THE SUPRARENAL CORTICAL SYNDROME: REPORT OF A CASE WITH CARCINOMA OF THE ADRENAL CORTEX
WILLIAM L. MCLAUGHLIN AND JOHN P. BOWLER
The Urology Service JARRETT H. FOLLEY
The Medical Service of the Hitchcock Clinic and Mary Hitchcock Memorial Hospital, Hanover, New Hampshire
The suprarenal cortical syndrome may be defined as the sum of metabolic changes produced in the body by the presence of an excessive amount of adrenal cortical steroids. Such over-elaboration of steroids may be the result of hyper- plasia of the adrenal cortex brought about by the adrenotropic hormone of the pituitary gland. On the other hand, primary adenoma or carcinoma of the adrenal cortex may be the source of excess steroids. This latter condition is rare, yet it presents to the internist and urologist one of the most fascinating and challenging problems in all of medicine.
An understanding of the clinical manifestations of hormonal neoplasms of the adrenal cortex and a scientific approach to their surgical management are best gained by a study of adrenal cortical physiology.
Steroids are organic compounds having a molecular structure similar to cholesterol. By virtue of varying side atoms and chains of atoms they possess distinct biologic properties which put them in the category of hormones. The testes and ovaries as well as the adrenal cortex are known to be sources of hor- monal steroids.
It has been well established that adrenal cortical steroids exert a profound influence on fluid and electrolyte balance; on protein, sugar and fat metabolism; on pigmentation; and on the masculinization and femininization of the body.
Some of the steroids of the crystalline fraction of whole adrenal extract include desoxycorticosterone, 17-hydroxy-11 dehydrocorticosterone (compound E of Kendall), dehydroisoandrosterone, estrone and progesterone. Bearing in mind that each of these is representative of a larger group of steroids, we believe that it may be worthwhile to consider briefly the biologic properties of each.
Desoxycorticosterone, frequently referred to as “doca”, is the only adrenal steroid that has been synthesized. At present it is finding widespread clinical use in the treatment of Addison’s disease. Its chief property is that of causing retention of water and sodium chloride and the elimination of potassium through an effect on the renal tubule. Exhibition of this substance in the normal human subject will produce abnormal sodium chloride and water retention.8 Its use in patients with Addison’s disease occasionally leads to hypertension and even cardiac failure. 29
17-hydroxy-11 dehydrocorticosterone appears to have little to do with elec- trolyte and fluid balance. It is thought by most investigators to play a role in the conversion of protein to sugar, a process known as “gluconeogenesis.” AI-
bright and Reifenstein,1 however, believe that this so-called “sugar hormone” does not act by converting proteins to sugar, but by inhibiting the synthesis of tissue. Experimentally diabetes mellitus and nitrogen loss may be produced by this steroid, especially in the presence of reduced insulin secretion.16 Of particular significance is the fact that atrophy of the adrenal cortex may be produced in the experimental animal by prolonged administration of this ster- oid.16 Another interesting action of this “sugar-hormone” is its ability to cause breakdown of lymphocytes with the release of immune globulin.10 This phe- nomenon suggests that it may play an important role in the body’s resistance to infection.
Dehydroisoandrosterone has androgenic properties. Structurally it is closely related to the testicular male sex hormone, testosterone. Exhibition of the latter, in addition to frank masculinization, will cause nitrogen retention and somatic growth. Estrone and progesterone, steroids also isolated from the adrenal cortex, have properties of the female sex hormone.
CLINICAL MANIFESTATIONS
The clinical features of a hormone-producing adrenal cortical neoplasm are therefore complex and variable. Cahill5 has stated it simply: “The syndromes are determined by the type and amount of hormones produced and by the sex and age of the patient.” The following outline may be useful in subdividing the suprarenal cortical syndrome;
I. Changes due to excess androgens or estrogens (adrenogenital syndrome); a. Female child toward adult masculinity; b. Female adult toward masculin- ity; c. Male child toward adult masculinity; d. Male adult toward femininity.
II. Changes due to excess steroids of metabolism with or without excess of androgens and estrogens (Cushing’s syndrome).
Of these two main clinical syndromes, the Cushing’s type appears to be more common. Briefly the Cushing’s syndrome is a clinical picture consisting of a rapid, sometimes painful, obesity affecting primarily the face, neck and abdomen, but usually sparing the limbs. The skin becomes thin, rubicund, and bruises easily. Purple striae form on the abdomen and thighs. Excessive hair often grows on the face. Susceptibility to infection, particularly of the skin, may be present. The muscles of the extremities undergo atrophy. Loss of libido and amenorrhea are usually present. Personality change with the development of a psychosis is common.18 The patients usually exhibit hypertensive cardi- ovascular disease. Mild erythrocytosis, slight neutrophilia, and mild diabetes may be present. The spine is often osteoporotic and collapse of the vertebral
1 Albright, F .: The Harvey Lectures Series 38: 123-186, 1942-1943.
2 Anderson, E., Haymaker, W., and Joseph, M .: Endocrinology, 23: 398-402, 1938.
3 Callow, N. H., Callow, R. K., and Emmens, C. W .: Biochem. J., 32: 1312, 1938.
4 Cahill, G. F .: Radiology, 37: 533-543, 1941.
5 Cahill, G. F., Melicow, M. M., and Darby, H. H .: Surg., Gynec., and Obst., 74: 281-305, 1942.
6 Cahill, G. F .: Medical Physics, 1944.
7 Cahill, G. F .: Surgery, 16: 194-227, 1944.
8 Clinton, M. and Thorn, G. W .: Bull. Johns Hopkins Hospital 72: 255-264, 1943.
bodies is common. There are many atypical or incomplete clinical pictures of this general metabolic disorder. The literature contains accounts of patients who showed only one or few of the cardinal features of the Cushing’s syndrome. One case was reported24 wherein the only manifestation of a hormonal adrenal cortical neoplasm was diabetes mellitus.
Some confusion has arisen from the fact that Teel’s27 and Cushing’s9 original reports described this syndrome associated with basophilic adenoma of the pituitary gland. We have since learned that the mechanism of the syndrome is always by way of adrenal cortical steroids.2 In a comprehensive review of the subject, using autopsy material, Thompson and Eisenhardt28 found a bas- ophilic adenoma of the pituitary in approximately 60 per cent of the cases presenting features of the syndrome. In about 20 per cent of the cases a neo- plasm of the adrenal cortex could be demonstrated. In their series thymic and ovarian tumors also gave rise to the syndrome. Nevertheless, in a surprisingly large number of patients no tumor of any gland could be found. Albright states that in his opinion these patients without any glandular tumor always have adrenal cortical hyperplasia, if the criteria for making the diagnosis be sufficiently accurate.
DIAGNOSIS
The first step in making the diagnosis of a neoplasm of the adrenal is the recognition of the clinical picture. Because of the rather inaccessible location of the adrenals, neoplasms arising in this area are rarely palpable.
Use has been made of the fact that steroids are normally excreted in the urine, and that when excessive amounts of steroids are present in the blood, large amounts will be found in the urine. By means of bio-assay or direct chemical analysis, quantitative and qualitative determinations of the urinary steroids may be obtained. The androgenic properties may be ascertained by observing the effect of a urinary extract on the growth of cock’s comb. A less cumbersome method of determining the amount of androgenic steroids in the urine is by chemical analysis. A test3 has been devised which detects the presence of steroids having a double-bonded oxygen on the seventeenth carbon atom. Known collectively as the 17-ketosteroids, these steroids appear to function chiefly as androgens. This test, although it requires more than the usual hospital laboratory facilities, is finding widespread use in clinical medi- cine.26
At the present time various tests are being perfected to detect the presence of the more elusive metabolic or “life-maintenance” steroids.23
9 Cushing, H .: Bull. Johns Hopkins Hosp., 50: 137, 1932.
10 De La Balze, F. A., Reifenstein, Jr., E. C. and Albright, F .: J. Clin. Endocrinol. 6: 312-319, 1946.
11 Engstrom, W. W., Mason, H. L., and Kepler, E. J .: J. Clin. Endocrinol., 4: 152-155, 1944.
12 Farber, J. E., Gustina, F. J. and Postatoff, A. V .: Am. J. Dis. Children, 65: 593-603, 1943.
13 Frank, A. T .: Proc. Soc. Exper. Biol. and Med., 31: 1204, 1934.
14 Heilman, F. R. and Kendal, E. C .: Endocrinology, 34: 416-420, 1944.
An adrenal tumor may be disclosed by roentgenography. By combining an excretory urogram with a plain film of the abdomen centered over the adrenals, one may occasionally demonstrate a mass displacing a kidney downward. The introduction of air into Gerota’s capsule will frequently outline an adrenal neoplasm. Devised by Carelli in 1921, the technique of perinephric air in- jection has been perfected by Cahill in his study of the adrenal.4,5,6,7 He has performed it in over 500 cases without fatality or complication.
In many patients exhibiting the Cushing’s syndrome the differentiation between hyperplasia and tumor of the adrenal may be difficult. Since hyper- plasia of the adrenals is frequently associated with a basophilic adenoma of the pituitary, all such cases should have a thorough evaluation of the intracranial status. From a diagnostic point of view it is unfortunate that basophilic adenomata are so small that neurologic signs and changes in the sella turcica are rarely produced. Often the diagnosis of hyperplasia or tumor of the adrenal is not established until the adrenals are exposed surgically. Walters30,31,32 pre- fers surgical exploration of the adrenal areas in all suspects without preliminary airography, stating that in his opinion surgery is no more hazardous than airography.
SURGICAL MANAGEMENT
The optimum surgical approach to the adrenal is debatable. Walters be- lieves the posterolateral extraperitoneal lumbar incision to be the one of choice. He has performed bilateral exposures to determine first the diseased side and second whether or not there is an adrenal on the other side. Cahill believes that the size of the tumor should govern the approach, reserving the trans- peritoneal incision for large neoplasms. Young devised a retractor which allows exposure of each adrenal simultaneously.
Clinical experience has brought out the fact that when features of the Cush- ing’s syndrome are associated with an adrenal tumor, the removal of the latter invariably brings on a transient period of adrenal insufficiency. This is attrib- uted to the fact that contralateral adrenal atrophy occurs in the presence of an excessive elaboration of metabolic steroids from a neoplasm.5 On the other hand, patients exhibiting the adrenogenital syndrome without evidence of the Cushing’s syndrome undergo surgical removal of an adrenal neoplasm without difficulty.5 Contralateral adrenal atrophy, therefore, does not appear to occur in the presence of excess sex hormone.
The postoperative insufficiency state may be manifest as a frank Addisonian
15 Keating, F. R. and Kepler, E. J .: Surg. Clinics N. Amer., 21: 1163-1172, 1941.
16 Kenyon, A. T .: Surgery, 16: 194-227, 1944.
17 Kepler, E. J. and Keating, F. R .: Arch. Int. Med., 63: 1010, 1941.
18 Maclay, W. S. and Stokes, A. B .: J. Neurol. and Psychiat., 1: 110, 1938. 19 Nissen, R .: Exper. Med. and Surg., 1: 309-313, 1943.
20 O’Crowley, C. R. and Martland, H. S .: J. Urol., 50: 6, 1943.
21 Reilly, W. A .: Clinics, 1: 669-676, 1942.
22 Scholl, A. J .: J. Urol., 39: 81-91, 1938.
23 Selye, H. and Schenker, V .: Proc. Soc. Exper. Biol. and Med., 39: 518, 1938.
24 Sprague, R. G., Priestley, J. T. and Dockerty, M. B .: J. Clin. Endocrinol., 3: 28-32, 1943.
crisis, culminating in death within 48 hours. The high mortality in this group of patients is attributable to such a phenomenon. Crises are characterized by nausea and vomiting, weakness and prostration, marked elevation in temper- ature and pulse, with fall in blood pressure. There is reduction in the blood sugar and serum sodium and elevation of the serum potassium and nonprotein nitrogen.
One should be prepared to detect and combat adrenal insufficiency after removal of an adrenal tumor producing the Cushing’s syndrome. Crises de- velop with great rapidity, which means that close observation of the vital signs must be made. When the insufficiency state seems imminent or has already become established, it should be combated by the administration of whole adrenal extract which contains the steroids controlling carbohydrate metab- olism and by the administration of the synthetic steroid, desoxycorticosterone acetate, which helps repair fluid and electrolyte imbalance.29 At the same time liberal amounts of sugar and sodium chloride should be given. Such replace- ment therapy must be continued until the remaining adrenal has recovered sufficient function to maintain life. This is usually a matter of a few days to a week. Large amounts of cortical extract may be given without danger. Des- oxycorticosterone, however, has a much narrower margin of therapeutic safety, because of the rapidity with which it can produce fluid retention and cardiac embarrassment.
Since patients with either the Cushing’s syndrome or Addison’s disease show an increased susceptibility to infection, it may be wise to give penicillin pro- phylactically during and after the operative procedure. The high incidence of pulmonary atelectasis and pneumonitis following surgery of the renal areas calls for diligent nursing care to prevent the accumulation of secretions in the bronchial tree.
Estimation of the postoperative fluid and electrolyte requirements may be put on a reasonably accurate basis by frequent determinations of the hemo- globin, hematocrit, plasma chlorides, carbon dioxide combining power and blood sugar. Frequent transfusions of whole blood, plasma, and amino acids may be necessary.
Albright has pointed out that exhibition of testosterone in patients with the Cushing’s syndrome will bring about a positive nitrogen, phosphorus, and potassium balance. The patient’s skin becomes less thin, the muscles stronger, and the bones denser. This, of course, is not meant to be a substitute for surgery when neoplasm is present. It may, however, be important in the re- habilitation of a patient after removal of an adrenal cortical tumor.
25 Sussman, M. L. and Copleman, B .: Radiology, 39: 288, 1942.
26 Talbot, N. B. and Butler, A. M .: J. Clin. Endocrinology, 2: 724, 1942.
27 Teel, H. M .: Arch. Neurol. and Psychiat., 26: 593-599, 1931.
28 Thompson, K. W. and Eisenhardt, L .: J. Clin. Endocrinol., 3: 452, 1943. 29 Thorn, G. W .: J.A.M.A., 125: 10-15, 1944.
30 Walters, W., Wilder, R. M. and Kepler, E. J .: Ann. Surg., 100: 670-688, 1934.
31 Walters, W. and Kepler, E. J .: Ann. Surg., 107: 881, 1938.
32 Walters, W .: South. M. J., 34: 1241-1247, 1941.
33 Warren, F. L .: Cancer Research, 5: 49-54, 1945.
At the present time the status of partial resection of the hyperplastic adrenal is not well established. If too much cortical tissue be removed, control of the postoperative deficiency state is exceedingly difficult. It is to be hoped that a potent steroid controlling sugar metabolism will be synthesized for the handling of this situation. Walters suggests that hyperplastic adrenals should be par- tially resected and that later deep x-ray therapy to the pituitary should be given.
CASE REPORT
The following is the case history of a patient with carcinoma of the adrenal, whose clinical picture was that of an atypical Cushing’s syndrome:
A 44 year old white male was admitted to Mary Hitchcock Memorial Hos- pital in March 1945, complaining of low back pain. His family history was non-contributory except that his mother died of carcinoma of the breast. Four- teen months previously he had undergone hemorrhoidectomy for hemorrhoids of several years’ duration. At that time his blood pressure was recorded at 120 systolic and 80 diastolic. A few weeks postoperatively phlebothrombosis of both legs developed. After multiple severe pulmonary infarcts, ligation of the inferior vena cava just proximal to the bifurcation of the iliacs was carried out by means of a right lower quadrant, extraperitoneal approach. In a few months he was able to return to work. His ankles, however, swelled moderately after he had been on his feet for several hours. His past history was otherwise entirely negative. He had always been exceptionally vigorous and active.
Nine months before this admission members of his family noticed progresive “bloating” of his face, particularly about the cheeks and under the chin. For the past 13 months he complained of low back pain which was aggravated by motion. There was no history of injury or heavy lifting.
On examination he was found to have normal respirations, pulse, and temper- ature. The blood pressure was 140 systolic and 90 diastolic. His face appeared slightly “moon-shaped.” The skin was thin, dry and atrophic. No rubor, striae, or acne was present. The musculature of the arms and legs was atrophic. No abdominal adiposity and no “buffalo-hump” in the cervico-thoracic region could be made out. The area of liver dullness appeared to be abnormally small. Bilateral spermatoceles were present.
The hemoglobin was 15.3 gm. per 100 cc blood and the red cell count 5,000, 000. The white cell count was 11,400 with 83 per cent polymorphonuclear leucocytes and 16 per cent lymphocytes. The sedimentation rate was 30 mm. in 1 hour. The urine was negative. The serum phosphorus, the serum cal- cium, the serum alkaline phosphatase, the serum albumin, the serum globulin, and the serum cholesterol were within normal limits. The serology was nega- tive. A bone marrow smear contained no abnormal forms. The basal meta- bolic rate was consistently low, ranging between minus 29 per cent and minus 32 per cent.
The roentgenograms of the spine revealed marked osteoporosis with com- pression fractures of the second, third, and fourth lumbar bodies. The chest was negative. Excretory urograms showed normally functioning kidneys with
the right kidney questionably depressed by a mass above it. Airograms of the adrenals were suggested, but not carried out at that time.
The patient was placed in bed with the spine in hyperextension, and accessory calcium and vitamin D were given. Because of his low basal metabolic rate, a regime of desiccated thyroid by mouth was instituted. He remained in the hospital 6 weeks and was discharged on the same regime and with a hyper- extension brace.
In May 1945, one month later, he was readmitted because his general condi- tion had grown worse. He had gradually fallen into a psychotic state char- acterized by severe mental depression and feelings of unworthiness. His blood pressure was higher, ranging between 150 and 180 systolic, 90 and 110 diastolic. His pulse rate ranged between 90 and 120. These changes per- sisted following discontinuation of the thyroid medication. The basal metabo- lism rate was still minus 14 per cent.
Physical examination revealed further wasting of the arms and legs, but was essentially as before.
The glucose tolerance curve, the hematocrit, the plasma chlorides, the carbon dioxide combining power and the plasma proteins were within normal limits.
The roentgenograms of the spine disclosed further osteoporosis with more narrowing of the vertebral bodies (fig. 1). The long bones and the skull ap- peared normal. Perinephric air insufflation (fig. 2) revealed a rounded mass above the right kidney. The outline of the left adrenal appeared large.
- 19.LE
On the sixteenth hospital day he received a transfusion of 500 cc whole citrated blood. On the eighteenth day he was given nitrous oxide-oxygen and ether anesthesia and the right adrenal area was explored through a posterolateral incision. The twelfth rib was resected. A neoplasm above the right kidney was found (fig. 3). The biopsy and immediate frozen section revealed normal-
appearing adrenal cortical tissue. It was then noted that the biopsy had been taken from the normal adrenal gland which was present as a thin shell on the anterior surface of the tumor. A small incision was made anteriorly into the peritoneal cavity. Palpation of the left adrenal area was not entirely satis- factory, but no abnormality was found. The liver had been displaced upward and rotated by the tumor, but felt normal. The tumor was well-encapsulated and was easily dissected. Many dilated veins, however, were encountered. Only a small pedicle was isolated and easily ligated. During the extraction of the tumor a small amount of necrotic tissue spilled into the wound. These
fragments were removed, but, as a precautionary measure, the wound was thoroughly swabbed with liquid ether. Two Penrose drains were brought out through the posterior angle of the wound. The operation lasted 2 hours and was well tolerated by the patient. During the procedure he was given 1000 cc whole citrated blood.
The neoplasm weighed 1000 gm. Except for an area of necrosis the capsule appeared intact. The sectioned surface (fig. 4) revealed different sized nodules of grey-yellow tissue interspersed with areas of hemorrhage and necrosis. Mi- croscopically there were two distinct patterns. In one (fig. 5, A) the cells were ” characterized by clear, light-staining cytoplasm and prominent nuclei with many mitotic figures. In the other (fig. 5, B) the cells were smaller, darker and
A
B
grouped in cords about widened vascular channels. It was the consensus of several pathologists that this was a cancer of the adrenal gland.
In the immediate postoperative period dramatic changes occurred (fig. 6). The blood pressure dropped, averaging about 100 systolic and 70 diastolic. The temperature, pulse, and respirations rose. Despite the unfavorable trend in his vital signs, his mind became much clearer and he was no longer depressed.
In an effort to combat what appeared to be an adrenal insufficiency state he was given adrenal cortical extract (Eschatin) by vein, and desoxycorticosterone acetate (Cortate) intramuscularly (fig. 6). For 4 days he received a slow, continuous infusion of 5 per cent dextrose in saline containing penicillin, which brought his total fluid intake to approximately 2500 cc per 24 hours. Despite
BLOOD PRESSURE
170
140
110
Systolic
80
Diastolic
TEMPERATURE
50
105
103
101
99
C.C./24 HRS.
50
30
Cortical Extract
10
MG / 24 HRS .
15
10
5
Desoxycorticosterone
1
2
3
4
5
6
7
18
Operation
Days
a regime of turning, deep breathing and coughing, on the first postoperative day he was found by x-ray to have a small amount of atelectasis above the right diaphragm. He became slightly dyspneic and was placed in an oxygen tent for 24 hours.
On the first postoperative day a blood sugar of 48 mg. per 100 cc was obtained. The non-protein nitrogen, plasma chlorides, carbon dioxide combining power, plasma proteins and hematocrit were normal at that time.
On the sixth postoperative day he appeared to be in a salt and fluid retention phase with lowered urinary output, generalized edema, lowered hematocrit and lowered plasma proteins. There was no clinical evidence of cardiac failure. This persisted despite the fact that he was given several transfusions of plasma and whole blood and despite the fact that desoxycorticosterone and supple- mentary salt had been discontinued on the third postoperative day. On the
seventh postoperative day he was allowed up out of bed with a brace on his back.
During the second and third postoperative weeks the generalized edema gradually disappeared except in the lower legs. His mental state, which imme- diately after the operation showed improvement, was again characterized by depression and marked aversion to food. He had to be tube fed for 3 days and was given daily infusions of amino acids.
A
B
The wound healed well. Despite the fact that no focus of infection could be found, the patient’s temperature remained elevated from 2 to 4 degrees until the eighteenth postoperative day.
On the thirty-sixth day he was started on a course of testosterone propionate. Striking improvement appeared to coincide with the institution of this therapy. At the time of his discharge on the forty-seventh postoperative day he was stronger and was no longer depressed (fig. 7, A).
As an out-patient he was given periodic injections of testosterone propionate intramuscularly, and in the course of the next 11 months he received 75 mg. weekly for a total dose of 2000 mg.
His general condition slowly improved, although the edema of the lower legs
persisted. The hemoglobin and plasma proteins remained low. He was placed on a high vitamin, high protein and high calcium diet.
Two months after the operation the spine appeared to have undergone slight recalcification. He was then allowed to be up and about as desired with a hyperextension brace on his back. By the end of the fourth month the edema of the lower legs had disappeared.
In June 1946, thirteen months after removal of the tumor, he appeared to be in excellent health (fig. 7, B). The pulse rate was 80. The blood pressure was 104 systolic, 70 diastolic. The swelling of the face had completely disappeared.
The musculature of the arms and legs had improved. The wound was solid and no abdominal masses could be felt.
There was no anemia. The white cell count was 7,000 with 55 per cent lymphocytes. The blood sugar, non-protein nitrogen, plasma chlorides, carbon dioxide combining power were within normal limits. The serum proteins, however, were still low.
The spine appeared to be completely recalcified (fig. 8), although narrowing of the bodies remained. An x-ray of the chest was negative.
For the past 2 months he has been at a full time job and has returned to his normal recreations including golf.
COMMENTS
The replacement therapy during the patient’s postoperative adrenal in- sufficiency phase was probably not adequate in regard to whole adrenal extract, the one containing the carbohydrate-controlling factors. A larger amount, had it been given, might have carried him through the insufficiency phase with less shock.
It is difficult to explain the postoperative fluid retention phase which per- sisted despite several transfusions of whole blood and plasma. The exhibition of desoxycorticosterone may have precipitated it, but it should be noted that only a small amount of this steroid was given and not at any time did hyper- tension develop, one of the characteristic features of desoxycorticosterone poisoning.
Testosterone propionate may have aided in the rehabilitation of this patient. It is possible that this steroid, in addition to building up the muscles and other tissues, increased the rate of recalcification of the spine by speeding up the formation of protein matrix on which calcium and phosphorus could be de- posited.
The slight, relative increase in the number of neutrophils at the height of the patient’s altered metabolism due to the adrenal tumor and the shift to relative lymphocytosis and neutropenia after removal of the tumor are probably mani- festations of the effect of one of the adrenal cortical steroids. The lympho- cytosis at present suggests an adrenal insufficiency state, although there are no other stigmata of such a condition.
To summarize, we have presented a brief discussion of the suprarenal cortical syndrome and the case history of a patient exhibiting many of the features of this syndrome. Attention has been called to the fact that a so-called “class- ical” picture will seldom occur because of the variances in the predominant steroid or steroids. Following the removal of a large carcinoma of the right adrenal, this patient went into a state of adrenal insufficiency, which, because of its Cushing’s syndrome-like background, could be anticipated. His re- covery was slow, but apparently complete. While it is to be regretted that it was not possible to document this case with an analysis of the type or types of excess steroid, the entire picture indicates that we were dealing with an adrenal cortical neoplasm which produced steroids of considerable biologic activity.