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The effect of endocrinectomy on ascites with especial reference to adrenalectomy and thyroidectomy
The Effect of Endocrinectomy on Ascites with Especial Reference to Adrenalectomy and Thyroidectomy IVAN D. BARONOFSKY,
M.D. AND JEROME W. CANTER, M.D., New York, New York
From tbe Department of Surgery, Tbe Mount Sinai Hospital, New York, New York. Tbis work was supported in part by U. S. Public Healtb Service grant No.
demonstrated the presence of an antidiuretic substance in the urine of patients with chronic Iiver disease and stated that the decreased concentration of sodium in the sweat and saIiva of these patients pointed to a genera1 mechanism of sodium retention. More recently, failure of the cirrhotic liver to inactivate aIdosterone, a strongly antidiuretic, sodium-retaining hormone of the adrenal cortex, has been suggested by severa investigators. There is evidence that aIdosterone activity is increased in patients with cirrhosis [5,6]. It seems unIikeIy that a mere increase in venous pressure is soIeIy responsibIe for the sodium retention, by affecting the reabsorption of sodium from the kidney tubuIe. Constriction of the abdominal vena cava beIow the diaphragm faiIs to produce permanent aIterations in sodium excretion despite elevation of renal venous pressure [7,8]. It was reasonable to assume that the saltretaining diathesis was an expression of increased aldosterone activity. It was also understood that this saIt-retaining mechanism was at least an important stage in the causation of wasting ascites whether it be primary or secondary. The probabIe sequence of events in the formation of ascites [g] was first an increase in the hepatic venous pressure folIowed by a shift of sodium and water from the intravascutar compartment to the peritoneal cavity. The adrena cortex is then stimulated to excrete more aIdosterone which, in turn, is not inactivated by the diseased liver and causes further retention of sodium and water. With the preceding in mind, it was specuIated that if elimination of aldosterone couId be
A-1717.
UCH intensive cIinicaI and experimental work has been undertaken in the past in an effort to eIucidate the cause of cirrhotic ascites. The folIowing etiologic mechanisms have, in generaI, been suggested: (I) porta hypertension; (2) liver damage resuIting in: (a) hypoproteinemia which causes a Iowering of the oncotic pressure within the intravascuIar compartment and, therefore, a transudation of ffuid into the peritonea1 cavity, (b) possibIe inactivation of the pituitary antidiuretic hormone, (c) either decreased inactivation or increased secretion of aIdosterone, (d) sodium retention as a resuIt of the previously mentioned aIterations, or (e) Iymphatic obstruction in the face of increased hepatic lymph production; and (3) forward failure of the heart.
M
ADRENAL
FACTOR IN ASCITES
Experimental and Laboratory Evidence. In recent years much interest has been focused on the sodium retention mechanism of ascites formation. It has been shown that the patient with cirrhosis has a marked inability to excrete sodium and that whatever the fundamental mechanism might be, it was probabIy the same in the patient with cirrhosis and cardiac disease [r-3]. Restriction of saIt wiI1 frequentIy bring about an ameIioration of the ascitic accumuIation. In the patient with wasting ascites it is, at times, not possibIe to control ascites formation with salt and water restriction alone. In 1951 Bongiovanni and Eisenmenger [4] American
Journal
of Surgery.
Volume
gg, April,
1960
3’2
Effect of Endocrinectomy TABLE METABOLIC
STUDY
OF DOGS
IN
CHRONIC
SUBTOTAL
Dog No.
Before.......................... After. Before, 2 1 After, Before 3 I After. Before.......................... 4 After. r
Water Intake (cc./24 hr.)
on Ascites
I* HEART
FAILURE
BEFORE
AND
AFTER
ADRENALECTOMY
Urinary Sodium (gm./24 hr.)
Urine output
(cc./24 hr.)
1,607 I.333
1,825 I ,677 1,261
1,489 2,655
132 329 355 479 198 468 1,443
Right Atria1 Pressure (mm. Hg)
PIasma Proteins (gm. %)
0.2
+9
2.97 I.5 I.96
+9
3.1 5.8 5.7 6.55 0.7 3.5 2.42 6.7 0.46 -3.9 r ed before adrenalectomy
I
I
Weight (Ib.)
+9
47.8 38.2 46.8 44.9
+10 +11.5
Z’”
+I5
50
fro
I
* FROM: SPRAFKA, J. L., HANNON, D. W. and BARONOFSKY, I. D. [IO].
ascites for many years. The maIe was fifty years oId; the female, thirty-eight years old. Liver function studies in both showed decreased Iiver function of moderate to severe degree. Because of the intractabiIity of the ascites (multiple paracenteses, etc.), biIatera1 adrenalectomy was elected as the procedure of choice. FoJIowing adrenaIectomy, the first patient has continued to do we11 three years foIIowing the initia1 surgery. On one occasion, about three months foIIowing discharge from the hospita1, he was readmitted because of a reaccumulation of a smaI1 amount of ascites folIowing the ingestion of a large amount of saIt contained in ham and bacon. The patient’s course, at that time, was remarkable in that the ascites cIeared very readiIy in a matter of four or five days on a diet of 500 mg. of sodium aIone. This was impossibIe prior to adrenalectomy. He was discharged on a reguIar saIt diet. The second patient died in hepatic coma two years folIowing surgery. She had returned to drinking heaviIy but appeared very we11 with no apparent ascites. She suddenIy became psychotic, had several episodes of deIirium tremens and was admitted to a psychiatric hospita1 where she continued to have the attacks. WhiIe there she became markedIy jaundiced and died in hepatic coma. Before the preceding episode the patient had been doing very weI1. A urinary determination showed no aIdosterone present in the urine. She was on a regular diet, with salt as desired, had no evidence of ascites and Iiver function was approaching normaI. It is important to note that in both patients
obtained with adrenaIectomy, a therapeutic breakthrough in the cycIe would be obtained. This point has been investigated by Sprafka and his group [IO] and Davis et aI. [II]. They have shown that controI of experimental ascites couId be definitely obtained when the adrena glands were removed. As a matter of fact, subtota1 adrenaIectomy was used by Baronofsky et al. and the ascites was controIIed without repIacement therapy. TeweII and Freeman [12] have shown in anima1 experiments that adrenalectomy and hypophysectomy cause reduced excretion of corticoids and that these were probably of adrenal origin. Hamilton [13] has stated that ascites occurring in dogs with mitra1 stenosis can be reversed with adrenalectomy. Clinical Approach. CIinicaIIy we have been unimpressed with the medica management of intractabIe ascites due to cirrhosis. AIthough most patients with ascites can and should be managed medicaIIy, it is this intractabIe group who require special attention. Continued remova1 of fluid from the abdomen eventuaIIy drains the patient of much protein necessary for body function. This is as maIignant as a malignant tumor. It will cause the patient’s death. Therefore, when confronted with two patients with intractabIe ascites, we eIected to treat these patients with biIatera1 adrenaIectomy. Previous to the surgica1 treatment of these two patients, Marson [r4] and subsequentIy Guiseffi et al. [15] had reported simiIar experiences with two patients. In summary, both patients [16] were aIcohoIics and had been receiving therapy for
5’3
Baronofsky
and Canter
L.C.
-I
zoooo ,,Qoa-
CUTPVT
+
FIG. I. CASES I (top) and II (bottom). Urinary volume, sodium, chIoride and potassium excretions before and after tota adrenalectomy for ascites. The arrows point to the days on which adrenaIectomy was performed as part of a two-stage procedure. Note the increase in all eIectroIyte excretions foIIowing the second stage adrenakctomy.
mentioned that such patients can and will accumuIate sodium if it is avaiIabIe to the body in more than the usua1 amounts ingested in a reguIar diet. These patients differ in this respect
an increase in the urinary sodium excretion was noted folIowing adrenaIectomy. (Fig. I.) This undoubtedIy was reIated to the absence of circulating aIdosterone. However, it must be 5’4
Effect of Endocrinectomy
on Ascites
EXCRETION YEWOAY
u)
URINE SODIUM EXCRETION MEQ./DAY
s, 30
.s 40 3, 30
___-________-___-------
2s 10 1, 10 5
4 IVC
CONSTRICTION
THYROIDECTOMY 0 AYS
DaiIy urinary sodium excretion, weight and measurement of abdominal girth in two animaIs who had complete relief of ascites folIowing thryoidectomy. Top, graph includes studies before the production of ascites; bottom, graph does not. FIG.
from
those
2.
having
adrenaIectomy
and extraperitonea1 exposure of the gland. The approach to the gland is exactIy the same as the approach to the kidney. C,Freful hemostasis is observed throughout. Dramage of the retroperitonea1 area is obtained by the use of soft rubber drains. They are usuaIIy removed on about the third or fourth day.
for cancer
[171.
Surgical Considerations. We have preferred bilateral staged tota adrenaIectomy. This staged procedure is accomplished with about a ten-day interva1 between stages. A IateraI decubitus position is preferred with Ioin incision 5’5
Baronofsky and Canter I
WITH
ASCITES
POST
THYROIDECTOMY
DOGS
FIG. 3. The effect of thyroidectomy on urinary sodium excretion. The bIack bars represent the average value for the two-week period immediateIy prior to thyroidectomy; the crosshatched bars represent the average vaIue for the twoweek period from the seventh to the twenty-first day foIIowing thyroidectomy.
URINE SODIUM EXCRETION YEP./DAY
FIG. 4. DaiIy urinary sodium excretion, weight and measurements of abdominal girth in an animal who had compIete reIief of ascites foIIowing thyroidectomy and in whom thyroid extract was subsequentIy started. Note retention of sodium and increase in ascites foIIowing administration of extract.
PreoperativeIy the patient is given 300 mg. of cortisone daiIy for four days. This is continued between stages. FoIIowing the second stage the dosage of cortisone is sIowIy decreased over a period of thirty days to 25 mg. per day and adjusted more or Iess depending on eIectroIyte studies and physica needs. Both
patients mentioned in the reports have been maintained on 12.5 mg. per day and the onIy saIt restriction made is to use saIt in moderation. We shouId Iike to emphasize the benignity of the patient’s course during surgery and postoperativeIy, and therefore are in great favor of this two-stage procedure. Food is aIIowed on 5’6
Effect of Endocrinectomy the second postoperative day and continued thereon. The diet, which at first is a continuation of the Iow saIt diet, is graduatly changed over a period of thirty days to a reguIar diet with littIe or no saIt restriction. We have utilized paracentesis preoperativley to faciIitate anesthesia, which couId be hindered by the presence of an elevated diaphragm. THYROID
FACTOR
IN
on Ascites
__--
_-_--_------INTAKE
i
ASCITES
In our Iaboratory an attempt has been made to evaluate the effect of thyroidectomy on ascites formation [r&19]. Certain relationships between the thyroid and adrena gIands have been known to exist [20]. BaIance studies were accurateIy performed on a series of dogs before, during and after the creation of ascites by supradiaphragmatic constriction of the inferior vena cava. These studies were repeated foIIowing thyroidectomy and in some instances foIlowing addition of thyroid extract to the diet. These animals were maintained on a constant sodium intake. Five dogs were subjected to a sham operation when ascites was attained. These animals were anesthetized as for thyroidectomy, the neck was opened and the thyroid gIands exposed, but their blood suppIy was not disturbed. FoIIowing the sham operation, the metabolic observations were resumed. The resuIts indicated a marked response of the ascites to biIatera1 tota thyroidectomy. Sixteen of twenty dogs subjected to this operation responded with significant ameIioration of their ascites. In thirteen of these animaIs the ascites was no Ionger detectabIe within one month foIIowing thyroidectomy. The clinica improvement was accompanied by a striking increase in urinary sodium and water excretion, which became maxima1 during the second and third week following thyroidectomy. (Figs. 2 and 3.) Three other dogs retained minima1 ascites but exhibited an appreciabIe diminution in the amount of abdominal Auid folIowing thyroidectomy. Four animals responded to thyroidectomy with natruresis but did not achieve negative sodium baIance. ConsequentIy, there was no significant change in the amount of their ascites. Six animaIs who became clinicaIIy free of ascites folIowing thyroidectomy were given thyroid extract in addition to their daiIy ration of food. These dogs graduaIIy reaccumuIated
DOGS
FIG. 5. The effect of a sham operation on urinary sodium excretion. The crosshatched bars represent the average vaIue for the two-week period immediately prior to the sham operation; the dotted bars represent the average vaIue for the two-week period from the seventh to the twenty-first day folIowing the sham operation.
cIinicaIIy apparent ascites, without further constriction of the inferior vena cava. When the thyroid extract was discontinued, the ascites promptIy cIeared. (Fig. 4.) Of five dogs undergoing sham operations, three had no significant change in their ascites foIIowing this procedure, and two dogs continued to accumuIate ascites foIIowing the sham procedure. (Fig. 5.) In four thyroidectomized animals, serial aIdosterone IeveIs were determined. There was a faII to normaI range folIowing thyroidectomy concomitant with improvement in the ascites. COMMENTS
The mechanism for the aforementioned observation is not clear at the present time. The fact that the disappearance of the ascites does not represent a spontaneous one is supported by the Iack of response of the dogs undergoing sham operations after an equal passage of time. The thyroid-adrenal interreIationship to aIdosterone has aIready been mentioned [20]. Recently evidence has been put forth that voIume receptors are important in the reguIation of ardosterone secretion and that experimenta1 ascites may be improved by thyrocarotid denervation [21]. It may be possibIe that during thyroidectomy this nerve may be injured and, therefore, ascites is ameliorated. However, recent evidence from our Iaboratory [22] would indicate that this is not the case. Autografting of the thyroid to the rectus muscle does not ameIiorate ascites. If the nerve were 5’7
Baronofsky
and Canter
the important structure, then even the autograft shouId be effective in causing iI decrease in ascites. REFERENCES
compounds in the blood. Relation of their quantity to arteria1 hypertension, renal insuffrciency and congestive heart faiIure. Arch. Int. Med., 68: 713, rg4r. 2. (a) FARNSWORTH, E. B. and KRAKUSIN, J. S. Electrolyte partition in patients with edema of various origins. Quahtative and quantitative definition of cations and anions in cardiac decompensation. J. Lab. &+ Clin. Med., 33: 1534,
IO.
I. RAA~, W. Adrenocortical
1948. (b) FARNSWORTH, E. B. and KRAKUSIN, J. S. EIectroIyte partition in patients with edema of various origins. Qualitative and quantitative definition of cations and anions in hepatic cirrhosis. J. Lab. r~ Clin. Med., 33: 1545, 1948. 3. DAVIS, J. O., PECHET, M. M., BALL, W. C., JR. and GOODKIND, M. J. Increased aldosterone secretion in dogs with right-sided congestive heart failure and in dogs with thoracic inferior vena cava constriction. J. Clin. Invest., 35: 689, 1957. 4. BONGIOVANNI, A. M. and EISEWMENGER, W. J. AdrenaI cortical metabolism in chronic liver disease. J. Clin. Endocrinol., I I : 152, 1951. 5. LEUTSCHER,J. A., JR. and JOHNSON,B. B. Observations on sodium-retaining corticoid (aIdosterone) in urine of children and ad&s in &ation to sodium batance and edema. J. Clin. Invest., 33: 1441. 1954. 6. LOBOTSKY, J., HANNGE, J. B. and LLOYD, C. W. Intravenous administration of aldosterone in adrenaIectomized rat as method of assay. J. Clin. Endocrinol., 15: 888, 1955. 7. (a) HOFFBAUER, F. W., BOLLMAN, J. L. and GRINDLAY, J. H. Factors influencing pressures in the portal vein as studied in the intact animal. Gustroenterology, 16: 194, 1950. (b) HWANG, W., AKMAN, L. C., MILLER, A. J., SILBER, E. N., STAMLER, J. and KATZ, L. N. Effects of sustained eIevation of renal venous pressure on sodium excretion in unanesthetized dogs. Am. J. Pbysiol., 162: 649, 1950. 8. STAMLER, J., GOLDBERG, H., GORDON, A., WEINSHEL, M., RUBENSTEIN, L. and KATZ, L. N. Further studies on the reIationship of eIevated renal venous pressure to edema formation and renal clearances of sodium in dogs. J. Lab. FY Clin. Med., 36: 992, 1950. g. BALL, W. C., JR., DAVIS, J. 0. and GOODKIND,M. J.
II.
12.
13.
Ascites formation without sodium intake in dogs with thoracic inferior vena cava constriction and dogs with right-sided congestive heart faiIure. Am. J. Pbysiol., 188: 578, 1957. SPRAFKA, J. L., HANNON, D. W. and BARONOFSKY, I. D. The effect of subtotal adrenalectomy upon the deveIopment of ascites in chronic heart failure. S. Forum, 5: 143, 1955. DAVIS, J. O., HOWELL, D. S. and SOUTHWORTH, J. A. Mechanisms of fluid and eIectroIyte retention in experimenta preparations in dogs. III. Effect of adrenaIectomy and subsequent desoxycorticosterone acetate administration of ascites formation. Circulation Res., I : 260, 1953. TEWELL, H. E., JR. and FREEMAN, S. Urinary excretion of corticosteroids and neutral 17-ketosteroids in aduIt femaIe dogs. Proc. Sot. Exper. Biol. TVMed., 85: 125, 1954. HAMILTON, W. F. The physioIogy of congestive failure of the circuIation. Minnesota Med., 37:
36, ‘954. 14. MARSON, F. G. TotaI adrenaIectomy in hepatic cirrhosis with ascites: preliminary communication. Lancer, 2: 847, 1954. 15. GIUSEFFI, J., WECK, E. E., JR., LARSON, P. V., SCHIFF, L. and ELLIOT, D. W. Effect of biIatera1 adrenaIectomy in a patient with massive ascites and postnecrotic cirrhosis, New England J. Med., 257: 796, 1957. 16. BARONOFSKY, I. D., FAUCETT, R. E. and WEISS, H. A. Total adrenalectomv in the treatment of intractable ascites. J. A. G. A., 172: 231, rg6o. 17. MENDELSOHN, M. L. and PEARSON, 0. H. AIterations in water and salt metabolism after biIatera1 adrenaIectomy in man. J. Clin. Endocrinol., 15: 4og, ‘955. 18. CANTER, J. W., KREEL, I., SEGAL, R. L., FRANKEL, A. and BARONOFSKY.I. D. Inffuence of thvroidectomy on experimental ascites. Proc. Sot. Exper. Biol. @ Med., IOO: 771, 1959. rg. KREEL, I., CANTER, J. W., SEGAL, R. L., FRANKEL, A. and BARONOFSKY, I. D. The inffuence of thyroidectomy on experimenta ascites. S. Forum, in press. 20. LEVIN, M. E. and DAUGHADAY, W. H. The inffuence of the thyroid on adrenocortica1 function. J. CZin Endocrinol., 15: 1499, 1955. 21. BARTTER, F. C., MILLS, I. H. and GANN, D. S. Increase of aIdosterone secretion by carotid artery constriction and its prevention by thyrocarotid arteria1 junction denervation (Abstr.). J. Clin. Invest., 38: 986, 1959. 22. POLL, M., SEITCHIK, M. W., KOMRAD, E., CANTER, J. W. and BARONOFSKY, I. D. Unpublished observations.
M.D. AND JEROME W. CANTER, M.D., New York, New York
From tbe Department of Surgery, Tbe Mount Sinai Hospital, New York, New York. Tbis work was supported in part by U. S. Public Healtb Service grant No.
demonstrated the presence of an antidiuretic substance in the urine of patients with chronic Iiver disease and stated that the decreased concentration of sodium in the sweat and saIiva of these patients pointed to a genera1 mechanism of sodium retention. More recently, failure of the cirrhotic liver to inactivate aIdosterone, a strongly antidiuretic, sodium-retaining hormone of the adrenal cortex, has been suggested by severa investigators. There is evidence that aIdosterone activity is increased in patients with cirrhosis [5,6]. It seems unIikeIy that a mere increase in venous pressure is soIeIy responsibIe for the sodium retention, by affecting the reabsorption of sodium from the kidney tubuIe. Constriction of the abdominal vena cava beIow the diaphragm faiIs to produce permanent aIterations in sodium excretion despite elevation of renal venous pressure [7,8]. It was reasonable to assume that the saltretaining diathesis was an expression of increased aldosterone activity. It was also understood that this saIt-retaining mechanism was at least an important stage in the causation of wasting ascites whether it be primary or secondary. The probabIe sequence of events in the formation of ascites [g] was first an increase in the hepatic venous pressure folIowed by a shift of sodium and water from the intravascutar compartment to the peritoneal cavity. The adrena cortex is then stimulated to excrete more aIdosterone which, in turn, is not inactivated by the diseased liver and causes further retention of sodium and water. With the preceding in mind, it was specuIated that if elimination of aldosterone couId be
A-1717.
UCH intensive cIinicaI and experimental work has been undertaken in the past in an effort to eIucidate the cause of cirrhotic ascites. The folIowing etiologic mechanisms have, in generaI, been suggested: (I) porta hypertension; (2) liver damage resuIting in: (a) hypoproteinemia which causes a Iowering of the oncotic pressure within the intravascuIar compartment and, therefore, a transudation of ffuid into the peritonea1 cavity, (b) possibIe inactivation of the pituitary antidiuretic hormone, (c) either decreased inactivation or increased secretion of aIdosterone, (d) sodium retention as a resuIt of the previously mentioned aIterations, or (e) Iymphatic obstruction in the face of increased hepatic lymph production; and (3) forward failure of the heart.
M
ADRENAL
FACTOR IN ASCITES
Experimental and Laboratory Evidence. In recent years much interest has been focused on the sodium retention mechanism of ascites formation. It has been shown that the patient with cirrhosis has a marked inability to excrete sodium and that whatever the fundamental mechanism might be, it was probabIy the same in the patient with cirrhosis and cardiac disease [r-3]. Restriction of saIt wiI1 frequentIy bring about an ameIioration of the ascitic accumuIation. In the patient with wasting ascites it is, at times, not possibIe to control ascites formation with salt and water restriction alone. In 1951 Bongiovanni and Eisenmenger [4] American
Journal
of Surgery.
Volume
gg, April,
1960
3’2
Effect of Endocrinectomy TABLE METABOLIC
STUDY
OF DOGS
IN
CHRONIC
SUBTOTAL
Dog No.
Before.......................... After. Before, 2 1 After, Before 3 I After. Before.......................... 4 After. r
Water Intake (cc./24 hr.)
on Ascites
I* HEART
FAILURE
BEFORE
AND
AFTER
ADRENALECTOMY
Urinary Sodium (gm./24 hr.)
Urine output
(cc./24 hr.)
1,607 I.333
1,825 I ,677 1,261
1,489 2,655
132 329 355 479 198 468 1,443
Right Atria1 Pressure (mm. Hg)
PIasma Proteins (gm. %)
0.2
+9
2.97 I.5 I.96
+9
3.1 5.8 5.7 6.55 0.7 3.5 2.42 6.7 0.46 -3.9 r ed before adrenalectomy
I
I
Weight (Ib.)
+9
47.8 38.2 46.8 44.9
+10 +11.5
Z’”
+I5
50
fro
I
* FROM: SPRAFKA, J. L., HANNON, D. W. and BARONOFSKY, I. D. [IO].
ascites for many years. The maIe was fifty years oId; the female, thirty-eight years old. Liver function studies in both showed decreased Iiver function of moderate to severe degree. Because of the intractabiIity of the ascites (multiple paracenteses, etc.), biIatera1 adrenalectomy was elected as the procedure of choice. FoJIowing adrenaIectomy, the first patient has continued to do we11 three years foIIowing the initia1 surgery. On one occasion, about three months foIIowing discharge from the hospita1, he was readmitted because of a reaccumulation of a smaI1 amount of ascites folIowing the ingestion of a large amount of saIt contained in ham and bacon. The patient’s course, at that time, was remarkable in that the ascites cIeared very readiIy in a matter of four or five days on a diet of 500 mg. of sodium aIone. This was impossibIe prior to adrenalectomy. He was discharged on a reguIar saIt diet. The second patient died in hepatic coma two years folIowing surgery. She had returned to drinking heaviIy but appeared very we11 with no apparent ascites. She suddenIy became psychotic, had several episodes of deIirium tremens and was admitted to a psychiatric hospita1 where she continued to have the attacks. WhiIe there she became markedIy jaundiced and died in hepatic coma. Before the preceding episode the patient had been doing very weI1. A urinary determination showed no aIdosterone present in the urine. She was on a regular diet, with salt as desired, had no evidence of ascites and Iiver function was approaching normaI. It is important to note that in both patients
obtained with adrenaIectomy, a therapeutic breakthrough in the cycIe would be obtained. This point has been investigated by Sprafka and his group [IO] and Davis et aI. [II]. They have shown that controI of experimental ascites couId be definitely obtained when the adrena glands were removed. As a matter of fact, subtota1 adrenaIectomy was used by Baronofsky et al. and the ascites was controIIed without repIacement therapy. TeweII and Freeman [12] have shown in anima1 experiments that adrenalectomy and hypophysectomy cause reduced excretion of corticoids and that these were probably of adrenal origin. Hamilton [13] has stated that ascites occurring in dogs with mitra1 stenosis can be reversed with adrenalectomy. Clinical Approach. CIinicaIIy we have been unimpressed with the medica management of intractabIe ascites due to cirrhosis. AIthough most patients with ascites can and should be managed medicaIIy, it is this intractabIe group who require special attention. Continued remova1 of fluid from the abdomen eventuaIIy drains the patient of much protein necessary for body function. This is as maIignant as a malignant tumor. It will cause the patient’s death. Therefore, when confronted with two patients with intractabIe ascites, we eIected to treat these patients with biIatera1 adrenaIectomy. Previous to the surgica1 treatment of these two patients, Marson [r4] and subsequentIy Guiseffi et al. [15] had reported simiIar experiences with two patients. In summary, both patients [16] were aIcohoIics and had been receiving therapy for
5’3
Baronofsky
and Canter
L.C.
-I
zoooo ,,Qoa-
CUTPVT
+
FIG. I. CASES I (top) and II (bottom). Urinary volume, sodium, chIoride and potassium excretions before and after tota adrenalectomy for ascites. The arrows point to the days on which adrenaIectomy was performed as part of a two-stage procedure. Note the increase in all eIectroIyte excretions foIIowing the second stage adrenakctomy.
mentioned that such patients can and will accumuIate sodium if it is avaiIabIe to the body in more than the usua1 amounts ingested in a reguIar diet. These patients differ in this respect
an increase in the urinary sodium excretion was noted folIowing adrenaIectomy. (Fig. I.) This undoubtedIy was reIated to the absence of circulating aIdosterone. However, it must be 5’4
Effect of Endocrinectomy
on Ascites
EXCRETION YEWOAY
u)
URINE SODIUM EXCRETION MEQ./DAY
s, 30
.s 40 3, 30
___-________-___-------
2s 10 1, 10 5
4 IVC
CONSTRICTION
THYROIDECTOMY 0 AYS
DaiIy urinary sodium excretion, weight and measurement of abdominal girth in two animaIs who had complete relief of ascites folIowing thryoidectomy. Top, graph includes studies before the production of ascites; bottom, graph does not. FIG.
from
those
2.
having
adrenaIectomy
and extraperitonea1 exposure of the gland. The approach to the gland is exactIy the same as the approach to the kidney. C,Freful hemostasis is observed throughout. Dramage of the retroperitonea1 area is obtained by the use of soft rubber drains. They are usuaIIy removed on about the third or fourth day.
for cancer
[171.
Surgical Considerations. We have preferred bilateral staged tota adrenaIectomy. This staged procedure is accomplished with about a ten-day interva1 between stages. A IateraI decubitus position is preferred with Ioin incision 5’5
Baronofsky and Canter I
WITH
ASCITES
POST
THYROIDECTOMY
DOGS
FIG. 3. The effect of thyroidectomy on urinary sodium excretion. The bIack bars represent the average value for the two-week period immediateIy prior to thyroidectomy; the crosshatched bars represent the average vaIue for the twoweek period from the seventh to the twenty-first day foIIowing thyroidectomy.
URINE SODIUM EXCRETION YEP./DAY
FIG. 4. DaiIy urinary sodium excretion, weight and measurements of abdominal girth in an animal who had compIete reIief of ascites foIIowing thyroidectomy and in whom thyroid extract was subsequentIy started. Note retention of sodium and increase in ascites foIIowing administration of extract.
PreoperativeIy the patient is given 300 mg. of cortisone daiIy for four days. This is continued between stages. FoIIowing the second stage the dosage of cortisone is sIowIy decreased over a period of thirty days to 25 mg. per day and adjusted more or Iess depending on eIectroIyte studies and physica needs. Both
patients mentioned in the reports have been maintained on 12.5 mg. per day and the onIy saIt restriction made is to use saIt in moderation. We shouId Iike to emphasize the benignity of the patient’s course during surgery and postoperativeIy, and therefore are in great favor of this two-stage procedure. Food is aIIowed on 5’6
Effect of Endocrinectomy the second postoperative day and continued thereon. The diet, which at first is a continuation of the Iow saIt diet, is graduatly changed over a period of thirty days to a reguIar diet with littIe or no saIt restriction. We have utilized paracentesis preoperativley to faciIitate anesthesia, which couId be hindered by the presence of an elevated diaphragm. THYROID
FACTOR
IN
on Ascites
__--
_-_--_------INTAKE
i
ASCITES
In our Iaboratory an attempt has been made to evaluate the effect of thyroidectomy on ascites formation [r&19]. Certain relationships between the thyroid and adrena gIands have been known to exist [20]. BaIance studies were accurateIy performed on a series of dogs before, during and after the creation of ascites by supradiaphragmatic constriction of the inferior vena cava. These studies were repeated foIIowing thyroidectomy and in some instances foIlowing addition of thyroid extract to the diet. These animals were maintained on a constant sodium intake. Five dogs were subjected to a sham operation when ascites was attained. These animals were anesthetized as for thyroidectomy, the neck was opened and the thyroid gIands exposed, but their blood suppIy was not disturbed. FoIIowing the sham operation, the metabolic observations were resumed. The resuIts indicated a marked response of the ascites to biIatera1 tota thyroidectomy. Sixteen of twenty dogs subjected to this operation responded with significant ameIioration of their ascites. In thirteen of these animaIs the ascites was no Ionger detectabIe within one month foIIowing thyroidectomy. The clinica improvement was accompanied by a striking increase in urinary sodium and water excretion, which became maxima1 during the second and third week following thyroidectomy. (Figs. 2 and 3.) Three other dogs retained minima1 ascites but exhibited an appreciabIe diminution in the amount of abdominal Auid folIowing thyroidectomy. Four animals responded to thyroidectomy with natruresis but did not achieve negative sodium baIance. ConsequentIy, there was no significant change in the amount of their ascites. Six animaIs who became clinicaIIy free of ascites folIowing thyroidectomy were given thyroid extract in addition to their daiIy ration of food. These dogs graduaIIy reaccumuIated
DOGS
FIG. 5. The effect of a sham operation on urinary sodium excretion. The crosshatched bars represent the average vaIue for the two-week period immediately prior to the sham operation; the dotted bars represent the average vaIue for the two-week period from the seventh to the twenty-first day folIowing the sham operation.
cIinicaIIy apparent ascites, without further constriction of the inferior vena cava. When the thyroid extract was discontinued, the ascites promptIy cIeared. (Fig. 4.) Of five dogs undergoing sham operations, three had no significant change in their ascites foIIowing this procedure, and two dogs continued to accumuIate ascites foIIowing the sham procedure. (Fig. 5.) In four thyroidectomized animals, serial aIdosterone IeveIs were determined. There was a faII to normaI range folIowing thyroidectomy concomitant with improvement in the ascites. COMMENTS
The mechanism for the aforementioned observation is not clear at the present time. The fact that the disappearance of the ascites does not represent a spontaneous one is supported by the Iack of response of the dogs undergoing sham operations after an equal passage of time. The thyroid-adrenal interreIationship to aIdosterone has aIready been mentioned [20]. Recently evidence has been put forth that voIume receptors are important in the reguIation of ardosterone secretion and that experimenta1 ascites may be improved by thyrocarotid denervation [21]. It may be possibIe that during thyroidectomy this nerve may be injured and, therefore, ascites is ameliorated. However, recent evidence from our Iaboratory [22] would indicate that this is not the case. Autografting of the thyroid to the rectus muscle does not ameIiorate ascites. If the nerve were 5’7
Baronofsky
and Canter
the important structure, then even the autograft shouId be effective in causing iI decrease in ascites. REFERENCES
compounds in the blood. Relation of their quantity to arteria1 hypertension, renal insuffrciency and congestive heart faiIure. Arch. Int. Med., 68: 713, rg4r. 2. (a) FARNSWORTH, E. B. and KRAKUSIN, J. S. Electrolyte partition in patients with edema of various origins. Quahtative and quantitative definition of cations and anions in cardiac decompensation. J. Lab. &+ Clin. Med., 33: 1534,
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1948. (b) FARNSWORTH, E. B. and KRAKUSIN, J. S. EIectroIyte partition in patients with edema of various origins. Qualitative and quantitative definition of cations and anions in hepatic cirrhosis. J. Lab. r~ Clin. Med., 33: 1545, 1948. 3. DAVIS, J. O., PECHET, M. M., BALL, W. C., JR. and GOODKIND, M. J. Increased aldosterone secretion in dogs with right-sided congestive heart failure and in dogs with thoracic inferior vena cava constriction. J. Clin. Invest., 35: 689, 1957. 4. BONGIOVANNI, A. M. and EISEWMENGER, W. J. AdrenaI cortical metabolism in chronic liver disease. J. Clin. Endocrinol., I I : 152, 1951. 5. LEUTSCHER,J. A., JR. and JOHNSON,B. B. Observations on sodium-retaining corticoid (aIdosterone) in urine of children and ad&s in &ation to sodium batance and edema. J. Clin. Invest., 33: 1441. 1954. 6. LOBOTSKY, J., HANNGE, J. B. and LLOYD, C. W. Intravenous administration of aldosterone in adrenaIectomized rat as method of assay. J. Clin. Endocrinol., 15: 888, 1955. 7. (a) HOFFBAUER, F. W., BOLLMAN, J. L. and GRINDLAY, J. H. Factors influencing pressures in the portal vein as studied in the intact animal. Gustroenterology, 16: 194, 1950. (b) HWANG, W., AKMAN, L. C., MILLER, A. J., SILBER, E. N., STAMLER, J. and KATZ, L. N. Effects of sustained eIevation of renal venous pressure on sodium excretion in unanesthetized dogs. Am. J. Pbysiol., 162: 649, 1950. 8. STAMLER, J., GOLDBERG, H., GORDON, A., WEINSHEL, M., RUBENSTEIN, L. and KATZ, L. N. Further studies on the reIationship of eIevated renal venous pressure to edema formation and renal clearances of sodium in dogs. J. Lab. FY Clin. Med., 36: 992, 1950. g. BALL, W. C., JR., DAVIS, J. 0. and GOODKIND,M. J.
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Ascites formation without sodium intake in dogs with thoracic inferior vena cava constriction and dogs with right-sided congestive heart faiIure. Am. J. Pbysiol., 188: 578, 1957. SPRAFKA, J. L., HANNON, D. W. and BARONOFSKY, I. D. The effect of subtotal adrenalectomy upon the deveIopment of ascites in chronic heart failure. S. Forum, 5: 143, 1955. DAVIS, J. O., HOWELL, D. S. and SOUTHWORTH, J. A. Mechanisms of fluid and eIectroIyte retention in experimenta preparations in dogs. III. Effect of adrenaIectomy and subsequent desoxycorticosterone acetate administration of ascites formation. Circulation Res., I : 260, 1953. TEWELL, H. E., JR. and FREEMAN, S. Urinary excretion of corticosteroids and neutral 17-ketosteroids in aduIt femaIe dogs. Proc. Sot. Exper. Biol. TVMed., 85: 125, 1954. HAMILTON, W. F. The physioIogy of congestive failure of the circuIation. Minnesota Med., 37:
36, ‘954. 14. MARSON, F. G. TotaI adrenaIectomy in hepatic cirrhosis with ascites: preliminary communication. Lancer, 2: 847, 1954. 15. GIUSEFFI, J., WECK, E. E., JR., LARSON, P. V., SCHIFF, L. and ELLIOT, D. W. Effect of biIatera1 adrenaIectomy in a patient with massive ascites and postnecrotic cirrhosis, New England J. Med., 257: 796, 1957. 16. BARONOFSKY, I. D., FAUCETT, R. E. and WEISS, H. A. Total adrenalectomv in the treatment of intractable ascites. J. A. G. A., 172: 231, rg6o. 17. MENDELSOHN, M. L. and PEARSON, 0. H. AIterations in water and salt metabolism after biIatera1 adrenaIectomy in man. J. Clin. Endocrinol., 15: 4og, ‘955. 18. CANTER, J. W., KREEL, I., SEGAL, R. L., FRANKEL, A. and BARONOFSKY.I. D. Inffuence of thvroidectomy on experimental ascites. Proc. Sot. Exper. Biol. @ Med., IOO: 771, 1959. rg. KREEL, I., CANTER, J. W., SEGAL, R. L., FRANKEL, A. and BARONOFSKY, I. D. The inffuence of thyroidectomy on experimenta ascites. S. Forum, in press. 20. LEVIN, M. E. and DAUGHADAY, W. H. The inffuence of the thyroid on adrenocortica1 function. J. CZin Endocrinol., 15: 1499, 1955. 21. BARTTER, F. C., MILLS, I. H. and GANN, D. S. Increase of aIdosterone secretion by carotid artery constriction and its prevention by thyrocarotid arteria1 junction denervation (Abstr.). J. Clin. Invest., 38: 986, 1959. 22. POLL, M., SEITCHIK, M. W., KOMRAD, E., CANTER, J. W. and BARONOFSKY, I. D. Unpublished observations.