised specimen confirmed complete excision of an ectopic parathyroid gland. The frozen section and histopathology of the 7 × 4 × 1 mm “tan nodule” confirmed the presence of a hypercellular parathyroid gland (Fig. 4) in the pericardium. The patient had an uneventful postoperative recovery, and symptoms resolved and PTH normalized.

  • View full-size image.
  • Figure 4. 

    Surgical specimen shows hypercellular parathyroid tissue forming follicular structures lined by cuboidal cells lacking cytologic atypia (hematoxylin and eosin stain, 400×). (Color version of figure is available onlline.)

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Discussion 

PHPT is a common endocrine disease characterized by pathologic hyperfunctioning of one or more of the parathyroid glands, leading to excessive parathyroid hormone secretion and hypercalcemia. PHPT is usually caused by a solitary adenoma (80%-88%); however, some patients have 2 or more adenomas (5%-12%), diffuse hyperplasia (5%-15%), or carcinoma (1%-2%).1, 2 PHPT affects approximately 1 in 500 women and 1 in 2000 men per year, accounting for nearly 1% of the adult population.2, 6, 16 The incidence of PHPT increases after age 55 years and is 2-3 times more prevalent in postmenopausal women than older men. The diagnosis can be made early with routine laboratory examinations or when patients present with the “classic” signs of hyperparathyroidism, such as “painful moans (reduced bone mineral density), renal stones, abdominal groans (gastric ulcer) and psychic moans (depression)” from hypercalcemia.

Most adults have 2 superior and 2 inferior parathyroid glands. Embryologically, the superior parathyroid glands arise from the fourth brachial cleft pouch, along with the thyroid gland, and the inferior parathyroid glands arise from the third brachial cleft pouch, along with the thymus. Supernumerary “fifth” glands are present in up to 13% of the population17 and are often associated with the thymus in the anterior mediastinum.15

Ectopic parathyroid glands occur in 20%-25% of patients and can be located at any anatomical location from the base of the tongue to the mediastinum. Inferior parathyroid glands are more frequently ectopic than superior glands. The ectopic superior parathyroid gland is usually found posteriorly in the tracheoesophageal groove or posterior superior mediastinum.18 The inferior ectopic parathyroid gland can be found in multiple locations in the lower neck: within the superior mediastinum closely associated with the thymus, within the tracheoesophageal groove, near the carotid bifurcation, along carotid sheath, within the aortopulmonary window, posterior to the carina, posterior to the esophagus, or within the posterior triangle of the neck.3, 16, 19, 20, 21, 22

According to the American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons (AACE/AAES) Task Force on PHPT Position Statement, parathyroidectomy is the only curative therapy for PHPT and is both safe and effective.6 Conventionally, bilateral neck exploration without preoperative imaging has been the standard treatment for patients with PHPT with success rates of 95%-98%.2, 3, 6, 7, 9, 11, 12, 23 Most pathologic parathyroid glands reside in the neck and superior mediastinum, thus offering themselves to complete excision. However, 2%-5% of patients present with persistent PHPT after previous failed bilateral neck exploration. An undiscovered ectopic parathyroid adenoma located deep within the mediastinum,15 unrecognized multiple gland enlargement, or failure to resect all the hyperfunctioning tissue during surgery are the most frequent causes of operative failures in patients with persistent or recurrent PHPT.3, 6, 13 Conventionally, parathyroid imaging is used primarily in these patients for accurate localization of the ectopic parathyroid glands when reoperating for persistent disease. However, re-explorations for persistent PHPT via median sternotomy or thoracotomy is associated with morbidity rates of up to 12% and decreased curative rates of 60% in comparison with the initial surgery.3, 8

Due to the advent of minimally invasive parathyroidectomy (MIP), fewer conventional bilateral neck explorations are being performed. MIP offers a more focused surgical approach and can be performed as an outpatient procedure.2, 6, 8, 10, 16, 23 A contributing factor to the increase in MIP is thought to be that 80%-88% of cases of PHPT are caused by a solitary adenoma and bilateral neck exploration is considered excessive when confronted with a solitary lesion. In their recently published article and review of the published data from 1994 to 2006 on video-assisted thoracoscopic surgery, Chae et al demonstrated video-assisted thoracoscopic surgery as a safe and effective procedure for removal of ectopic parathyroid glands by reducing operative time and hospital stay and resulting in fewer postoperative complications.8 Additionally, iPTH measurement and radio-isotope–guided surgery for precise localization have improved the rates of successful resection with MIP.11, 12 Significant decrease in iPTH levels (at least 50%) 10 minutes after excision of a hyperfunctioning gland suggests successful surgical resection. Hence, iPTH is regularly used to assess the completeness of removal of the hypercellular adenoma and to assess the necessity of further exploration during MIP.3

However, MIP obligates accurate preoperative imaging to localize the lesion and confirm single gland disease. Adjunct imaging modalities include ultrasound (US), dual-phase or dual-tracer subtraction scintigraphy, sestamibi SPECT, CT or MRI, and venous blood sampling.6, 16, 22 Caron et al3 recommend that all patients with persistent or recurrent hyperparathyroidism have a minimum of 2 noninvasive localizing studies. There is general consensus regarding the low sensitivity (57%) of US in the evaluation of parathyroid adenomas, especially those that are ectopic. Selective venous sampling is an invasive procedure, and hence not routinely recommended, except in complicated equivocal cases.24 Sestamibi imaging is widely accepted as a modality for imaging and localizing parathyroid adenomas. In their study of 158 patients with sporadic PHPT, Mihai et al25 concluded that sestamibi scans were negative in 52 subjects (32%) of which 45 had single adenomas. Another study of 40 patients with PHPT by Shen et al13 disclosed that unilateral neck exploration guided by sestamibi scanning would have failed in 10% of the patients. Ansquer et al23 in their study of 59 patients with PHPT reported that the sensitivity of double-phase 99mTc-sestamibi/99mTcO4 scintigraphy was higher than that of early or late scintigraphy alone. This can be explained by the fact that a reasonable percentage of parathyroid adenomas have a rapid sestamibi washout, producing false-negative results on delayed sestamibi scintigraphy alone. Therefore, it is precisely that ectopic pericardial parathyroid in our patient was missed during the first preoperative late sestamibi imaging, thus necessitating a second surgery. Recent published reports support dual-tracer subtraction scintigraphy in lieu of dual-phase scintigraphy. It has been reported that SPECT increases the sensitivity of scintigraphy from 85% to 92% and is useful to confirm doubtful foci and to localize ectopic lesions, a fact reconfirmed in our case.26 Ansquer's group also reported that a combination of neck ultrasound, dual-phase 99mTc-sestamibi/99mTcO4 planar scintigraphy and SPECT has the highest sensitivity of 96% and is the most accurate method for the detection of parathyroid lesions and should be performed before MIP.23

Moka et al27 reported a sensitivity of 95% for parathyroid detection with SPECT performed 120 minutes after methoxy isobutyl isonitrile injection, whereas Lorberboym et al26 reported an increased sensitivity from 79% to 96% with early SPECT. SPECT with fusion CT/MRI imaging is superior to SPECT alone, especially in patients with previous neck surgery. Fusion imaging not only provides accurate three-dimensional localization but also superior spatial resolution and a roadmap for surgeons for MIP. SPECT with fusion CT/MRI is emerging as a new powerful tool in parathyroid localization as was exemplified in our complicated case as well.28

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Conclusion 

In summary, this case report confirms that ectopic parathyroid adenomas can be located anywhere from the base of tongue to the mediastinum, including the pericardium. Ectopic parathyroid adenoma causing persistent PHPT is a diagnostic dilemma as no single imaging technique has the capability to accurately detect the hypersecreting parathyroid gland. Review of current published medical studies suggests accurate preoperative localization using a combination of multimodality imaging procedures, such as US, dual-tracer subtraction imaging, and SPECT sestamibi with CT/MRI (fusion imaging) are successfully guiding surgeons in their pursuit of minimally invasive surgery not only during re-exploration for ectopic parathyroid adenoma but also as a initial surgery for parathyroid adenoma.4, 8, 26, 29, 30 Apart from accurate preoperative localization, iPTH assay is a prerequisite for increased success rate with MIP.

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References 

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PII: S0037-198X(09)00066-2

doi:10.1053/j.ro.2009.07.002

Seminars in Roentgenology
Volume 45, Issue 1 , Pages 53-56, January 2010

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