Results of surgical treatment for hyperadrenocorticism caused by adrenocortical neoplasia in the dog: 25 cases (1980-1984)
Thomas D. Scavelli, DVM; Mark E. Peterson, DVM; David T. Matthiesen, DVM
SUMMARY
Results of surgical treatment for neoplasia of the adrenal cortex that caused hyperadrenocorticism were evaluated in 25 dogs. Surgical examination of the adrenal glands was performed by use of a ventral midline approach in 24 dogs and a retroperitoneal approach in 1 dog. All 25 dogs had a unilateral, adrenocortical tumor. Histologic examination identi- fied 14 adrenocortical carcinomas and 11 adenomas. Seven dogs with carcinoma had visible metastasis to the liver, 3 had local invasion into the caudal vena cava, and 1 had extension into the adjacent renal vein. Seven of the 9 dogs with metastasis were eu- thanatized at time of surgery. Of the remaining 18 dogs that survived surgery, 9 (4 with carcinoma and 5 with adenoma) developed serious postoperative com- plications including acute renal failure, pneumonia, and pulmonary artery thromboembolism; 8 of these dogs died or were euthanatized. Of the remaining 10 dogs, clinical signs associated with hyperadrenocor- ticism resolved in the 7 dogs that had adrenocortical adenoma and in 1 of the 3 dogs that had carcinoma. The remaining 2 dogs with carcinoma had persistent hyperadrenocorticism and were treated with high doses of mitotane. Although no response was ob- served in 1 dog with visible hepatic metastasis, a decrease in serum cortisol concentrations and resolu- tion of clinical signs were detected in the other dog during prolonged daily administration of mitotane.
ADRENOCORTICAL NEOPLASIA is the underlying cause of hyperadrenocorticism (Cushing’s syndrome) in 10% to 20% of the dogs affected with the disorder.1-3 Although the clinical findings, diagnosis, and gen- eral management of dogs with hyperadrenocorticism caused by adrenal neoplasia have been discussed,1-5
the results of surgical management and postopera- tive follow-up evaluations of a large number of such dogs have not been reported.
The purpose of this report was to evaluate the results of treatment in 25 dogs with hyperadrenocor- ticism caused by adrenocortical adenoma or car- cinoma. In addition, it was our purpose to determine the complications and survival times associated with adrenalectomy for adrenocortical neoplasia in these dogs.
Criteria for Selection of Cases
From January 1980 to December 1984, surgery was used in treatment of 25 dogs with hyper- adrenocorticism caused by an adrenocortical tumor. Hyperadrenocorticism was suspected clinically on the basis of history, clinical signs, and results of physical examination, serum biochemical and hema- tologic testing, urinalysis, and thoracic and abdomi- nal radiography. Hyperadrenocorticism was con- firmed by detecting an exaggerated increase in the serum cortisol concentration 2 hours after injection of ACTH gela (20 U, IM) and/or inadequate suppres- sion (lowering) of the serum cortisol concentration 8 hours after administration of a low dose of dex- amethasoneb (0.015 mg/kg of body weight, IM), as described.2,3,5 A tentative diagnosis of adrenocortical tumor was based on lack of adequate serum cortisol suppression following administration of a high dose of dexamethasone (1.0 mg/kg, IM or IV) in all dogs, in combination with the finding of low to low-normal basal plasma ACTH concentrations in 20 dogs and/or the finding on radiographs of a mineralized mass in the area of one of the adrenal glands.2-4,6 In all dogs, adrenocortical tumors were confirmed on the basis of histologic examination of surgical biopsy specimens. Serum cortisol and plasma ACTH concentrations were determined by radioimmunoassay procedures, validated for the dog.6,7
Materials and Methods
Anesthetic induction was performed, using thiamylal sodium (3 to 6 mg/kg, Iv) or oxymorphone (0.1 to 0.3 mg/kg,
aActhar, Armour Pharmaceutical Co, Phoenix, Ariz.
bAzium, Schering Corp, Kenilworth, NJ.
IV). Halothane and oxygen were used to maintain general anesthesia. Throughout surgery, lactated Ringer’s solution (5 ml/kg/hr, IV) was used as fluid replacement. At the time of induction or immediately before surgical removal of the suspected neoplastic adrenal gland, dexamethasone (0.1 to 0.2 mg/kg, Iv) was given for corticosteroid supplementa- tion.8 On completion of surgery, this glucocorticoid was again administered at this dosage.
In 24 dogs, exploratory surgery of the abdominal cavity was performed, using a ventral midline abdominal ap- proach. After the abnormal adrenal gland was identified in 4 of these dogs, the ventral incision was extended para- costally to improve exposure of the adrenal tumor.8 A retroperitoneal (paracostal) approach was used in the re- maining dog.9-12 In the dogs in which a ventral midline approach was used, the area of and around both adrenal glands was visually inspected and palpated, and sites of gross metastasis were determined. In all 24 dogs, a neo- plastic adrenal gland was readily apparent, whereas the contralateral adrenal gland was judged to be small (atro- phied) in all dogs and could not be readily identified in 5 dogs. The neoplastic adrenal gland was surgically resected, using reported techniques.8-12 In each dog, the body wall was apposed with either steel or nylon suture material to help prevent dehiscence.
Correction of fluid, electrolyte, and acid-base im- balances and repeat serum biochemical and hematologic testing and radiography were performed after surgery. An ACTH stimulation test also was done on all surviving dogs on the first postoperative day to determine the degree of adrenocortical reserve. In dogs with postoperative adrenal insufficiency (based on results of ACTH stimulation test- ing), prednisone was administered during the first 3 postoperative days at a dosage of 0.5 mg/kg, PO, BID, which was gradually tapered over a 10- to 14-day period to an approximate maintenance dosage of 0.2 mg/kg, PO, SID.8 Prednisone was continued at this dosage until the remain- ing adrenal gland was considered to be functioning nor- mally, based on the results of ACTH stimulation testing that was performed at 2- to 4-week intervals. In 2 dogs with adrenocortical carcinoma and persistent hyperadrenocor- ticism, treatment with mitotane™ was initiated at a daily dosage of 30 to 50 mg/kg during the postoperative period, and the dosage was adjusted based on results of subsequent ACTH stimulation testing.
Results
Mean age of the 25 dogs was 10.5 years (range, 5 to 14 years). Fifteen were females (8 spayed) and 10 were males (3 castrated). Breeds included Poodle (5), mixed (5), Dachshund (3), Wire Fox Terrier (2), and Shih Tzu, German Shepherd Dog, Schnauzer, Labrador Retriever, Vizsla, German Shorthaired Pointer, Old English Sheepdog, Lhasa Apso, Afghan Hound, and Keeshond (1 each). The dogs ranged in body weight from 4.9 to 40 kg (mean, 19.1 kg); 12 dogs weighed more than 20 kg.
Clinical signs included polyuria and polydipsia (24), pendulous abdomen (22), hepatomegaly (20), muscle weakness (20), polyphagia (17), obesity (17), lethargy (17), muscle atrophy (12), hair loss (11), panting (8), comedones (8), hyperpigmentation (4), calcinosis cutis (3), and facial nerve palsy (2).
Abdominal radiographs aided in the diagnosis and localization of an adrenocortical tumor in 11 of 25
dogs, based on mineralization in the area of the affected adrenal gland in 10 dogs (40%) and increased soft tissue density in the area of the affected adrenal gland in the other dog. Of the 10 dogs with adrenal mineralization, 7 had adrenal carcinoma.
Unilateral adrenocortical tumors were confirmed by exploratory surgery in all 25 dogs. In all dogs, the neoplastic adrenal gland was large (range, approx 2 to 6 cm3), whereas the contralateral adrenal gland was markedly atrophied. Fifteen tumors were located in the left adrenal gland and 10 in the right. Results of histologic examination identified 14 adrenocortical carcinomas and 11 adenomas.
Seven of the 14 dogs with adrenocortical car- cinoma had visible metastasis to the liver. Local invasion of the carcinoma into the caudal vena cava was visible in 3 dogs; 2 of these were among those with hepatic metastasis. In 1 dog with carcinoma, the tumor extended into the adjacent renal vein and nephrectomy was required. Metastasis or local inva- sion into the vena cava or renal vessels was not seen in the remaining 5 dogs with carcinoma or in any of the 11 dogs with adrenocortical adenoma.
Of the 14 dogs with adrenocortical carcinoma, 7 were euthanatized at time of surgery because of metastasis, 2 died of cardiac arrest during the imme- diate postoperative period, and 2 died within 2 weeks after surgery because of acute renal failure and pneumonia, respectively (Table 1). Two of the remain- ing 3 dogs were treated with mitotane after adre- nalectomy; 1 of the dogs treated with mitotane had visible hepatic metastasis (No. 12) and both had persisting normal to high serum cortisol concentra- tions following exogenous ACTH stimulation (No. 12 and 14; Table 1). In dog 12, no decrease in serum cortisol concentrations or resolution of clinical signs was seen despite prolonged daily treatment with mitotane at dosages ranging from 50 to 200 mg/kg. The dog died at home 7 months after surgery; necropsy was not permitted. In the other dog treated with mitotane (No. 14), both basal and post-ACTH serum cortisol concentrations decreased into normal resting range and clinical signs improved during prolonged daily administration of mitotane at a dosage of 30 to 60 mg/kg. This dog was euthanatized 51 months after surgery because of congestive heart failure; necropsy was not permitted. The remaining dog (No. 13) was free of clinical signs of hyper- adrenocorticism and on no medication 28 months after adrenalectomy.
Of the 11 dogs, 4 (36%) with adrenocortical ade- noma died or were euthanatized within 2 weeks after surgery (Table 2). One was euthanatized because of severe postoperative pancreatitis that did not respond to medical management; at necropsy, a gauze sponge foreign body was found in the peripancreatic area. Another dog developed vomiting, diarrhea, and weakness and died acutely 1 week after surgery; although the exact cause of death was not known, glucocorticoid deficiency probably contributed be- cause the owners failed to reliably administer pred- nisone during the postoperative period. The other 2 dogs died 2 and 10 days after surgery after developing
cLysodren, Bristol Laboratories, Syracuse, NY.
| Dog No. | Survival time | Outcome |
|---|---|---|
| 1 | ... | Liver metastasis and vena cava involvement (euthanatized at surgery) |
| 2 | ... | Liver metastasis and vena cava involvement (euthanatized at surgery) |
| 3 | ... | Liver metastasis (euthanatized at surgery) |
| 4 | ... | Liver metastasis (euthanatized at surgery) |
| 5 | ... | Liver metastasis (euthanatized at surgery) |
| 6 | ... | Liver metastasis (euthanatized at surgery) |
| 7 | ... | Vena cava involvement (euthanatized at surgery) |
| 8 | ... | Renal vein involvement and cardiac arrest during anesthetic recovery (died) |
| 9 | ... | Cardiac arrest during anesthetic recovery (died) |
| 10 | 6 days | Acute renal failure (euthanatized) |
| 11 | 14 days | Pneumonia (died) |
| 12 | 7 mo | Liver metastasis; no response to mitotane treatment (died; no necropsy) |
| 13 | >28 mo | Clinically normal (alive) |
| 14 | 51 mo | Persistent hyperadrenocorticism; good response to mitotane; chronic congestive heart failure (euthanatized) |
acute dyspnea; at necropsy, both had pulmonary artery thrombosis. The remaining 7 dogs with adre- nocortical adenoma had complete resolution of clinical signs of hyperadrenocorticism after adre- nalectomy. Of these 7 dogs, 1 died of unknown causes 10 months after surgery, 4 were euthanatized because of unrelated medical problems 3 to 24 months after surgery, and 2 were alive at 32- and 70-month follow- up evaluations (Table 2).
Of the 16 dogs alive on the day after surgery, all except 2 dogs (No. 12 and 14, Table 1) with carcinoma had adrenal insufficiency, evidenced by low to low- normal resting serum cortisol concentrations, with little or no increase after exogenous ACTH admin- istration. The 8 dogs with postoperative adrenal insufficiency that survived longer than 2 weeks after surgery (No. 13, Table 1 and No. 5 to 11, Table 2) all regained normal adrenocortical function by 9 weeks (range, 3 to 9 weeks). Administration of maintenance doses of glucocorticoid was discontinued in these dogs at this time without adverse side effects.
Overall, serious postoperative complications de- veloped in 9 (50%) of the 18 dogs of this study that were not euthanatized at time of surgery. Complica- tions included cardiac arrest (2), pneumonia (2), pulmonary artery thromboembolism (2), pancreatitis (1), acute renal failure (1), and probable glucocorticoid insufficiency (1). Eight of these 9 dogs died or were euthanatized as a result of these complications. Minor complications associated with adrenalectomy included delayed healing of the skin incision in 2 dogs; however, dehiscence of the body wall did not occur in any of these dogs.
In 14 of the 22 dogs that died or were euthanatized, necropsy and histologic examination of tissues were performed. The pituitary gland was histologically normal in these 14 dogs. Twelve of the 14 dogs died or were euthanatized within 2 weeks after surgery, and in these 12, the contralateral adrenal gland was atrophied.
Discussion
Exploratory abdominal surgery is currently the most useful diagnostic technique available to defini-
tively diagnose and localize an adrenocortical tumor in the dog. Surgical examination of a dog’s adrenal glands can be achieved by use of a ventral midline abdominal approach or a retroperitoneal (paracostal) approach.8-12 The retroperitoneal approach mini- mizes surgical dissection and provides adequate ex- posure of the adrenal gland, kidney, and retro- peritoneal space on that side, while keeping anesthesia time to a minimum. This approach also minimizes the potential for problems with wound healing and dehiscence by avoiding a ventral weight- bearing incision. The disadvantages of the retro- peritoneal approach are that it does not allow vi- sualization of the contralateral adrenal gland, and complete abdominal exploration to identify metasta- sis is not possible.
The ventral midline approach permits complete examination of the abdominal cavity, with inspection of both adrenal glands, and allows one to identify potential metastatic lesions for biopsy. In addition, in our experience this surgical approach does not result in a substantial increase in anesthesia time when compared with the retroperitoneal approach. This is especially true in cases in which preoperative later- alization of the tumor cannot be determined radio- graphically; therefore, to prevent needless explora- tion of the contralateral non-neoplastic adrenal gland and avoid bilateral flank incisions, the ventral midline abdominal approach was used in 24 of 25 dogs in this series. Because cortisol delays wound healing,13 there was a risk of dehiscence of the ventral abdominal incision; however, none of our dogs had this complication. Iatrogenic damage to the pancreas also is a possible complication with this approach,9,14 but only 1 dog was euthanatized because of severe, acute, necrotizing pancreatitis, and this was secon- dary to a gauze sponge foreign body that was inadver- tently left at the time of surgery. Thus, we recom- mend generally the ventral midline approach, but caution that each case of adrenocortical tumor in the dog should be evaluated individually, because in some cases the retroperitoneal approach would be the preferred technique.
The technique of adrenalectomy in the dog has been described.9-12 The major intraoperative compli- cations are associated with hemostasis and tissue
| Dog No. | Survival time | Outcome |
|---|---|---|
| 1 | 2 days | Pulmonary thromboembolism (died) |
| 2 | 7 days | Necrotizing pancreatitis secondary to gauze sponge foreign body (euthanatized) |
| 3 | 7 days | Sudden death (glucocorticoid deficiency) |
| 4 | 10 days | Pulmonary thromboembolism (died) |
| 5 | 3 mo | Transitional cell carcinoma of urinary bladder (euthanatized) |
| 6 | 4 mo | Tetraparesis after cervical trauma (euthanatized) |
| 7 | 10 mo | Pneumonia during immediate postoperative period (resolved); sudden death after episode of acute dyspnea (no necropsy) |
| 8 | 11 mo | Multicentric lymphosarcoma (euthanatized) |
| 9 | 24 mo | Chronic, progressive hindlimb paresis (euthanatized) |
| 10 | >32 mo | Clinically normal (alive) |
| 11 | >70 mo | Clinically normal (alive) |
dissection of major arteries and veins. The right adrenal gland is closely associated with the caudal vena cava, and this complicates adrenalectomy. The vena cava and renal vessels should be examined carefully for evidence of metastasis. In human pa- tients, adrenocortical carcinoma occasionally metas- tasizes to the caudal vena cava.15,16 Of the 14 dogs with carcinoma in this study, 3 had invasion of the caudal vena cava and 1 had extension of the tumor into the adjacent renal vein. The right adrenal gland was involved in all dogs with vena caval metastasis.
Because the unaffected adrenal gland is chron- ically suppressed and atrophied in dogs with uni- lateral cortisol-secreting adrenal tumors, adreno- cortical insufficiency will develop after successful adrenalectomy unless large doses of glucocorticoids are given during and after surgery. To evaluate adrenal reserve and help exclude occult metastasis after resection of all visible tumor, we recommend that ACTH stimulation testing be performed on the first to second postoperative day. It is important to realize, however, that most glucocorticoid prepara- tions other than dexamethasone will cross-react in most cortisol assays to falsely increase endogenous cortisol determinations.3 Therefore, if prednisone, prednisolone, or cortisone have been given during or after surgery, glucocorticoid supplementation should be changed to dexamethasone for 1 to 2 days before ACTH stimulation testing to ensure reliable results. Curative surgery should result in low to low-normal resting serum cortisol concentrations with little or no rise after ACTH administration. If normal to exag- gerated serum cortisol responses are detected in the immediate postoperative period, residual or meta- static adrenal tumor should be suspected. In dogs with adrenal insufficiency, glucocorticoid supple- mentation should be gradually tapered to mainte- nance dosage over the first 10 to 14 postoperative days. Glucocorticoids should then be continued at maintenance dosage until the remaining adrenal gland is functioning normally, as determined by ACTH stimulation testing; in most dogs, glucocor- ticoids can be discontinued within 2 months after surgery.
In the dogs of this series, mineralocorticoid sup- plementation was not considered necessary because postoperative serum electrolyte values were normal. Although circulating ACTH is a primary factor in stimulating glucocorticoid secretion, it is less impor- tant in mineralocorticoid secretion.17 Therefore, whereas glucocorticoid supplementation is impor- tant after unilateral adrenalectomy for cortisol-se- creting adrenal tumors, mineralocorticoid supple- mentation usually is not necessary.
In dogs with nonresectable primary and/or meta- static adrenocortical carcinoma (based on results of surgical exploratory and postoperative ACTH stim- ulation testing), chemotherapy with the adrenocor- ticolytic agent mitotane can be attempted. Of the 2 dogs of this report that were treated with mitotane, there was no resolution of clinical signs or reduction in resting and post-ACTH serum cortisol concentra- tions in 1 dog with visible hepatic metastasis, despite
progressive increase in daily drug dosage to 200 mg/kg. The other dog with adrenocortical carcinoma did not have visible metastasis, but had persistent signs of hyperadrenocorticism after surgery and hyperresponded to ACTH stimulation on postopera- tive examination; therefore, a presumptive diagnosis of metastatic carcinoma was made and treatment with mitotane was initiated. The dog survived 51 months and had substantial improvement in clinical signs and reduction of serum cortisol concentrations. In 1 study, human patients with adrenocortical car- cinoma had a mean duration of tumor regression of 10.2 months while undergoing treatment with mito- tane.18 The results of treatment with mitotane in these 2 dogs and in human patients with adrenocor- tical carcinoma suggest that this drug may tem- porarily control the clinical signs of hyperadrenocor- ticism and increase survival time in some dogs with metastatic adrenocortical carcinoma.
Serious postoperative complications were seen in half of the dogs of this study. Complications included pneumonia, pulmonary artery thromboembolism, acute renal failure, and poor anesthetic recovery with cardiac arrest. To help prevent these complications, dogs with hyperadrenocorticism should be monitored closely, especially during the operative and immedi- ate postoperative periods. Capillary refill time, rectal temperature, heart and lung sounds, electrocar- diogram, and blood pressure should all be monitored continuously during surgery. Bronchopneumonia is a potential complication, secondary to possible immu- nosuppression caused by high cortisol concentra- tions. Therefore, dogs with hyperadrenocorticism that undergo surgery or general anesthesia should be administered bacteriocidal antibiotics both during and after surgery. Because many anesthetic drugs (administered Iv or via inhalation) lower cardiac output and systemic arterial pressure,19 renal perfu- sion also might be decreased; and many dogs with adrenal tumors are older dogs that might have some degree of subclinical renal disease. Therefore, it is important to administer a balanced isotonic fluid solution during the perioperative period and to moni- tor renal function and fluid and serum electrolyte status postoperatively. Fluid, electrolyte, and acid- base imbalances should be corrected as needed.
Pulmonary thromboembolism is a reported com- plication of hyperadrenocorticism20-23 and was seen after surgery in 2 dogs of this study. In human patients, pulmonary thromboembolism is a common cause of mortality following adrenalectomy.21,22 Pul- monary thromboembolism should be considered in dogs with intractable dyspnea, right-sided heart failure, or unexplained acute death following adre- nalectomy. Diagnosis is based on thoracic radiogra- phy, which may reveal hypovascularity of the obstructed pulmonary vasculature or increased di- ameter of the pulmonary artery segment.22 Arterial blood gases might indicate hypoxemia and hypocap- nia. Angiocardiography can be used to confirm the diagnosis.
The cause of pulmonary thromboembolism associ- ated with hyperadrenocorticism is unknown at this
time. Dogs with hyperadrenocorticism have been shown to have high concentrations of coagulation factors V, X, XI, and fibrinogen (factor I).24 These abnormally high factor concentrations potentially lead to the creation of a hypercoagulable state that predisposes these dogs to thrombosis. Similar in- creased coagulation factors also have been reported in human patients with hyperadrenocortism.22,23
The high short-term mortality rate (60% died or were euthanatized within 2 weeks after surgery) in the dogs of this study can be misleading when attempting to determine whether surgical explora- tion and adrenalectomy are beneficial in dogs with adrenocortical tumors. Greater than 70% of the short-term mortalities (11 of 15) were dogs with carcinomas. Seven of these 11 dogs had extensive tumor volume, and their owners requested eu- thanasia at the time of surgery on the basis of the presence of metastasis in the liver and/or vena cava. Because one half of the dogs with carcinomas were euthanatized during surgery, it is difficult for us to draw conclusions regarding prognosis for long-term survival in dogs with this type of malignant tumor. Nevertheless, because of the presence of or potential for development of widespread metastasis in these dogs, the long-term prognosis for adrenal carcinoma remains guarded. In contrast, when surgical and postoperative complications can be avoided, the long- term prognosis for resolution of clinical signs of hyperadrenocorticism is good to excellent for dogs with resectable adenomas.
Our current approach in dogs in which a tentative diagnosis of adrenocortical tumor has been made is to evaluate each case individually. If the dog is a poor surgical and anesthetic risk because of severe, ad- vanced hyperadrenocorticism or concurrent physical problems (eg, heart disease, pulmonary disease, or other metabolic disorder), we recommend use of mitotane without surgery. If mitotane treatment can control hyperadrenocorticism and reverse the meta- bolic derangements that increase anesthetic and surgical risks, surgical exploration should be consid- ered. In dogs initially judged to be acceptable surgical and anesthetic risks, exploratory surgery of the abdomen is recommended. If a unilateral adrenocor- tical mass without widespread metastasis or invasion of the great vessels (ie, vena cava) is identified, we advocate adrenalectomy and medical management as has been discussed. If hyperadrenocorticism per- sists in the immediate postoperative period, un- detected metastasis should be suspected and treat- ment with mitotane initiated. In dogs with an adrenocortical mass that is judged to be nonresecta- ble and/or has widespread metastasis, euthanasia should be considered. Alternatively, surgical reduc- tion of tumor volume and treatment with large doses of mitotane can be attempted; however, mitotane may
only be of partial or minimal benefit in those dogs with a large residual tumor volume.
References
1. Feldman EC. The adrenal cortex. In: Ettinger SJ, ed. Text- book of veterinary internal medicine. 2nd ed. Philadelphia: WB Saunders Co, 1983;1650-1696.
2. Peterson ME. Hyperadrenocorticism. Vet Clin North Am [Small Anim Pract] 1984;14:731-749.
3. Peterson ME. Canine hyperadrenocorticism. In: Kirk RW, ed. Current veterinary therapy IX. Philadelphia: WB Saunders Co, 1986;963-972.
4. Feldman EC. Effect of functional adrenocortical tumors on plasma cortisol and corticotropin concentrations in dogs. J Am Vet Med Assoc 1981;178;823-826.
5. Peterson ME, Gilbertson SR, Drucker WD. Plasma cortisol response to exogenous ACTH in 22 dogs with hyperadrenocor- ticism caused by adrenocortical neoplasia. J Am Vet Med Assoc 1982;180:542-544.
6. Peterson ME, Orth DN, Halmi NS, et al. Plasma immu- noreactive proopiomelanocortin (POMC) peptides and cortisol in normal dogs and dogs with Addison’s disease and Cushing’s syn- drome: basal concentrations. Endocrinology 1986;119:720-723.
7. Peterson ME, Winkler B, Kintzer PP, et al. Effect of spon- taneous hyperadrenocorticism on endogenous production and uti- lization of glucose in the dog. Domest Anim Endocrinol 1986;3:117-125.
8. Peterson ME, Birchard SJ, Mehlhaff CJ. Anesthetic and surgical management of endocrine disorders. Vet Clin North Am [Small Anim Pract] 1984;14:911-925.
9. Siegel ET, Kelly DF, Berg P. Cushing’s syndrome in the dog. J Am Vet Med Assoc 1970;157:2081-2089.
10. Johnston DE. Adrenalectomy via retroperitoneal approach in dogs. J Am Vet Med Assoc 1977;170:1092-1095.
11. Johnston DE. Adrenalectomy in the dog. In: Bojrab MJ, ed. Current techniques in small animal surgery. Philadelphia: Lea & Febiger, 1983;386-388.
12. Eigenmann JE, Lubberink AAME. The adrenals. In: Slat- ter DH, ed. Textbook of small animal surgery. Philadelphia: WB Saunders Co, 1985;1851-1865.
13. Johnston DE. Skin and subcutaneous tissue. In: Bojrab MJ, ed. Pathophysiology in small animal surgery. Philadelphia: Lea & Febiger, 1981;405-419.
14. Carey LC, Ellison EH. Adrenalectomy techniques, errors and pitfalls. Surg Clin North Am 1966;46:1283-1292.
15. Cahill PH, Sarkov RJ. Inferior vena caval involvement by adrenal cortical carcinoma. Urology 1977;10:604-607.
16. Dunnick NR, Doppmen JL, Geelhold GW. Intravenous extension of endocrine tumors. Am J Radiol 1980;135:471-476.
17. Baxter JD, Tyrrell JB. The adrenal cortex. In: Felig P, Baxter JD, Broadus AE, et al, eds. Endocrinology and metabolism. New York: McGraw-Hill Book Co, 1981;385-510.
18. Hutter AM, Kayhoe DE. Adrenal cortical carcinoma, re- sults of treatment with o,p’DDD in 138 patients. Am J Med 1966;41:581-592.
19. Hubbell J, Muir W, Robinson E, et al. Fluid administration during anesthesia. In: Muir W, ed. An outline of veterinary anesthesia. Columbus, Ohio: The Ohio State University Press, 1983;249.
20. Burns MG, Kelly AB, Hornof WJ, et al. Pulmonary artery thrombosis in 3 dogs with hyperadrenocorticism. J Am Vet Med Assoc 1981;178:388-393.
21. Blichert-Toft M, Bagerskov A, Lockwood K, et al. Operative treatment, surgical approach and related complications in 195 operations upon the adrenal glands. Surg Gynecol Obstet 1972;135:261-266.
22. Sjoberg HE, Blomback M, Granberg PO. Thromboembolic complications, heparin treatment, and increased coagulation fac- tors in Cushing’s syndrome. Acta Med Scand 1976;199:95-98.
23. Small M, Lowe GDO, Forbes CD, et al. Thromboembolic complications in Cushing’s syndrome. Clin Endocrinol 1983;19:503-511.
24. Feldman BF, Feldman EC, Cowgill LD. Thrombotic disease in canine Cushing’s and nephrotic syndromes, in Proceedings. Annu Meet Am Coll Vet Intern Med 1982:84.