Preoperative localization of abnormal parathyroid tissue

Preoperative Localization of Abnormal Parat hyroid Tissue Cumulative Experience with Venous Sampling and Arteriography

J. P. BILEZIKIAN.

M.D.*

J. L. DOPPMAN,

M.D.

P. M. SHIMKIN,

M.D.?

Bethesda.

Maryland

D. POWELL,

M.R.C.P.

Boston, Massachusetb

S. A. WELLS,

M.D.$

D. A. HEATH,

M.R.C.P.

A. S. KETCHAM, Bethesda.

J. MONCHIK. Washington.

M.D.$ D.C.

L. E. MALLETTE. Befhesda.

M.D.

Maryland

M.D.,

Ph.D.

Maryland

J. T. POTTS, Jr.,

M.D.

Boston, Massachusetts G. D. AURBACH, Bethesda,

M.D.

Maryland

From thesection on Mineral Metabolism, Metabolic Diseases Branch, National Institute of Arthritis, Metabolism and Digestive Diseases; the Department of Diagnostic Radiology, Clinical Center; and the Surgery Branch, National Cancer Institute; National Institutes of Health, Bethesda, Maryland: the Endocrine Unit, Massachusetts General Hospital and the Department of Medicine, Harvard Medical School, Boston, Massachusetts; and The Endocrine Unit, Walter Reed Hospital, Washington, D.C. Requests for reprints should be addressed to Dr. G. D. Aurbach, Bldg. 10, Room 9D-20, National Institute of Arthritis, Metabolism and Digestive Diseases. National Institutes of Health, Bethesda, Maryland 20014. Manuscript accepted June 21,1973. * Present address: Department of Medicine, Columbia-Presbyterian Medical Center, College of Physicians and Surgeons, 630 West 168th Street, New York, New York 10032. t Present address: Department of Radiology, Bridgeport Hospital, Bridgeport, Connecticut. $ Present address: Duke University Hospital, Durham, North Carolina. 5 Present address: Rhode Island Hospital, Providence, Rhode Island 02902.

Selective venous catheterization has been utilized with radioimmunoassay for parathyroid hormone as a preoperative localization technic in 94 patients with primary hyperparathyroidism. Sampling from thyroid veins provided localizing data in 82 per cent Of patients with adenoma and 74 per cent of patients with hyperplasia. Failures were due to inability to catheterize important draining thyroid veins. Large vein sampling was much less helpful, localizing disease in only 29 per cent of patients with adenoma and 13 per cent of patients with hyperplasia. Thyroid venous sampling was also successful in patients who had had previous neck surgery (72 per cent). In addition, this technic differentiated between adenoma and hyperplasia; 98 per cent of patients with unilateral gradients had adenoma; 85 per cent of patients with bilateral elevations had hyperplasia. Selective thyroid venous sampling was more reliable (78 per cent) than arteriography (39 per cent). Venous sampling alone would not be useful for diagnostic purposes because high concentrations of parathyroid hormone were also detected in the inferior thyroid veins of control populations. The results indicate that selective venous sampling and radioimmunoassay of parathyroid hormone are useful preoperative adjuncts to surgical exploration especially in patients who have had previous neck surgery. Surgery for primary hyperparathyroidism is difficult because most abnormal parathyroid glands are small in size, variable in location and nonuniform in appearance. Thus, a simple and reliable method for identifying adenomatous or hyperplastid glands would be desirable. Several procedures for this purpose, including scanning with 75selenium-labeled methionine [l-3], esophagography [4], intraoperative vital staining with toluidine blue [5-81, thermography [9] or arteriography [lo-141, have been applied with limited success [l-14] and sometimes unacceptable side effects [5-81. Indeed, none of these methods allows specific identification of functional parathyroid tissue. The advent of a sensitive radioimmunoassay for parathyroid hormone [15] provided a tool for more accurate and specific identification of the source(s) of abnormal parathyroid hormone secretion [16]. Determination of parathyroid hormone in samples obiained from jugular and innominate veins (hereafter referred to as “large vein sampling”) showed promise. Preoperative localization was possible in five of six patients initially studied [17]. However, this procedure was not consistently effective 118,191 because the. concentration of hormone undoubtedly is diluted markedly before the venous effluent from the glands reaches the large cervical veins.

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of obtaining venous blood directly veins, which drain effluent directly from the parathyroid veins [20], and the finding that the thyroid venous plexus, although a rich anastomotic network, functions as a unilateral drainage system [21], provided the basis for a more sensitive and consistent localization proce-

The

from

feasibility

thyroid

dure. Initial studies showed that determining gradients of hormone concentration across the thyroid venous system was valuable for preoperative localization of parathyroid adenomas as well as an index of parathyroid hyperplasia [22]. Further studies have confirmed this impression [23-251. Patients with adenoma showed unilateral high concentrations, with results for contralateral veins equal to peripheral venous samples. Hyperplasia of several glands was characterized by bilateral elevations of parathyroid hormone in thyroid veins relative to the mean peripheral concentration. Selective venous sampling might also be a useful means to locate parathyroid glands in patients who have had previous neck surgery. This represents a particularly difficult and important localization problem, because the vasculature is frequently distorted or scarred in the course of surgery. Further surgery and localization technics are therefore more difficult to perform. Thus, application of a preoperative localization method to patients who have undergone previous neck surgery, provides a critical test for utility of the procedure. Earlier reports [26,27] indicated that the technic was indeed useful in this circumstance. We present here our experience with thyroid venous sampling and parathyroid hormone radioimmunoassay in 94 cases of primary hyperparathyroidism examined during the past 4 years. Results with this procedure are analyzed in terms of (1) a preoperative localization technic in pa-

ET AL

dure has been described in previous communications [20,26]. Under local anesthesia, a deflectible catheter system (Muller, U.S. Catheter and Instrument Corp.) is introduced percutaneously into a femoral vein. A 100 cm guide wire attached to a flexible external handle provided maneuverability at the tip of the catheter, which was guided with the aid of image-intensified fluoroscopy. The anatomy of the thyroid venous bed was outlined by serial films during retrograde injection of contrast material into a thyroid vein (Figure 1). Heparinized blood samples were obtained from the thyroid veins, the large cervical veins, and from hepatic, renal and iliac veins. The position of the catheter tip was recorded on a spot roentgenogram for each sample taken. An example of a sampling “roadmap” is seen in Figure 2. The blood samples were chilled to 4”C, the plasma was separated by centrifugation and stored at -20°C until parathyroid hormone radioimmunoassay was performed. Patients were up and walking about 3 to 4 hours after completion of the procedure and, except for a few small hematomas, no complications were encountered. Compilation of Results. Selective thyroid vein samples were obtained in 91 of the 94 cases and large vein samples in all. Thus, it was possible to compare results between selective and large vein samples on

tients with or without previous neck surgery, (2) a means for distinguishing adenoma from four-gland

hyperplasia, (3) a comparison vein sampling and arteriography, tial diagnostic tool in primary ism. MATERIALS

AND

between thyroid and (4) a potenhyperparathyroid-

METHODS

Routine clinical evaluation and diPatient Popdation. agnostic tests for primary hyperparathyroidism were completed on all patients in the series. Those considered candidates for surgery underwent selective venous sampling and form the basis for this report. Characterization of some of this population is detailed elsewhere [25,28]. Catheterization Procedure. The catheterization proce-

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Figure

1. Ine thyroid venous prexus. Contrast material was injected into the common inferior thyroid. Force of retrograde injection outlines the entire thyroid venous plexus. Inferior thyroid veins are indicated by arrows.

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f’T ALL

tion from human glands was used as standard. The normal range for fasting adults is 0.3 to 0 8 ngiml (human standard). Samples were processed at one or more dilutions in quadruplicate. Serum calcium WI the fasting state was measured by atomic absorption spectrometry. Phosphate was determined by the method of Fiske and Subbarow (291 adapted for automated analysis. RESULTS

Venous sampling “roadFigure 2. map. ” Venogram marked with numbers indicating site from which samples were taken. Sample numbers 1.2-common inferior thyroid, 3,4left inferior thyroid. 6-right inferior thyroid.

virtually the same patient population. A ratio for concentration of hormone in a neck vessel to concentration in the peripheral circulation (or mean background concentration) of at least 2:l was considered significant. Arteriography. Twenty-three patients underwent bilateral selective thyroid arteriography. Under local anesthesia, the catheter was introduced percutaneously into the femoral artery. Contrast material was injected into the inferior thyroid arteries. In some cases the superior thyroid arteries were studied also. Results were evaluated by direct roentgenograms, and after bony and soft tissue shadows were neutralized by subtraction. A lesion was interpreted as significant if it appeared as an area of persistent staining without significant uptake on thyroid scan. In one patient a hemorrhage developed locally at the site of femoral puncture. Otherwise, there were no complications in the patients reported here. They remained supine for 6 to 8 hours after completion of the procedure. Parathyroid Hormone Radioimmunoassay and Clinical Parathyroid hormone was deterLaboratory Methods. mined by radioimmunoassay as previously reported hormone was prepared 1151. 1251-bovine parathyroid and either pure bovine or a partially purified prepara-

Characteristics of Hyperparathyroid Population. Ninety-four patients with suspected primary hyperparathyroidism were studied. There were 56 females (60 per cent) and 38 males (40 per cent) with average ages of 50.6 f 15 and 49.6 f 12, respectively. The patients ranged in age from 12 to 88 years. Eighty-one patients underwent neck exploration; single adenomas were found in 56 and multiglandular dlsease in 23. In two patients surgery was unsuccessful. Characteristics of the patients with adenoma or hyperplasia are compared in Table I. The concentration of parathyroid hormone in peripheral plasma was above normal limits in 74 per cent of patients with adenoma and in 82 per cent of patients with hyperplasia. In practically all patients, however, concentrations of parathyroid hormone were inappropriately high relative to serum calcium even though in some results were within the normal range. In patients with single adenoma, hormone and calcium levels were higher and phosphate levels lower than in the corresponding population with multiglandular involvement. In this group of 94 patients, 26 (28 per cent) had undergone previous neck surgery: in 20 surgery had been carried out once, in 4 twice, and in 2 thrice previously. Results from Sampling Thyroid Veins Versus Large Veins. Adenoma: A schematized diagram of the venous anatomy and typical assay results for a patient with a single adenoma is shown in Figure 3. The inferior thyroid vein draining the side of the adenoma shows a very high hormone content; that on the contralateral side shows a concentration equal to the mean background concentration. This “unilateral gradient” is the criterion for a preoperative diagnosis of adenoma. In patients with adenoma, localization was achieved in 46 (82 per cent) by thyroid venous sampling, but in only 16 (29 per cent) by large vein sampling (Table II). In three instances, results of thyroid venous sampling did not provide localizing information but large vein sampling did. Bilateral inferior thyroid samples were not obtained from these patients.

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A Comparison Between 56 Patients with Parathyroid Adenoma and 23 with Hyperplasia

I

Hyperplasia

Adenoma Males (no.) Females (no.) Average age (yr) PTH in plasmat (0.3-0.8 ng/ml)

10 (43%) 13 (57%) 45 f 15 1.35 * 0.71 (82% above normal) 11.5 f 1.1

20 (36%)

Serum calcium1 mg/lOOml) (8.8-10.6 Serum phosphates (2.5-4.5 mg/lOO ml) deviation. t Differentiation between $ Differentiation between 8 As phosphorus.

1.6

36 (64%) 53 * 13* 1.64 k 1.42 (74% above normal) 12.1* 1.33

2.54f 0.46

1

2.93zt0.66

* f standard

patientgroups; patientgroups;

p >0.05. p
?TH MB1=1.25ng/ml Hyperptasra Figure

4. Venogram of patient with parathyroid hyperplasia. Note bilateral elevations in thyroid veins.

TABLE

II

Localization by Large Vein and Thyroid Sampling in Patients With and Without Previous Neck Surgery

Large Vein Patients Localization (no.) Adenoma Previous surgery No previous surgery Average (56 patients) Hyperplasia Previous surgery No previous surgery Average (23 patients) Adenoma and hyperplasia Previous surgery No previous surgery Average (79 patients)

peripheral = 1.9 ng/ml PTH L inferior adenoma

Figure 3. Venogram of patient with left inferior parathyroid adenoma. Note high concentration of parathyroid hormone in left inferior thyroid vein.

A schematic venogram of a paHyperplasia: tient with hyperplasia is illustrated in Figure 4. In this case, both inferior thyroid veins showed an elevation of parathyroid hormone compared to mean background. The unilateral drainage of the thyroid plexus suggests that bilateral elevations are due to bilateral disease. The hyperfunctioning glands or remaining glands (in those with previous surgery) were correctly lateralized in 17 (74 per cent) by thyroid vein sampling, but in only three

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Vein

Selective Thyroid Vein Localization

No.

%

No.

%

20 36

6 10

30 28 29

14 32

70 89 82

5 18

1 2

20 11 13

4 13

80 72 74

25 54

7 12

28 23 24

18 45

72 83 80

patients (13 per cent) by large vein sampling (Table I I). Adenoma and hyperplasia: Combined data (Table I I) for both populations clearly indicate that thyroid vein sampling is a more successful localization technic (80 per cent) than large vein sampling (24 per cent). The 16 failures, 10 with adenomas and 6 with hyperplasia, reflect primarily technical difficulties. Forty-four of 46 patients with adenoma (96 per cent), in whom bilateral samples

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were obtained, were correctly lateralized. Nonlocalization in 8 of 10 patients with adenoma was due to inability to catheterize the inferior thyroid vein on the side of the lesion. Unilateral samples only were obtainable from five of six patients with hyperplasia in whom bilateral gradients were not detected. Thus, in this series, failures were primarily due to inability of the angiographer to obtain sample(s) from the important thyroid veins. Localization in Patients With or Without Previous Neck Surgery. In the 25 patients with previous neck surgery, who underwent subsequent successful surgery, localization was achieved in 18 (72 per cent) by thyroid vein sampling compared with only 7 (28 per cent) by large vein sampling. Thyroid vein sampling in these patients compares favorably with sampling performed in patients without previous neck surgery (83 per cent). As noted for the population with no previous neck surgery, failure in these cases was a reflection primarily of unsuccessful catheterization of the thyroid vein draining the source of excess parathyroid hormone. It is clear, nevertheless, that in these patients with difficult localization problems, selective venous sampling provided very helpful and consistent preoperative localization data. Differentiation Between Adenoma and HyperplaThese results also provide data to predict sia. the nature of the parathyroid disease. Unilateral elevation of parathyroid hormone suggests adenoma, and bilateral elevations suggest hyperplasia (Table I I I). Forty-nine patients showed unilateral gradients (Table Ill); adenoma was found at operation in 47 (98 per cent). Two patients with a unilateral gradient showed four-gland hyperplasia, but in both only unilateral samples had been obtained. Twenty patients showed bilateral gradients; 17 (85 per cent) of these were proved to have bilateral disease. In three patients, however, a single adenoma was found even though bilateral gradients were detected. In 10 patients no gradients were detected. A single adenoma was found in seven, hyperplasia in two and metastatic parathyroid carcinoma in one. Technical Difficulties in Sampling. Since drainage from superior and inferior parathyroid glands occurs via the ipsilateral inferior thyroid vein [20], the utility of selective thyroid venous sampling depends on successful bilateral sampling of inferior thyroid veins. Distortion of the venous anatomy or ligation of thyroid veins from previous surgery diminishes the probability for successful sampling (Table IV). Thirty-four of the total 124 patients who underwent venous catheterizations had had previous surgery. Successful bilateral inferior thy-

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Differentiation Between Parathyroid Adenoma and Hyperplasia by Selective Thyroid Venous Sampling and Radioimmunoassay

III

Unilateral Bilateral No -Elevation Elevation Elevation (49 patients) (20 patients) (10 patients)* Adenoma

47

Hyperplasia * One patient had metastatic

TABLE

IV

parathyroid

Success Rate for Sampling

--Inferior thyroid vein sampled on each side At least one thyroid vein sampled on each side (not necessarily inferior)

7 2

carcinoma.

of Thyroid Veins

Previous No Previous Surgery Surgery Total (34 patients) (90 patients) (124patients)* -__ .~_ No. % No. % No. % 10

29

49

53

59

47

19

56

69

75

88

70

* Includes “normal” subjects, and those with other diseases.

TABLE V

3 17

2

hyperparathyroid

subjects

A Comparison of Localization by Arteriography and Selective Venous Sampling in 23 Patients

ArterioNo Arteriographic graphic Localization Localization No.

%

No.

%

Venous localization No venous localization

7 2

30 9

11 3

48 13

Total

9

39

14

61

Total ___ No. % 18 5

78 22

roid samples were obtained in only 29 per cent of the patients with previous surgery compared to 53 per cent in the remaining patients with no previous surgery. Many patients with previous surgery had semi- or total thyroidectomies. It was possible, however, to obtain bilateral thyroid venous samples (not necessarily inferior) in 75 per cent of new cases and in 56 per cent of those with previous surgery. Three patients in the latter group underwent catheterization twice because samples obtained on the first attempt were not from diagnostically important vessels. Two showed localization on the second venous catheterization. The difficulty in obtaining bilateral thyroid venous

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samples was a major cause for failures in preoperative localization. TwentyArteriography and Venous Sampling. three patients underwent thyroid arteriography as well as selective venous sampling; 18 had undergone prior surgery of the neck. In general, arteriography was performed on all patients with prior surgery to help delineate the thyroid venous anatomy as well as to possibly uncover lesion(s) potentially representing parathyroid tissue. Arteriography allowed identification of the site of adenoma in 9 patients (39 per cent) whereas selective venous sampling and parathyroid hormone radioimmunoassay provided localization in 18 (78 per cent) of this group (Table V). Selective venous sampling allowed localization in 11 of the 14 patients in whom arteriography was not helpful. Conversely, in two of five patients who showed no gradient on venous catheterization, arteriography outlined the lesion. There were seven patients (30 per cent) in whom both procedures, arteriography and selective venous sampling, provided preoperative localization. In three patients neither arteriography nor selective venous sampling was helpful. Positive delineation by arteriography, comFigure 6. The venous phase of thyroid arteriogram showing inferior thyroid vein draining blood supply to the lesion (film by subtraction). Sample subsequently obtained from this vein (arrow) showed a very high concentration of parathyroid hormone.

Figure 5. Arteriogram of the right inferior thyroid artery showing a large inferior parathyroid (arrows). Print made by removing soft tissue and bony structure (subtraction.)

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bined with identification by radioimmunoassay on venous samples, obviously provides the most definitive localization of abnormal parathyroid tissue. An example of definitive localization by arteriography and venous sampling is depicted in Figures 5 and 6. Arteriography delineated a suspicious lesion (Figure 5). The venous phase of the arteriogram showed a vein draining this lesion (Figure 6). At selective venous catheterization, this vein was successfully sampled and showed an extremely high concentration of parathyroid hormone, thus confirming the nature of the lesion. Results in Patients with Normal Parathyroid Function. Ten patients with no known disorder of calcium metabolism were studied in the course of venous catheterization for other purposes. Analysis of selective inferior thyroid samples showed significant hormone gradients in several cases (Table VI). Another group characterized by normocalcemia, nephrolithiasis and hypercalciuria was studied also. The concentration gradient for hormone in this group was sometimes as high as 20 but aver-

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aged two times the mean background (Table VII). Given this information on groups without hyperparathyroidism, it is clear that defining a gradient of hormone in thyroid veins is not alone sufficient evidence to establish the diagnosis of primary hyperparathyroidism. On the other hand, none of the patients with nephrolithiasis alone has undergone surgical exploration; hyperparathyroidism is extremely unlikely but not beyond possibility in some of these cases. COMMENTS The patient sample in this study is skewed towards the extremes of the spectrum of hyperparathyroidism. Some patients were referred because the disease was relatively mild and not clearly established by investigations elsewhere. Others (32 per cent) were grossly affected but had been unsuccessfully treated by surgery. In view of the relatively high percentage of patients who had had previous neck surgery, it is probably fair to say that this series is biased toward the more difficult problems of localization. Large vein sampling provided Venous Sampling. localization in only 24 per cent of this series. In earlier studies, results seemed better, ranging from 83 to 50 percent [17-19,301. The innominate and jugular systems (large cervical veins) are rapid flow systems that receive drainage from the entire upper thorax and head. As parathyroid effluent blood drains into the thyroid veins and thence into the large neck vein system, there is a large dilution of hormone. This effect probably ex-

TABLE VI

Selective Thyroid Vein Sampling in 10 Patients with No Known Calcium Disorder

PTH (ng/mb

Mean Back-

PTHin Thyroid Veins (ng/ml)

ground Patient (normal ._ No.* 0.4-0.8)Superior

Right Middle

Left Inferior

Superior Middle

11.4

Inferior 12.2

1

0.61

...

...

.,.

2 3

0.56 0.63

0.63 ...

0.70 7.8

... ...

... ...

0.70 6.5

4

0.55

r..

...

?x

0.69 0.48

... ...

-2.5 1.3 1.2

...

5 6

... ...

... ...

2.0 9.6

7 8 9 10

0.40 0.40 0.25 0.35

... ... ...

8.0 ...

* All patients

had normal

serum

...

...

...

1.55 3.6 >3.5

... ... ...

...

calcium.

...

...

,..

...

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TABLE VII

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in 11

Selective Thyroid Vein Sampling Patients with Nephrolithiasis

PTH (ng/ml) Mean BackPa- ground tient (normal No.*0.4-0.8)

PTH In Thyroid Vems (q/ml) Left.

Right Superior

Middle

lnferror

Superior

Middle

Inferior

. 0.97

. . 1.38 0.24 3.36

1 2 3 4 6

0.45 0.63 0.65 0.47 0.40

... 1.58 ... 0.77 ...

... ... ... ... ...

0.81 .. 1.44 0.41 9.22

0.98

7 8 9

0.60 0.50 0.40

0.60 0.32 0.40

... ... ...

0.56 ..

. 1.32 0.40

10 11

0.40 0.40

... ...

0.40 ...

... 1.23

* All patients

had

normal

.

serum

... ... ...

.,.

. .

0.48 1.28 8.00

0.64

1.10‘ 0.32

...

calcium.

plains the relatively low success rate for large neck vein sampling. In addition, the left innominate vein may receive drainage from either side of the neck and from the mediastinum [31]; an elevation at this site does not help locate the side of the lesion. Selective thyroid venous sampling, on the other hand, has proved to be a more successful preoperative localization technic. Because thyroid veins drain the parathyroid venous effluent directly, dilutional effects are minimized. In patients with no previous neck surgery, adenomas (89 per cent) or multiglandular disease (72 per cent) were predicted correctly with high accuracy. In this population with primary hyperparathyroidism, therefore, selective venous sampling was superior to large vein sampling and was a consistent, effective means of locating sources of parathyroid hormone excess. Patients With Previous Surgery. In this group, surgery is more difficult and time-consuming, and causes higher morbidity. Prior surgery with distortion or ligation of venous channels makes catheterization more difficult. It is in this group that preoperative localization is most important. The slightly reduced over-all success rate (72 per cent versus 83 per cent for new cases) was attributable in part to greater difficulty in obtaining samples bilaterally from the inferior thyroid veins. Nevertheless, it is clear for this population also that selective venous sampling is a reliable procedure for preoperative localization of parathyroid hormone tissue. The results are in agreement with previous series (26,271. Because this population

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tends to have more severe disease and a potential for further difficult and unrewarding surgery, it is important that selective venous sampling be made available to this group before further surgery. Differentiation Between Adenoma and HyperplaIn a previous report, it was emphasized that sia. selective thyroid venous sampling was a reliable means of differentiating between adenoma and four-gland hyperplasia [22]. The current study comprising a much larger number of patients supports, in general, this contention. Results were based upon the patients who showed either a unilateral or bilateral gradient. In only 2 of 49 patients with unilateral gradients, was four-gland hyperplasia found. In these two patients contralateral sampling was not successful. Three of 20 patients with bilateral elevations had adenoma. Although adenoma can be differentiated from hyperplasia by this procedure in most cases, thorough exploration of the neck in an attempt to identify all parathyroid glands is still an important surgical approach. Limitations of Venous Sampling as a Localization Preoperative localization by venous Technic. sampling and radioimmunoassay of parathyroid hormone identifies the side or sides of excess parathyroid hormone production. It does not, however, provide anatomic localization. The superior as well as inferior thyroid blood supplies exit mainly via the ipsilateral inferior thyroid vein [20], and parathyroid veins likewise drain mainly through the inferior thyroid vein. A high concentration of hormone in an inferior thyroid vein, therefore, provides lateralization, but not discrimination between superior or inferior adenomas. When the hormone content is elevated in a superior vein as well as an inferior vein, a superior parathyroid gland is a suspected source of overactive parathyroid hormone production. Even then, however, anatomic localization is not established. The position of parathyroid glands is notoriously variable [32] so that evidence for a superior gland source does not define an exact location. This technic therefore provides information on lateralization but not for specific location. In addition, a major limitation of this technic occurs when bilateral inferior samples cannot be obtained. In this series, the vast majority of failures (14/16) in the cases of adenoma were due to failure to catheterize the inferior vein on the side of the lesion or, in the cases of hyperplasia, to failure to obtain samples from both sides. Arteriography and Venous Sampling. Arteriography, in contrast to selective venous catheterization, may define the exact anatomic site of abnor-

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mally vascular tissue, but it does not necessarily define specifically the nature of the lesion. Certain characteristics of parathyroid adenomas, particularly an oval, well outlined configuration [12], help the angiographer to differentiate between parathyroid and thyroid tissue; thyroid scans are also helpful in some cases [33]. Arteriography, however, allowed localization in 39 per cent compared with lateralization by venous catheterization in 78 per cent of patients having undergone both procedures. On the other hand, successful arteriography combined with selective venous sampling provides the optimum information, allowing anatomic localization as well as functional identification. In 7 of the 23 patients studied by both technics, this definitive information was obtained. We employ arteriography, however, only in patients who have had previous neck surgery and who may benefit from delineation of the vascular anatomy prior to venous catheterization. Sometimes a vein draining a suspected lesion can thereby be detected. Results in Patients with Normal Serum Calcium Levels. The possibility of “normocalcemic” primary hyperparathyroidism exists in certain patients with disorders of calcium metabolism, such as nephrolithiasis, or hypercalciuria, for whom there may be no other evidence for hyperparathyroidism. A high concentration of parathyroid hormone in the thyroid veins in these cases might suggest a diagnosis of hyperparathyroidism. Evaluation of results in the latter group, however, requires studies on a normal group free of parathyroid disease [34]. In the control patients, with no known abnormality of hormone secretion, there were indeed elevations of parathyroid hormone in the thyroid veins and in some cases the concentrations were extremely high. It seems probable that hormone content in venous effluent reflects proximity of the catheter to the source of glandular secretion. The high concentration of parathyroid hormone in thyroid veins, thus, cannot be taken as the sole criterion for hyperparathyroidism. Selective venous catheterization has provided accurate and extremely useful information in preparation for parathyroid surgery. Based on the results presented, we suggest a set of criteria for the future use of this technic: (1) Patients who have had previous unsuccessful neck surgery should undergo selective venous sampling before further surgical intervention. These patients are also candidates for selective arteriography (if there are no contraindications) prior to sampling to outline venous

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“anatomy” sion (s)

and

to

indicate

suspicious

le-

(2) Patients who have not had previous surgery are candidates for selective sampling if they are hospitalized in a center that provides this service. (3) It must be stressed that selective venous sampling and radioimmunoassay of parathyroid hormone require a team of specially trained personnel and facilities not widely available. Close collaboration between the angiographer, endocrinologist, assayist and surgeon is essential for success with the method.

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(4) The technic cannot be used to establish the diagnosis of primary hyperparathyroidism in patients without hypercalcemia. (5) Selective venous sampling is in general a reliable means of differentiating parathyroid adenoma from hyperplasia. ACKNOWLEDGMENT

We would like to thank the following physicians who made important contributions during phases of this study: Drs. Richard Winickoff, Stephen Marx, Kent Pearson, David Kumpe and Robert Beazfey. We also acknowledge the expert secretarial assistance of Mrs. Lillian Perry.

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3. 4.

5.

6.

7.

8. 9. 10. 11. 12.

13.

14. 15.

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