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Usefulness of Adrenal Venography and Iodocholesterol Scan in Adrenal Surgery
0022-5347 /79/1221-0007$02.00/0 Vol. 122, July
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1979 by The Williams & Wilkins Co.
Original Articles USEFULNESS OF ADRENAL VENOGRAPHY AND IODOCHOLESTEROL SCAN IN ADRENAL SURGERY KARL R. HERWIG*
AND
L. PAUL SONDA, III
From the Section of Urology, Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan
ABSTRACT
Adrenal scintiscanning and venography with sampling of adrenal venous blood are valuable methods to localize adrenal cortical lesions of Cushing's syndrome and primary aldosteronism. Adrenal scintiscanning with dexamethasone suppression is most useful in differentiating adenoma from hyperplasia of primary aldosteronism. The diagnosis of adrenal cortical disease involves accurate laboratory assessment and careful interpretation of these results. At times the laboratory tests cannot differentiate between bilateral and unilateral disease. In addition, if an adenoma or tumor is suggested the laboratory diagnosis offers little help in determining which adrenal gland harbors the lesion. During the last decade 3 methods of visualizing and localizing lesions of the adrenal cortex have evolved: 1) adrenal venography, 2) iodocholesterol scanning and 3) hormone analysis of the venous blood from each adrenal. Their use allows accurate localization, which helps the surgeon plan the operative approach and differentiate bilateral from unilateral disease.
RESULTS
Cushing's syndrome (table 1). Venography: Adrenal venography was performed on only 3 patients suspected of having an adenoma causing Cushing's syndrome. In all 3 cases the venogram accurately located the tumor. Venography was not used in patients suspected of having hyperplasia because of excellent visualization by adrenal scintiscanning. Four patients had suspected carcinoma of the adrenal cortex. All had suspicious lesions above the kidney, causing displacement of the kidney pyelographically. These cases were confirmed by arteriography. Venography was not performed on these patients. Only 1 patient had adrenal venous blood analysis performed. The procedure was not done for localization purposes but was done to determine the hormones produced by the adenoma. In this particular patient the adenoma was found to produce androgen and not cortisol. Adrenal scintiscanning: Adrenal scintiscanning with 1311-19iodocholesterol accurately depicted the adrenal lesion in 14 of 26 patients with Cushing's syndrome: 6 had adenoma, 6 had bilateral hyperplasia and 2 had remnants that localized. In 2 patients the scan was able to differentiate hyperplasia from adenoma despite conflicting laboratory studies. Two patients with adrenocortical carcinoma demonstrated no isotope concentration in the tumor, which may be owing to low function per unit weight of the tumor or synthesis of hormone occurring by alternate pathways. Primary aldosteronism (table 2). Venography: Venography was attempted in 33 patients with primary aldosteronism. Venography was unsuccessful in 3 patients because of technical difficulties (9 per cent). The venogram accurately predicted the cause of the disease in 26 patients (87 per cent): 22 had an adenoma and 4 had bilateral hyperplasia. Within the group of adenomas 1 patient was found to have bilateral adenomas. Three patients with adenomas had negative venograms. All 3 adenomas in these patients were <8 mm. in size. One venogram was interpreted as showing an adenoma but none was found at operation. Review of this venogram suggested overinterpretation originally. Adrenal vein blood analysis: Separate adrenal vein blood analysis was attempted in 16 patients. Three were not performed because of technical difficulties (19 per cent). When technically successful adrenal vein blood analysis predicted the site of the lesion in 12 of 13 patients (91 per cent). The 1 failure occurred in a patient with hyperplasia in whom blood from the right adrenal vein contained more aldosterone than the left vein. Unilateral hyperplasia has been advanced as the
MATERIALS
Between 1970 and 1977, 63 patients with either Cushing's syndrome or primary aldosteronism were referred to the senior author for operation. Of these 63 patients 38 had primary aldosteronism and 25 had Cushing's syndrome. All patients with primary aldosteronism were suspected of having an adenoma of the adrenal cortex. Thirteen patients with Cushing's syndrome were thought to have an adenoma or carcinoma. Twelve patients had adrenocorticotropic hormonedependent Cushing's syndrome and had not responded to other forms of therapy for this disease. Among these were 2 patients who previously had undergone total bilateral adrenalectomy and had recurrence of the hyperadrenocorticism. In these 2 patients actively functioning remnants of the adrenal cortex were suspected but the site was unknown. Localization studies were done on all patients with primary aldosteronism and most patients with Cushing's syndrome. Venography was performed by the technique described by Reuter and associates. 1 At the time of venography blood was obtained from each adrenal vein and the inferior vena cava for comparative analysis of hormone production by each adrenal gland in a small number of patients. 2 Adrenal scintiscanning was done using 131I-19-iodocholesterol as described by Lieberman and associates. 3 Twenty-three patients with primary aldosteronism unde1went additional scanning after dexamethasone suppression. 4 Accepted for publication September 15, 1978. Read at annual meeting of Western Section, American Urological Association, Seattle, Washington, July 16-20, 1978. * Requests for reprints: Department of Urology, Scripps Clinic Medical Institution, 10666 N. Torrey Pines Rd., La Jolla, California 92037. 7
8
HERWIG AND SONDA TABLE
1. Accuracy oflocalization studies in the diagnosis of Cushing's syndrome Adenoma Hyperplasia Ca
Venography, 3 Adrenal scintiscan, 16 TABLE
3/3 6/6
0 8/8
0
0/2
2. Accuracy of localization studies in the diagnosis of primary aldosteronism
Venography, 33* Adrenal venous blood, 16* Adrenal scintiscan, 36 Dexamethasone suppression, 23
* Technically unsuccessful,
Adenoma
Hyperplasia
22/25 9/9 23/29 17/19
4/5 3/4 4/7 4/4
3 patients.
cause since the patient no longer has primary aldosteronism after a right total adrenalectomy. Adrenal scintiscanning: Adrenal scintiscanning with 131 I-19iodocholesterol was performed on 36 patients with primary aldosteronism. At operation adenoma was found in 29 patients and bilateral hyperplasia was found in 7. The scan accurately predicted the condition of 27 patients: 23 adenomas and 4 hyperplasias (75 per cent). In 6 patients with adenoma the scan was interpreted as showing hyperplasia. One of these patients had bilateral adenoma. In 3 patients with bilateral hyperplasia the scan was interpreted as showing adenoma. Two of these patients were seen early in the experience with iodocholesterol scanning and probably represent over-enthusiastic interpretation. The other patient had unilateral uptake but was found to have hyperplasia. This patient also lateralized with adrenal vein blood analysis and may represent unilateral hyperplasia. Dexamethasone suppression scanning was done on 23 patients and was accurate in predicting lesions in 21 (91 per cent): 19 adenomas and 4 hyperplasias. In 2 patients lateralization did not occur. One was found to have carcinoma and 1 had bilateral adenomas. DISCUSSION
When an operation ensues for disease of the adrenal cortex the surgeon can better plan and execute the operation if the site of the lesion is known. Direct physical examination is not helpful except with large lesions, such as adrenal cysts or carcinoma. Indirect methods, such as pyelography, also are of little help except in the large lesions. Since most adrenal adenomas are small, especially those of primary aldosteronism, methods have evolved to visualize the adrenal gland directly. V enography is a direct extension of the techniques of arteriography and represents a marked advance in diagnosis. However, the technical expertise required to cannulate the adrenal veins takes patience and is not always successful, as shown in this group of patients. The venous system of the adrenal gland easily ruptures, leading to pain and hematoma formation. One patient in this series suffered flank pain after venography and the laboratory signs of primary aldosteronism disappeared, which probably resulted from ischemia of the adrenal gland from venous rupture. The primary aldosteronism returned and was cured after removal of an adenoma of the adrenal.
At the time of venography samples from each adrenal vein can be taken for analysis of hormone, such as aldosterone. Again, the technical problems of accurate collection make this a formidable procedure. Requiring only an intravenous injection and, thus, less invasive is the adrenal scintiscan. It can be done on outpatients and it requires no special precautions. In patients with Cushing's syndrome it is highly accurate and can be used in place of dexamethasone suppression tests to differentiate adenoma from hyperplasia. However, computerized tomography may replace it in the diagnosis ofCushing's syndrome, since adenomas are distinguished easily by this procedure because of their size.'' Adrenal scintiscanning continues to be of greatest aid in finding hormonally active remnants of the adrenal cortex after so-called bilateral adrenalectomy. 6 The value of iodocholesterol scanning in patients with primary aldosteronism appears most promising. Although the unsuppressed scan is less accurate than venography, development of dexamethasone suppression has made it highly accurate in localizing adenomas and differentiating bilateral hyperplasia from adenoma. 7 Dexamethasone suppresses the production of adrenocorticotropic hormone and prevents the normal adrenal cortex from concentrating iodocholesterol. However, autonomous tissue, such as found in an adenoma, will concentrate the isotope and appear on the scintiscan as an area of increased uptake. Currently, these 3 methods of adrenal localization are useful but computerized tomography may replace them in the future. This is especially true for lesions causing Cushing's syndrome. However, the resolution power of computerized tomography may miss the small adenoma of primary aldosteronism and in these cases adrenal scintiscanning with dexamethasone suppression appears most helpful. REFERENCES
1. Reuter, S. R., Blair, A. J., Schteingart, D. E. and Bookstein, J. J.: Adrenal venography. Radiology, 89: 805, 1967. 2. Melby, J.C., Spark, R. F., Dale, S. L., Egdahl, R.H. and Kahn, P. C.: Diagnosis and localization of aldosterone-producing adenomas by adrenal-vein catheterization. New Engl. J. Med., 277: 1050, 1967. 3. Lieberman, L. M., Beierwaltes, W. H., Conn, J. W., Ansari, A. N. and Nishiyama, H.: Diagnosis of adrenal disease by visualization of human adrenal glands with 131-1-19-iodocholesterol. New Engl. J. Med., 285: 1387, 1971. 4. Conn, J. W., Morita, R., Cohen, E. L., Beierwaltes, W. H., McDonald, W. J. and Herwig, K. R.: Primary aldosteronism. Photoscanning of tumors after administration of 131-1-19-iodocholesterol. Arch. Intern. Med., 129: 417, 1972. 5. Schaner, E. G., Dunnick, N. R., Doppman, J. L., Strott, C. A., Gill, J. R., Jr. and Javadpour, N.: Adrenal cortical tumors with low attenuation coefficients. A pitfall in computed tomography diagnosis. J. Comp. Ass. Tomogr., 2: 11, 1978. 6. Herwig, K. R. and Schteingart, D. E.: Successful removal of adrenal remnant localized by 131-I-19-iodocholesterol. J. Urol., 111: 713, 1974. 7. Conn, J. W., Cohen, E. L. and Herwig, K. R.: Primary aldosteronism: a noninvasive procedure for tumor localization as well as for distinction from bilateral hyperplasia. In: Advances in Nephrology. Edited by J. Hamburger, J. Crosnier, J. Greenfeld and M. H. Maxwell. Chicago: Year Book Medical Publishers, Inc., vol. 7, p. 157, 1977.
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright © 1979 by The Williams & Wilkins Co.
Original Articles USEFULNESS OF ADRENAL VENOGRAPHY AND IODOCHOLESTEROL SCAN IN ADRENAL SURGERY KARL R. HERWIG*
AND
L. PAUL SONDA, III
From the Section of Urology, Department of Surgery, University of Michigan Medical Center, Ann Arbor, Michigan
ABSTRACT
Adrenal scintiscanning and venography with sampling of adrenal venous blood are valuable methods to localize adrenal cortical lesions of Cushing's syndrome and primary aldosteronism. Adrenal scintiscanning with dexamethasone suppression is most useful in differentiating adenoma from hyperplasia of primary aldosteronism. The diagnosis of adrenal cortical disease involves accurate laboratory assessment and careful interpretation of these results. At times the laboratory tests cannot differentiate between bilateral and unilateral disease. In addition, if an adenoma or tumor is suggested the laboratory diagnosis offers little help in determining which adrenal gland harbors the lesion. During the last decade 3 methods of visualizing and localizing lesions of the adrenal cortex have evolved: 1) adrenal venography, 2) iodocholesterol scanning and 3) hormone analysis of the venous blood from each adrenal. Their use allows accurate localization, which helps the surgeon plan the operative approach and differentiate bilateral from unilateral disease.
RESULTS
Cushing's syndrome (table 1). Venography: Adrenal venography was performed on only 3 patients suspected of having an adenoma causing Cushing's syndrome. In all 3 cases the venogram accurately located the tumor. Venography was not used in patients suspected of having hyperplasia because of excellent visualization by adrenal scintiscanning. Four patients had suspected carcinoma of the adrenal cortex. All had suspicious lesions above the kidney, causing displacement of the kidney pyelographically. These cases were confirmed by arteriography. Venography was not performed on these patients. Only 1 patient had adrenal venous blood analysis performed. The procedure was not done for localization purposes but was done to determine the hormones produced by the adenoma. In this particular patient the adenoma was found to produce androgen and not cortisol. Adrenal scintiscanning: Adrenal scintiscanning with 1311-19iodocholesterol accurately depicted the adrenal lesion in 14 of 26 patients with Cushing's syndrome: 6 had adenoma, 6 had bilateral hyperplasia and 2 had remnants that localized. In 2 patients the scan was able to differentiate hyperplasia from adenoma despite conflicting laboratory studies. Two patients with adrenocortical carcinoma demonstrated no isotope concentration in the tumor, which may be owing to low function per unit weight of the tumor or synthesis of hormone occurring by alternate pathways. Primary aldosteronism (table 2). Venography: Venography was attempted in 33 patients with primary aldosteronism. Venography was unsuccessful in 3 patients because of technical difficulties (9 per cent). The venogram accurately predicted the cause of the disease in 26 patients (87 per cent): 22 had an adenoma and 4 had bilateral hyperplasia. Within the group of adenomas 1 patient was found to have bilateral adenomas. Three patients with adenomas had negative venograms. All 3 adenomas in these patients were <8 mm. in size. One venogram was interpreted as showing an adenoma but none was found at operation. Review of this venogram suggested overinterpretation originally. Adrenal vein blood analysis: Separate adrenal vein blood analysis was attempted in 16 patients. Three were not performed because of technical difficulties (19 per cent). When technically successful adrenal vein blood analysis predicted the site of the lesion in 12 of 13 patients (91 per cent). The 1 failure occurred in a patient with hyperplasia in whom blood from the right adrenal vein contained more aldosterone than the left vein. Unilateral hyperplasia has been advanced as the
MATERIALS
Between 1970 and 1977, 63 patients with either Cushing's syndrome or primary aldosteronism were referred to the senior author for operation. Of these 63 patients 38 had primary aldosteronism and 25 had Cushing's syndrome. All patients with primary aldosteronism were suspected of having an adenoma of the adrenal cortex. Thirteen patients with Cushing's syndrome were thought to have an adenoma or carcinoma. Twelve patients had adrenocorticotropic hormonedependent Cushing's syndrome and had not responded to other forms of therapy for this disease. Among these were 2 patients who previously had undergone total bilateral adrenalectomy and had recurrence of the hyperadrenocorticism. In these 2 patients actively functioning remnants of the adrenal cortex were suspected but the site was unknown. Localization studies were done on all patients with primary aldosteronism and most patients with Cushing's syndrome. Venography was performed by the technique described by Reuter and associates. 1 At the time of venography blood was obtained from each adrenal vein and the inferior vena cava for comparative analysis of hormone production by each adrenal gland in a small number of patients. 2 Adrenal scintiscanning was done using 131I-19-iodocholesterol as described by Lieberman and associates. 3 Twenty-three patients with primary aldosteronism unde1went additional scanning after dexamethasone suppression. 4 Accepted for publication September 15, 1978. Read at annual meeting of Western Section, American Urological Association, Seattle, Washington, July 16-20, 1978. * Requests for reprints: Department of Urology, Scripps Clinic Medical Institution, 10666 N. Torrey Pines Rd., La Jolla, California 92037. 7
8
HERWIG AND SONDA TABLE
1. Accuracy oflocalization studies in the diagnosis of Cushing's syndrome Adenoma Hyperplasia Ca
Venography, 3 Adrenal scintiscan, 16 TABLE
3/3 6/6
0 8/8
0
0/2
2. Accuracy of localization studies in the diagnosis of primary aldosteronism
Venography, 33* Adrenal venous blood, 16* Adrenal scintiscan, 36 Dexamethasone suppression, 23
* Technically unsuccessful,
Adenoma
Hyperplasia
22/25 9/9 23/29 17/19
4/5 3/4 4/7 4/4
3 patients.
cause since the patient no longer has primary aldosteronism after a right total adrenalectomy. Adrenal scintiscanning: Adrenal scintiscanning with 131 I-19iodocholesterol was performed on 36 patients with primary aldosteronism. At operation adenoma was found in 29 patients and bilateral hyperplasia was found in 7. The scan accurately predicted the condition of 27 patients: 23 adenomas and 4 hyperplasias (75 per cent). In 6 patients with adenoma the scan was interpreted as showing hyperplasia. One of these patients had bilateral adenoma. In 3 patients with bilateral hyperplasia the scan was interpreted as showing adenoma. Two of these patients were seen early in the experience with iodocholesterol scanning and probably represent over-enthusiastic interpretation. The other patient had unilateral uptake but was found to have hyperplasia. This patient also lateralized with adrenal vein blood analysis and may represent unilateral hyperplasia. Dexamethasone suppression scanning was done on 23 patients and was accurate in predicting lesions in 21 (91 per cent): 19 adenomas and 4 hyperplasias. In 2 patients lateralization did not occur. One was found to have carcinoma and 1 had bilateral adenomas. DISCUSSION
When an operation ensues for disease of the adrenal cortex the surgeon can better plan and execute the operation if the site of the lesion is known. Direct physical examination is not helpful except with large lesions, such as adrenal cysts or carcinoma. Indirect methods, such as pyelography, also are of little help except in the large lesions. Since most adrenal adenomas are small, especially those of primary aldosteronism, methods have evolved to visualize the adrenal gland directly. V enography is a direct extension of the techniques of arteriography and represents a marked advance in diagnosis. However, the technical expertise required to cannulate the adrenal veins takes patience and is not always successful, as shown in this group of patients. The venous system of the adrenal gland easily ruptures, leading to pain and hematoma formation. One patient in this series suffered flank pain after venography and the laboratory signs of primary aldosteronism disappeared, which probably resulted from ischemia of the adrenal gland from venous rupture. The primary aldosteronism returned and was cured after removal of an adenoma of the adrenal.
At the time of venography samples from each adrenal vein can be taken for analysis of hormone, such as aldosterone. Again, the technical problems of accurate collection make this a formidable procedure. Requiring only an intravenous injection and, thus, less invasive is the adrenal scintiscan. It can be done on outpatients and it requires no special precautions. In patients with Cushing's syndrome it is highly accurate and can be used in place of dexamethasone suppression tests to differentiate adenoma from hyperplasia. However, computerized tomography may replace it in the diagnosis ofCushing's syndrome, since adenomas are distinguished easily by this procedure because of their size.'' Adrenal scintiscanning continues to be of greatest aid in finding hormonally active remnants of the adrenal cortex after so-called bilateral adrenalectomy. 6 The value of iodocholesterol scanning in patients with primary aldosteronism appears most promising. Although the unsuppressed scan is less accurate than venography, development of dexamethasone suppression has made it highly accurate in localizing adenomas and differentiating bilateral hyperplasia from adenoma. 7 Dexamethasone suppresses the production of adrenocorticotropic hormone and prevents the normal adrenal cortex from concentrating iodocholesterol. However, autonomous tissue, such as found in an adenoma, will concentrate the isotope and appear on the scintiscan as an area of increased uptake. Currently, these 3 methods of adrenal localization are useful but computerized tomography may replace them in the future. This is especially true for lesions causing Cushing's syndrome. However, the resolution power of computerized tomography may miss the small adenoma of primary aldosteronism and in these cases adrenal scintiscanning with dexamethasone suppression appears most helpful. REFERENCES
1. Reuter, S. R., Blair, A. J., Schteingart, D. E. and Bookstein, J. J.: Adrenal venography. Radiology, 89: 805, 1967. 2. Melby, J.C., Spark, R. F., Dale, S. L., Egdahl, R.H. and Kahn, P. C.: Diagnosis and localization of aldosterone-producing adenomas by adrenal-vein catheterization. New Engl. J. Med., 277: 1050, 1967. 3. Lieberman, L. M., Beierwaltes, W. H., Conn, J. W., Ansari, A. N. and Nishiyama, H.: Diagnosis of adrenal disease by visualization of human adrenal glands with 131-1-19-iodocholesterol. New Engl. J. Med., 285: 1387, 1971. 4. Conn, J. W., Morita, R., Cohen, E. L., Beierwaltes, W. H., McDonald, W. J. and Herwig, K. R.: Primary aldosteronism. Photoscanning of tumors after administration of 131-1-19-iodocholesterol. Arch. Intern. Med., 129: 417, 1972. 5. Schaner, E. G., Dunnick, N. R., Doppman, J. L., Strott, C. A., Gill, J. R., Jr. and Javadpour, N.: Adrenal cortical tumors with low attenuation coefficients. A pitfall in computed tomography diagnosis. J. Comp. Ass. Tomogr., 2: 11, 1978. 6. Herwig, K. R. and Schteingart, D. E.: Successful removal of adrenal remnant localized by 131-I-19-iodocholesterol. J. Urol., 111: 713, 1974. 7. Conn, J. W., Cohen, E. L. and Herwig, K. R.: Primary aldosteronism: a noninvasive procedure for tumor localization as well as for distinction from bilateral hyperplasia. In: Advances in Nephrology. Edited by J. Hamburger, J. Crosnier, J. Greenfeld and M. H. Maxwell. Chicago: Year Book Medical Publishers, Inc., vol. 7, p. 157, 1977.