Adrenalectomy for treatment of hyperadrenocorticism in cats: 10 cases (1988-1992)
Cindy A. Duesberg, DVM; Richard W. Nelson, DVM; Edward C. Feldman, DVM; Shelly L. Vaden, DVM, PhD; J. Catharine R. Scott-Moncrieff, MA, Vet MB, MS
Summary: Outcome of and complications associated with bilateral adrenalectomy in 8 cats with pituitary-dependent hyperadrenocorticism and bilateral adrenocortical hyperpla- sia and outcome of and complications associated with uni- lateral adrenalectomy in 2 cats with adrenocortical tumor (adrenocortical adenoma, 1 cat; adrenocortical carcinoma, 1 cat) and unilateral adrenomegaly were determined. Gluco- corticoids were administered to all cats at the time of sur- gery, and mineralocorticoids were administered to the 8 cats that underwent bilateral adrenalectomy. A ventral midline celiotomy was performed in all cats.
Intraoperative complications did not develop in any cat. Postoperative complications developed in all cats and in- cluded abnormal serum electrolyte concentrations (n = 8), skin lacerations (n = 5), pancreatitis (n = 3), hypoglycemia (n = 2), pneumonia (n = 1), and venous thrombosis (n = 1). Three cats died within 5 weeks after surgery of compli- cations associated with sepsis (n = 2) or thromboembolism (n = 1). Clinical signs and physical abnormalities caused by hyperadrenocorticism resolved in the remaining 7 cats 2 to 4 months after adrenalectomy. Insulin treatment was dis- continued in 4 of 6 cats with diabetes mellitus. Median sur- vival time for these 7 cats was 12 months (range, 3 to > 30 months). Two cats died of acute adrenocortical insuffi- ciency 3 and 6 months after bilateral adrenalectomy, 2 cats were euthanatized because of chronic renal failure 3 and 12 months after bilateral (n = 1) or unilateral (n = 1) adren- alectomy, and 2 cats were alive 9 and 14 months after bi- lateral adrenalectomy. In the remaining cat, clinical signs recurred 10 months after the cat had undergone unilateral adrenalectomy. The remaining adrenal gland was found to contain an adrenocortical adenoma and was removed. The cat was doing well when it was lost to follow-up 15 months after the second surgery.
N aturally acquired hyperadrenocorticism is rare in cats.1-3 If left untreated, this condition’s deleterious effects on metabolic, immune, and cardiovascular func- tion lead to progressive debilitation and, ultimately, death or euthanasia. Although a few cats with hyperad- renocorticism have been treated with the adrenocorti- colytic drug mitotane or with the enzyme inhibitors ketoconazole and metyrapone,1-6 long-term results of treatment have been discouraging, and a reliable medical treatment for cats with hyperadrenocorticism has yet to
be identified. Historically, adrenalectomy was the pri- mary treatment for hyperadrenocorticism caused by ei- ther adrenal or pituitary neoplasia in human beings,7-9 and adrenalectomy is an accepted treatment for dogs with hyperadrenocorticism caused by adrenocortical neoplasia.10 A few case reports have suggested that ad- renalectomy might be an useful alternative for treatment of hyperadrenocorticism in cats1,11,12; however, results in only a few cats have been reported. The purpose of the study reported here was to determine outcome of and postoperative complications associated with adren- alectomy in a larger group of cats with naturally acquired hyperadrenocorticism.
Criteria for Selection of Cases
Medical records of all cats in which naturally ac- quired hyperadrenocorticism was diagnosed between January 1988 and December 1992 at the University of California-Davis, Purdue University, and North Carolina State University were reviewed. Only those cats that un- derwent adrenalectomy were included in this study. In- formation obtained from each record included signal- ment, history, results of routine clinicopathologic studies and tests of endocrine function, results of abdominal ra- diography and ultrasonography, surgical findings, and outcome.
Results
Hyperadrenocorticism was diagnosed in 22 cats during the study period; however, 5 cats that were not treated for hyperadrenocorticism, 4 that were treated with mitotane, 2 that were treated with ketoconazole, 2 that were treated with metyrapone, and 1 that under- went cobalt irradiation of the pituitary gland were ex- cluded from the study. These 12 cats all died or were euthanatized within 2 months after hyperadrenocorti- cism was diagnosed because of progression of clinical signs and physical abnormalities. The remaining 10 cats all underwent adrenalectomy and were the basis of this study.
Signalment, history, and clinical signs-Cats were be- tween 4 and 14 years old (mean, 9.5 years) and weighed between 3.5 and 8.8 kg (mean, 5.5 kg). Breeds included domestic long- and shorthair (n = 8) and Siamese (n = 2). Four cats were spayed females, and 6 were neutered males.
In all cats, diabetes mellitus had been diagnosed 1 to 12 months (mean, 4.3 months) prior to the time that hyperadrenocorticism was diagnosed. At the time of ad- renalectomy, clinical signs of diabetes were poorly con- trolled in 4 cats receiving intermediate- or long-acting insulin at dosages ranging from 2.6 to 7.5 U/kg of body weight/d and were well controlled in 3 cats receiving intermediate-acting insulin at dosages ranging from 0.4
From the Departments of Medicine (Duesberg, Nelson) and Repro- duction (Feldman), School of Veterinary Medicine, University of Cal- ifornia, Davis, CA 95616; the Department of Anatomy, Physiologic Sciences and Radiology, College of Veterinary Medicine, North Caro- lina State University, Raleigh, NC 27600 (Vaden); and the Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47906 (Scott-Moncrieff).
to 1.5 U/kg/d; the remaining 3 cats did not require in- sulin treatment to maintain blood glucose concentration < 200 mg/dl.
Clinical signs in all cats were consistent with either diabetes mellitus or hyperadrenocorticism and included polyuria and polydipsia (n = 9), polyphagia (n = 7), lethargy (n = 7), and weight loss (n = 4). Five cats had a history of recent or recurrent bacterial infections in- volving the urinary tract (n = 3), skin (n = 1), or oral cavity (n = 1). All cats had typical dermatologic mani- festations of hyperadrenocorticism, including thin, frag- ile skin (n = 7), skin lacerations (n = 5), alopecia involving the trunk (n = 6) or limbs (n = 2), poor skin elasticity (n = 3), and folded pinnae (n = 1). Additional abnormalities identified on physical examination in- cluded a pot-bellied appearance (n = 9), generalized muscle atrophy (n = 7), obesity (n = 5), hepatomegaly (n = 3), and an abnormal gait (n = 3).
Results of clinicopathologic testing-Hematologic, se- rum biochemical, and urinary abnormalities were con- sistent with those previously reported for cats with hyperadrenocorticism.1 Baseline serum thyroxine con- centration was within the reference range, and results of bacteriologic culture of urine and an ELISA test for FeLV were negative in all cats.
Diagnostic imaging-Abdominal radiography was performed in 6 cats. Hepatomegaly was seen in 1 cat, and in another cat, an adrenal mass could be seen. Ab- dominal ultrasonography was performed in 8 cats, using a real-time sector scanner,a to evaluate adrenal size. Bi- lateral enlargement of the adrenal glands was seen in 6 cats. Mean length of the longitudinal axis of the adrenal gland was 1.3 cm (range, 1.0 to 1.5 cm). In 2 cats, a mass could be seen in 1 adrenal gland, and the contra- lateral adrenal gland could not be imaged. None of the cats had ultrasonographic evidence of abdominal metas- tases; however, 3 had evidence of hepatomegaly.
Computed tomographyb of the pituitary gland was performed in 2 cats. One cat had a small, contrast-en- hancing lesion in the pituitary fossa; the other cat did not have any tomographic lesions.
Results of endocrine function testing-An adrenocor- ticotropic hormone (ACTH) stimulation test was per- formed on 9 cats, using 1 of 2 protocols: plasma cortisol concentration was determined before and 60 and 120 minutes after administration of 2 IU of porcine ACTH/ kg, IM, in 7 cats; plasma cortisol concentration was de- termined before and 30 and 60 minutes after adminis- tration of 0.125 mg of synthetic ACTH,d IM, in the other 2. Results for 6 of the 9 cats were consistent with a diagnosis of hyperadrenocorticism. A low-dosage dexa- methasone suppression test (plasma cortisol concentra- tion determined before and 8 hours after administration of 0.01 mg of dexamethasonee/kg, Iv) was performed in 7 cats; results for all 7 were consistent with a diagnosis of hyperadrenocorticism.1,13 A high-dosage dexametha- sone suppression test (plasma cortisol concentration de- termined before and 8 hours after administration of 0.1 mg of dexamethasone/kg, IV) was performed in 6 cats; plasma cortisol concentration 8 hours after IV adminis- tration of dexamethasone was < 50% of baseline cortisol
concentration in 2 of 6. Baseline plasma endogenous ACTH concentration was measured in 4 cats and ranged from 93 to > 1,000 pg/ml.13
Surgical treatment-A tentative diagnosis of pitui- tary-dependent hyperadrenocorticism (PDH) could be made, on the basis of results of preoperative tests, in 6 cats, and a tentative diagnosis of adrenocortical tumor could be made in another 2. In the remaining 2 cats, test results could not be used to conclusively differen- tiate between PDH and adrenocortical tumor.
Adrenalectomy was performed in all cats within 1 month of the time that the diagnosis of hyperadreno- corticism was established. Food was withheld for 12 hours prior to surgery and antibiotics were given pro- phylactically. The 7 cats that had been receiving insulin were given half their usual morning dose of insulin the morning of surgery.
Glucocorticoids were administered to all cats at the time of surgery and mineralocorticoids were adminis- tered to the 8 cats that underwent bilateral adrenalec- tomy. However, the protocol for adrenocortical hormone supplementation varied. Two cats were given predniso- lonef (2.5 and 5.0 mg, PO) and fludrocortisone acetateg (0.1 mg, PO) 2 hours before induction of anesthesia. Four cats received a continuous IV infusion of hydro- cortisoneh (625 µg/kg/h) and 3 received a continuous IV infusion of dexamethasonee (40 µg/kg/h). One cat was given prednisolone sodium succinatei (1.5 mg/kg, Iv) af- ter induction of anesthesia. The 3 cats that received a continuous infusion of dexamethasone also were given desoxycorticosterone acetate (1 mg, IM) at the time both adrenal glands were excised.
A ventral midline celiotomy was performed in all cats.14 The size and shape of both adrenal glands was assessed, and abdominal viscera were inspected for me- tastases. Fibrous adhesion of an adrenal gland to the vena cava was identified in 1 cat with PDH and 1 cat with a unilateral adrenocortical tumor. Bilateral adreno- megaly was confirmed in the 6 cats in which PDH had been suspected and in the 2 cats in which preoperative test results could not be used to differentiate between PDH and adrenocortical tumor. Bilateral adrenalectomy was performed in these 8 cats, and histologic evaluation of the excised adrenal glands revealed bilateral adreno- cortical hyperplasia. Unilateral adrenomegaly with atro- phy of the contralateral adrenal gland was identified in the 2 cats suspected of having adrenocortical tumor. Unilateral adrenalectomy was performed in these 2 cats, and histologic evaluation of the excised gland revealed adrenocortical adenoma in 1 cat and adrenocortical car- cinoma in the other.
Treatment during the early postoperative period in- cluded continued Iv administration of lactated Ringer’s solution and parenteral administration of antibiotics. Cats were not allowed to eat or drink anything. Treat- ment with intermediate-acting insulin was continued in the 7 cats that had been receiving insulin prior to surgery. Insulin dosages ranged from 0.2 to 1.1 U/kg/d. Adreno- cortical hormone supplementation was continued, at the same dosages used in the perioperative period, for the first 48 hours after surgery. After that time, 9 cats were treated with prednisolone (2.5 to 7.5 mg/d, PO), and 8 cats were
treated with fludrocortisone acetate (0.1 mg/d, PO). In 1 cat that was debilitated and had undergone bilateral ad- renalectomy, parenteral administration of dexamethasone and desoxycorticosterone acetate was continued, because of postoperative complications.
Complications-Postoperative complications were common and included abnormalities of serum electro- lyte concentrations (n = 8), additional skin lacerations (n = 5), pancreatitis (n = 3), hypoglycemia (n = 2), and pneumonia (n = 1). Hypokalemia (median serum potassium concentration, 3.3 mEq/L; range, 2.6 to 3.6 mEq/L) was identified in 7 cats within 24 hours after adrenalectomy. Hyperkalemia (median serum potassium concentration, 5.6 mEq/L; range, 5.4 to 6.2 mEq/L) and hyponatremia (median serum sodium concentration, 140 mEq/L; range, 130 to 143 mEq/L) was identified in 4 cats 4 to 8 days after bilateral adrenalectomy. Abnor- mal serum electrolyte concentrations resolved after the dosage of fludrocortisone acetate was increased.
Outcome-Two cats with PDH died within 1 week after undergoing bilateral adrenalectomy. Both cats had been debilitated prior to surgery. One cat sloughed large regions of skin 48 hours prior to death, and the other cat developed severe pancreatitis and septic peritonitis. Necropsy of the first cat revealed a large pituitary car- cinoma infiltrating into the hypothalamus and thalamus. A third cat that underwent bilateral adrenalectomy re- covered from surgery, but developed dyspnea 2 weeks later. Chylothorax was identified, and the cat died 3 weeks later of respiratory failure, despite undergoing in- termittent thoracentesis. Necropsy revealed a large thrombus extending from the proximal portion of the cranial vena cava to both jugular veins and extensive necrosis of the pituitary gland.
The remaining cats survived the early postoperative period and were discharged from the hospital. All 7 cats received prednisolone (2.5 to 7.5 mg/d) for the first month after adrenalectomy. The prednisolone dosage was subsequently reduced on the basis of the cat’s atti- tude and appetite. Administration of prednisolone was discontinued by 2 months after surgery in the 2 cats with adrenocortical tumor that had undergone unilateral ad- renalectomy. In 4 of 5 cats that had undergone bilateral adrenalectomy, the dosage of prednisolone was tapered to 2.5 mg/d by 3 months after surgery. The fifth cat required 5.0 to 7.5 mg of prednisolone/d to prevent leth- argy, inappetence, and vomiting.
The dosage of fludrocortisone acetate was adjusted on the basis of results of periodic measurement of serum electrolyte concentrations. The dosage was increased in all cats during the first month after surgery and even- tually stabilized at a median dosage of 0.3 mg/d (range, 0.2 to 0.5 mg/d).
Clinical signs and physical examination abnormal- ities resolved in these 7 cats by 2 to 4 months after adrenalectomy. The dosage of insulin required decreased within days after adrenalectomy in all 6 cats that were receiving insulin prior to adrenalectomy. Insulin treat- ment was discontinued in both cats with adrenocortical tumor by 2 months after surgery when postoperative glucocorticoid treatment was discontinued, and in 2 cats with PDH by 2 and 8 months after surgery. In the re-
maining 2 cats, insulin treatment was still required; how- ever, the dosage of insulin required to maintain serum glucose concentrations between 100 and 300 mg/dl de- creased by 1.5 and 0.5 U/kg.
Median survival time for the 7 cats that survived the initial postoperative period was 12 months (range, 3 to > 30 months). Two cats with PDH that had undergone bilateral adrenalectomy developed progressive inappe- tence and lethargy and died 3 and 6 months after bilat- eral adrenalectomy. Historical information and results of serum biochemical analyses obtained from the referring veterinarians suggested poor owner compliance with treatment, and adrenal insufficiency was the likely cause of death in these cats. One of these cats had a contrast- enhancing mass identified by means of computed to- mography prior to bilateral adrenalectomy. One cat with PDH that had undergone bilateral adrenalectomy and 1 cat with adrenocortical carcinoma that had undergone unilateral adrenalectomy were euthanatized 3 and 12 months after surgery, respectively, because of chronic renal failure. Necropsy of the cat with adrenocortical car- cinoma revealed regrowth of the tumor and extensive mesenteric and hepatic metastases. Two cats with PDH that had undergone bilateral adrenalectomy were alive 9 and 15 months after surgery. One of these cats devel- oped lethargy, anorexia, and vomiting 12 months after adrenalectomy, but recovered after dehydration, and ab- normalities of serum electrolyte concentrations were cor- rected and the dosage of fludrocortisone acetate was increased from 0.2 to 0.3 mg/d. In the cat with adren- ocortical adenoma that had undergone unilateral adren- alectomy, clinical signs recurred 10 months after sur- gery. Results of tests of the pituitary-adrenocortical axis were consistent with hyperadrenocorticism, the remain- ing adrenal gland was found to be enlarged, and the cat again underwent adrenalectomy. The excised adrenal gland was found histologically to contain an adreno- cortical adenoma. The cat was doing well 15 months after the second surgery but was then lost to follow-up.
Discussion
Four of the 6 cats with suspected insulin-dependent diabetes mellitus that also survived the early postoper- ative period no longer needed insulin to maintain serum glucose concentration in the reference range. This sug- gests that these cats had some functioning pancreatic beta cells. In the remaining 2 cats, the dosage of insulin required was reduced. Glucocorticoids cause carbohy- drate intolerance by increasing hepatic gluconeogenesis and decreasing glucose use in peripheral tissues.15,16 De- creased glucose use may be a result of alterations in in- sulin receptor binding sites on the cell membrane, postreceptor defects, or alterations in the number or ef- ficacy of intracellular glucose transporters.17,18
Intraoperative complications were not encountered in any of these cats; however, postoperative complica- tions were common and resulted in the death of 3 cats. Mortality rate in these cats was higher than that reported for human beings undergoing adrenalectomy,7,19 but lower than that for dogs.10
Most postoperative complications were a conse- quence of prolonged preoperative hypercortisolism or inadequate adrenocortical hormone supplementation af-
ter bilateral adrenalectomy. Abnormalities of serum elec- trolyte concentrations were the most frequently encoun- tered complications, but were easily corrected by means of fluid therapy or by adjustment of mineralocorticoid treatment. Hypokalemia was attributed to increased uri- nary potassium excretion caused by excess mineralocor- ticoid supplementation or to insulin-induced shift of potassium ions from the extracellular to the intracellular space. Hyperkalemia and hyponatremia were attributed to inadequate mineralocorticoid supplementation. There- fore, we suggest that serum electrolyte concentrations be measured frequently during the immediate postoperative period and periodically during the initial 2 months after surgery so that the dosage of mineralocorticoid supple- mentation can be appropriately modified.
Differences in adrenocortical hormone treatment regimens used in these cats reflected differences in avail- ability of mineralocorticoid drugs, ease of administra- tion, and clinician preference. The small number of cats in each treatment group preclude critical comparison of treatment regimens; however, abnormalities of serum electrolyte concentrations developed postoperatively with all treatment regimens. We currently begin a con- tinuous infusion of hydrocortisone (625 µg/kg/h) at the time of anesthetic induction and continue it for 24 to 48 hours after surgery. Administration of prednisolone (2.5 mg, PO, q 12 h) and, in cats that undergo bilateral adrenalectomy, fludrocortisone acetate (0.1 mg/d) is in- itiated when infusion of hydrocortisone is discontinued. Repository administration of desoxycorticosterone piva- latek may be more reliable and more convenient in cats that require long-term mineralocorticoid supplementa- tion; however, desoxycorticosterone pivalate was not used in any of these cats.
Postoperative complications attributed, in part, to prolonged preoperative hypercortisolism included sep- sis, pancreatitis, and venous thrombosis. Thromboem- bolism is a life-threatening complication of naturally acquired hyperadrenocorticism in dogs20 and cats,1 and was the cause of death in 1 of the cats in this study. In human beings and dogs, hypercortisolism may induce a hypercoagulable state by increasing plasma clotting fac- tor and prothrombin concentrations.9,21,1 Additional pre- disposing factors described in human beings include obesity, hypertension, high PCV, sepsis, hypovolemia, periods of prolonged recumbency, and phlebitis induced by indwelling Iv catheters.9,19,21,22 In the 1 cat in this study with venous thrombosis, a large thrombus was identified in the cranial vena cava near the site of a jug- ular catheter that had been placed prior to surgery and was maintained for 72 hours after surgery. It would seem prudent to minimize or eliminate factors that may in- crease the risk of thrombogenesis during the periopera- tive period. It is unclear whether perioperative antico- agulant or antiplatelet treatment would be of benefit.
In our cats, complications caused by sepsis had the greatest impact on morbidity and mortality rates. Sepsis developed in 5 of 10 cats and was responsible, in part, for the death of 2. Cats with hyperadrenocorticism are predisposed to sepsis because of the deleterious conse- quences of chronic hypercortisolism on skin integrity, beta cell function, leukocyte kinetics, lymphocyte blas- togenesis, and cytokine production.23 In these cats, there
appeared to be an association between severity of catab- olism at the time of adrenalectomy and development of sepsis, in that the 2 cats with the most severe skin lesions and greatest preoperative weight loss both died of sepsis within 7 days after adrenalectomy. Measures that may help reduce the risk of sepsis include administering an- tibiotics prophylactically, using strict aseptic technique during placement and care of Iv catheters, minimizing duration of use of Iv catheters, controlling hyperglycemia with insulin, and maintaining skin integrity through gen- tle handling of the cat, using meticulous care when clip- ping the coat, and avoiding tape on the skin.
Because hyperadrenocorticism is a progressive de- bilitating disease in cats,1-4 early diagnosis and treatment should help minimize the risk of postoperative compli- cations, especially those related to sepsis, in cats under- going adrenalectomy. However, early recognition of hyperadrenocorticism in cats is difficult because the dis- ease is uncommon and many of its clinical and biochem- ical manifestations are indistinguishable from those caused by poorly regulated diabetes mellitus.1 Preoper- ative medical treatment of hyperadrenocorticism re- duced the postoperative morbidity and mortality rate in human beings undergoing adrenalectomy,24,25 and would likely have a similar effect in cats. Unfortunately, mitotane and ketoconazole have been ineffective in the treatment of hyperadrenocorticism in cats.1,2,4-6 Metyra- pone, on the other hand, was effective in controlling clinical signs of hyperadrenocorticism in 1 cat for 1 month prior to adrenalectomy.3
The most important determinant of long-term prog- nosis in these cats was the ability of the owner and re- ferring veterinarian to successfully manage the adreno- cortical insufficiency caused by bilateral adrenalectomy. Acute adrenocortical insufficiency developed in 3 cats 3, 6, and 12 months after bilateral adrenalectomy and was believed to be responsible for the death of 2 cats. Ad- ministration of desoxycorticosterone pivalate may im- prove long-term prognosis for cats that are difficult to medicate with fludrocortisone. Adrenocortical insuffi- ciency should be transient following unilateral adrena- lectomy in cats with adrenocortical neoplasia. Fifty percent of dogs with hyperadrenocorticism caused by an adrenocortical tumor have a malignant tumor.10 It is not known what percentage of cats with an adrenocortical tumor have a malignant tumor.
aALT Ultramark 8, Advanced Laboratories Inc, Bothell, Wash. bGE 8800, General Electric Co, Medical Systems Division, Milwau- kee, Wis.
“Cortigel-40 (repository corticotropin injection, USP), Savage Lab- oratories, Melville, NY.
dCortrosyn, Organon Inc, West Orange, NJ.
Azium-SP, Schering Corp, Kenilworth, NJ.
fPrednisolone, Richlyn Laboratories, Philadelphia, Pa. &Florinef Acetate, ER Squibb & Sons Inc, Princeton, NJ.
hA-Hydrocort, Abbott Laboratories, North Chicago, Ill.
iSolu-delta cortef, The Upjohn Co, Kalamazoo, Mich. JDesoxycorticosterone acetate, Organon Inc, West Orange, NJ. kPercorten, Ciba- Geigy Pharmaceutical Co, Animal Health Divi- sion, Greensboro, NC.
1Feldman BF, Feldman EC, Cowgill LD. Thrombotic disease in ca- nine Cushing’s and nephrotic syndromes (abstr), in Proceedings. Am Coll Vet Intern Med 1982;84.
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