Generated on 2024-10-30 15:08 GMT / https://hdl . handle. net/2027/uc1. 31175017624878 Creative Commons Attribution-NonCommercial-NoDerivatives / http://www.hathitrust.org/access_use#cc-by-nc-nd-4.0
Hyperadrenocorticism in cats: Seven cases (1978-1987)
R. W. Nelson, DVM; E. C. Feldman, DVM; M. C. Smith, DVM
Summary: Hyperadrenocorticism was diagnosed in 7 cats with concurrent diabetes mellitus. Four cats had pituitary adenoma with bilateral adrenocortical hyper- plasia, 1 cat had pituitary carcinoma with bilateral adrenocortical hyperplasia, 1 cat had adrenocortical carcinoma, and 1 cat had adrenocortical adenoma of the left adrenal gland. One year later, adrenocortical adenoma involving the right adrenal gland also was diagnosed in this cat. Clinical signs included polyuria and polydipsia (n = 7), development of pot-bellied ap- pearance (n = 5), dermatologic alterations (n = 5), leth- argy (n =3), weight loss (n=3), dyspnea/panting (n = 2), and recurrent bacterial infections (n = 2). In 6. cats, the diagnosis of hyperadrenocorticism was estab- lished before death on the basis of results of the ACTH stimulation test (n = 3) and the dexamethasone screen- ing test (n = 5). Pituitary-dependent hyperadrenocorti- cism was differentiated from adrenocortical neoplasia on the basis of results of the dexamethasone suppression test (n = 4), endogenous ACTH concentration (n = 3), results of abdominal radiography and ultrasonography (n=3), and exploratory celiotomy (n=1). Four cats died or were euthanatized without treatment attempts. Treatment with mitotane followed by 60Co teletherapy was ineffective in one cat with pituitary adenoma. One cat with pituitary carcinoma died one week after bilateral adrenalectomy. Bilateral adrenocortical ade- nomas were removed surgically in the affected cat.
H yperadrenocorticism is a multisystemic disor- der resulting from excessive circulating cor- tisol concentration. It is a well-documented disorder in the dog, arising from excessive secretion of ACTH from the pituitary gland, which causes adrenocor- tical hyperplasia, or from excessive cortisol secretion by a functional tumor of the adrenal cortex.1 Hyper- adrenocorticism rarely is recognized in the cat. Diagnosis was confirmed in 4 cats; 3 had pituitary- dependent hyperadrenocorticism (PDH),2-4 and 1
From the Department of Small Animal Clinics, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907 (Nelson), and the Department of Reproduction (Feldman) and the Veterinary Medical Teaching Hospital (Smith), School of Veterinary Medicine, University of California, Davis, CA 95616.
had adrenocortical adenoma.5 These 4 reports were published over a span of 12 years. In the study reported here, we describe clinical signs, laboratory findings, results of endocrinologic tests, treatment, and outcome in 7 cats with hyperadrenocorticism.
Criteria for selection of cases
From 1978 to 1987, hyperadrenocorticism was diagnosed in 7 cats. Hyperadrenocorticism was confirmed at necropsy in 6 cats (Table 1). Pituitary adenoma with bilateral adrenocortical hyperplasia was found in 4 cats, and pituitary carcinoma with bilateral adrenocortical hyperplasia was found in 1 cat. Adrenocortical carcinoma with contralateral adrenocortical atrophy was found in one cat. In one cat with bilateral adrenocortical adenomas, hypera- drenocorticism was confirmed histologically after adrenalectomy. The left adrenocortical adenoma was identified first, and at the time of adrenalectomy, the right adrenal gland appeared to be atrophied. One year later, adenoma was diagnosed in the right adrenal gland, which then was surgically removed. Therefore, hyperadrenocorticism was diagnosed twice in this cat.
Clinical evaluation
The cats of this study ranged in age from 8 to 15 years (mean, 10 years). All cats were of mixed breeding (domestic longhair and shorthair), and 4 were females.
The most common clinical signs of hyperadre- nocorticism were polyuria and polydipsia (n = 7) and polyphagia (n = 5). Dermatologic manifestations were seen in 5 of the 7 cats and included patchy endocrine alopecia involving the trunk and flanks (n =4), generalized truncal alopecia (n= 1), thin, easily wrinkled skin (n = 3), and hyperpigmentation (n = 1; Fig 1). During the initial examination of the cat with pituitary carcinoma and the second exam- ination of the cat with bilateral adrenocortical ade- nomas, multiple self-induced tears of the skin were observed on the trunk. They apparently had devel- oped as a result of grooming behavior. Other clinical signs included lethargy (n = 3), weight loss (n = 3), dyspnea/panting (n= 2), and recurrent bacterial infections (n = 2).
Creative Commons Attribution-NonCommercial-NoDerivatives / http://www.hathitrust.org/access_use#cc-by-nc-nd-4.0
Generated on 2024-10-30 15:08 GMT / https: //hdl . handle. net/2027/uc1. 31175017624878
| Cat No. | Plasma ACTH concentration (pg/ml) | ACTH stimulation test | Dexamethasone screening test | Dexamethasone suppression test | Histo- pathologic diagnosis | Treatment | Outcome | |||
|---|---|---|---|---|---|---|---|---|---|---|
| 0 hours | 1 hour | 0 hours | 8 hours | 0 hours | 8 hours | |||||
| 1 | 487 | 8.0 | 26.0 | ND | ... | ND | ... | PA; BAH | ND | Died of sepsis |
| 2 | 281 | 11.5 | 22.0 | ND | ... | ND | ... | PA; BAH | Exploratory celiotomy | Euthanatized during surgery |
| 3 | ND | ND | ... | ND | ... | ND | ... | AC (right; left atrophied) | ND | Died during testing |
| 4 | 90 | 7.4 | 13.7 | 6.3 | 6.2 | 4.6 | 1.5 | PA; BAH | Mitotane, then 60Co teletherapy | NA; euthanatized 2 weeks after completion of teletherapy |
| 5 | ND | ND | ... | 5.2 6.6 | 1.8 5.6 | 3.9 7.1 | <0.1 4.7 | PA; BAH AA (left; right atrophied) | ND UA (left) | Died during testing Resolution of clinical signs for |
| 6* | ND | ND | ... | 3.9 | 2.9 | 6.2 | 4.7 | AA (right) | UA (right) | 1 year, followed by recurrence Doing well 2 years after second UA; glucocorticoid |
| 7 | ND | 5.8 | 9.6 | 9.4 | 3.4 | ND | ... | PC; BAH | BA | and mineralocorticoid supplemented Died 1 week after surgery |
| Normal | 10 to 61 | 1.8 ± 1.8 | 8.4 ±1.8 | 1.8±1.8 | 0.4±0.5 | 1.8 ±1.8 | 0.5 ±0.4 | ... | ... | ... |
| (mean ± so; n =15) | (range) | |||||||||
| Diabetic (mean ± so; n =5) | ND | 1.8 ±1.7 | 6.6±2.0 | ND | ... | ND | ... | ... | ... | ... |
*This cat had adrenocortical adenoma (bilateral) diagnosed on separate occasions. Data are expressed as µg of cortisol/dl of plasma unless indicated otherwise. ND = not done; PA = pituitary adenoma; Pc = pituitary carcinoma; BAH = bilateral adrenocortical hyperplasia; Ac = adrenocortical carcinoma; AA = adrenocortical adenoma; UA = unilateral adrenalectomy; BA = bilateral adrenalectomy; NR = no response to treatment.
246 Reports of Retrospective Studies
The most consistent abnormalities observed during physical examination were abdominal en- largement resulting in pot-bellied appearance (n =5), the aforementioned dermatopathologic changes, and generalized muscular wasting (n = 4), which was viewed as weight loss by the owner(s). Hepatomegaly (n = 2), dyspnea (n = 1), and panting (n = 1) were found less often.
Diagnostic evaluation
The results of a hemogram, serum biochemical analysis, and urinalysis did not reveal specific ab- normalities that were helpful in establishing a diag- nosis of hyperadrenocorticism. Results of total RBC and wBC counts were within the reference range. Of the 7 cats, 3 had detectable eosinophil number, and 2 cats had normal or increased lymphocyte number.
The most frequently observed abnormalities on the serum biochemistry profile were increased se- rum glucose concentration (mean, 375 mg/dl; range, 296 to 469 mg/dl; normal, 70 to 120 mg/dl) and serum cholesterol concentration (mean, 249 mg/dl; range, 169 to 427 mg/dl; normal, 40 to 145 mg/dl). Serum alkaline phosphatase activity was increased in 1 cat (171 IU/L; normal, 15 to 35 IU/L), and serum alanine transaminase activity was increased in 2 cats (111 and 339 IU/L; normal, 10 to 60 IU/ L).
The urinalysis results were not consistent with the clinical sign of polyuria, because urine specific gravity was >1.030 in 6 of 8 randomly obtained urine specimens from the 7 cats. Hyposthenuria was not observed in any cat. Glucose was detected in all
Generated on 2024-10-30 15:08 GMT / https ://hdl . handle. net/2027/uc1. 31175017624878 Creative Commons Attribution-NonCommercial-NoDerivatives / http://www.hathitrust.org/access_use#cc-by-nc-nd-4.0
urine specimens, and protein was detected in 7 of 8 specimens. Bacteria were not evident in any urine specimen nor were bacteria isolated from bacterio- logic culture of urine specimens obtained by ante- pubic cystocentesis from 3 cats.
Abdominal radiography performed on 5 of the 7 cats (including twice on the cat with bilateral adrenocortical adenomas) revealed hepatomegaly in 3 cats and a mass in the region of the left adrenal gland in the cat with bilateral adrenocortical ade- nomas (during initial evaluation). Other radio- graphic abnormalities were not found. Abdominal ultrasonography was performed on 2 cats. The adrenal glands in one cat were visualized and were similar to one another in size and shape. Ultraso- nography twice correctly identified unilateral adre- nomegaly in the cat with bilateral adrenocortical adenomas; the contralateral adrenal gland in this cat was not visualized during the initial ultrasonography.
All 7 cats had poorly regulated diabetes mellitus and were persistently hyperglycemic and glycosuric despite insulin administration. At the time of eval- uation, exogenous insulin dosages ranged from 1.0 to 2.2 U/kg of body weight. Glucose determinations performed serially in 3 of the cats indicated apparent insulin antagonism, attributable to failure of the serum glucose concentration to decrease despite high insulin dosages.
Endocrinologic evaluation
All endocrinologic studies were initiated be- tween 8:00 and 10:00 AM. Blood samples for determination of plasma ACTH concentration were collected in heparinized plastic syringes, were im- mediately transferred to plastic tubes placed on ice, and then were centrifuged. The plasma was obtained and was stored at - 70 C until assayed. Plasma ACTH concentration was determined by radioim- munoassay, as described.6.7 The ACTH stimulation test was performed by collecting heparinized blood samples before and 1 hour after IM administration of 0.25 mg of synthetic ACTH.ª The dexamethasone screening and suppression tests were performed by collecting blood samples in heparinized syringes before and 8 hours after the Iv administration of 0.01 mg and 0.1 mg of dexamethasone sodium phosphateb/kg, respectively. During the 8 hours after dexamethasone administration, other procedures were not performed, and each cat was kept as quiet as possible in its cage. Plasma specimens obtained from the aforementioned blood samples were stored at - 70 C until assayed. Plasma cortisol values were determined by enzyme immunoassay, as described.7 The mean (+ SD) base-line plasma cortisol concen- tration for clinically normal cats was 1.8 ±1.8 µg/ dl. After administration of ACTH, it was 8.4±1.8 µg/dl; 8 hours after Iv administration of 0.01 mg of dexamethasone/kg, it was 0.4±0.5 µg/dl; and 8
hours after Iv administration of 0.1 mg of dexa- methasone/kg, it was 0.5 ± 0.4 µg/dl.
The ACTH stimulation test also was performed on 5 cats with well-controlled diabetes mellitus. In these cats, the mean base-line plasma cortisol con- centration was 1.8+1.7 ug/dl, and 1 hour after ACTH administration, it was 6.6 ±2.0 µg/dl. These results were similar to those obtained in clinically normal cats.
Of the 7 cats, 6 underwent at least one endocri- nologic test. (One cat died from acute respiratory tract complications before endocrinologic tests could be performed.) Of the 4 cats in which the ACTH stimulation test was performed, 3 had results that were consistent with a diagnosis of hyperadrenocor- ticism (Table 1). These 3 cats had PDH, and each had increased plasma cortisol concentration (above the normal reference range) after ACTH administration. One cat with pituitary carcinoma had normal plasma cortisol response to ACTH administration. Results for the 5 cats undergoing the dexamethasone (0.01 mg/ kg) screening test were consistent with hyperadre- nocorticism. In each instance, the postdexametha- sone plasma cortisol concentration failed to be suppressed to a value within the reference range (Table 1).
Plasma ACTH concentration was increased in 3 cats with PDH, correctly identifying the cause of the hyperadrenocorticism. Unfortunately, plasma en- dogenous ACTH concentration was not measured in either cat with adrenocortical tumor(s).
In the 4 cats in which the dexamethasone (0.1 mg/kg) suppression test was performed, results correctly identified the cause of hyperadrenocorti- cism. Arbitrarily, postdexamethasone plasma corti- sol concentration <50% of the predexamethasone plasma cortisol concentration was considered indic- ative of adrenocortical suppression and of PDH.8 Failure of plasma cortisol concentration to be sup- pressed <50% was considered supportive of, but not diagnostic for, functional adrenocortical neopla- sia. In 2 cats with PDH, the plasma cortisol concen- tration was suppressed to <50% of the predexa- methasone value, but in the cat with bilateral adrenocortical adenomas, plasma cortisol concentra- tion was not suppressed (Table 1).
Patient management
Treatment was not attempted in 4 of the 7 cats. Of these 4 cats, 2 died before the diagnosis was established. Shortly after hospitalization, both cats developed respiratory distress (dyspnea, open- mouth breathing), which progressed to acute cardi- opulmonary collapse; both died despite attempts at resuscitation. Histologic examination of the lungs from one of these cats revealed organized thrombi in many of the pulmonary vessels, with some pulmonary atelectasis and hemorrhage. In the other cat, hypertrophic cardiomyopathy was found at necropsy.
“Cortrosyn, Organon Inc, West Orange, NJ.
৳Dex-A-Vet, Anthony Products, Arcadia, Calif.
Generated on 2024-10-30 15:08 GMT / https://hdl . handle. net/2027/uc1.31175017624878 Creative Commons Attribution-NonCommercial-NoDerivatives / http://www.hathitrust.org/access use#cc-by-nc-nd-4.0
Treatment was not attempted in the 2 remaining cats, because one cat developed severe periorbital Nocardia asteroides infection while awaiting surgery and died 3 weeks later, despite treatment of nocar- diosis. The other nontreated cat was euthanatized after exploratory celiotomy revealed bilateral adrenal gland enlargement.
Of the 3 cats in which treatment was attempted, PDH was diagnosed in one on the basis of results of the dexamethasone suppression test, the endogenous ACTH concentration, and ultrasonographic evalua- tion of the adrenal glands. Mitotanec (25 mg/kg/day) was given for 25 consecutive days. Adverse reactions to the drug were not observed. Mitotane treatment did not result in clinical response, and daily insulin requirement remained high (2.2 U of insulind/kg, q 24 h). Results of ACTH stimulation tests repeated during the treatment period failed to reveal signifi- cant change, compared with pretreatment test re- sults. Mitotane treatment was discontinued, and cobalt irradiation (600 rads of 6ºCo/treatment; 6
treatments) of the pituitary gland tumor was at- tempted. At the completion of 6ºCo teletherapy, clinical signs were resolving, and responsiveness to insulin had returned. Daily insulin requirement decreased from 2.2 to 0.8 U of insulin/kg. Unfor- tunately, 2 weeks after 6ºCo teletherapy was com- pleted, the cat became depressed, developed periph- eral neuropathy of the hind limbs, and was euthanatized. Histologic examination of the pituitary gland revealed adenoma of the pars distalis. Inflam- mation and necrosis of the tumor or surrounding tissue was not evident.
Unilateral adrenal gland tumor was diagnosed in one cat on the basis of results of the dexametha- sone suppression test, abdominal radiography, and ultrasonographic evaluation of the adrenal glands. Unilateral adrenalectomy was performed. The his- topathologic diagnosis was adrenocortical adenoma. Postoperative management included Iv administra- tion of polyionic fluidse for 3 days; dexamethasone,b 0.1 mg/kg, Iv, daily for 3 days; prednisone,f 2.2 mg/ kg, Po, in 2 equally divided doses, daily; and insulin, 1.0 U/kg, sc, daily. Mineralocorticoid deficiency did not develop after surgery. Glucocorticoid supple- ment gradually was reduced and then was discon- tinued over a 2-month period. Clinical signs re- solved, and daily insulin requirement decreased to 0.6 U of insulin/kg, sc, daily.
Truncal alopecia, epidermal atrophy, and pot- bellied appearance began to redevelop 12 months after surgery. Glucocorticoids had not been admin- istered for 10 months. On the basis of results of the dexamethasone suppression test (Table 1) and ultra- sonographic evaluation of the remaining adrenal
Lysodren, Bristol Laboratories, Division of Bristol-Myers, Syracuse, NY, by Anabolic Inc, Irvine, Calif.
‘Protamine zinc insulin (100 U/ml), Eli Lilly and Co, Indian- apolis, Ind.
·Lactated Ringer USP, Abbott Laboratories, North Chicago, Ill. Prednisone tablets USP, TechAmerica Inc, Elwood, Kan.
gland, adrenal tumor was suspected. Celiotomy, with adrenalectomy, was performed. Adrenocortical adenoma was confirmed histopathologically. The postoperative management protocol used after initial surgery was repeated, but prednisone treatment was maintained after the dosage was reduced. In addi- tion, desoxycorticosterone acetates (1.0 mg, IM, daily) was given for 3 days after surgery, followed by fludrocortisone acetateh (0.1 mg, PO, in 2 equal divided doses, daily). Six weeks after surgery, the skin lesions and pot-bellied appearance began to resolve, the daily insulin requirement had decreased to 0.2 U of insulin/kg, and glycosuria was detected rarely. During the next 6 months, the daily dosage of insulin continued to decrease, and insulin admin- istration eventually was discontinued, without re- currence of glycosuria. The cat continued to be healthy 2 years after the second adrenalectomy.
Pituitary-dependent hyperadrenocorticism was diagnosed in 1 cat after exploratory celiotomy revealed bilateral adrenomegaly; therefore, bilateral adrenalectomy was performed. The postoperative management protocol was the same as that for the cat with bilateral adrenocortical adenomas after the second adrenalectomy. During the ensuing week, all the skin on the cat’s trunk sloughed, persistent hypothermia developed, and the cat died 7 days after adrenalectomy. Macroscopic and histologic examination of the pituitary gland revealed carci- noma invading the adjacent neuropil of the midbrain and hypothalamus.
Complete necropsy was performed on 6 of the 7 cats. In addition to the pathologic changes involv- ing the pituitary-adrenocortical axis (Table 1), diffuse hepatocellular degeneration (n = 4), islet cell degen- eration and reduction in islet cell number (n = 4), inflammation of the pancreatic parenchyma (n = 2), hypertrophic cardiomyopathy (n = 1), and pulmo- nary thromboemboli (n = 1) also were found. The pancreatic islets were considered normal in 2 of the 6 cats, despite clinical signs of diabetes mellitus.
Discussion
In cats, strong correlation may exist between hyperadrenocorticism and diabetes mellitus. Of 11 cats with hyperadrenocorticism reported by us and by others,2-5 10 had diabetes mellitus,2-4 and glycos- uria was observed in the eleventh cat.5 In 9 of the 10 cats, diabetes was regulated poorly. Although these 2 disorders may not be causally related, diabetes mellitus in some cats with hyperadrenocor- ticism may result from the insulin antagonistic action of glucocorticoids. Glucocorticoids promote hepatic gluconeogenesis, decrease peripheral tissue glucose utilization, inhibit cellular receptor affinity for in- sulin, and exert a postreceptor influence that inhibits insulin action.9-12 If the pancreatic ß cells remain functional, resolution of insulin antagonism should
&DOCA acetate, Organon Inc, West Orange, NJ. “Florinef acetate, E. R. Squibb and Sons Inc, Princeton, NJ.
248 Reports of Retrospective Studies
http://www.hathitrust.org/access_use#cc-by-nc-nd-4.0
https://hdl.handle.net/2027/uc1.31175017624878
Generated on 2024-10-30 15:08 GMT
Creative Commons Attribution-NonCommercial -NoDerivatives
improve glucose intolerance. This was suggested in one cat of this report in which exogenous insulin administration was discontinued after successful treatment of hyperadrenocorticism.
Chronic hypercortisolemia and insulin resis- tance may cause ß-cell exhaustion, cell death, and, subsequently, hypoinsulinemic diabetes mellitus. Re- duction in the number of islet cells, as well as diffuse vacuolar degeneration and hyalinization of islet cells, was observed in 4 of our cats and in 2 others, reported previously.2,3 These changes were consistent with those seen in some diabetic cats. However, 2 of our cats had normal pancreatic islet number, typical of some human beings with diabetes melli- tus.13,14 In pancreatic islets of such affected human beings, ß cells often are lacking or their number is reduced, but normal numbers of « and ô cells are observed.
Clinical signs in cats, similar to those in dogs with hyperadrenocorticism, developed after glucose intolerance. The apparent lack of clinical signs before the onset of hyperglycemia and glycosuria was consistent with the insidious nature of hyperadre- nocorticism in human beings and dogs. Although polyuria, polydipsia, and polyphagia were the most frequently observed clinical signs in our cats, these may have reflected hyperglycemia and glycosuria, rather than hypercortisolemia. Compatible with this hypothesis were (1) the inability to document polyuria and polydipsia in cats treated with gluco- corticoids until severe glucose intolerance had developed15,16 and (2) the concentrated urine specific gravity in 6 of 8 urine specimens from our cats.
Dermatologic manifestations were observed in 5 of the 7 cats and in the 4 cats reported previously.2-5 Alterations were similar to those in dogs with hyperadrenocorticism; however, the truncal alopecia tended to be less severe than that commonly seen in dogs. The normal grooming behavior of cats also could cause tears in the skin after development of epidermal and dermal atrophy.15 In addition to the dermatologic alterations, abdominal enlargement resulting in pot-bellied appearance and generalized muscular wasting were other clinical findings often seen in dogs with hyperadrenocorticism.
Steroid-induced hepatopathy, which commonly develops in dogs with hyperadrenocorticism, is characterized by hepatomegaly, increased serum alkaline phosphatase activity, and diffuse vacuolation of hepatocytes with intracytoplasmic glycogen ac- cumulation.17 Comparable alterations were not com- monly observed in our 7 cats or in those reported previously.2-5 Evaluation of all 11 cats revealed mild hepatomegaly during physical examination of 3 cats; radiography revealed hepatomegaly in 4 others. Histologic examination of the liver of 9 cats (6 of this study) revealed hepatic lipidosis in 4, hepato- cellular degeneration and necrosis in 3, and no abnormalities in 2. Steroid-induced hepatopathy was not observed.
Increased serum alkaline phosphatase activity
was observed in 1 of our cats, but was not found in any of the other affected cats reported previously.2-5 Inability to document histologic changes in the liver consistent with steroid-induced hepatopathy, poten- tial lack of the steroid-induced alkaline phosphatase isoenzyme activity, and the relatively short half-life of serum alkaline phosphatase activity in cats might account for the lack of an observed increase in serum alkaline phosphatase activity.18,19
Evaluation of the other components of a he- mogram, serum biochemical profile, and urinalysis was helpful in eliminating other potential causes for the clinical signs; however, changes specifically helpful in diagnosing hyperadrenocorticism were not detected. Classic clinicopathologic alterations seen in dogs with hyperadrenocorticism were not observed consistently in our cats. The only consistent alterations (ie, hyperglycemia, glycosuria, hypercho- lesterolemia) could be explained by concurrent poorly regulated diabetes mellitus. Neutrophilic leukocytosis with lymphopenia and eosinopenia was not seen in any of our cats and has been documented in only 2 other cats with hyperadrenocorticism.3.4
Establishing a diagnosis of feline hyperadreno- corticism requires endocrinologic testing of the pituitary-adrenocortical axis. Although the number of tests performed in these cats was small, interpre- tation of results appeared to be comparable with interpretation of results in dogs.9,20 Establishing the diagnosis of hyperadrenocorticism was accom- plished by such observed test results as exaggerated response to exogenous ACTH administration or fail- ure of suppression of plasma cortisol concentration 8 hours after Iv administration of 0.01 mg of dexamethasone/kg. Differentiating PDH from adre- nocortical neoplasia was accomplished by evaluating the suppressive effects of Iv administered dexameth- asone (0.1 mg/kg) in conjunction with results of abdominal radiography and ultrasonography. In the 3 cats in which it was measured, base-line plasma ACTH concentration (Table 1) identified PDH. Unfor- tunately, base-line plasma ACTH concentration was not measured in either of the cats with adrenocortical neoplasia. Of 18 clinically normal cats, 7 had plasma ACTH concentration <20 pg/ml, thus making this test of questionable value in confirming functioning adrenocortical tumor in cats.7
The deleterious effects of chronic hypercorti- solism on immune and cardiovascular functions may have been responsible for the death of 6 untreated cats shortly after the diagnosis of hyperadrenocor- ticism was established.2-4 The immunosuppressive effects of glucocorticoids predispose a poorly regu- lated diabetic animal to infections.21 Recurring infec- tion was a problem in 2 of our cats and in 3 others.2-4 Of these 5 cats, 3 died as a direct result of overwhelming sepsis.
Chronic hypercortisolism also may affect the cardiovascular system, through the development of systemic hypertension, pulmonary thromboemboli, or congestive heart failure.22-24 Two of the cats of
Generated on 2024-10-30 15:08 GMT / https://hdl . handle. net/2027/uc1.31175017624878 Creative Commons Attribution-NonCommercial-NoDerivatives / http://www.hathitrust.org/access_use#cc-by-nc-nd-4.0
our study developed respiratory distress and died before definitive diagnosis and treatment could be established. Necropsy revealed diffuse pulmonary thromboemboli in one cat and hypertrophic cardi- omyopathy in the other. Cardiomyopathy, with features of the hypertrophic and congestive forms, was believed responsible for the death of a third cat with hyperadrenocorticism.3
Treatment is indicated after hyperadrenocorti- cism has been diagnosed; however, effective treat- ment for feline hyperadrenocorticism is yet to be determined. Extrapolating from treatment results in human beings and dogs, potential options include the use of the adrenocorticolytic agent mitotane, blockers of cortisol synthesis and secretion (eg, metyrapone), surgical removal of adrenocortical tu- mor, bilateral adrenalectomy for PDH, or radiotherapy of pituitary adenoma.25 Although accumulated data are small, surgery may offer the best success. Adrenalectomy was accomplished successfully twice in one of our cats and in 2 others.5.26 In our cat (with bilateral adrenocortical adenomas), the second sur- gery created mineralocorticoid-dependent hypoa- drenocorticism, which responded well to fludrocor- tisone acetate supplementation. This response would support the use of bilateral adrenalectomy for the treatment of PDH in cats, especially given the ineffec- tiveness of mitotane treatment in one of our cats with PDH.
Teletherapy, using 60Co, is not readily available, and its effectiveness remains to be determined. Although preliminary results were promising in one cat with PDH that was treated with 60Co teletherapy, the development of complications prompting eutha- nasia 2 weeks after completion of teletherapy pre- cludes any statements regarding long-term effective- ness.
In contrast to its efficacy in dogs with hypera- drenocorticism, ketoconazole does not suppress plasma cortisol concentration in clinically normal cats and may not be an effective treatment for feline hyperadrenocorticism.27,i
‘Bruyette DS, Feldman EC. Medical management of canine hyperadrenocorticism with ketoconazole (abstr), in Proceedings. Am Coll Vet Intern Med, 1987;885.
References
1. Ling GV, Stabenfeldt GH, Comer KM, et al. Canine hyperadrenocorticism: pretreatment clinical and laboratory eval- uation of 117 cases. J Am Vet Med Assoc 1979;174:1211-1215.
2. Fox JG, Beatty JO. A case report of complicated diabetes mellitus in a cat. J Am Anim Hosp Assoc 1975;11:129-134.
3. Peterson ME, Steele P. Pituitary-dependent hyperadre- nocorticism in a cat. J Am Vet Med Assoc 1986;189:680-683.
4. Zerbe CA, Nachreiner RF, Dunstan RW, et al. Hypera- drenocorticism in a cat. J Am Vet Med Assoc 1987;190:559-563.
5. Meijer JC, Lubberink AAME, Gruys E. Cushing’s syn-
drome due to adrenocortical adenoma in a cat. Tijdschr Dierge- neeskd 1978;103:1048-1051.
6. Grizzle WE, Dallman MF, Schramm LP, et al. Inhibitory and facilitatory hypothalamic areas mediating ACTH release in the cat. Endocrinology 1974;95:1450-1461.
7. Smith MC, Feldman EC. Plasma endogenous ACTH concentrations and plasma cortisol response to synthetic ACTH and dexamethasone sodium phosphate in healthy cats. Am J Vet Res 1987;48:1719-1724.
8. Feldman EC. Distinguishing dogs with functioning adre- nocortical tumors from dogs with pituitary-dependent hypera- drenocorticism. J Am Vet Med Assoc 1983;183:195-200.
9. Grunfeld C, Baird K, Van Obberghen E, et al. Glucocor- ticoid-induced insulin resistance in vitro: evidence of both receptor and postreceptor defects. Endocrinology 1981;109:1723- 1730
10. Nosadini R, Del Prato S, Tiengo A, et al. Insulin resistance in Cushing’s syndrome. J Clin Endocrinol Metab 1983;57:529-536.
11. Pagano G, Cavallo-Perin P, Cassader M, et al. An in vivo and in vitro study of the mechanism of prednisone-induced insulin resistance in healthy subjects. J Clin Invest 1983;72:1814- 1820.
12. Ganong WF. Review of medical physiology. 11th ed. Los Altos, Calif: Lange Medical Publications, 1983.
13. Gepts W, DeMey J. Islet cell survival determined by morphology. Diabetes 1978;27(suppl 1):251-261.
14. Foulis AK, Stewart JA. The pancreas in recent-onset type I (insulin-dependent) diabetes mellitus: insulin content of islets, insulitis and associated changes in the exocrine acinar tissue. Diabetologia 1984;26:456-461.
15. Scott DW, Manning TO, Reimers TJ. Iatrogenic Cushing’s syndrome in the cat. Feline Pract 1982;12:30-36.
16. Scott DW, Kirk RW, Bentinck-Smith J. Some effects of short-term methylprednisolone therapy in normal cats. Cornell Vet 1979;69:104-115.
17. Badylak SF, Van Vleet JF. Sequential morphologic and clinicopathologic alterations in dogs with experimentally induced glucocorticoid hepatopathy. Am J Vet Res 1981;42:1310-1318.
18. Dorner JL, Hoffman WE, Long GH. Corticosteroid induction of an isoenzyme of alkaline phosphatase in the dog. Am J Vet Res 1974;35:1457-1458.
19. Everett RM, Duncan JR, Prasse KW. Alkaline phospha- tase, leucine aminopeptidase, and alanine aminotransferase activ- ities with obstructive and toxic hepatic disease in cats. Am J Vet Res 1977;38:963-966.
20. Feldman EC. Comparison of ACTH response and dexamethasone suppression as screening tests in canine hypera- drenocorticism. J Am Vet Med Assoc 1983;183:505-510.
21. Parrillo JE, Fauci AS. Mechanisms of glucocorticoid action on immune processes. Annu Rev Pharmacol Toxicol 1979;19:179-201.
22. Williams GH, Braunwald E. Endocrine and metabolic disorders. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. Philadelphia: WB Saunders Co, 1984;1722-1747.
23. Clark AF, Tandler B, Vignos PJ. Glucocorticoid-induced alterations in the rabbit heart. Lab Invest 1982;47:603-610.
24. Burns MG, Kelley AB, Hornof WJ, et al. Pulmonary artery thrombosis in three dogs with hyperadrenocorticism. J Am Vet Med Assoc 1981;178:388-393.
25. Feldman EC, Nelson RW. Hyperadrenocorticism. In, Feldman EC, Nelson RW, eds. Canine and feline endocrinology and reproduction. Philadelphia: WB Saunders Co, 1987;137-194.
26. Swift GA, Brown RH. Surgical treatment of Cushing’s syndrome in the cat. Vet Rec 1976;99:374-375.
27. Willard MD, Nachreiner RF, Howard VC, et al. Effect of long-term administration of ketoconazole in cats. Am J Vet Res 1986;47:2510-2513.