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Pre- and Postoperative Care in Adrenal Surgery
THE JOURNAL OF UROLOGY
Vol. 70, No. 2, August 1953 Printed in U.S.A.
PRE- AND POSTOPERATIVE CARE IN ADRENAL SURGERY JOSEPH W. JAILER From the Departments of Obstetrics and Gynecology and of M ed-icine, College of Physicians and Surgeons, Columbia University, New York, N. Y.
Specific problems of adrenal surgery have been discussed by the previous speakers. I should like to review the overall topic and discuss problems and therapy in the light of our knowledge of adrenal physiology and steroid chemistry. Bilateral total adrenalectomy without suitable replacement therapy in the experimental animal invariably results in death within 10 days. Addison's disease was considered a fatal condition. With the synthesis and widespread use of desoxycorticosterone (DOA) in this condition, this was no longer considered so. However, it soon became evident in clinical practice as well as in the study of the experimental animal deprived of its adrenals, that this steroid (DOA) alone could not be used for complete adrenocortical replacement. DOA in itself does not have all the physiological effects necessary to cope with crises which may develop. Adrenal cortical extract had to be used to supplement the former steroid. Therefore it is only since the introduction of cortisone into the armamentarium of the clinician that it has been possible to perform radical adrenal surgery with little risk. Total adrenalectomy was performed in the pre-cortisone era; however, results were not satisfactory since life could not be maintained for sufficient length of time due to the relative impotency of the adrenocortical extracts available. Before discussing replacement therapy I should like to review briefly some of the aspects of adrenal physiology and chemistry (table 1). As you know, several different biologically active steroids have been isolated from adrenal tissue of animals. The adrenal cortex, as an endocrine gland, differs from the thyroid, pancreas and testes in that some of the steroids elaborated in the adrenal have markedly different physiological effects. It is with an understanding of these principles that we can better prepare a patient for adrenal surgery and maintain normal homeostasis postoperatively. Desoxycorticosterone, as the name implies (Desoxy), lacks an oxygen at the eleventh carbon; its effect is primarily on salt and water metabolism, having but little effect on protein and carbohydrate metabolism. Moreover there is a paradox in its action in that DOA can maintain the life of the adrenalectomized animal but is not very effective in protecting the animal against a stress-cold, infection, toxins, etc. The 11-oxysteroids on the other hand as represented by cortisone, compound F and to a lesser extent corticosterone or compound B are more effective against stress. They effect protein catabolism, gluconeogenesis, cause a fall in eosinophils and lymphocytes and increase the capacity of muscles to perform work. They are salt-retaining steroids as well but are not as efficient as desoxycorticosterone. One of their important effects is to suppress ACTH production by the pituitary. Another hormone at our disposal is ACTH; suffice it to say that for all pracRead at annual meeting, American Association of Genito-Urinary Surgeons, Absecon, N. J., June 19, 1952.
137
138
JOSEPH W. JAILER
tical purposes its effects are mediated through the adrenal and it is ineffective in the absence of the adrenal cortex. We do not know, at present, which steroids the human adrenal secretes. There is some evidence that compound F may be one of them however. There is no direct proof that DCA itself is secreted. Adrenal surgery is performed for several different reasons and in different diseases. In order to understand the therapy employed, certain concepts of the disease must be borne in mind. 1) Total adrenalectomy has been performed for malignant hypertension, prostatic and mammary carcinoma. We have had very little personal experience in this field and I am embarrassed to discuss this in front of Doctors Baker and Harrison since the regimen outlined is taken from their published works. If adrenalectomy is done in two stages, usually no special preparation is necessary for the first stage. The following regimen is usually followed for the second stage or when a bilateral operation is performed at one sitting. Day before operation: The patient is given 200 mg. cortisone intramuscularly, since this will have its greatest effect the following day. On the day of the operation 200 mg. more TABLE
1. Comparison of the active corticosteroids by different assay methods SURVIVAL TEST
COMPOUND
Na
RETENTION
INGLE TEST
ANTI-INSULIN
I ''B" "F" "E" DCA
r
H H
1+ 4+
2+ 0 0
4+
GLYCOGEN DEPOSITION
2+ 4+ 4+
2+ 4+ 4+
3+ 4+ 4+
0
0
0
plus 5 mg. DCA. First day postoperative-200 mg. plus 5 mg. DCA --t cortisone is then tapered off gradually. 2) Adrenalectomy for Cushing's syndrome: It has not been definitely established whether Cushing's syndrome is primarily pituitary or primarily adrenal cortical disease. (In other words, too much ACTH versus too much compound F). However, there is no doubt that the clinical manifestations of the disease are due to excessive corticoid secretion. All the signs and symptoms of the disease have been produced by chronic administration of large doses of cortisone. Therefore, removal of the source of these steroids is a rational approach to therapy in this condition. Cushing's syndrome may be due to an adrenocortical adenoma or carcinoma. When this pathological condition occurs there can be no dispute as to the course of action. It should be borne in mind however that when a tumor exists in the presence of this clinical entity, the contralateral adrenal gland is invariably atrophic; so that if no hormonal preparation is done prior to the removal of the tumor, the surgeon may find himself with an essentially adrenalectomized patient who has just been severely stressed. Such a condition is not compatible with life. The rationale of therapy is replacement with cortisone and DCA for the immediate replacement effect together with ACTH to stimulate the function of that atrophic contralateral gland (table 2).
PRE- AND POSTOPERATIVE CARE IN ADRENAL SURGERY
139
If in the immediate postoperative period, the blood pressure falls, infusions of nor-adrenaline or neo-synephrine and blood should be employed. Serum sodium and potassium levels should be carefully followed and these electrolytes replaced, of course, if their concentrations fall. This is especially so for the K which may be lost in the urine as a result of excessive cortisone replacement therapy. TABLE
Na.
DATE
2. C. R., Cushing's syndrome
K. I
I
Cl.
I
co,
TREATMENT
(mEq/liter)
143.0 144.0 Surgery
2.3 2.6
92.2 93.0
12/13 (a.m.)
144.1
2.1
94.3
12/14 (a.m.) 12/15 12/16 12/17 12/18 12/19 12/20 12/22 12/26
139.0 141.0
2.1 2.6
92.2 96.9
35.1 35.0
141. 7 140.3 142.3 140.6 140.5 141.5
2.5 1. 9 2.2 2.4 2.8 3.5
96.5 93.5
38.7 36.6
99.6 100.0
34.3 30.2
12/10 12/11 12/12
TABLE
39.6 41.8
200 mg. "E" 300 mg. "E"; 5 mg. DCA; 25 mg. ACTH i.v. 200 mg. "E"; 5 mg. DCA; 25 mg. ACTH i.v. 200 mg. "E"; ACTH i.v. 100 mg. "E"; ACTH i.v. 75 mg. "E"; ACTH i.v. 50 mg. "E"; ACTH i.v. 25 mg. "E"; ACTH i.v. 25 mg. "E"; 15 mg. ACTH i.v. 25 mg. "E"; 10 mg. ACTH i.v.
3. Steroidal pre- and postoperative care for adrenalectomy in Cushing's syndrome Preoperative Day 2 200 mg. cortisone l.m. Day 1 200 mg. cortisone l.m. Day of adrenalectomy-100 mg. cortisone early a.m.-5 mg. DCA Postoperative Day 1 200 mg. cortisone 5 mg. DCA Day 2 200 mg. cortisone 5 mg. DCA Day 3 200 mg. cortisone DCA if needed Day 4 150 mg. cortisone DCA if needed Day 5 Gradual tapering of cortisone dosage
Cushing's syndrome is more frequently due to adrenal hyperplasia than neoplasm. Even though in some cases the adrenals may not be enlarged anatomically, there is no doubt of their physiologic over-activity. Occasionally a spontaneous remission may occur. Furthermore, in the series at the Presbyterian Hospital about one-third of the patients have benefited by radiation of the pituitary gland. But apparently it becomes necessary to operate on a good number of these patients. Between 90-100 per cent of the adrenal tissue must be removed in most cases to effect a remission in this condition, otherwise regeneration of the remaining tissue may again result in the disease. The usual routine is to remove 90 per cent of one adrenal and at some future date to do a complete adrenalectomy on the contralateral side. If one side is to
140
JOSEPH W. JAILER
be removed, aside from the usual surgical precautions, no hormonal support is necessary. It must be borne in mind that these patients heal poorly and wounds disrupt easily. We have recently followed three hyperadrenal patients through an uneventful single stage adrenalectomy without any steroidal support. It is with the second stage that we are concerned. As a result of the surgical procedure the patients proceed from a state of hyperadrenalism to one of hypoadrenalism with all the attendant metabolic effects. Therefore, the transformation must be made gradual. Preparation in these cases proceeds as it does in the total adrenalectomy. For two days preoperatively we have given 200 mg. intramuscular cortisone which is continued for several days thereafter, the length of time depending upon the clinical condition as well as the electrolyte and carbohydrate state. Following this, the dose of cortisone is gradually tapered down. Anywhere from 12.5 to 50 mg. a day is needed to maintain the patients. Some may require none at all. DCA is given on the day of operation and the first postoperative day. This is continued only if needed as judged by the concentration of sodium in the serum. This is summarized in table 3. 3) Adrenogenital syndrome: The adrenogenital syndrome or adrenal virilism also concerns the genito-urinary surgeon. Here, too, the cause may be adrenal hyperplasia or neoplasm. Due to the differences in the steroids elaborated by the adrenal in this condition as compared to the Cushing's syndrome the metabolic alterations are not at all similar and the operative procedure is attendant with different problems. The metabolic alterations in CHO, protein and electrolyte spheres are not present. These patients withstand surgery well, heal promptly and are no problem. In our experience, very little or no hormonal support is needed. One word of caution is necessary, and this must be stressed, adrenal carcinoma showing the mixed syndrome, namely elements of both the adrenogenital syndrome and Cushing's, should be handled like the latter. They differ from the true Cushing in that in addition to excessive corticoid secretion the adrenals are elaborating androgens as well. They must be prepared for operation with hormonal support as outlined above. The patients with benign adenomas, on the other hand, require no hormonal support. Being an internist, I should like to close this discussion with a demonstration of how a medical adrenalectomy can be performed. As you know, ACTH stimulates the adrenal cortex and, conversely, cortisone or compound F inhibits the pituitary from secreting more ACTH. Thus, in patients with adrenal virilism due to bilateral adrenal hyperplasia, the administration of cortisone results in an indirect decrease of adrenal secretion and at the same time the substitution of a more normal adrenal steroid for the abnormal ones being elaborated in this syndrome. ·when a carcinoma is present, on the other hand, cortisone is without effect upon the 17-ketosteroids. We have one further piece of evidence to uphold the thesis that adrenal carcinoma is completely independent of pituitary stimulation. One of our patients with an adrenal carcinoma and Cushing's syndrome was subsequently hypophysectomized. This procedure had no effect on the course of the disease nor on the 17-ketosteroids.
Vol. 70, No. 2, August 1953 Printed in U.S.A.
PRE- AND POSTOPERATIVE CARE IN ADRENAL SURGERY JOSEPH W. JAILER From the Departments of Obstetrics and Gynecology and of M ed-icine, College of Physicians and Surgeons, Columbia University, New York, N. Y.
Specific problems of adrenal surgery have been discussed by the previous speakers. I should like to review the overall topic and discuss problems and therapy in the light of our knowledge of adrenal physiology and steroid chemistry. Bilateral total adrenalectomy without suitable replacement therapy in the experimental animal invariably results in death within 10 days. Addison's disease was considered a fatal condition. With the synthesis and widespread use of desoxycorticosterone (DOA) in this condition, this was no longer considered so. However, it soon became evident in clinical practice as well as in the study of the experimental animal deprived of its adrenals, that this steroid (DOA) alone could not be used for complete adrenocortical replacement. DOA in itself does not have all the physiological effects necessary to cope with crises which may develop. Adrenal cortical extract had to be used to supplement the former steroid. Therefore it is only since the introduction of cortisone into the armamentarium of the clinician that it has been possible to perform radical adrenal surgery with little risk. Total adrenalectomy was performed in the pre-cortisone era; however, results were not satisfactory since life could not be maintained for sufficient length of time due to the relative impotency of the adrenocortical extracts available. Before discussing replacement therapy I should like to review briefly some of the aspects of adrenal physiology and chemistry (table 1). As you know, several different biologically active steroids have been isolated from adrenal tissue of animals. The adrenal cortex, as an endocrine gland, differs from the thyroid, pancreas and testes in that some of the steroids elaborated in the adrenal have markedly different physiological effects. It is with an understanding of these principles that we can better prepare a patient for adrenal surgery and maintain normal homeostasis postoperatively. Desoxycorticosterone, as the name implies (Desoxy), lacks an oxygen at the eleventh carbon; its effect is primarily on salt and water metabolism, having but little effect on protein and carbohydrate metabolism. Moreover there is a paradox in its action in that DOA can maintain the life of the adrenalectomized animal but is not very effective in protecting the animal against a stress-cold, infection, toxins, etc. The 11-oxysteroids on the other hand as represented by cortisone, compound F and to a lesser extent corticosterone or compound B are more effective against stress. They effect protein catabolism, gluconeogenesis, cause a fall in eosinophils and lymphocytes and increase the capacity of muscles to perform work. They are salt-retaining steroids as well but are not as efficient as desoxycorticosterone. One of their important effects is to suppress ACTH production by the pituitary. Another hormone at our disposal is ACTH; suffice it to say that for all pracRead at annual meeting, American Association of Genito-Urinary Surgeons, Absecon, N. J., June 19, 1952.
137
138
JOSEPH W. JAILER
tical purposes its effects are mediated through the adrenal and it is ineffective in the absence of the adrenal cortex. We do not know, at present, which steroids the human adrenal secretes. There is some evidence that compound F may be one of them however. There is no direct proof that DCA itself is secreted. Adrenal surgery is performed for several different reasons and in different diseases. In order to understand the therapy employed, certain concepts of the disease must be borne in mind. 1) Total adrenalectomy has been performed for malignant hypertension, prostatic and mammary carcinoma. We have had very little personal experience in this field and I am embarrassed to discuss this in front of Doctors Baker and Harrison since the regimen outlined is taken from their published works. If adrenalectomy is done in two stages, usually no special preparation is necessary for the first stage. The following regimen is usually followed for the second stage or when a bilateral operation is performed at one sitting. Day before operation: The patient is given 200 mg. cortisone intramuscularly, since this will have its greatest effect the following day. On the day of the operation 200 mg. more TABLE
1. Comparison of the active corticosteroids by different assay methods SURVIVAL TEST
COMPOUND
Na
RETENTION
INGLE TEST
ANTI-INSULIN
I ''B" "F" "E" DCA
r
H H
1+ 4+
2+ 0 0
4+
GLYCOGEN DEPOSITION
2+ 4+ 4+
2+ 4+ 4+
3+ 4+ 4+
0
0
0
plus 5 mg. DCA. First day postoperative-200 mg. plus 5 mg. DCA --t cortisone is then tapered off gradually. 2) Adrenalectomy for Cushing's syndrome: It has not been definitely established whether Cushing's syndrome is primarily pituitary or primarily adrenal cortical disease. (In other words, too much ACTH versus too much compound F). However, there is no doubt that the clinical manifestations of the disease are due to excessive corticoid secretion. All the signs and symptoms of the disease have been produced by chronic administration of large doses of cortisone. Therefore, removal of the source of these steroids is a rational approach to therapy in this condition. Cushing's syndrome may be due to an adrenocortical adenoma or carcinoma. When this pathological condition occurs there can be no dispute as to the course of action. It should be borne in mind however that when a tumor exists in the presence of this clinical entity, the contralateral adrenal gland is invariably atrophic; so that if no hormonal preparation is done prior to the removal of the tumor, the surgeon may find himself with an essentially adrenalectomized patient who has just been severely stressed. Such a condition is not compatible with life. The rationale of therapy is replacement with cortisone and DCA for the immediate replacement effect together with ACTH to stimulate the function of that atrophic contralateral gland (table 2).
PRE- AND POSTOPERATIVE CARE IN ADRENAL SURGERY
139
If in the immediate postoperative period, the blood pressure falls, infusions of nor-adrenaline or neo-synephrine and blood should be employed. Serum sodium and potassium levels should be carefully followed and these electrolytes replaced, of course, if their concentrations fall. This is especially so for the K which may be lost in the urine as a result of excessive cortisone replacement therapy. TABLE
Na.
DATE
2. C. R., Cushing's syndrome
K. I
I
Cl.
I
co,
TREATMENT
(mEq/liter)
143.0 144.0 Surgery
2.3 2.6
92.2 93.0
12/13 (a.m.)
144.1
2.1
94.3
12/14 (a.m.) 12/15 12/16 12/17 12/18 12/19 12/20 12/22 12/26
139.0 141.0
2.1 2.6
92.2 96.9
35.1 35.0
141. 7 140.3 142.3 140.6 140.5 141.5
2.5 1. 9 2.2 2.4 2.8 3.5
96.5 93.5
38.7 36.6
99.6 100.0
34.3 30.2
12/10 12/11 12/12
TABLE
39.6 41.8
200 mg. "E" 300 mg. "E"; 5 mg. DCA; 25 mg. ACTH i.v. 200 mg. "E"; 5 mg. DCA; 25 mg. ACTH i.v. 200 mg. "E"; ACTH i.v. 100 mg. "E"; ACTH i.v. 75 mg. "E"; ACTH i.v. 50 mg. "E"; ACTH i.v. 25 mg. "E"; ACTH i.v. 25 mg. "E"; 15 mg. ACTH i.v. 25 mg. "E"; 10 mg. ACTH i.v.
3. Steroidal pre- and postoperative care for adrenalectomy in Cushing's syndrome Preoperative Day 2 200 mg. cortisone l.m. Day 1 200 mg. cortisone l.m. Day of adrenalectomy-100 mg. cortisone early a.m.-5 mg. DCA Postoperative Day 1 200 mg. cortisone 5 mg. DCA Day 2 200 mg. cortisone 5 mg. DCA Day 3 200 mg. cortisone DCA if needed Day 4 150 mg. cortisone DCA if needed Day 5 Gradual tapering of cortisone dosage
Cushing's syndrome is more frequently due to adrenal hyperplasia than neoplasm. Even though in some cases the adrenals may not be enlarged anatomically, there is no doubt of their physiologic over-activity. Occasionally a spontaneous remission may occur. Furthermore, in the series at the Presbyterian Hospital about one-third of the patients have benefited by radiation of the pituitary gland. But apparently it becomes necessary to operate on a good number of these patients. Between 90-100 per cent of the adrenal tissue must be removed in most cases to effect a remission in this condition, otherwise regeneration of the remaining tissue may again result in the disease. The usual routine is to remove 90 per cent of one adrenal and at some future date to do a complete adrenalectomy on the contralateral side. If one side is to
140
JOSEPH W. JAILER
be removed, aside from the usual surgical precautions, no hormonal support is necessary. It must be borne in mind that these patients heal poorly and wounds disrupt easily. We have recently followed three hyperadrenal patients through an uneventful single stage adrenalectomy without any steroidal support. It is with the second stage that we are concerned. As a result of the surgical procedure the patients proceed from a state of hyperadrenalism to one of hypoadrenalism with all the attendant metabolic effects. Therefore, the transformation must be made gradual. Preparation in these cases proceeds as it does in the total adrenalectomy. For two days preoperatively we have given 200 mg. intramuscular cortisone which is continued for several days thereafter, the length of time depending upon the clinical condition as well as the electrolyte and carbohydrate state. Following this, the dose of cortisone is gradually tapered down. Anywhere from 12.5 to 50 mg. a day is needed to maintain the patients. Some may require none at all. DCA is given on the day of operation and the first postoperative day. This is continued only if needed as judged by the concentration of sodium in the serum. This is summarized in table 3. 3) Adrenogenital syndrome: The adrenogenital syndrome or adrenal virilism also concerns the genito-urinary surgeon. Here, too, the cause may be adrenal hyperplasia or neoplasm. Due to the differences in the steroids elaborated by the adrenal in this condition as compared to the Cushing's syndrome the metabolic alterations are not at all similar and the operative procedure is attendant with different problems. The metabolic alterations in CHO, protein and electrolyte spheres are not present. These patients withstand surgery well, heal promptly and are no problem. In our experience, very little or no hormonal support is needed. One word of caution is necessary, and this must be stressed, adrenal carcinoma showing the mixed syndrome, namely elements of both the adrenogenital syndrome and Cushing's, should be handled like the latter. They differ from the true Cushing in that in addition to excessive corticoid secretion the adrenals are elaborating androgens as well. They must be prepared for operation with hormonal support as outlined above. The patients with benign adenomas, on the other hand, require no hormonal support. Being an internist, I should like to close this discussion with a demonstration of how a medical adrenalectomy can be performed. As you know, ACTH stimulates the adrenal cortex and, conversely, cortisone or compound F inhibits the pituitary from secreting more ACTH. Thus, in patients with adrenal virilism due to bilateral adrenal hyperplasia, the administration of cortisone results in an indirect decrease of adrenal secretion and at the same time the substitution of a more normal adrenal steroid for the abnormal ones being elaborated in this syndrome. ·when a carcinoma is present, on the other hand, cortisone is without effect upon the 17-ketosteroids. We have one further piece of evidence to uphold the thesis that adrenal carcinoma is completely independent of pituitary stimulation. One of our patients with an adrenal carcinoma and Cushing's syndrome was subsequently hypophysectomized. This procedure had no effect on the course of the disease nor on the 17-ketosteroids.