Parathyroid Scintigraphy

Gabriel Soudry, M.D.

Kevin J Donohoe, M.D.

April 11, 1995

Case Presentation:

A 44 year old women presented for persistent hyperparathyroidism and nephrocalcinosis. She had removal of the two superior parathyroid glands at surgery 20 years earlier with only partial improvement after surgery. At the time of surgical exploration the lower parathyroid glands could not be identified. Her past medical history is remarkable for the diagnosis of Multiple Endocrine Neoplasia type I since age 22 including resection of a pancreatic insulinoma. To evaluate the hyperparathyroidism double phase technetium-99m sestamibi parathyroid scintigraphy was performed.

Findings:

Parathyroid scintigraphy (59k bytes) was performed 20 minutes and 2 hours after injection of technetium-99m-sestamibi. The 20 minute scan showed uptake in a normal appearing thyroid gland (arrows, 59k bytes) as well as uptake in two ovoid areas in the upper mediastinum (arrow heads). The 2 hour image showed wash out of activity from the thyroid (arrows), and persistence of activity in the upper mediastinum (arrow heads).

Diagnosis and Clinical Course

She underwent bilateral neck exploration, cervical thymectomy, with excision of intra-thymic bilateral inferior parathyroid glands. A portion of the parathyroid tissues was auto-transplantationed into left forearm. Her post operative course was complicated only by transient hypocalcemia. Pathologic examination of the surgical specimen revealed hypercellular chief cell and oxyphilic cell nodules with decreased intracellular fat consistent with hyperplasia.

Discussion:

Etiology of Hyperparathyroidism:

Hyperparathyroidism is a generalized disorder of calcium, phosphate and bone metabolism that results from increased secretion of parathyroid hormone. Primary hyperparathyroidism is the most common cause of hypercalcemia in non-hospitalized persons and is most common in post-menopausal women. The disease may involve either a single gland (81% adenoma, 4% carcinoma) or multiple glands(15%). Secondary hyperparathyroidism occurs in patients with chronic renal disease and vitamin D deficiency.

Scintigraphic Evaluation of Hyperparathyroidism:

Different scintigraphic techniques have been used for detection of abnormal parathyroid glands using a combination of radiotracers including thallium-201 chloride or technetium-99m sestamibi for localization of abnormal parathyroid glands and technetium-99m-sodium pertechnetate or iodine-123 sodium iodide for thyroid localization. The subsequent processing of those digital images includes background correction and subtraction of the thyroid image from the composite thyroid and parathyroid image. Those methods exploit the different biological behavior and tissue distribution of the two tracers, namely the thyroid specific pertechnetate or iodine uptake relative to the more diffuse perfusion dependent distribution of Thallium or sestamibi.

In 1992, Taillefer et al described a technique of detection and localization of parathyroid adenomas using early and late imaging with injection of Technetium-99m sestamibi. The rationale for this approach came from the observation that the washout of Technetium-99m sestamibi from parathyroid adenoma is slower than that from thyroid tissue. An area of persistent tracer activity on the delayed images is therefore suggestive of the presence of hyperfunctioning parathyroid tissue.

Twenty-three consecutive patients with hyperparathyroidism were included in the study prospectively. They were injected with 20-25 mCi of technetium-99m sestamibi. Planar imaging of the neck and upper thorax were obtained in the anterior view for 10 minutes. Images were acquired on a large field of view camera with a low energy, high resolution, parallel hole collimator. Two sets of images were obtained, the initial set at 10-15 min. and the second set at 2-3 hours after injection of the radiotracer. The readers were asked to interpret early and late images and give the exact location of the adenoma(s). All parathyroid glands were identified at surgery and the gross surgical findings, location of parathyroid adenomas, weight of excised glands and histopathologic findings were recorded for each patient. The sensitivity of the study to detect parathyroid adenomas was 90% (19 positive scan/21 adenomas). There was one false positive scan showing persistent uptake in a follicular adenoma of the thyroid. Two cases of parathyroid hyperplasia were undetected on the parathyroid scans(1).

This single radionuclide, double phase imaging procedure has several advantages over dual radionuclide imaging. The patient requires only one injection and does not need to remain immobile during extended periods of time, the images do not need additional computer processing with background correction and image subtraction and technetium-99m has superior physical characteristics for gamma camera imaging.

Comparison of Pertechnetate / Thallium Parathyroid Scintigraphy with Other Imaging Techniques:

In a prospective blinded study involving 100 patients with primary hyperparathyroidism, thallium-201/technetium-99m subtraction scintigraphy was compared with computed tomography, ultrasonography, and magnetic resonance. The imaging reports were correlated with surgical findings to score their accuracy. Overall sensitivities and specificities were (2):

                        Sens     Spec
Pertechnetate / Tl       73%      94%
Computed Tomography      68%      92%
Ultrasonography          55%      95%
Magnetic Resonance       50%      87%

Impact of Pre-operative Localization in the Treatment of Parathyroid Tumors:

The literature on the value of pre-operative localization of parathyroid tumors reveals a lack of consensus. One group of studies recommend that attempts at pre-operative localization be done in all patients (3,4), while another group of studies recommend against pre-operative localization in patient undergoing initial parathyroid surgery (5,6). However there is virtually universal agreement that localization procedures are warranted in the setting of re-operation in patients with persistent or recurrent hyperparathyroidism after initial surgery (5,7). Localization studies help by suggesting the most direct approach to the abnormal parathyroid tissue including whether surgery begins with a neck or mediastinal exploration.

Patients with primary hyperparathyroidism, when operated on by an experienced endocrine surgeon, have been treated successfully using parathyroidectomy without the use of localizing studies, with reported cure rates of 90 to 96% (4). Several investigators have analyzed the reasons for failure in patients undergoing re-operation. In approximately one third of their failures, multiglandular disease was present, in one third the gland was in an ectopic location, and in one third surgeon inexperience was a factor (8,9).

How many of those repeat surgeries could have been avoided with the use of pre-operative localization is a matter of controversy. In a series of 64 patients operated on for primary hyperparathyroidism, the use of pre-operative imaging resulted in an increased number of successful operations. There was no negative explorations in this series as compared with 19 negative explorations (2.6%) in the author's prior experience with 720 operations. The operative time was shortened from 1 to 1.5 hour to 25 to 40 minutes (3).

Roe et al attempted to evaluate the effect and cost-effectiveness of pre-operative localization studies in the surgical management of patients with primary hyperparathyroidism. The records of 113 patients were retrospectively reviewed. The mean operative time was decreased from 162 minutes to 134 minutes, and assuming a 5% failure rate, the cost per valuable study was calculated at $23,400 (6). However, the scintigraphic study used was thallium-technetium pertechnetate scintigraphy, not technetium-99m sestamibi double phase study, and the calculations were made assuming that thallium-technetium pertechnetate scintigraphy sensitivity was only 60%. Furthermore, the estimated cost per valuable study was not compared with the cost of repeat surgery and potential surgical complications.

Miller suggests that there may be only two circumstances in which localization procedures should be performed prior to initial parathyroid surgery. One is when the patient has had previous thyroid surgery and the other is when the patient is undergoing a parathyroid crisis with life threatening hypercalcemia (5).

The disadvantages of pre-operative localization in patients undergoing initial exploration are:

Increased cost
Possibility of false positive result misleading the surgeon
Inability to reliably locate hyperplastic glands
High success rate of surgery without pre-operative localization

The advantages of pre-operative localization are:

Decreased operative time and morbidity
Aid in surgical planning, particularly for patients with ectopic glands who may need thoracotomy or median sternotomy rather than cervical approach
Increased number of successful operations and decreased need for repeat surgery

Conclusions:

Technetium-99m-sestamibi double phase scintigraphy is the preferred method for detection and localization of parathyroid adenomas.
The indications and cost effectiveness of routine pre-operative parathyroid localization in patients undergoing initial surgery is a matter of controversy among endocrine surgeons.
There is universal agreement that in patients undergoing repeat parathyroid surgery, full pre-operative attempts at parathyroid gland localization should be undertaken.

References:

1. Taillefer R, Boucher Y, Potvin C, Lambert R. Detection and localization of parathyroid adenomas in patients with hyperparathyroidism using a single radionuclide imaging procedure with technetium-99m-sestamibi (Double-phase study). J Nucl Med 1992; 33:1801-1807.

2. Krubsack AJ, Wilson SD, Lawson TL et al. Prospective comparison of radionuclide computed tomographic, sonographic, and magnetic resonance localization of parathyroid tumors. Surgery 1989; 106:639-646.

3. Attie JN, Khan A, Rumancik WM, Moskowitz GW, Hirsh MA, Herman PG. Preoperative localization of parathyroid adenomas. Am J Surg 1988; 156:323-326.

4. Irvin GL, Prudhomme DL, Derisco GT, Sfakianakis GS, Chandarlapaty SKC. A new approach to parathyroidectomy. Ann Surg 1994; 219(5):574-581.

5. Miller DM. Pre-operative localization and interventional treatment of parathyroid tumors: When and how? World J Surg 1991; 15:706-715.

6. Roe SM, Burns RP, Graham LD et al. Cost-effectiveness of preoperative localization studies in primary hyperthyroid disease. Ann Surg 1994; 219(5):582-586.

7. Carty SE, Norton JA. Management of patients with persistent or recurrent primary hyperthyroidism. World J Surg 1991; 15:716-723.

8. Levin KE, Clark OH. The reasons for failure in parathyroid operations. Arch Surg 1989; 124:911-915.

9. Bruining HA, BirkenhŠger JC, Ong JL, Lamberts SWJ. Causes of failure in operations for hyperparathyroidism. Surgery 1987; 101:562-567.

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J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu