Parathyroid imaging: Its current status and future role

Parathyroid Imaging: Its Current Status and Future Role Eugene J. Fine The management of autonomous (primary or tertiary) hyperparathyroidism is controversial for t w o i m p o r t a n t reasons: (1) Diagnosis of primary or t e r t i a r y hyperparathyroidism (as distinct f r o m reactive or secondary hyperparathyroidism) has been revolutionized in the past 20 years as a result of routine inclusion of serum calcium concentration assays in serum m u l t i a u t o m a t e d analysis, n o w obtained routinely for both hospitalized as well as a m b u l a t o r y patients. The prevalence of primary h y p e r p a r a t h y roidism in t h e general population has appeared to rise as a consequence of this assay and the enhanced detection of this disease. This situation has confused t h e management of hyperparathyroidism since most patients n o w present w i t h asymptomatic disease, and the need for surgical t r e a t m e n t is controversial in asymptomatic individuals. (2) Primary hyperparathyroidism usually is caused by hypersecretion of parathyroid hormone by an autonomously functioning parathyroid adenoma. In a small percentage of cases, multigland hyperplasia is present. In experienced hands, surgical removal of an adenoma w i t h i n the thyroid bed cures t h e hyperparathyroidism 90% t o 95% of the time, w i t h o u t performance of a preoperative procedure t o localize the adenoma. A p p r o x i m a t e l y 10% of parathyroid tissue is ectopic in location, however. Furthermore, a p p r o x i m a t e l y t w o thirds of " m i s s e d " adenomas are w i t h i n the thyroid bed. Reexploration in the e v e n t of a failed operation t h e r e f o r e is not an uncommon occurrence. Parathy-

roid localization procedures clearly are indicated in patients w i t h primary hyperparathyroidism w h o have evidence of persistent disease after a failed a t t e m p t at surgical cure. In patients first presenting w i t h primary hyperparathyroidism, t h e need for a localization procedure is less clear, since surgery appears t o be successful much of the t i m e w i t h o u t it. Regardless of the nature of the above controversies, surgery for autonomous hyperparathyroidism continues, and localization procedures become more popular. Preoperative localization procedures such as angiography and v e n o g r a p h y w i t h venous sampling for p a r a t h o r m o n e are cumbersome and invasive. Noninvasive tests t o localize t h e parathyroid glands have emerged in t h e past 10 years, including dual tracer radionuclide scintigraphy w i t h 201-thalIous chloride and 9 9 m - t e c h n e t i u m p e r t e c h n e t a t e , high-resolution c o m p u t e r tomography, and fine parts ultrasonography, Dual tracer scintigraphy w i t h thallium and technetium is reported to have a localization sensitivity of 70%-90%. False-negative studies occur primarily in patients w i t h small adenomatous or hyperplastic glands. False-positive studies are seen most commonly in patients w i t h coincident thyroid nodules. The ultimate utility of scintigraphy, computer tomography, ultrasonography, and even magnetic resonance imaging, all depend on a v a r i e t y of factors including resolution of the controversies described above.

OCALIZATION of parathyroid tissue preoperatively has become a more widely used procedure in the past several years owing to simultaneous advances in several fields. However, indications for localization procedures are not without controversy. The purpose of this review is to discuss these advances, as well as the controversial issues, with particular emphasis on radionuclide imaging. It is important first to address the fundamental anatomy, histology, physiology, and pathophysiology involved in the functioning of these glands.

roid. This is not invariable, however. Five glands or more is not uncommon; or in contrast, three glands or fewer may be present. 1'2 In approximately 10% of cases, the parathyroids are aberrant in location. Aberrant glands are located in the mediastinum or, more rarely, may be intrathyroidal or retroesophageal. The mean weight of the parathyroid is approximately 30 mg per gland, but the range extends from about 10 mg up to about 70 mg. The blood supply usually is from the inferior thyroidal artery although mediastinal glands may be supplied by the internal mammary artery. Each gland has a poorly defined fibrous capsule. Histologically, the predominant cell is the chief cell which secretes parathyroid hormone (parathormone, PTH). This is, therefore, the important functional cell of the parathyroid gland. Oxyphil cells are of uncertain function and origin and may represent degenerate chief cells. Furthermore, transitional cells exist which appear histologically intermediate between chief and oxyphil cells.

L

ANATOMY

Most commonly, there are four parathyroid glands, usually situated at the poles of the thyFrom the Department of Nuclear Medicine, Albert Einstein College of Medicine, Bronx, NY. Address reprint requests to Eugene J. Fine, MD, Albert Einstein College of Medicine, Department of Nuclear Medicine, 1300 Morris Park Ave, Bronx, N Y 10461. 9 1987 by Grune & Stratton, Inc. 0001-2998/87/1704-0007505.00/0 350

9 1 9 8 7 b y Grune & S t r a t t o n , Inc.

Seminars in Nuclear Medicine, Vol XVII, No. 4 (October), 1987: pp 350-359

PARATHYROID IMAGING: STATUS AND FUTURE ROLE

HISTORICAL CAPSULE

In 1852, the parathyroid gland was first identified in the dissection of an Indian rhinoceros but was not named until 1880. In 1898, tetany was first noted in dogs and cats following removal of the parathyroid glands. The histology of the glands was described in the same year. In 1903, a relation was noted between the parathyroid glands and diseases of bone. In 1914, it was discovered that parathyroid hyperplasia developed in response to a low calcium diet. An important advance was made in 1921 when a convenient measure of serum calcium concentration became available. In 1924 and 1925, Collip 3 demonstrated that extract of parathyroid tissue relieved tetany in dogs. He further demonstrated that the same extract caused an increase in the serum calcium of otherwise normal dogs. In 1926, MandP performed the first parathyroid surgery in humans, removing an adenoma. In 1933, McLean and Hastings 5 noted the relationship of serum calcium to tetany. Rasmussen and Craig, 6 in 1959, isolated purified parathyroid hormone and found it to be an 84 chain amino acid polypeptide. In the 1960s, radioimmunoassays of P T H were first developed. 7 Today there are radioimmunoassays involving the carboxyterminal end of the polypeptide and of the amino terminal, as well as a midrange radioimmunoassay. PHYSIOLOGY

Calcium Metabolism In order to understand the actions of parathyroid hormone, it is essential first to review the role of calcium in biological processes. Calcium is, of course, essential for its structural role in the composition of bones and teeth; it is a cofactor in enzymatic reactions (allowing the functioning of such enzymes as adenylate cyclase, guanilate cyclase, thrombokinase, and many others); it regulates muscle contraction (striated muscle, mitotic spindle formation, and cardiac muscle are all dependent upon the proper concentration of calcium in their milieu); membrane permeability depends upon proper serum calcium concentration; nerve and muscle excitability and cardiac rhythmicity are sensitive to concentrations of calcium; the renal tubular concentrating mechanism is dependent upon calcium concentrations. This list is by no means exhaustive and

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calcium also plays a vital role in fetal development as well as other important biological processes.

Parathyroid Hormone (PTH) The actions of P T H were discovered over a period of many years, beginning with the isolation of the first active extract of P T H by Collip 3 in 1924, accompanied by the first bioassay of its effects in dogs; culminating in the widespread use of sensitive radioimmunoassays today. The primary importance of P T H is in its action to regulate extracellular fluid calcium concentration. It accomplishes this by binding to cell membrane surface receptors, with consequent elevations in the intracellular concentration of cyclic AMP. In osteocytes, this stimulates bony resorption. Renal tubular cells reabsorb calcium under the stimulation of P T H and excrete phosphate. In addition, parathormone stimulates production of the active form of vitamin D. This occurs in the kidney by conversion of circulating 25-hydroxy vitamin D. to the biologically active 1,25-dihydroxy form of the vitamin, which then enhances calcium absorption in the gastrointestinal tract. The net result of these actions is that increased levels of P T H generally cause increases in the serum calcium concentration, while decreased levels will be associated with a decrease in serum calcium. A feedback mechanism on the parathyroid glands establishes a "set point" for serum calcium concentration. Values above that level turn off the secretion of P T H by the parathyroid glands, and above that level stimulate secretion of P T H to maintain serum calcium within a narrow concentration range. PATHOPHYSIOLOGY

Hyperparathyroidism Hyperparathyroidism is a condition characterized by excess secretion of parathyroid hormone. As such, it is usually, but not inevitably, associated with elevations of serum calcium concentration. However, the diagnosis of hyperparathyroidism depends upon more than elevated serum calcium concentration alone, since hypercalcemia is associated with a broad differential diagnosis (see Table 1). Therefore, the diagnosis of hyperparathyroidism depends on the presence

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Table 1. Causes of Hypercalcemia Malignancy 1. Multiple myeloma 2. Lymphoma, leukemia 3. Bony metastases 4. Production of PTH, PTH-like substance, or prostaglandins by other tumors Drugs and Ingestibles 1. Milk-alkali syndrome 2. Thiazide diuretics 3. Vitamin D toxicity Endocrine 1. Hyperparathyroidism (primary, tertiary) 2. Hyperthyroidism 3. Acromegaly 4. Adrenal insufficiency Miscellaneous 1. Sarcoidosis 2. Tuberculosis 3. Immobilization (espec. in Paget's disease of bone)

of hypercalcemia in the absence of other possible causes. Between 80% and 95% of patients with hyperparathyroidism have a solitary adenoma of the parathyroid glands81~in which there is proliferation of chief cells. These adenomas range from 100rag to >20 g. In some cases, more than one adenoma is present and responsible for the hyperthyroidism. In 5% to 15% of cases, hyperparathyroidism is caused by hyperplasia of chief cells. This is detected pathologically as proliferation of the chief cells in all of the parathyroid glands of the affected individual, and all of the glands are enlarged. It is unclear whether cases

of multiple adenomas represent "formes frustes" of parathyroid hyperplasia, as the histological distinction between adenoma and hyperplasia often is not clear. Carcinoma of the parathyroid gland is a rare cause of hyperparathyroidism and it occurs in <4% and probably < 1% of cases. Hyperparathyroidism is divided into three classes: primary, secondary, and tertiary forms. Primary hyperparathyroidism implies autonomous, unregulated secretion of PTH by adenomatous or hyperplastic glands, usually associated with hypercalcemia. Secondary hyperparathyroidism is not associated with hypercalcemia. Most commonly it is found in patients with renal

Table 2. Manifestations of Primary Hyperparathyroidism Renal Stones (25% to 35% of symptomatic primary hyperparathyroidism) Nephrocalcinosis Skeletal Bone pain, pathologic fractures, "'brown" tumors Nonspecific joint pain Osteitis fibrosa cystica Gastrointestinal Increased incidence peptic ulcer disease and pancreatitis Neurological Emotional lability Decreased mentation Easy fatiguability Muscle weakness Other (some secondary to hypercalcemia) Ectopic calcification Electrocardiographic changes Pruritis Anemia Hypertension

PARATHYROID IMAGING: STATUS AND FUTURE ROLE

failure. Inability of the failing kidney to manufacture 1,25-dihydroxy vitamin D leads to reduced calcium absorption from the gut, although normal serum levels of free, ionic calcium are maintained by the reactive or secondary hyperparathyroidism. The histology of the parathyroid glands in such patients reveals hyperplasia. Total serum calcium concentrations are often low due to reduced protein binding present secondary to hypoproteinemia common in this condition. Secondary hyperparathyroidism represents a normal response of the parathyroid glands to pathology elsewhere in the body's calcium homeostatic mechanisms. Tertiary hyperparathyroidism occurs in the setting of chronic renal failure as well. However, in the tertiary form, the parathyroid glands become autonomous in a manner similar to primary hyperparathyroidism, and cause elevations in serum calcium. Excess parathormone has many systemic manifestations. Mild hyperparathyroidism may be asymptomatic. More severe disease can affect many organ systems (see Table 2). As recently as 15 years ago, patients with primary hyperparathyroidism would present with such signs and symptoms. Since the widespread adoption of serum multiautomated blood sampling assays (SMA) such as the SMA-20, serum calcium concentration now is obtained routinely in blood screening examinations. This was not available previously. Consequently, there has been a tremendous increase in the detection of people with asymptomatic hypercalcemia who prove to have hyperparathyroidism by subsequent RIAs of PTH levels/~ In fact, only 10% of patients with hyperparathyroidism now present with manifestations of their disease. The other 90% are detected with asymptomatic hypercalcemia, and supportive high serum PTH levels. Another way of describing the same phenomenon is that the apparent prevalence of hyperparathyroidism has increased from 1:10,000 20 years ago to 1:1,000 upon the use of routine procedures to screen serum calcium concentration] 2 One serious consequence of the new high prevalence of asymptomatic hyperparathyroidism is the general lack of previous experience in treating such patients. It is unclear whether surgical removal of hypersecreting parathyroid tissue is indicated in an asymptomatic individual. One

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may argue that the asymptomatic hyperparathyroid patients of today are those who would have remained undiscovered 15 years ago. On the other hand, one may argue that asymptomatic patients are the best surgical risks since they are healthy. The risks of asymptomatic hyperparathyroidism are unknown and may indeed be quite low. A survey from the Mayo Clinic, however, followed 118 such patients for 10 years and suggests that as many as 20% may develop symptoms due to their disease. ~3 This is by no means a settled issue. PARATHYROID LOCALIZATION

Indications for localizing the parathyroid glands prior to surgery are correspondingly controversial. In experienced surgical hands, 90% to 95% of first attempts at curing hyperparathyroidism are successful.Z4The need for a preoperative localization procedure, therefore, is questionable. It is clear, on the other hand, that a failed operation mandates a localization procedure before reoperation. Most failed operations miss parathyroid tissue in the neck, is and distortion of the anatomy by prior surgery makes localization imperative. Determination of mediastinal parathyroid tissue by a localization procedure after a failed operation is equally important. In patients who are being explored for the first time, one may argue that a localization procedure may shorten operative and anaesthesia time by directing the surgeon to the site of abnormality. However this has not been proven. The choice of preoperative localization procedures is wide, as can be seen in Table 3.16"38 Among the listed procedures, arteriography and selective venography, while accurate, are invasire. Only high-resolution CT, fine parts ultrasonography, and radionuclide scintigraphy have Table 3. Methods for Preoperative Localization of Abnormal Parathyroid Tissue

Cine-esophagography Mediastinography CT Arteriography Selective venography (with PTH assay by RIA) Fine parts ultrasonography Thermography Radionuclide scintigraphy Abbreviation: RIA, radioimmunoassay.

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EUGENE J. FINE Table 4. Characteristics of Parathyroid Imaging Agents 7SSe_methionine T~ Photon energies (keV) Uptake mechanisms

2OLT1

120 days 136, 265, 280, 560 Incorporation into protein

evolved as potentially useful noninvasive procedures. In the late 1960s, 75-Se-selenomethionine was investigated for its potential to localize parathyroid tissue, z~'22Methionine is, of course, an amino acid and is incorporated into protein within cells. Se-75 substitutes for sulfur in this amino acid, and permits it to retain its biological properties. As such, the tracer behaves as methionine and incorporates into both thyroid and parathyroid glands. Synthesis of thyroglobulin in the thyroid gland ceases when pituitary secretion of thyroid stimulating hormone (TSH) is suppressed by administration of exogenous L-thyroxine. Under such circumstances, only the parathyroid glands would be visualized upon administration of 75selenomethionine. However, this agent was abandoned due to its poor imaging characteristics with resultant insensitivity for adenomas smaller than 2 g.39 In the late 1970s, the first case reports emerged from Japan using 210-thallium chloride as an agent to visualize parathyroid glands.4~ T1-201 has a physical half-life of 73 hours and decays by electron capture. While its photon energies are not ideal, being 90% abundant in the 69 to 83 keV range, this is superior to the characteristics of Se-75 (see Table 4) which has photon energies at 136, 265, 280, and 560 keV, and a half-life of 120 days. T1-210 appears to behave as an analog of potassium, the most abundant intracellular cation in the body. Thallium in the + 1 valence state mimics potassium in that its uptake is inhibited (1) competitively by K + and (2) by poisoning the Na+-K + adenosine triphosphatase (ATP'ase) dependent membrane pump. 4~'42 Consequently, TI + is concentrated by all cells of the body when administered in tracer doses. In macroscopic doses, thallium is, of course, a heavy metal and as such is poisonous. No toxic effects of thallium are noted in the tracer quantities used for radionuclide studies. After T1-201 administration a scinti-image in the region of the neck will demonstrate both parathyroid and thyroid tissue. The sternocleidomastoid muscles in the neck also concentrate

73 hours 69-83, 135, 169 K + analog: intracellular cation

T1-201 and provide background activity. Generally, this is of a lower order of activity than the thyroid and parathyroids because the latter are much more vascular. An image of Tc-99mpertechnetate or 1-123 would visualize the thyroid gland only. Excess Tl-201 in regions not seen on the Tc-99m or 1-123 images may represent parathyroid tissue. Indeed, the case report from Japan led to several series from Japan, Europe, and the United States reporting sensitivities for the localization of parathyroid abnormalities in the range of 70% to 90%.23-29It has been observed that the sensitivity depends upon the size of the abnormal parathyroid gland, with gland sizes smaller than 300 mg being much more difficult to detect. In addition, hyperplasia of the parathyroids has been reported more difficult to detect than parathyroid adenomas. This, however, appears to relate again to gland size, 3~ as Blake et a134 have shown, rather elegantly. It also has been found that the detectability of abnormal parathyroid tissue appears to correlate with the degree of elevation of serum parathyroid hormone concentration. It should be noted that comparison of thallium and technetium images is necessary for parathyroid tissue in the neck only. In the case of mediastinal parathyroid tissue, the pertechnetate or iodide image is not necessary. The protocol for parathyroid imaging as performed at the Albert Einstein College of Medicine/Montefiore Medical Center 29is as follows: 1. Patient in the supine position; 2. Insert butterfly intravenous cannula in forearm; 3. Immobilize head (eg, with tape); 4. Inject 2 mCi T1-201; 5. After waiting approximately 10 minutes, using low-energy all purpose (LEAP) collimator obtain scinti-image and computer image over chest and neck for 300,000 counts. 6. Obtain 300,000 count image over neck in magnification mode, or 50,000 to I00,000 counts using pinhole collimator; 7. Inject 6 mCi Tc-99m-pertechnetate through the same indwelling cannula;

PARATHYROID IMAGING: STATUS AND FUTURE ROLE

8. Repeak pulse height analyzer for Tc99m; 9. Repeat image over the neck using same technique (magnification mode or pinhole), without moving the patient's head; and 10. Before the patient has left the imaging table, it is essential for the physician to palpate the neck and mark palpable nodules on the film. Many of the items in the protocol are somewhat controversial or otherwise deserve comment. 1. The order of injection of tracers is one topic which remains unresolved in the literature. We feel that the injection of T1-201 first has several advantages. In particular, 90% of the T1-201 photons are in the 69 to 83 keV range, constituting the daughter x-rays of Hg-201. Only 10% are in the range of 135 or 169 keV. Injection of Tc-99m first may cause degradation of a subsequent T1-201 image by Compton scatter of the

Fig 1. Increased thallium activity in the region of the mediastinum (arrow) is detected in this female with chronic renal failure and tertiary hyparparathyroidism, Five parathyroid glands had already been removed surgically with persistent hypercalcemia (serum calcium concentration, 12.2 mg/dL). Arteriography demonstrated a blush in this region (not shown). At surgery, a 9,000 mg parathyroid adenoma was resected.

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Fig 2. Excess thallium activity is noted in the region of the left lower pole (arrow) in comparison to the Tc99m pertechnetate image. Computer subtraction of the technetium from the thallium image demonstrates the same finding. At surgery, a 615 mg adenoma was removed from this location.

Tc-99m photons into the energy window of the predominant lower energies of T1-201. If one administers lower activities of Tc-99m to minimize this problem, one risks patient head movement from discomfort and restlessness over correspondingly longer imaging times. We feel it is more sensible to inject two mCi of T1-201 first. We are able to obtain reasonable images of 300,000 counts in 5 to 10 minutes, with an energy window of 20% centered around 75 keV. 2. If one wishes to perform computer subtraction of the T1-201 and Tc-99m images, it is essential that the patient does not move his head or neck. The subsequent injection of 6 mCi of Tc-99m pertechnetate through the same IV cannula minimizes the likelihood of patient motion that a separate venipuncture might precipitate. 3. We can calculate quickly that the T1-201 photons at 135 and 169 keV will contribute no more than 3% of the total counts in the Tc-99m window since (A) the abundance of these T1-201 photons is about 10% per disintegration, and (B) we administer 2 mCi of T1-201 and 6 mCi of Tc-99m. 4. Palpation of the thyroid gland is essential

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Fig 3. Excess thallium activity appears to overlie the entire left thyroid lobe (arrow} in comparison to the Tc99m image. The subtraction image is shown once again, In contrast to Fig 2, it is t h e actual relative amounts of radioactivity noted over the entire lobe rather than a contour effect that allows visual determination of t h e relevant finding. A t surgery, a 4.3 g adenoma was resected from t h e left superior pole. The adenoma was pendulous, accounting for its topographic appearance overlying t h e left lobe of the thyroid.

because thyroid nodules (A) often coexist with parathyroid adenomas, 32and (B) may contribute to false-positive scinti-images.33This arises from the observation that most thyroid nodules are "cold" by either Tc-99m pertechnetate or radioiodine scintiscanning. "Warm" or "hot" nodules probably constitute only 5% to l 0% of all

EUGENE J. FINE

nodules scanned. T1-201, however, is likely to accumulate in any nodule, regardless of the appearance on Tc-99m pertechnetate or radioiodine scinti-images, It is clear that a nodule which accumulates T1-201 and not Tc-99m satisfies our criteria for a positive study. This creates a problem in interpretation, and mandates palpation of the neck by the nuclear medicine physician. Thyroid nodules often are more easily palpable than parathyroid adenomas, because the latter are usually smaller and are located more posteriorly within the thyroid gland. Therefore, a palpable abnormality within the thyroid gland most often represents a thyroid abnormality and not a parathyroid adenoma. In general, patients with nodular thyroid glands are relatively poor candidates for a preoperative localization study since it may be difficult to localize parathyroid tissue. If one takes special care to mark palpable abnormalities on the scan, one could look for parathyroid abnormalities distant from the thyroid nodules. IMAGE INTERPRETATION

Interpretation of images is performed best with the aid of a computer with an excellent display monitor. One should examine the chest image first where a mediastinal adenoma should be apparent on the T1-201 image alone (Fig 1). In most cases, the abnormality is in the neck, where the computer images become even more important. If the patient did not move during the scanning period, one can attempt computerized subtraction of images in addition to direct visual comparison. (Some investigators have imple-

Fig 4. A contour effect (arrow) is noted in t h e left upper pole of the thyroid where there is excess thallium activity in c o m p a r i s o n to t h e T c 9 9 m image. Computer subtraction added no information. A 1.5 g adenoma was resected from the left superior pole.

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Fig 5. This patient cancelled her surgical appointment but is included to demonstrate a contour effect in the right thyroid lobe w h e r e t h e r e is excess thallium in comparison to t h e Tc99m image (arrow). In addition, t h e r e appears to be excess a c t i v i t y in t h e l e f t superior pole. No surgical confirmation of multiple adanomas or hyperplasia, h o w e v e r , is available.

Ti.201

~

Fig 6. This male has a multinodular goiter (arrow) w i t h excess thallium activity in the left lower pole, This, h o w e v e r , constitutes a false-positive finding due to t h e presence of a thyroid nodule in this location.

Fig 7. A 900 mg parathyroid adenoma was surgically removed from t h e left upper pole. This was not detected on t h e scintiimages. This constit u t e s a false-negative examination.

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mented software modifications that permit alignment of Tc-99m and T1-201 images even in the event of patient motion. This is not yet widely available, and requires further testing to assure clinical reliability.) Even with direct comparison, image manipulation is an important component in the evaluation of Tc-99m/T1-201 scintiimages. The image quality is different for each tracer, with TI-201 usually providing higher levels of background activity. In the experience at Albert Einstein College of Medicine/Montefiore Medical Center, it was important to adjust the intensity and contrast of the images to render them visualiy more comparable. Figures 2 through 7 demonstrate the variety of abnormalities detectable on T1-201/Tc-99m scinti-images. Parathyroid localization using T1-201 and Tc99m scintigraphy appears to be a useful adjunct in patients with primary or tertiary hyperparathyroidism who have had failed explorations in which their endocrine disorder persists following surgery. The benefit of the procedure is that is it noninvasive and has a sensitivity for localizing such lesions in the range of approximately 70% to 90%. It is less clear whether this procedure should be used routinely prior to a first operation searching for abnormal parathyroid tissue. False-negative examinations may occur in patients who have small adenomatous or hyperplastic glands. In larger adenomas, false-negative examinations are unexplained, but appear to be relatively uncommon. False-positive examinations may occur in patients who have thyroid nodules. 33Controversies still exist with respect to technical aspects of the procedure including: the order of injection of the radiotracers, the relative activities of the tracers used (which depends as

well on the order of injection), the value of computer subtraction techniques, and computer alignment procedures. Computer subtraction may provide a useful adjunct to image interpretation but probably shouldn't be relied on to the exclusion of simple inspection of the T1-201 and Tc-99m images. It is essential to have an excellent computer display in order to adjust and enhance contrast between the T1-201 and Tc99m images. In conclusion, radionuclide scintigraphy has become increasingly popular as a noninvasive tool for localizing abnormal parathyroid tissue. Its ultimate utility as a routine tool will depend on the perceived need by head and neck surgeons and endocrinologists and by the results of further investigation. Competing noninvasive modalities such as high-resolution computed tomography (CT) scanning and fine parts ultrasonography will undoubtedly also play a role in such future investigations.3842 CT and ultrasonography have demonstrated similar localization sensitivities as T1-201/Tc-99m scintigraphy. Each has advantages and disadvantages that determine their utility in individual situations. Sonography is limited in examinations of the mediastinum because air within the lung and bone interfere with transmission of ultrasound waves. CT is somewhat more expensive than either of the other techniques and provides more local radiation to the patient. Finally, nuclear magnetic resonant imaging may have an impact as well. Differences in institutional expertise with each imaging modality also will be a factor. It will be interesting to see the relative role that each modality plays in the future of parathyroid localization.

REFERENCES

1. Rasmussen H, Riefenstein EC Jr: The parathyroid glands, in Williams RH (ed): Textbook of Endocrinology. Philadelphia, Saunders, 1962, chap 11 2. Wang CA: The anatomic basis of parathyroid surgery. Ann Surg 183:271, 1976 3. Collip JB: The extraction of a parathyroid hormone which will prevent or control parathyroid tetany and which regulates the level of blood calcium. J Biol Chem 63:395, 1925 4. Mandl F: Klinisches und Experimentalles zur Frage der lokalisierten und generaliserten Ostitis Fibrosa (unter besonderer Beriicksichtigung der Therapie der letzteren) Arch Klin Chir 143:245-284, 1926 5. McLean FC, Hastings AB: Clinical estimation and

significance of calcium ion concentrations in the blood. Am J Med Sci 189:601, 1935 6. Rasmussen H and Craig LC: Purification of parathyroid hormone by use of countercurrent distribution. J Am Chem Soc 81:5003, 1959 7. Berson SA, Yalow RS, Aurbach GD, et al: Immunoassay of bovine and human parathyroid hormone. Proc Natl Acad Sci USA 49:613, 1963 8. Dekker A, Watson CG, Barnes EL Jr: The pathologic assessment of primary hyperparathyroidism and its impact on therapy: A prospective evaluation of 50 cases with oil red-O stain. Ann Surg 190:671, 1975 9. Krementz ET, Yeager R, Hawley W, et al: The first

PARATHYROID IMAGING: STATUS AND FUTURE ROLE

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