Asymptomatic Adrenal Tumor ; 386 Cases in Japan Including Our 7 Cases
NORIYOSHI YAMAKITA1, MASAYUKI SAITOH1 2, LEILANI BASA MERCADO-ASIS1, MASAHISA KITADA2, HIROYUKI MORITA1, KEIGO YASUDA1 and KIYOSHI MIURA1
The Third Department of Internal Medicine, Gifu University School of Medicine, 40, Tsukasa-machi, Gifu 500, Japan1, Department of Medicine, Matsunami General Hospital, Kasamatsu, Gifu 501-61, Japan2
Abstract
To clarify the indication of surgery in incidentally discovered asymptomatic adrenal masses, we analyzed 386 Japanese cases, 379 cases reported in Japan during the past 25 years (from 1964 to 1988) and 7 cases from our own ex- perience. From a total of 460 patients, we carefully selected 379 patients satisfying our criterion of the absence of symptoms and signs suggestive of active hormone over-secretion as described in each case report. From the Japanese series, there was a high incidence of pheochromocytoma patients (20 of 37 patients) who had no symptoms and signs but had high plasma or urine catecholamines. Scintigraphy with 131I-meta-iodo-benzyl-guanidine was useful in the diagnosis of pheochromocytoma. For the other asymptomatic adrenal tumors, except for myelolipoma and adrenal cyst, differential diagnosis between malignant and benign adrenal lesions by imaging procedures such as whole body computed tomography (CT), ultrasonography (US), adrenocortical scintigraphy, and angiography was not always possible. In addition, among the 109 patients with cortical tumors whose hormonal data were reported, no clear-cut differentiation of malignant tumor from benign by means of these data could be obtained. Since 1980 whole body CT scanner and high resolu- tion US scanner have become widely available, and there have been 283 cases of asymptomatic adrenal tumors who satisfied our criterion. Cortical carcinomas smaller than 3 cm and 6 cm in diameter account for 3.8% and 6.6%, respec- tively, of the total of 101 cases of cortical carcinoma, cortical adenoma, ganglioneuroma, and hemangioma during this period. The size of the smal- lest cortical carcinoma with metastasis was 2 cm in diameter in this series. Pre-operatively, an adrenocortical carcinoma 2.8 cm in diameter in our patient could not be diagnosed as such by imaging techniques and measurement of plasma hormones. These findings suggest that an adrenal mass larger than 3 cm should be removed and a patient with a smaller cortical tumor should be carefully followed up.
This work was supported by the following grants : “The disorders of adrenal hormones, 1986-1988 ” and “The disorders of the hypo- thalamo-pituitary gland, 1986-1988 ” from Re- search Committees of the Ministry of Health
and Welfare, Japan.
Reprint requests to NORIYOSHI YAMAKITA, M. D. The Third Department of Internal Medicine, Gifu University School of Medicine, 40, Tsukasa-machi, Gifu, 500, Japan.
Incidental discovery of an adrenal mass without clinical manifestations has been increasing due to the development of imaging techniques such as computed to- mography (CT) and ultrasonography (US). Geelhoed and Druy (1982) first named such adrenal masses “adrenal incidentaloma” in patients with no signs and symptoms suggestive of adrenal lesion. However, at present, such a disease entity and indica- tions for surgical removal are controversial. We have examined 7 patients with adrenal masses which were incidentally discovered with imaging procedures, and the patholog- ical characteristics were finally confirmed. Their sizes ranged from 1.5 to 5.0 cm includ- ing a 2.8 cm cortical carcinoma (Table 1). Both clinically and biochemically, there was no active hormone excess of glucocorticoids, mineralocorticoids, sex hormones or cate- cholamines. Using image diagnosis with CT, US, adrenocortical scintigraphy and
magnetic resonance images (MRI), we could not tell whether these masses were benign or malignant. From this experience, in order to clarify the indication for opera- tive removal of an incidentally discovered adrenal mass, we analyzed the ” asympto- matic adrenal masses ” reported in Japan during the past 25 years dividing it into two periods, before 1979 and after 1980.
Analyzed Patients and Methods
In the present study, we defined asympto- matic adrenal tumors as the adrenal masses which were incidentally found in patients who had no symptoms or signs suggestive of ex- cessive secretion of active adrenal hormones such as glucocorticoids, mineralocorticoids, sex steroids, or catecholamines. We carefully col- lected only the cases which satisfied the defini- tion given above among the total of 460 Japanese patients with adrenal tumors in the literature
| Case No. Adrenal lesion (side) | 1 cortical adenoma (right) | 2 cortical carcinoma (left) | 3 metastasis of thyroid cancer (right) |
|---|---|---|---|
| Maximal diameter of the mass (cm) | 3.3 | 2.8 | 3.4 |
| Sex | F | F | F |
| Age (yrs) | 47 | 66 | 60 |
| Year of admission | 1983 | 1986 | 1988 |
| Complaints at the | left lumbago | abdominal full-sensation | dyspnea |
| out-patient clinic | |||
| Method of discovering the lesion | CT | CT | US |
| Blood pressure during admission without drugs (mmHg) | 94/60 | 152/80 | 120/80 |
| Physical examination on admission | n. p. | n. p. | giant struma |
| Diseases coexisted | nothing | ITP chr. hepatitis chr. pancreatitis | thyroid cancer (papillary adenocarcinoma) |
* : Blood pressure was well controlled with calcium antagonist in the out-patient clinic, but
** : Blood pressure became nearly normal without drugs after admission, but rose again after M : male, F : female, CT : computed tomography, US : ultrasonography, n. p. : not
published during the past 25 years (from 1964 to 1988). Even when the terms ” non-active ”, and “incidentally discovered ” were used in the titles of case reports, not a few patients were excluded for the following reasons : 1) they were found to have symptoms and signs suggestive of active hormone excess, 2) the masses were incidentally discovered during ab- dominal operation or autopsy, 3) they had other adrenal disorders with signs and symptoms of active hormone excess, 4) they had extra-adrenal pheochromocytomas or pheochromocytomas ac- companied with multiple endocrine adenomatosis, and 5) their case reports provided little informa- tion to make a clear diagnosis possible. How- ever, the patients who had no signs or symptoms of active hormone excess but were found to have hypersecretion of active hormone after the discovery of an adrenal mass were included in this study. We eventually accumulated a total of 379 patients, who were subjected to the pres- ent study. The references for these 379 patients (Group A and Group B) and 81 other patients excluded from the study (Grup C) are shown in the APPENDIX with the number. Since whole
body CT scanning and high resolution US scan- ning have been widely available in Japan since the early 1980s, smaller abdominal masses have become easily detectable. We analysed the cases reported in the 1960s and 1970s (Group A) separately from those reported in the 1980s (Group B). For analysis, our own 7 cases were included in Group B.
The values were expressed as the mean±SD and Student’s t-test was used for the statistical analysis. A P value less than 0.05 was judged significant.
Results
Four hundred and sixty patients were reported to have ” non-functioning ”, ” non- active ”, or ” incidentally discovered ” ad- renal lesions. However, among them, in 3 adrenocortical carcinomas (APPENDIX No. I-C-4, 17, 35) and 3 pheochromocytomas (No. VII-C-1, 7, 13), we suspected signs and symptoms of hypersecretion of active
| 4 ; ganglio- neuroma (right) | 5 cortical nodular hyperplasia (left) | 6 cortical adenoma (left) | 7 cortical adenoma (left) |
|---|---|---|---|
| 5.0 | 1.5 | 4.0 | 3.0 |
| M | M | F | F |
| 44 | 71 | 70 | 59 |
| 1988 | 1989 | 1989 | 1989 |
| back pain | hiccup | abdominal pain | headache |
| CT | CT | CT | US |
| 118/72 | 180/90* | 122/64 | 148/90 ** |
| n. p. | n. p. | soft inguinal mass | n. p. |
| liver cirrhosis | sequela of brain thrombosis, liver cyst, hypertension* | inguinal hernia | hypertension ** |
did not improve after the operation.
the operation, followed by normalization with calcium antagonist.
particular, ITP : idiopathic thrombocytopenia purpura.
| Patient No. | 1* | 2 | 5 | 6 | 7 cortical adenoma | normal range |
|---|---|---|---|---|---|---|
| Adrenal lesion | cortical adenoma | cortical carcinoma | cortical nodular hyperplasia | cortical adenoma | ||
| Plasma F (µg/dl) | ||||||
| 0300 | 10.9 | 11.0 | 6.6 | 9.1 | 7.6 | 5.3~21.8 |
| 2100 | 2.7 | 4.7 | / | 4.7 | 2.7 | |
| After Dex 1 mg | 0.6 | 4.4 | 0.8 | 3.8 | 0.7 | |
| 8 mg | / | / | / | 3.6 | / | <5.0 |
| Urine | ||||||
| free F (µg/day) | 1 | / | <30.0 | / | 60.2 | <120 |
| 17-OHCS (mg/day) | 6.8 | / | 3.4 | 5.4 | 9.0 | 2.9~10.2 |
| 17-KS (mg/day) | 2.9 | / | 2.4 | 2.1 | 3.2 | 3.0~13.0 |
| PAC (pg/ml) | 48 | 120 | 42 | 57 | trace | 20~120 |
| PRA (ng/ml/hr) | ||||||
| base | 0.45 | 0.34 | 1.1 | 0.7 | 0.6 | 0.3~2.0 |
| after 2 hr-upright posture | 5.77 | 0.60 | 8.6 | / | 2.0 | 0.6~6.0 |
| Plasma | ||||||
| DHEA (ng/ml) | 0.5 | 1 | 1.4 | / | 0.4 | 1.2~7.5 |
| B (ng/ml) | 0.55 | 2.78 | / | 1 | 2.57 | 1.0~10.0 |
| DOC (ng/ml) | 0.09 | 0.16 | / | / | 0.22 | 0.02~0.20 |
| A-dione (ng/ml) | 1 | / | 0.5 | / | 0.2 | 0.5~2.4 |
| Urine | ||||||
| epinephrine (µg/day) | 4.2 | 2.0 | 5.7 | / | 2.6 | <10 |
| norepinephrine (ug/day) | 39.9 | 32.5 | 85.8 | / | 110.3 | 10.0~90.0 |
| dopamine (µg/day) | 1 | 370 | 597 | / | 1011 | 190~740 |
| VMA (mg/day) | 4.0 | / | / | / | 3.1 | 2.0~8.0 |
F : cortisol, Dex : dexamethasone,
17-OHCS : 17-hydroxycorticosteroids, 17-KS: 17-
ketosteroids, PAC: plasma aldosterone concentration, PRA : plasma renin activity, DHEA : dehydroepiandrosterone, B : corticosterone, A-dione : androstenedione, VMA : vanilly1 mandelic acid, *: In this patient, in vitro steroidogenesis of the tumor tissue was evaluated and reported (Folia Endocrinol. Jap. 61 : 677~689, 1985), and almost normal steroidogenesis was shown in this tumor tissue.
hormones based on the respective reports. Twenty cortical carcinomas (No. I-C-2, 3, 7, 8, 11, 14, 19~29, 33, 34), 2 pheochromo- cytomas (No. VII-C-3, 6) and 1 myelolipoma (No. VI-C-1) were accidentally found for the first time during operation or autopsy. In 3 patients, in addition to the incidentally discovered cortical adenomas, Cushing’s disease (No. II-C-1), primary aldosteronism due to aldosterone producing adenoma (No. II-C-5) or nodular cortical hyperplasia (No. II-C-6) coexisted, respectively. Seven pa- tients with pheochromocytoma (No. VII-C- 2, 4, 5, 8, 9, 10, 12) were accompanied with
multiple endocrine adenomatosis and 4 (No. VII-C-11, 14~16) were in extraadrenal regions. In all of the remaining 38 case reports, there were insufficient data to get a definite diagnosis. The total number of these adrenal masses was 81 and they were excluded from the present study. Sub- sequently, a total of 386 patients including 379 patients and our 7 patients, 95 with cortical carcinomas, 81 cortical adenomas, 68 adrenal cysts, 49 myelolipomas, 37 pheochromocytomas, 22 ganglioneuromas, 12 hemangiomas, 4 neurofibromas, 5 cortical nodular hyperplasias, 3 hematomas, 4 ad-
renal metastases of lung cancer and thyroid cancer, 2 lymphomas, and one each of teratoma, nodular fibrous hyperplasia, ma- lignant fibrous histocytoma and fibroma were collected as asymptomatic adrenal tumors according to our criterion. Both adrenal glands were involved with the same lesion in each patient in 9 of them, 5 (No. I-A-12, 22 and No. I-B-2, 17, 38) with cortical carcinoma, 2 (No. II-B-24, 47) with cortical adenoma and one each with cyst (No. V-B-18), myelolipoma (No. VI-B-29) and pheochromocytoma (No. VII-B-25).
Concerning the diagnostic procedures,
the results were as follows ; cysts or mye-
lolipomas subjected to CT or US examina-
tion were diagnosed before the operation.
In 20 (No. VII-B-1, 3, 8, 1113, 15, 17,
1925) of 37 patients with pheochromo-
cytomas during 25 years, not only hyper-
tension but also signs and symtoms sug-
gestive of hypersecretion of catecholamines
such as sweating, palpitation and headache
were not seen, but the catecholamine levels
in plasma and urine were high when me-
asured after the discovery of adrenal masses.
They were strongly suspected to have pheo-
chromocytoma before operation. Further-
more, in all the 6 patients with pheo-
chromocytoma (No. VII-B-17, 18, 21, 23, 24,
25) examined by scintigraphy with 131I-
meta-iodo-benzyl-guanidine (MIBG), which
became available only in the 1980s, a
tumor image was clearly demonstrated.
However, the other types of adrenal masses
could not be easily characterized before
operation. Ganglioneuroma showed homo-
genous and low density or low density or
low echogenicity in CT or US (No. III-B-
8, 9, 10, 13, 18, 19, and our patient #4)
but there were no characteristic findings in
angiography (No. III-5, 9, 10, 13, 15, 18, 19).
Adrenocortical tumors showed similar pic-
tures. In hemangiomas also there were no
characteristic findings with these imaging
procedures (No. IV-A-1, 2, 3, 4 and IV-B-
1, 2, 5, 6, 7, 8). In most cases of cortical
carcinomas examined with CT or US (No. I-A-6, 14, 15, 35, 36 and I-B-2, 5, 7, 9, 13, 15, 23, 28, 31, 34, 36, 38, 40, and our patient #2), intratumorous heterogeneity, irregular shape, or calcification, that is suggestive of malignancy, was demonstrated. Invasion of surrounding organs or metastatic findings were sometimes observed (No. I-B-13, 33, 38) in US or CT imaging. With angio- graphy, hypervascularity, irregular tumor staining or vascular encasement was also found (No. I-A-4, 15, 32, 35, and I-B-13, 18, 24, 40). However, among the 8 patients with cortical carcinomas smaller than 6 cm, characteristics of malignancy by imaging techniques could be seen in only 3 patients (No. I-A-22 and I-B-18, 40). The smaller 2.5 cm cortical carcinoma in patient No. I- B-17 who had bilateral cortical carcinomas showed a homogenous CT image. In an- other patient (No. I-B-29), the US image of the 5.5 cm cortical carcinoma was also reported to be homogenous. However, even in some patients with cortical adenomas, imaging findings suggestive of malignancy were found (No. II-B-1, 5, 11, 16, 18, 37, 49, 50). With angiography, hypervascularity and irregular tumor staining were often observed even in patients with cortical adenomas (No. II-A-4 and II-B-2, 10, 30, 44, 48~50). The above results suggest that imaging diagnostic findings could not be used to clearly differentiate a malignant adrenal mass from a benign one except when metastasis or invasive evidence was found. An increase in urinary excretion of 17-ketosteroids and/or plasma levels of cortical non-active hormones was seen in patients with cortical carcinoma (No. I-A- 1, 3, 16, 21, 26 and I-B-9, 16, 29, 32, 40), but was also observed in patients with cortical adenoma (No. II-B-2, 18, 23, 50).
The maximum diameter of the cortical
carcinomas remotely metastasizing and/or
which caused the patient’s death (No. I-A-
1, 57, 13, 14, 21, 28, 31, 34, 37 and I-
B-1, 13, 1720, 35, 37, 38, 40) was 14.9
| Adrenal lesion | Number of patients examined | Age <years old> [range] | Male : Female | Maximal diameter <cm> [range] | Weight <g> [range] |
|---|---|---|---|---|---|
| Cortical carcinoma | |||||
| Group A | 41 | 45±18(40) [1~79] | 23 : 17 | 15.2±5.3(29) [5~28] | 1095±944(30) [1.3~4000] |
| Group B | 54 | 51±14(51) [9~78] | 30: 21 | 11.6±5.1d(38) | 836±644(37) |
| [1.2~20] | [5.0~2700] | ||||
| Cortical adenoma | |||||
| Group A | 8 | 44±17(8) | 5: 3 | 17.3±4.3(6) | 1182±620(6) |
| [13~59] | [13~22] | [0.5~1500] | |||
| Group B | 73 | 56±11ad(60) [22~81] | 27: 32 | 5.5±5.2be(45) [1.5~18] | 216±456be(33) |
| [550~1970] | |||||
| Ganglioneuroma | |||||
| Group A | 2 | 4, 18 (2) | 0 :2 | 6.5(1) | 120(1) |
| Group B | 20 | 45±13(19) | 14 : 5 | 9.1±4.9(16) | 188±262c(13) |
| [21~66] | [5.0~23.0] | [15~990] | |||
| Hemangioma | |||||
| Group A | 4 | 54±6(4) [48~62] | 2 : 2 | 14.5, 18, 19 (3) | 1954±2184(4) |
| [55~5000] | |||||
| Group B | 8 | 60±18(8) | 6 :2 | 11.1±5.1(7) | 500±454(7) |
| [28~78] | [7.5~19.0] | [95~1250] | |||
| Cyst | |||||
| Group A | 31 | 46±14(30) | 11:19 | 11.5±6.1a(18) | 640±860(12) |
| [0~72] | [4~26] | [9.2~2500] | |||
| Group B | 37 | 50±14(36) | 17:18 | 10.6±6.8(18) | 242±460%(8) |
| [22~83] | [3.4~27] | [7~1370] | |||
| Myelolipoma | |||||
| Group A | 3 | 56, 56, 51 (3) | 0:3 | 20(1) | 1930, 1930, 1200 (3) |
| Group B | 46 | 51±10(42) [30~71] | 26 : 15 | 10.5±6.0(32) [2.5~16.5] | 473±5368(33) |
| [10~1950] | |||||
| Pheochromocytoma | |||||
| Group A | 8 | 41±28(7) [2~62] | 3 : 4 | 14, 26, 12 (3) | 808±1253(6) |
| [210~3360] | |||||
| Group B | 29 | 49±16(28) | 19 : 9 | 9.4±5.0(11) | 522±703(16) |
| [10~73] | [2.5~16.5] | [9.5~2500] | |||
| Others | |||||
| Group A | 6 | 51±22(6) [11~70] | 5: 1 | 12, 4 (2) | 600, 18.5(2) |
| Group B | 16 | 57±9(16) | 8 :8 | 4.9±3.1(9) | 194±119c(4) |
| [46~75] | [1.5~11.0] | [36~300] | |||
| Total | |||||
| Group A | 103 | 45±17(99) | 49: 51 | 14.4±5.9(63) | 1021±1033(71) |
| Group B | 283 | 52±13°(260) | 160 : 110 | 9.0±5.8ce(176) | 448±551be(147) |
Group A : cases from 1964 to 1979, Group B : cases from 1980 to 1988. Significantly dif- ferent from the values for cortical carcinoma patients among Group A or Group B patients, respectively, ª: p<0.05, b: p<0.001, c: p<0.005. Significantly different between Group A and Group B patients, d: p<0.01, e: p<0.001. ( ): number of cases
| Adrenal lesion | <3.0 cm | 3.1 ~6.0 cm | 6.1 ~12.0 cm | 12.1 ~18.0 cm | 18.1 cm > | Total | |
|---|---|---|---|---|---|---|---|
| Cortical carcinoma | Group A | 1 | 1 | 6 | 14 | 8 | 30 |
| Group B | 4 | 2 | 16 | 14 | 2 | 38 | |
| Cortical adenoma | Group A | 0 | 0 | 0 | 3 | 3 | 6 |
| Group B | 20 | 15 | 4 | 5 | 1 | 45 | |
| Ganglioneuroma | Group A | 0 | 0 | 1 | 0 | 0 | 1 |
| Group B | 0 | 5 | 8 | 2 | 1 | 16 | |
| Hemangioma | Group A | 0 | 0 | 1 | 2 | 1 | 4 |
| Group B | 0 | 1 | 4 | 1 | 1 | 7 | |
| Cyst | Group A | 0 | 4 | 6 | 6 | 2 | 18 |
| Group B | 0 | 6 | 8 | 0 | 4 | 18 | |
| Myelolipoma | Group A | 0 | 0 | 0 | 0 | 1 | 1 |
| Group B | 3 | 5 | 12 | 7 | 5 | 32 | |
| Pheochromocytoma | Group A | 0 | 0 | 1 | 1 | 1 | 3 |
| Group B | 1 | 2 | 5 | 3 | 0 | 11 | |
| Others | Group A | 0 | 1 | 1 | 0 | 0 | 2 |
| Group B | 3 | 5 | 1 | 0 | 0 | 9 | |
| Total | Group A | 1 | 6 | 16 | 26 | 16 | 65 |
| Group B | 31 | 41 | 58 | 32 | 14 | 176 |
Group A : cases from 1964 to 1979, Group B : cases from 1980 to 1988 and our cases.
±5.5 cm (n=20). This was not different from the diameter of the cortical carcinoma (12.7±5.1 cm, n=25) in patients who were alive and had no metastases at the time of case reports (No. I-A-10, 15, 16, 18, 20, 24~27, 36 and I-B-3, 7, 8, 10, 13, 18, 21, 23, 27, 28, 33, 39, 40 and our case #2). Furthermore, among the 16 patients whose cortical carcinomas were smaller than 12 cm, 7 (No. I-A-5, 22, and I-B-17, 18, 38, 40) had metastases and/or died of the orig- inal disease. Among the 31 metastasizing cortical carcinomas whose sizes were report- ed, the smallest (No. I-B-18) was 2 cm in diameter.
In 386 patients with asymptomatic ad- renal tumor, there were 286 patients in Group B. As shown in Tables 3 and 4, Group B is composed of more cases of smaller adrenal asymptomatic tumors than Group A. The 117 asymptomatic adrenal tumors in Group B were initially examined with either CT or US and they were small (7.0±4.9 cm in diameter, n=82). Among
them there were 9 patients with cortical carcinomas, also relatively small (10.4±4.5 cm, n=8). In Group B, the overall size of the cortical carcinoma was greater than that of the adenoma (p<0.001) or all of the asymptomatic adrenal tumors (p<0.05). Four cases of adrenocortical carcinoma (No. I-B-17, 18, 40, and our case #2) and 20 of adrenocortical adenoma (No. II-B-4 ~8, 12,15, 17, 21, 23, 24, 30, 39, 40, 47, 49, and our case #7) smaller than 3 cm account for 3.8% and 19%, respectively, of the total of 106 cases of cortical car- cinomas, cortical adenomas, ganglioneuro- mas, and hemangiomas. Neither ganglio- neuroma nor hemangioma belonged to this size range.
Discussion
From the clinical point of view, it is im- portant to know how to manage incidentally discovered asymptomatic adrenal masses.
The aim of this study lies here. In analys- ing this series, however, we should take into consideration the following: 1) this study was made based on the data of the patients who underwent surgery or autopsy and histological examination of their tumors, and 2) there should exist a lot of small adrenal incidentalomas being followed- up without undergoing surgery and sub- sequently not included in this series. The actual prevalence of cortical carcinomas among overall asymptomatic adrenal tumors therefore remains unclear. Their prevalence appears to be much less than observed in this series. However, at present we have no other method by which to solve this problem in such a large number of cases with adrenal incidentalomas in which histo- logical confirmation was made.
In vitro investigation of “non-hyperfunc- tioning” adrenocortical carcinoma implicated the deficiency of 30-hydroxysteroids de- hydrogenase (Neville & O’Hare, 1981; Ojima, 1989). If such an enzyme deficiency in the tumor tissue results into an increase in the production of precursor steroids, measurement of the latter in plasma or urine may be useful in differentiating car- cinoma from adenoma. In asymptomatic patients with cortical carcinoma (No. I-B- 28, 40), increased plasma levels of such non-active steroids were found as recently reported by Ojima (1989). However, in- creased urinary excretion of 17-ketosteroids (No. II-A-4 and II-B-2, 18, 23, 50) and high plasma levels of progesterone and 17a- hydroxypregnenolone (Ojima, 1989) were also found even in patients with cortical adenoma who showed no clinical signs or symptoms. Therefore, at present it seems likely that the differentiation of cortical carcinoma from adenoma can not be made by merely measuring peripheral steroid levels.
In agreement with the reports of Glazer et al. (1988) and Saitoh et al. (1989), our study demonstrated that CT or US was
unable to characterize asymptomatic cortical tumors. In this study, however, myelolipoma was found to be similarly low-dense to fat in CT and high-echoic and multilobular in US as reported by Vick et al. (1984). Ad- renal cyst showed a fluid-filled sac image in CT and US. These image character- istics are useful for pre-operative diagnosis of such adrenal tumors. On the use of 131I-iodocholesterol scintigraphy on cortical tumors, no convincing information could be obtained on tumor classification. Since hypervascularity, vascular encasement, and irregular tumor staining on angiography were sometimes seen even in patients with cortical adenomas in this series, the utility of angiography in differential diagnosis appeared to be limited. CT and US images and the angiographic image characteristics of ganglioneuroma and hemangioma were not always useful in the differentiation be- tween cortical adenoma and carcinoma. Although the usefulness of MRI in the characterization of adrenal tumors has been proposed in recent years (Quint et al., 1987 ; Glazer, 1988), MRI examination was done in only one patient (No. I-B-40) in this series. In addition, MRI examination per- formed in our 3 patients (#4, 5, 7) did not provide clear cut differentiation, as was suggested by Reinig et al. (1986) and Glazer (1988). Therefore, preoperative differentia- tion of adrenocortical carcinoma from cor- tical adenoma, adrenal ganglioneuroma, and adrenal hemangioma by means of the above procedures was not always possible.
Since large adrenal masses were more likely to be malignant as shown in this study, surgical removal should be the choice of therapy. In 176 patients reported since 1980, 84% (32) of 38 cortical carcinomas were larger than 6 cm in diameter and 90% (34) were larger than 3 cm. According to our estimation, if all tumors larger than 3 cm were operated on, 56% of the adenomas will be operated on but 10% of the car- cinoma is left unoperated on. Copeland
(1983) claimed that all of the 5 patients with nonmetastatic cortical carcinoma smal- ler than 5 cm could be alive for at least 5 years, whereas 48 of 54 patients with larger lesions or metastases could not live longer than 5 years. However, this obser- vation was not seen in our study and the smallest carcinoma that metastasised was only 2 cm in diameter. In addition, there was even a report (No. I-C-11) in which the abnormal clinical presentation of the patient was that of brain tumor, and post- mortem examination revealed a 1.5 cm ad- renocortical carcinoma which metastasized to the brain. This suggests that even a small cortical carcinoma is capable of me- tastasis. Although the guidelines for opera- tive treatment of asymptomatic adrenal tumors have not been uniform in previous reports (Athani & Mulholland, 1981 ; Prints et al., 1982; Copeland 1983 ; O’Lenny & Ooi, 1986), it was concluded from the present study that indications for operation have to be decided only by the size of the tumor.
Often few signs or symptoms have been seen in patients with classical pheochromo- cytoma (Taubman et al., 1974). It was reported (Sutton et al., 1981 ; Krane, 1986) that many patients with pheochromocytoma were not recognized as having the disease before operation or autopy. Since serum or urine catecholamine levels were high in 20 of 37 patients with pheochromocytomas without signs or symptoms in this series, endocrine examination was valuable in di- agnosing pheochromocytoma. In addition, 131I-MIBG scintigraphy was useful in di- agnosing pheochromocytoma, as Gross et al. (1984) and Quint et al. (1987) reported.
From these results, we recommend sur- gery as the first choice of treatment for adrenocortical incidentalomas more than 3 cm in diameter regardless of plasma steroid levels or image findings. However, since there still remains the risk of missing the smaller adrenocortical carcinoma, patients
in this group should be carefully followed up.
References
Athani, V. J. and S. G. Mulholland (1981). Primary nonfunctioning adrenal tumors in adults. Urology 18, 131-133.
Copeland, P. M. (1983). The incidentally dis- covered adrenal mass. Ann. Intern. Med. 98, 940-945.
Geelhoed, G. W. and E. M. Druy (1982). Man- agement of the adrenal “incidentaloma”. Surgery 92, 866-874.
Glazer, G. M. (1988). MR imaging of the liver, kidneys, and adrenal glands. Radiology 166, 303-312.
Gross, M. D., B. Shapiro, J. H. Thrall, J. E. Freitas, and W. H. Beierwaltes (1984). The scintigraphic imaging of endocrine organs. Endocr. Rev. 5, 221-281.
Krane, N. K. (1986). Clinically unsuspected pheochromocytomas. Experience at Henry Ford Hospital and a review of the interature. Arch. Intern. Med. 146, 54-57.
Ojima, M. (1989). In vivo and in vitro steroid analysis in patients with nonfunctioning ad- renal adenoma. Folia Endocrinol. Jap. 65, 862. (in Japanese)
O’Leary, T. J. and T. C. Ooi (1986). The ad- renal incidentaloma. Can. J. Surg. 29, 6-8.
Prinz, R. A., M. H. Brooks, R. Churchill, J. L. Graner, A. M. Lawrence, E. Paloyan, and M. Sparagana (1982). Incidentally asymp- tomatic adrenal masses detected by computed tomographic scanning-Is operation required ? -JAMA 248, 701-704.
Quint, L. E., G. M. Glazer, I. R. Francis, B. Shapiro, and T. L. Chenevert (1987). Pheo- chromocytoma and paraganglioma: Comparison of MR imaging with CT and I-131 MIBG scintigraphy. Radiology 165, 89-93.
Reinig, J. W., J. L. Doppman, A. J. Dwyer, A. R. Johnson, and R. H. Knop (1986). Adrenal masses differentiated by MR. Radiol- ogy 158, 81-84.
Saitoh, T., Y. Tanahashi, K. Taguchi, S. Toyota, Y. Chiba, S. Itoh, K. Suzuki, H. Nakagawa, and S. Orihata (1989). Echographic diagnosis of adrenal gland-Ultrasound and CAT scan diagnosis in asymptomatic adrenal region tumor-Proceedings of 55th Meeting of The
Japan Soc. Ultrasonics Med. 733-734. (in Japanese)
Sutton, M. G. S. J., S. G. Sheps, and J. T. Lie (1981). Prevalence of clinically unsuspect- ed pheochromocytoma. Review of a 50-year autopsy series. Mayo Clin. Proc. 56, 354-360. Taubman, I., O. H. Pearson, and A. H. Anton (1974). An asymptomatic catecholamine- secreting pheochromocytoma. Am. J. Med. 57, 953-956.
Vick, C. W. H., R. H. Zeman, E. Mannes, J. J. Cronan, and J. W. Walsh (1984). Ad- renal myelolipoma : CT and ultrasound find- ings. Urol. Radiol. 6, 7-13.
Appendix
I) Cortical carcinoma
A) Group A
1) Kurita, T. Acta Urol. Jap. 10: 142, 1964.
2) Araki, Y. Arch. Jpn. Chir. 33 : 453, 1964. 3) Tsuchiya, S. Surgery 26: 372, 1964. 4) Shigematsu, S. Hifu To Hinyo 27: 699, 1965. 5) Minei, S. Acta Urol. Jap. 11: 1288, 1965. 6) Hirasawa, K. J. Jpn. Soc. Int. Med. 56: 410, 1967. 7) Murakami, M. Int. Med. 20: 1322, 1967. 8) Hukaura, S. J. Jpn. Soc. Int. Med .. 57: 490, 1968. 9) Nakashima, T. Jpn. J. Clin. Exper. Med. 45: 1089, 1968. 10) Kasai, Y. Surg. Diag. Treatm. 10: 633, 1968. 11)-Nango, C. Jpn. J. Urol. 60: 804, 1969. 12) Nao, Y. J. Jpn. Soc. Int. Med. 58 : 1236, 1969. 13) Oda, K. J. Jpn. Soc. Int. Med. 58 : 364, 1969. 14) Shiramatsu, Y. J. Jpn. Pract. Surg. Soc. 32 : 177, 1971. 15) Koyama, R. J. Jpn. Soc. Int. Med. 60 : 680, 1971. 16) Nishio, S. Acta Urol. Jap. 18 : 783, 1972. 17) Kusa- shina, H. J. Jpn. Soc. Int. Med. 61 : 865, 1972. 18) Yokoyama, A. Jpn. J. Pediatr. Surg. 9: 132, 1973. 19) Ohtsuka, M. Shinshu Med. J. 21 : 630, 1973. 20) Kumamoto, Y. Jpn. J. Urol. 65 : 285, 1974. 21) Yoshida, K. Acta Urol. Jap. 20 : 813, 1974. 22) Okazaki, I. Clin. Endocrinol. (Tokyo) 22 : 529, 1974. 23) Maru- yama, Y. Tr. Soc. Pathol. Jpn. 63 : 211, 1974. 24) Tanda, H. Jpn. J. Urol. 65: 247, 1974. 25) Furukawa, K. Surg. 37: 644, 1975. 26) Kawano, S. Nishinihon J. Urol. 38 : 156, 1976. 27) Yokoyama, I. J. Jpn. Pract. Surg. Soc. 37 : 654, 1976. 28) Doi, H. Surg. Diag. Treatm. 19 : 606, 1977. 29) Furumoto, M. J. Jpn. Soc. Int. Med. 66: 870, 1977. 30) Tanaka, H. J.
Jpn. Scc. Int. Med. 67: 1443, 1978. 31) Iwa- saki, S. Nishinihon J. Urol. 40 : 139, 1978. 32) Akao, T. Jpn. J. Cancer Clin. 24 : 1255, 1978. 33) Muramoto, T. J. Jpn. Surg. Soc. 79 : 167, 1978. 34) Ogawa, S. J. Jpn. Surg. Soc. 79 : 233, 1978. 35) Moriyama, M. Acta Urol. Jap. 25 : 921, 1979. 36) Sakamoto, K. Jpn. J. Clin. Exper. Med. 56: 1894, 1979. 37) Suga, M. J. Jpn. Soc. Int. Med. 68 : 444, 1979. 38) Kureya, T. Jpn. J. Gastroenterol. 76: 1023, 1979.
B) Group B
1) Tsujimoto, Y. Nishinihon J. Urol. 42 : 1089, 1980. 2) Kudo, O. Jpn. J. Urol. 72 : 1362, 1981. 3) Enomoto, K. Surgery 43 : 304, 1981. 4) Itoh, T. J. Hiroshima Med. Ass. 34 : 635, 1981. 5) Majima, I. Kagawa Chuô Byoin Igaku Zasshi 1: 99, 1982. 6) Ichikawa, H. J. Jpn. Pract. Surg. Soc. 43 : 391, 1982. 7) Wata- nabe, S. Jpn. J. Clin. Urol. 36 : 369, 1982. 8) Fujihiro, S. Acta Urol. Jap. 28 : 409, 1982. 9) Ishigami, H. J. Clin. Surg. 38: 1541, 1983. 10) Kurosaki, N. J. Jpn. Pract. Surg. Soc. 44 : 1371, 1983. 11) Tokui, M. Jpn. J. Urol. 74 : 1279, 1983. 12) Kamiyama, M. J. Jpn. Pract. Surg. Soc. 45: 214, 1984. 13) Sanefuji, T. Nishinihon J. Urol. 46 : 439, 1984. 14) Katoh, N. J. Jpn. Soc. Int. Med. 73 : 1721, 1984. 15) Katsumi, T. Jpn. J. Clin. Urol. 38 : 237, 1984. 16) Minami, Y. Nishinihon J. Urol. 46: 226, 1984. 17) Demura, T. Jpn. J. Clin. Urol. 38 : 233, 1984. 18) Arakawa, S. Nishinihon J. Urol. 46 : 1283, 1984. 19) Ogawa, N. J. Jpn. Pract. Surg. Soc. 46 : 48, 1985. 20) Kishikawa, H. Jpn. J. Pediatr. Surg. 17: 409, 1985. 21) Yamashiro, S. Jpn. J. Urol. 76 : 143, 1985. 22) Ikeda, M. J. Jpn. Pract. Surg. Soc. 46 : 679, 1985. 23) Sakai, H. Jpn. Red. Cross Med. J. 37 : 58, 1985. 24) Matsuo, T. Proceed. 46th Meeting Japan Soc. Ultrasonics Med. 773, 1985. 25) Kadota, K. Okayama-Igakkai-Zasshi 97: 359, 1985. 26) Kawabata, T. Nishinihon J. Urol. 48 : 1781, 1986. 27) Chô, Y. Chiba Med. J. 62 : 245, 1986. 28) Kobatake, T. Clin. Endocrinol. (Tokyo) 34 : 647, 1986. 29) Saitoh, To. Proceed. 50th Meeting Japan Soc. Ultra- sonics Med. 941, 1987. 30) Ikeguchi, M. Surg. Diag. Treatm. 29 : 671, 1987. 31) Kobayashi, T. Jpn. J. Urol. 78 : 2233, 1987. 32) Shimada, Y. J. Jpn. Pract. Surg. Soc. 48 : 1353, 1987. 33) Takami, H. J. Jpn. Pract. Surg. Med. 48 : 1353, 1987. 34) Hikichi, K. Jpn. J. Urol. 78 : 742, 1987. 35) Miyagi, T. Ishikawaken-Chuo- Byoin-Igaku-Zasshi 9 : 51, 1987. 36) Suzuki, T.
Ochanomizu Med. J. 35 : 81, 1987. 37) Fukuda, M. J. Jpn. Soc. Clin. Cytol. 27 : 414, 1988. 38) Yamashita, M. Nishinihon J. Urol. 50: 677, 1988. 39) Tacho, T. Nishinihon J. Urol. 50: 354, 1988. 40) Sumiya, H. Nishinihon J. Urol. 50: 1473, 1988.
C) Cases excluded from this study
1) Yamashita, T. Shouwa Med. J. 24 : 29, 1964. 2) Torikai, K. J. Jpn. Soc. Int. Med. 53: 114, 1964. 3) Yamamoto, M. J. Jpn. Soc. Int. Med. 55 : 840, 1966. 4) Sakauchi, N. J. Jpn. Soc. Int. Med. 44 : 195, 1968. 5) Fujimura, N. Jpn. J. Urol. 61: 313, 1970. 6) Nakai, W. Hirosaki Med. J. 22 : 307, 1970. 7) Kosaka, S. Med. J. Aomori 15: 307, 1970. 8) Kitami, T. J. Jpn. Soc. Int. Med. 60 : 590, 1971. 9) Kitamura, H. J. Hiroshima Med. Ass. 25: 1012, 1972. 10) Tanaka, M. J. Clin. Pediatr. 21: 68, 1973. 11) Sugano, J. J. Jpn. Soc. Int. Med. 62 : 327, 1973. 12) Mitsuhashi, K. Nishinihon J. Urol. 42 : 1207, 1973. 13) Minakami, E. Jpn. J. Soc. Int. Med. 63 : 211, 1974. 14) Uehara, A. Jpn. J. Urol. 66 : 39, 1975. 15) Tsukada, M. Tr. Soc. Pathol. Jpn. 65 : 266, 1976. 16) Miura, K. Jpn. J. Urol. 67 : 309, 1976. 17) Kojima, T. J. Jpn. Soc. Int. Med. 65: 1073, 1976. 18) Ujiie, S. J. Jpn. Soc. Cancer Ther. 11: 515, 1976. 19) Hamazaki, Y. J. Jpn. Soc. Int. Med. 66: 254, 1977. 20) Mitsunaga, H. J. Jpn. Soc. Int. Med. 67 : 96, 1978. 21) Egusa, Y. J. Jpn. Surg. Soc. 79 : 167, 1978. 22) Hino, K. J. Jpn. Soc. Int. Med. 68 : 128, 1979. 23) Tamaoki, T. J. Jpn. Soc. Int. Med. 67 : 666, 1978. 24) Matsumoto, K. Jpn. J. Cancer Clin. 25: 708, 1979. 25) Matsuo, T. J. Jpn. Soc. Int. Med. 69: 530, 1980. 26) Ishioka, A. J. Jpn. Soc. Int. Med. 69 : 625, 1980. 27) Hashimoto, T. J. Jpn. Surg. Soc. 81: 99, 1980. 28) Tsuda, A. Jpn. J. Urol. 73 : 1472, 1982. 29) Zama, H. Jpn. J. Urol. 74: 446, 1983. 30) Minota, K. Nishinihon J. Urol. 46 : 1523, 1984. 31) Hoshiyama, K. J. Jpn. Soc. Cancer Ther. 19: 2191, 1984. 32) Kaii, O. Nipp. Act. Radiol. 45 : 773, 1985. 33) Nakada, M. Jpn. J. Cancer Clin. 32 : 1855, 1986. 34) Tada, H. Lung Cancer 26: 453, 1986. 35) Kobatake, T. Clin. Endocrinol. (Tokyo) 34 : 647, 1986. 36) Kobayashi, H. Jpn. J. Clin. Urol. 41: 879, 1987. 37) Yamamoto, Y. Hok- kaido J. Surg. 32: 178, 1987.
II) Cortical adenoma
A) Group A
1) Kurita, T. Acta Urol. Jap. 10: 142, 1964.
2) Nakanishi, S. Surgery 29: 454, 1967. 3) Yamauchi, A. Kokura Memorial Hosp. J. Med. 1: 67, 1968. 4) Ueda, K. Jpn. J. Cancer Clin. 17 : 232, 1971. 5) Yamamoto, S. J. Jpn. Pract. Surg. Soc. 33 : 578, 1972. 6) Yamazaki, T. Jpn. J. Urol. 66 : 216, 1975. 7) Furukawa, H. Jpn. J. Pediatr. Surg. 9 : 588, 1977.
B) Group B
1) Itoh, H. Clin. Endocrinol. (Tokyo). 31 (Suppl. autumn) : 153, 1980. 2) Ohe, T. Jpn. J. Cancer Clin. 27: 1377, 1981. 3) Hamazaki, K. Surg. Diag. Treatm. 24 : 97, 1982. 4) Yama- shita, S. Jpn. J. Clin. Urol. 36 : 477, 1982. 5) Satoh, Ka. Jpn. J. Urol. 73 : 831, 1982. 6) Yoshimura, N. Jpn. J. Urol. 74 : 267, 1983. 7) Kato, E. Teishin-Igaku 35 : 224, 1983. 8) Kana- mori, Y. Acta Urol. Jap. 30: 1039, 1984. 9) Matsumoto, N. Endocr. Surg. 1: 249, 1984. 10) Shimomae, H. Nishinihon J. Urol. 47: 1271, 1985. 11) Shibata, N. J. Jpn. Pract. Surg. Soc. 45 : 1368, 1985. 12) Tsuda, M. Proceed. 46th Meeting Japan Soc. Ultrasonics Med. 779, 1985. 13) Hashimoto, M. J. Jpn. Pract. Surg. Soc. 46: 1396, 1985. 14) Wakabayashi, K. Jpn. J. Urol. 76: 940, 1985. 15) Tanaka, K. Jpn. J. Urol. 76 : 767, 1985. 16) Sakakibara, N. Jpn. J. Urol. 76 : 263, 1985. 17) Doukita, S. Nishi- nihon J. Urol. 47 : 1451, 1985. 18) Kudo, T. Jpn. J. Urol. 76 : 423, 1985. 19) Shiramizu, M. Acta Urol. Jap. 31: 2007, 1985. 20) Tanabe, N. Jpn. J. Urol. 77: 15, 1986. 21) Kitagawa, M. Folia Endocrinol. Jap. 62 : 940, 1986. 22) Ueno, Y. Clin. Endocrinol. (Tokyo) 34 : 421, 1986. 23) Sasagawa, T. Nishinihon J. Urol. 48 : 1287, 1986. 24) Takasaki, I. J. Jpn. Soc. Int. Med. 75: 1822, 1986. 25) Kakimoto, S. Acta Urol. Jap. 32 : 757, 1986. 26) Kunimi, K. Jpn. J. Urol. 77 : 190, 1986. 27) Narimatsu, Y. Jpn. J. Urol. 77 : 2044, 1986. 28) Hirose, T. Folia Endocrinol. Jap. 62 : 1070, 1986. 29) Takahara, J. Folia Endocrinol. Jap. 62: 1071, 1986. 30) Yoshino, S. Jpn. J. Clin. Urol. 40: 1003, 1986. 31) Murakami, O. Folia Endocrinol. Jap. 62 : 1070, 1986. 32) Komatsu, K. Nishi- nihon J. Urol. 48 : 2134, 1986. 33) Satoh, Ke. Juntendo Med. J. 32 : 370, 1986. 34) Hirobe, S. J. Jpn. Pract. Surg. Soc. 47: 1136, 1986. 35) Kunisaki, C. J. Jpn. Pract. Surg. Soc. 47 : 1146, 1986. 36) Kirime, S. Jpn. J. Urol. 78 : 196, 1987. 37) Inaba, T. Jpn. J. Urol. 78 : 197, 1987. 38) Saitoh, To. Proceed. 50th Meeting Iapan Soc. Ultrasonics Med. 941, 1987. 39) Ishii, T. Acta Urol. Jap. 33 : 223, 1987. 40)
Saitoh, B. Jpn. J. Urol. 78 : 944, 1987. 41) Shiotsu, K. J. Hyogo Ass. Surg. 92 : 69, 1987. 42) Honda, M. Kaijou-Igaku-Kenkyu 24 : 317, 1987. 43) Funatsu, M. Nishinihon J. Urol. 49 : 1300, 1987. 44) Umeda, H. J. Jpn. Pract. Surg. Soc. 48 : 1354, 1987. 45) Morimoto, S. Acta Urol. Jap. 34 : 423, 1988. 46) Satoh, No. Acta Urol. Jap. 34 : 1613, 1988. 47) Satoh, Na. Jpn. J. Clin. Urol. 42 : 731, 1988. 48) Furuya, Y. Nishinihon J. Urol. 50 : 1001, 1988. 49) Tsuji, A. Jpn. J. Urol. 79: 1592, 1988. 50) Yasui, M. Surg. Diag. Treatm. 30: 704, 1988. 51) Aki, M. Jpn. J. Urol. 79: 355, 1988. 52) Ohnishi, N. Jpn. J. Clin. Radiol. 33 : 89, 1988.
C) Cases excluded from this study
1) Aida, M. Igaku-No.Ayumi 105 : 1010, 1978. 2) Koyama, A. Nipp. Act. Radiol. 45: 446, 1985. 3) Kaii, O. Nipp. Act. Radiol. 45 : 773, 1985. 4) Kawai, K. Acta Med. Nagasaki 31 : 189, 1986. 5) Nakagawa, J. Jpn. J. Circ. J. 51 (Suppl. II) : 316, 1988. 6) Ando, T. Clin. Endo- crinol. (Tokyo) 35 (Suppl. spring) : 224 : 1987.
III) Adrenal ganglioneuroma
A) Group A
1) Kurotsuchi, M. Jpn. J. Urol. 59 : 84, 1968.
2) Nonomura, T. Jpn. J. Urol. 70: 1295, 1979.
B) Group B
1) Kajiya, Y. Jpn. J. Clin. Radiol. 28 : 419, 1983. 2) Chohji, K. Nipp. Act. Radiol. 44 : 865, 1984. 3) Shimada, N. Chiba Med. J. 60 : 338, 1984. 4) Nishida, T. Jpn. J. Urol. 75 : 1010, 1984. 5) Mori, Y. Jpn. J. Clin. Urol. 38 : 804, 1984. 6) Kawano, M. J. Jpn. Pract. Surg. Soc. 46: 1202, 1985. 7) Niwa, W. Clin. Neurol. 26 : 537, 1986. 8) Terasaki, T. J. Kyoto Pref. Univ. 95: 1639, 1986. 9) Nakagawa, H. Acta Urol. Jap. 32 : 735, 1986. 10) Nakajima, F. Acta Urol. Jap. 33 : 735, 1986. 11) Miyagi, T. Jpn. J. Clin. Urol. 39: 951, 1986. 12) Hamada, Y. Jpn. J. Urol. 77 : 1233, 1986. 13) Tanaka, M. Nishinihon J. Urol. 48 : 497, 1986. 14) Tsumaya, K. Jpn. J. Urol. 76: 196, 1987.
15) Hosokawa, H. Jpn. J. Urol. 78 : 379, 1987.
16) Miyake, M. Jpn. J. Urol. 78 : 1282, 1987. 17) Hirai, M. Jpn. J. Urol. 78 : 1452, 1987.
18) Ito, S. Jpn. J. Clin. Urol. 42 : 59, 1988.
19) Miyazaki, F. Nishinihon J. Urol. 50: 717, 1988.
C) Cases excluded from this study
1) Itoh, Saishin-Igaku 28: 1847, 1973. 2) Kashiya, Okayama-Igakkai-Zasshi 96 : 251, 1984.
3) Kaii, O. Nipp. Act. Radiol. 45 : 773, 1984.
IV) Adrenal hemangioma
A) Group A
1) Nagatani, M. Int. Med. 24: 383, 1969. 2) Shima, M. Jpn. J. Clin. Urol. 24 : 35, 1970. 3) Ishikawa, T. Jpn. J. Nation. Med. Serv. 28 (Suppl. 2) : 376, 1974. 4) Nagata, S. Nishinihon J. Urol. 39 : 294, 1978.
B) Group B
1) Hirano, S. Jpn. J. Clin. Urol. 35 : 887, 1981. 2) Kanemura, M. Jpn. J. Urol. 72 : 1371,
1981. 3) Kotani, T. Jpn. J. Urol. 73: 242, 1982. 4) Hasuo, K. Nishinihon J. Urol. 47 : 1910, 1985. 5) Yoshie, T. Jpn. J. Urol. 77 : 949, 1986. 6) Ishito, N. Nishinihon J. Urol. 48 : 1295, 1986. 7) Tada, Y. Jpn. J. Urol. 78 : 2199, 1987. 8) Fujimoto, T. Jpn. J. Med. Ultrasonics 14 : 165, 1987.
C) Cases excluded from this study None
V) Adrenal cyst
A) Group A
1) Ishii, T. Jpn. J. Urol. 56 : 768, 1965. 2) Fujimura, S. Jpn. J. Urol. 47 : 1145, 1965. 3) Furumoto, M. J. Clin. Surg. 21: 1157, 1966. 4) Kaneko, C. J. Clin. Surg. 21: 1165, 1965. 5) Arichi, S. Nipp. Act Radiol. 27: 644, 1967. 6) Shiba, M. Jpn. J. Clin. Urol. 22 : 209, 1968. 7) Minami, T. Jpn. J. Urol. 59 : 439, 1968. 8) Tsuchiya, F. Jpn. J. Urol. 59 : 434, 1968. 9) Sasaki, T. Nipp. Act. Radiol. 28 : 1201, 1968. 10) Isurugi, T. Jpn. J. Urol. 61: 837, 1970. 11) Yokoyama, S. Jpn. J. Clin. Urol. 24 : 1129, 1970. 12) Ueda, S. Nishinihon J. Urol. 33 : 658, 1971. 13) Kohdaira, T. Yokohama Med. Bull. 24 : 43, 1973. 14) Usui, T. Nishinihon J. Urol. 35: 36, 1973. 15) Ohmura, I. J. Jpn. Soc. Int. Med. 62 : 811, 1973. 16) Shibata, K. Okayama-Igakkai-Zasshi 86: 186, 1973. 17) Higashibara, E. Jpn. J. Urol. 65: 595, 1974. 18) Kazuno, H. Surg. Diag. Treatm. 18: 951, 1976. 19) Chin, K. Surg. Diag. Treatm. 18 : 1492, 1976. 20) Inoue, T. Jpn. J. Clin. Urol. 31: 351, 1977. 21) Yomonaga, A. J. Jpn. Soc. Int. Med. 66:1318, 1977. 22) Fujioka, T. Jpn. J. Urol. 68 : 988, 1977. 23) Itomo, K. J. Jpn. Surg. Soc. 78 : 1117, 1977. 24) Tamura, M. J. Hiroshima Med. Ass. 30: 1096, 1977. 25) Naitoh, K. Jpn. J. Clin. Urol. 32 : 1145, 1978. 26) Nakamura, T. Jpn. J. Cancer Clin. 24 : 848,
Vol. 37, No. 5
1978. 27) Anezaki, M. Jpn. J. Urol. 70: 365, 69: 501, 1978. 1979.
B) Group B
1) Ishizuka, H. Jpn. J. Clin. Exper. Med. 57 : 3291, 1980. 2) Rinsho, K. Acta Urol. Jap. 27 : 75, 1981. 3) Nakada, J. Acta Urol. Jap. 27 : 157, 1981. 4) Hatano, T. J. Jpn. Soc. Int. Med. 72 : 121, 1981. 5) Takai, S. J. Jpn. Pract. Surg. Soc. 43 : 392, 1982. 6) Hamada, K. Jpn. J. Urol. 73: 1356, 1982. 7) Yoshioka, M. J. Jpn. Soc. Int. Med. 71: 1646, 1982. 8) Matsui, S. Akita J. Rural Med. 29 : 47, 1983. 9) Mino- wada, S. Jpn. J. Urol. 74: 1720, 1983. 10) Morozumi, M. Jpn. J. Urol. 74: 1709, 1983. 11) Itoh, T. Jpn. J. Urol. 74 : 1286, 1983. 12) Inaba, S. Jpn. J. Urol. 74: 1700, 1983. 13) Katoh, M. Jpn. J. Urol. 74 : 1269, 1983. 14) Yoshii, S. Jpn. J. Urol. 75 : 1670, 1984. 15) Saitoh, R. Jpn. J. Urol. 75: 1518, 1984. 16) Sekiguchi, H. Jpn. J. Urol. 75: 1518, 1984. 17) Ikai, K. Jpn. J. Urol. 75: 1489, 1984. 18) Fujiwara, Y. Ibaragi-Rinsho-Igakkai-Zasshi 21: 88, 1985. 19) Kawano, M. J. Jpn. Pract. Surg. Soc. 46 : 1202, 1985. 20) Baba, Y. J. Osaka Rosai Hosp. 9 : 61, 1985. 21) Demura, K. Jpn. J. Urol. 76 : 771, 1985. 22) Suemori, T. Jpn. J. Urol. 76: 940, 1985. 23) Kudo, J. Jpn. J. Urol. 76 : 767, 1985. 24) Sakurai, M. J. Jpn. Soc. Int. Med. 75: 985, 1986. 25) Yagibashi, Y. Jpn. J. Urol. 77 : 871, 1986. 26) Tanji, S. Jpn. J. Urol. 77: 362, 1986. 27) Terachi, T. Acta Urol. Jap. 32 : 1497, 1986. 28) Saitoh, M. Jpn. J. Urol. 77: 354, 1986. 29) Tanoguchi, H. Jpn. J. Urol. 77: 332, 1986. 30) Kunisaki, C. J. Jpn. Pract. Surg. Soc. 47 : 1146, 1986. 31) Funatsu, M. Nishinihon J. Urol. 49 : 1300, 1987. 32) Kushimoto, T. Jpn. J. Clin. Urol. 41: 251, 1987.
C) Cases excluded from this study
1) Sasaki, T. Jpn. J. Urol. 62 : 395, 1971. 2) Kobayashi, I. J. Jpn. Surg. Soc. 74: 625, 1973. 3) Sasao, T. J. Jpn. Surg. Soc. 77: 1453, 1976. 4) Nakamatsu, S. J. Jpn. Pract. Surg. Soc. 38 : 697, 1973. 5) Torii, Y. Jpn. J. Urol. 68 : 1100, 1977. 6) Kamiya, J. J. Jpn. Surg. Soc. 80: 80, 1979.
VI) Adrenal myelolipoma
A) Group A
1) Shirasaka, S. J. Jpn. Soc. Int. Med. 64 : 283, 1975. 2) Saitoh, Ta. Jpn. Red. Cross Med. J. 30: 73, 1978. 3) Tohma, T. Jpn. J. Urol.
B) Group B
1) Kadowaki, T. Jpn. J. Urol. 72 : 254, 1981. 2) Sakurai, K. J. Medical Imagings 2 : 571, 1982. 3) Watanabe, C. J. Jpn. Pract. Surg. Soc. 43 : 1167, 1982. 4) Kanaji, Y. Clin. Endocrinol. (Tokyo) 30 : 1101, 1982. 5) Oikawa, M. J. Jpn. Soc. Clin. Cyto1. 22 : 1043, 1983. 6) Satoh, I. Proceed. 42nd Meeting Jap. Soc. Ultrasonics Med. 333, 1983. 7) Dohmen, K. Jpn. J. Med. Ultrasonics 15 : 83, 1983. 8) Aoki, S. Nippon J. Tomogr. 11: 155, 1984. 9) Ohtomo, K. J. Medical Imagings 4 : 767, 1984. 10) Taniguchi, M. Niigata Med. J. 98 : 464, 1984. 11) Kami- ryo, Y. Jpn. J. Clin. Urol. 38 : 417, 1984. 12) Kawamoto, S. Nipp. Act. Radiol. 45: 1630, 1985. 13) Funada, T. J. Jpn. Pract. Surg. Soc. 46 : 48, 1985. 14) Tanaka, S. Jpn. J. Urol. 76: 939, 1985. 15) Noguchi, T. J. Jpn. Surg. Soc. 86: 640, 1985. 16) Ui, M. Niigata Med. J. 99 : 144, 1985. 17) Kin, M. Nishinihon J. Urol. 48 : 863, 1986. 18) Sumi, S. Jpn. J. Urol. 77 : 1012, 1986. 19) Narimatsu, Y. 77 : 2044, 1986. 20) Murai, T. Int. Med. 57: 987, 1986. 21) Fuse, M. J. Med. Soc. Toho 32: 673, 1986. 22) Nakano, I. J. Jpn. Soc. Int. Med. 75 : 598, 1986. 23) Fujimoto, H. Jpn. J. Urol. 77 : 695, 1986. 24) Moriyama, N. Jpn. J. Urol. 77 : 1023, 1986. 25) Sakai, S. Jpn. J. Urol. 78 : 379, 1987. 26) Hayashi, T. Nishinihon J. Urol. 49 : 1300, 1987. 27) Matsui, J. Proceed. 50th Meeting Jap. Soc. Ultrasonics Med. 945, 1987. 28) Sakamoto, Y. Acta Urol. Jap. 33 : 1092, 1987. 29) Tamura, S. Jap. J. Med. Imag. 6: 293, 1987. 30) Tanaka, H. Nipp. Act. Radiol. 47 : 867, 1987. 31) Amemiya, H. Nishinihon J. Urol. 49 : 837, 1987. 32) Nakashima, M. Nii- gata Med. J. 101: 473, 1987. 33) Saitoh, To. Proceed. 50th Meeting Jap. Soc. Ultrasonics Med. 941, 1987. 34) Kamoshita, T. Proceed. 50th Meeting Jap. Soc. Ultrasonics Med. 943, 1987. 35) Saitoh, S. Jpn. J. Clin. Urol. 41: 809, 1987. 36) Furuya, Y. Jpn. J. Clin. Urol. 42 : 63, 1988. 37) Eguchi, T. Surg. Diag. Treatm. 30 : 700, 1988. 38) Murakami, Y. J. Jpn. Surg. Soc. 89 : 464, 1988. 39) Takeda, H. Nishinihon J. Urol. 50: 683, 1988.
C) Cases excluded from this study
1) Ishikawa, H. Jpn. J. Urol. 72: 121, 1981.
2) Sakai, Niigata Med. J. 100: 782, 1986.
VII) Pheochromocytoma
A) Group A
1) Yamada, R. Metabolism and Disease 4: 684, 1967. 2) Yamada, A. J. Jpn. Soc. Int. Med. 63 : 686, 1974. 3) Fujita, S. J. Jpn. Soc. Int. Med. 66 : 1623, 1977. 4) Tajika, T. Jpn. J. Cancer Clin. 24 : 1081, 1978. 5) Murata, T. Jpn. J. Gastroenterol. 73 : 993, 1978. 6) Hirai, K. J. Jpn. Soc. Int. Med. 67: 204, 1978.
B) Group B
1) Harada, H. Diagnosis and Treatment 68 : 2003, 1980. 2) Sakamoto, F. Jpn. J. Clin. Urol. 36: 157, 1982. 3) Asayama, I. Jpn. J. Urol. 73 : 1488, 1982. 4) Sasaki, A. J. Jpn. Soc. Int. Med. 71: 1475, 1982. 5) Tago, K. Jpn. J. Urol. 73 : 1481, 1982. 6) Tada, Y. Nishinihon J. Urol. 45 : 1119, 1983. 7) Fuse, N. J. Jpn. Soc. Int. Med. 72 : 357, 1983. 8) Naruse, T. Jpn. J. Surg. 14 : 239, 1984. 9) Shimada, N. Chiba Med. J. 60: 338, 1984. 10) Hirano, S. Acta Urol. Jap. 30: 709, 1984. 11) Nakamitsu, A. J. Hiroshima Med. Ass. 37: 1440, 1984. 12) Tawada, M. Int. Med. 55: 794, 1985. 13) Kaneko, M. Jpn. J. Urol. 76: 442, 1985. 14) Tsuda, M. Proceed. 46th Meeting Jap. Soc. Ultrasonics Med. 779, 1985. 15) Yamamoto, M. Acta Urol. Jap. 31: 1427, 1985. 16) Iio, S. Jpn. J. Urol. 77: 165, 1986. 17) Uchida, K. Nishinihon J. Urol. 49 : 215, 1987. 18) Inoue, Y. Jpn. J. Clin. Urol. 41: 813, 1987. 19) Hashimoto, K. Jpn. J. Urol. 78 : 379, 1987. 20) Yamada, I. Nishinihon J. Urol. 49: 319, 1987. 21) Murayama, Y. Clin. Endocrinol. (Tokyo) 34 (suppl.) : 306, 1987. 22) Morimoto, S. Acta Urol. Jap. 34 : 423, 1988. 23) Shiohara, E. Proceed. 24th Annual Meeting of Chubu Surg. Ass. 54, 1988. 24) Yano, S. Nishinihon J. Urol. 50 : 1359, 1988. 25) Ikuyama, S. Int. Med. 62: 172, 1988. 26) Hosoda, N. Jpn. J. Pediatr. 41: 2385, 1988. 28) Takahashi, K. J. Japan Soc. Clin. Anesthe. 8: 106, 1988.
C) Cases excluded from this study
1) Funew, T. Clin. Endocrinol. (Tokyo) 16 :
397, 1968. 2) Ikekubo, K. Nipp. Act. Radiol. 35 : 612, 1975. 3) Hiratsuka, Y. Nishinihon J. Urol. 37 : 828, 1975. 4) Obara, T. J. Jpn. Soc. Int. Med. 51: 439, 1975. 5) Ikekubo, K. Nipp. Act. Radiol. 35 : 613, 1975. 6) Miyaji, K. Gan-No-Rinsho (Kyowa Hakko) 68: 43, 1977. 7) Miwa, M. Acta Urol. Jap. 26: 835, 1980. 8) Nakamura, A. Jpn. J. Urol. 73 : 670, 1982. 9) Takai, S. Proceed. 16th Meeting for Thyroid Surg. p. 32, 1983. 10) Yamada, S. Proceed. 17th Meeting for Thyroid Surg. p. 16, 1984. 11) Arai, K. Nipp. Act. Radiol. 44 : 1204, 1984. 12) Morita, D. J. Jpn. Soc. Int. Med. 74 : 833, 1985. 13) Yamamoto, T. Acta Urol. Jap. 31: 1427, 1985. 14) Tokunaga, U. Nippon-Kekkan- Zouei Intervent Radiol .- Kenkyukai-Zasshi 1: 26, 1986. 15) Iinuma, H. Nipp. Act. Radiol. 47 : 858, 1987. 16) Nomura, N. Surg. Diag. Treatm. 30: 551, 1988.
VIII) Other adrenal masses
A) Group A
1) Ochiai, K. Jpn. J. Urol. 57: 498, 1966. 2) Momose, G. Jpn. J. Urol. 60: 702, 1969.
3) Hidai, H. Yokohama Med. Bull. 27: 1976. 4) Katami, S. Jpn. Red. Cross Med. J. 28 : 76, 1976. 5) Ohtake, H. Jpn. J. Urol. 68: 211, 1977.
B) Group B
1) Hirano, T. Jpn. J. Urol. 74 : 1700, 1983. 2) Kubo, A. Folia Endocrinol. Jap. 62: 1071, 1986. 3) Ishii, T. Acta Urol. Jap. 33 : 223, 1987. 4) Asano, Y. Nishinihon J. Urol. 49 : 1481, 1987. 5) Saitoh, To. Proceed. 50th Meet- ing Jap. Soc. Ultrasonics Med. 941, 1987. 6) Kawano, T. Jpn. J. Urol. 78 : 552, 1987. 7) Umeda, H. J. Jpn. Soc. Pract. Surg. Soc. 48 : 1354, 1987. 8) Morimoto, S. Acta Urol. Jap. 34 : 423, 1988. 9) Sumiya, H. Nishinihon J. Urol. 50: 1473, 1988.
C) Cases excluded from this study
1) Kaii, O. Nipp. Act. Radiol. 45 : 773, 1985.