Comparison of mitotane treatment for adrenal tumor versus pituitary-dependent hyperadrenocorticism in dogs
Edward C. Feldman, DVM; Richard W. Nelson, DVM; Marsha S. Feldman, MS; Thomas B. Farver, PhD
Summary: The purpose of this study was to determine the sensitivity of dogs with hyperadrenocorticism to treatment with the adrenocorticolytic agent mitotane. Specifically, we looked for differences in response to treatment using this drug in dogs with adrenocortical tumors (adrenal tumor hyperadrenocorticism, ATH) vs those with pituitary-dependent hyperadrenocorticism (PDH). For inclusion in this study, each dog must have had clinical signs, data base laboratory abnormalities, and endocrine screening test results consistent with the diagnosis of hyperadrenocorticism. Further, each dog had to have been treated for at least 6 months with mitotane and have histologic evidence for adrenocor- tical or pituitary neoplasia (all dogs were necropsied). Thirteen dogs with ATH (8 carcinomas, 5 adenomas) were identified. The ages and body weights of these 13 dogs were computer-matched to 13 dogs with PDH. All dogs were initially treated with approximately 50 mg of mitotane/kg/d of body weight. Reexaminations were performed after 7, 30, 90, and 180 days of treatment.
Individual dosages varied widely after the initial 5 to 12 days of treatment. The mean (± SD) dose of mitotane (mg/kg/d) for the first 7 days of treatment was 47.5 ± 9.4 for dogs with ATH vs 45.7 ± 11.9 for dogs with PDH. The mean plasma cortisol concentra- tions 1 hour after ACTH administration at the 7-day recheck were significantly higher in dogs with ATH (502 ± 386 nmol/L) than in dogs with PDH (88 ± 94 nmol/L). At 30 days, the mean daily dose of mitotane and post-ACTH cortisol concentration were signifi- cantly greater in dogs with ATH (28.8 ± 15.4 mg/ kg/d; 392 ± 356 nmol/L, respectively) than in dogs with PDH (10.5 ± 7.5 mg/kg/d; 99 ± 72 nmol/L, respectively). After 90 days of treatment, these values were larger (25.3 ± 16.8 mg/kg/d; 340 ± 193 nmol/L in dogs with ATH vs those in dogs with PDH (5.4 ± 2.5 mg/kg/d, 110 ± 94 nmol/L) and again
From the Departments of Reproduction (E Feldman, M Feldman), Medicine (Nelson), and Epidemiology and Preven- tive Medicine (Farver), School of Veterinary Medicine, Univer- sity of California, Davis, CA 95616.
Supported by financial contributions from Ms. Ruth Johnston, San Mateo, Calif, and the Companion Animal Program Fund, School of Veterinary Medicine, University of California, Davis.
after 180 days (26.0 ± 22.1 mg/kg/d, 268 ± 152 nmol/L in dogs with ATH vs 6.3 ± 3.4 mg/kg/d, 80 ± 116 nmol/L in dogs with PDH). Clinical signs were consistent with laboratory values, that is, corti- sol control was not as good in dogs with ATH as in the dogs with PDH. On the basis of these findings, we sug- gest that dogs with hyperadrenocorticism caused by ATH are more resistant to mitotane than are dogs with PDH.
T he adrenocorticolytic effects of mitotaneª in dogs were first described in 1949.1 This agent was recommended for the medical management of dogs with naturally acquired hyperadrenocorticism in 1973.2 In the years since, use of mitotane has become routine in the treatment of this syn- drome.3-5 The 2 major causes of naturally acquired hyperadrenocorticism in dogs are pituitary-depen- dent hyperadrenocorticism (PDH) and functioning adrenocortical adenoma or carcinoma (adrenal tu- mor hyperadrenocorticism, ATH). 6-8 Although mi- totane is accepted as a successful mode of treat- ment for PDH, to our knowledge, critical assessment of its efficacy in the treatment of ATH has not been reported.
The purpose of the study reported here was to determine the sensitivity of dogs with hyper- adrenocorticism to treatment with mitotane. Spe- cifically, we evaluated dogs with ATH and compared their mitotane treatment response with that in dogs with PDH. This evaluation concentrated on objec- tive assessments of biochemical response and dos- age requirements needed to control the disease. Subjective clinical response to treatment was also assessed by review of owners opinions.
Materials and Methods
Dogs-To be included in the study, a dog must have had abnormalities consistent with the diag- nosis of hyperadrenocorticism on review of clini- cal signs, a hemogram, serum biochemical profile, and urinalysis results. Confirmation of hyper- adrenocorticism by use of adrenocorticotropin (ACTH) stimulation or low-dose dexamethasone
ªLysodren, Bristol-Myers Co, Evansville, Ind.
testing must have been obtained.7 Each dog must have been treated for at least 6 months with mito- tane as the first and only treatment for hyper- adrenocorticism. All dogs in this study must have been necropsied with owner permission, and each must have had histologic evidence for ATH or PDH. Dogs with ATH could not have evidence of a pitu- itary tumor, all dogs with PDH had to have a pitu- itary tumor, and dogs with PDH did not have an ad- renal tumor.
Included in the study were 26 dogs with hyper- adrenocorticism. Thirteen dogs with ATH were identified as meeting the criteria described. Each of these 13 dogs with ATH was then computer- matched by age and body weight to a dog with PDH. The 13 dogs with PDH were otherwise selected ran- domly from a pool of > 50 dogs with PDH and that met the described criteria for inclusion in the study.
Treatment protocol-Each of the 26 dogs was treated with mitotane at a loading dose of approx- imately 50 mg/kg/d of body weight, PO, for 5 to 9 days. Following successful loading-dose adminis- tration, maintenance dosages of mitotane were initially 25 to 50 mg/kg/wk.5 Further dose adjust- ments were individualized to each dog. Each dog was evaluated after 7, 30, 90; and 180 days of treatment. The evaluations included notation of clinical (subjective) observations regarding re- sponse to treatment and to an ACTH stimulation test (plasma obtained before and 1 hour after IM administration of 0.25 mg of synthetic ACTHb). The dosage of mitotane was adjusted, as needed, to at- tain or sustain the goals of treatment. These goals included improvement or resolution of the clinical signs related to hyperadrenocorticism together with post-ACTH plasma cortisol concentrations < 110 nmol/L but > 25 nmol/L. These plasma cortisol concentrations were arbitrarily established as demonstrating an excellent response to treat- ment but avoiding overdosage.3,4 If plasma cortisol response to exogenous ACTH decreased below 25 nmol/L, the mitotane dosage was reduced or tran- siently discontinued. If plasma cortisol concentra- tions failed to decrease to the ideal concentration, daily treatment was continued or maintenance dosages were increased. None of the dogs in this study were given glucocorticoids at any time.
Hormone assays-Blood samples obtained for plasma cortisol determination were immediately centrifuged, and the plasma was frozen at -20 C until assayed. Plasma cortisol concentration was determined by use of an enzyme immunoassay.9 The assay used antiserum raised in rabbits to a cortisol 3-0 carboxymethyloxime-bovine serum albumin immunogen and cortisol 3-0 carboxyme- thyloxime-horseradish peroxidase as the label. The assay was specific for cortisol. Cross-reactivity to other corticosteroids was: prednisone, 6.3%; pred- nisolone, 9.9%; 11 alpha-deoxycorticosterone, 6%;
cortisone, 5%; and corticosterone, 0.7%. For all other steroids, including dexamethasone, cross- reactivity was lower. Cortisol standards were pre- pared in ethanol to give a standard curve range of 0.1 to 250 pg/well. The intraplate coefficient of variation was 1.9%. The interplate assay precision determinations gave coefficients of variation of 8.8% for low (24.4 nmol/L, n = 45), 7.3% for me- dium (513 nmol/L, n = 41), and 8% for high (1,137 nmol/L, n = 40) concentrations of cortisol in 3 pooled serum samples. The interassay coeffi- cients of variation were 12.4, 10.5, and 6.8% for the same 3 pools of serum. The sensitivity of the system was 0.25 pg/well or 1.4 nmol of cortisol/L in canine plasma. Recovery was determined by as- saying several samples, to which various known amounts of cortisol had been added: mean amount recovered was 98.8%, with range of 94 to 104%.
Statistical analysis-All results are reported as mean ± SD. Data were analyzed by use of repeat- ed-measures analyses of variance. Differences be- tween group means were evaluated, using the Student-Newman-Keul’s test.10 Values of P < 0.05 were considered significant.
Results
The dogs with hyperadrenocorticism meeting the criteria for evaluation in this study included 13 dogs with adrenocortical tumors, 5 with a solitary adenoma and 8 with a solitary carcinoma. Their mean age at the time of initiating mitotane treat- ment was 11.3 ± 2.3 years and their mean body weight was 13.6 ± 7.9 kg. As previously de- scribed, each ATH dog was computer-matched by age and weight to a dog with PDH meeting the cri- teria for evaluation in this study. Thus, 13 dogs with PDH were included and there was no significant difference in their age (mean 11.0 ± 2.3 years) or body weight (mean, 13.2 ± 8.7 kg) when com- pared with the dogs with ATH.
The ACTH stimulation tests were performed on all of the dogs before initiating mitotane treatment. The basal plasma cortisol concentrations were not significantly different (ATH, 132.4 ± 41.4 nmol/L; PDH, 184.8 ± 110 nmol/L). The mean post-ACTH plasma cortisol concentration from the dogs with ATH (762 ± 409 nmol/L; range, 245 to 1,404 nmol/L) was not significantly different from that in the 13 dogs with PDH (690 ± 295 nmol/L; range, 232 to 1,333 nmol/L). The post-ACTH range of plasma cortisol concentrations in healthy dogs is 155 to 415 nmol/L.7 The 26 dogs began mitotane treatment at a dosage of approximately 50 mg/ kg/d. The mean dosages administered during the first 7 days of treatment were 47.5 ± 9.4 mg/kg/d for the dogs with ATH and 45.7 ± 11.9 mg/kg/d for the dogs with PDH. These dosages were not signif- icantly (P > 0.05) different. Following 7 days of treatment, significant differences in response to ACTH were obvious when the 2 groups of dogs were compared. The mean basal plasma cortisol con-
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Figure 1-The mean (±SD) daily dose of mitotane for the first 7 days of treatment, as well as the mean (±SD) basal (pre) and post-ACTH stimulation plasma cortisol concentra- tions prior to and following 7 days of treatment in dogs with hyperadrenocorticism. Top = dogs with adrenal tumor (ATH); bottom = dogs with pituitary-dependent hyper- adrenocorticism (PDH).
centration of the dogs with PDH (49.5 ± 33.0 nmol/L) was significantly (P < 0.004) less than that of the dogs with ATH (110 ± 57.8 nmol/L). Eleven of the 13 dogs with PDH had post-ACTH plasma cortisol concentrations < 110 nmol/L vs only 1 of 13 dogs with ATH. In the 13 dogs with PDH, mean post-ACTH plasma cortisol concentration was 88 ± 94 nmol/L vs 502 ± 386 nmol/L (P < 0.001) in the 13 dogs with ATH (Fig 1).
Days 8 through 30 of treatment consisted of mitotane dosage adjustments, with dogs having post-ACTH plasma cortisol concentrations < 110 nmol/L given 25 to 50 mg of mitotane/kg/wk. Those dogs with a post-ACTH plasma cortisol con- centration between 110 nmol/L and their pretreat- ment concentration were given mitotane at a dos- age between 50 mg/kg/d and 50 mg/kg/wk. Dosage varied among the dogs of both groups. The mean dosage of mitotane administered days 8 through 30 was 28.8 ± 15.4 mg/kg/d to the dogs with ATH, which was significantly (P < 0.001) greater than the dosage of 10.5 ± 7.5 mg/kg/d given to the dogs with PDH. The mean basal plasma cortisol concen- tration of the dogs with PDH (52.2 ± 24.8 nmol/L) was significantly (P < 0.03) less than that of the dogs with ATH (90.8 ± 55.0 nmol/L). The mean post-ACTH plasma cortisol concentration of 99 ± 72 nmol/L for the dogs with PDH was significantly
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(P <0.01) less than the mean of 392 ± 356 nmol/L for the dogs with ATH (Fig 2). One of the 13 dogs with ATH and 10 of the 13 dogs with PDH had a post-ACTH plasma cortisol concentration < 110 nmol/L.
The pattern of response to mitotane treatment observed in the first 30 days persisted for days 31 through 90. The mean dosage of mitotane admin- istered to the dogs with ATH was 25.3 ± 16.8 mg/ kg/d and their mean post-ACTH plasma cortisol concentration following 90 days of treatment was 340 ± 193 nmol/L. The mean basal plasma corti- sol concentration of the dogs with PDH (68.8 ± 90.8 nmol/L) was not different from that of the dogs with ATH (77.0 ± 55.0 nmol/L). However, the mean post-ACTH plasma cortisol concentration in the dogs with PDH was 110 ± 94 nmol/L, which is sig- nificantly (P < 0.001) less than the values in the dogs with ATH. The mean dosage of mitotane was 5.4 ± 2.5 mg/kg/d, which also is significantly (P < 0.001) less than that given to the dogs with ATH (Fig 3). Two of the 13 dogs with ATH vs 9 of the 13 dogs with PDH had post-ACTH plasma cortisol concentrations < 110 nmol/L.
The final assessment period was that of 91 through 180 days of treatment. The mean basal plasma cortisol concentration of the dogs with PDH (46.8 ± 41.2 nmol/L) was significantly (P < 0.04) less than that of the dogs with ATH (93.5 ± 60.5 nmol/L). The mean dosage of mitotane adminis- tered to the dogs with PDH was 6.3 ± 3.4 mg/kg/d
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and the mean post-ACTH plasma cortisol concen- tration following 180 days of treatment was 80 ± 116 nmol/L. Both these values were signifi- cantly (P < 0.005) less than those obtained from the dogs with ATH. The mean post-ACTH plasma cortisol concentration in the dogs with ATH was 268 ± 152 nmol/L and the mean dosage of mito- tane was 26.0 ± 22.1 mg/kg/d (Fig 4). Two of the 13 dogs with ATH vs 11 of the 13 dogs with PDH had post-ACTH plasma cortisol concentrations < 110 nmol/L.
The response to mitotane in dogs with adreno- cortical adenomas was not different from those with adrenocortical carcinomas. At no time before or during treatment were the mean plasma cortisol concentrations of these 2 groups different. Prior to treatment, the mean post-ACTH plasma cortisol concentration in the group with adenoma (706.3 ± 430.9 nmol/L) was not significantly dif- ferent from that in the group with carcinoma (827.7 ± 402.8 nmol/L). Lack of significant (P > 0.05) difference, using this variable in these 2 groups, also was demonstrated after 7 days of treatment (458 ± 259.3 nmol/L vs 573.9 ± 449.7 nmol/L, respectively), 30 days of treatment (325.6 ± 212.4 nmol/L vs 469 ± 488.3 nmol/L, respectively), 90 days of treatment (355.9 ± 209.7 nmol/L vs 320 ± 187.6 nmol/L, respectively), and 180 days of treatment (320 ± 187.6 nmol/L vs 206.9 ± 69.0 nmol/L, respectively). The dogs with decreasing plasma cortisol concentrations
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had clinical improvement. The dogs that had per- sistent increases in post-ACTH plasma cortisol con- centration had little or no clinical improvement.
Clinical observations were difficult to analyze objectively. Subjectively, there was a much better clinical response in the dogs with PDH. All 13 own- ers of dogs with PDH thought their dogs were much improved after 30 days of treatment. Twelve of these owners reported that their dogs were virtually normal after both the 90- and 180-day reexamina- tions, and the remaining owner considered his dog much better but not normal. After 30 days of treat- ment in the dogs with ATH, 1 owner reported that their dog was much improved, 4 believed their dogs were improved and 8 observed no improvement or worsening signs. Following 90 and 180 days of treatment, 4 owners believed their dogs (2 with adenomas, 2 with carcinomas) were much im- proved, 3 observed some improvement (1 with an adenoma, 2 with carcinomas), 2 reported no change (1 with an adenoma, 1 with a carcinoma), and 4 were convinced that their dogs (1 with an adenoma, 3 with carcinomas) had deteriorated with continuing signs of hyperadrenocorticism.
The observations made by pathologists corre- lated with the subjective owner opinions and were consistent with the hormonal test results. The ad- renal cortices from those dogs with PDH were shrunken, collapsed, and fibrotic. Additionally, necrosis, hemorrhage, and invasion by substantial numbers of macrophages were observed. These
changes were described as being typical of mito- tane-induced destruction.11,12 In contrast, the 13 adrenocortical tumors were recognized and classi- fied without difficulty. The 5 adrenocortical ade- nomas were distinguished from the 8 carcinomas. Although it is appreciated that classification of en- docrine tumors histologically is not a perfect science, all 13 dogs were definitely classified as having adrenocortical neoplasia and further classi- fication of adenomas vs carcinomas were made with confidence. Little evidence of the type and severity of destruction observed in the hyperplas- tic adrenal cortices were described in the adreno- cortical tumors.
Discussion
Naturally acquired hyperadrenocorticism is a well-recognized endocrine disturbance in dogs. Further, it is generally accepted that approximately 80 to 90% of dogs with this disorder have PDH, VS the minority that have ATH.13,14 The procedures most frequently recommended for discriminating between PDH and ATH include the high-dose dex- amethasone test, measurement of endogenous plasma ACTH concentrations, abdominal radiogra- phy, ultrasonography, computerized tomography, and less frequently corticotropin releasing hor- mone stimulation or metyrapone response tests. 15 None of these tests are perfect and they can be ex- pensive, difficult to interpret, difficult to obtain, require sophisticated equipment, or not be widely understood. Making a correct diagnosis of hyper- adrenocorticism is often considerably easier than discriminating between the 2 major subgroups that comprise this syndrome.
It is appreciated that some veterinary practi- tioners do not proceed beyond the step of making a diagnosis of hyperadrenocorticism, whereas oth- ers perform discrimination procedures that occa- sionally provide vague results. Further, although mitotane is currently the recommended treatment for PDH, treatment options are not available if a dog with ATH has an inoperable tumor, has metastases at the time of diagnosis, is too debilitated to be a reasonable candidate for surgery, or cannot un- dergo surgery because of owner constraints. It is obvious that some dogs with ATH, recognized or not, will be treated with mitotane because few al- ternatives exist.
Dogs with ATH, in this study, were given at least 4 times the amount of mitotane administered to the dogs with PDH throughout the 6 months of obser- vation. Yet, the post-ACTH plasma cortisol concen- tration, in the dogs with ATH, were at least 3 times the values obtained from the dogs with PDH throughout the study. Clinical response assessed by owners were consistently poorer in the dogs with ATH than in the dogs with PDH. The implications of the results of this study suggest that dogs with ATH, specifically their adrenocortical tumors, are con- siderably more resistant to the adrenocorticolytic
effects of mitotane than are dogs with PDH. Thus, one potential recommendation arising from this study would be that dogs with undiscriminated hy- peradrenocorticism be classified as sensitive or re- sistant to mitotane treatment. If discrimination testing had not been performed prior to initiating treatment, those dogs that are resistant to treat- ment, defined as little or no reduction in post-ACTH plasma cortisol concentration after 30 days, should be further evaluated to determine whether an adrenocortical tumor is an explanation for the re- sistance. If so, more aggressive treatment with sur- gery, higher mitotane dosages, or ketoconazolec treatment can be considered.16 If a dog with hyperadrenocorticism has an excellent response to mitotane treatment, further discrimination testing may not be warranted.
On the basis of our findings, dogs with ATH are more resistant to the adrenocorticolytic effects of mitotane as compared with dogs with PDH. Dogs with ATH can be managed with mitotane, as dem- onstrated in 2 dogs with an excellent response, but at a success rate below that of PDH. It is reasonable to suggest that dogs known to have ATH be treated with surgery and if this is not possible, that higher initial mitotane dosages be used than are currently used successfully in dogs with PDH.
“Nizoral, Janssen Pharmaceutical Inc, Piscataway, NJ.
References
1. Nelson AA, Woodard G. Severe adrenal cortical atro- phy (cytotoxic) and hepatic damage produced in dogs by feed- ing 2,2-bis (parachlorophenyl)-1, 1-trichloroethane (DDD or TDE). Arch Pathol 1949;47:387-394.
2. Schechter RD, Stabenfeldt GH, Gribble DH, et al. Treatment of Cushing’s syndrome in the dog with an adreno- corticolytic agent (o,p’DDD). J Am Vet Med Assoc 1973;162: 629-639.
3. Feldman EC, Nelson RW. Canine and feline endocri- nology and reproduction. Philadelphia: WB Saunders Co, 1987; 137.
4. Peterson ME. o,p’DDD (mitotane) treatment of canine pituitary-dependent hyperadrenocorticism. J Am Vet Med Assoc 1983;182:527-528.
5. Lornez MD. Diagnosis and medical management of canine Cushing’s syndrome: a study of 57 consecutive cases. J Am Anim Hosp Assoc 1982;18:707-716.
6. Feldman EC. Effect of functional adrenocortical tu- mors on plasma cortisol and corticotropin concentrations in dogs. J Am Vet Med Assoc 1981;178:823-826.
7. Feldman EC. Comparison of ACTH response and dex- amethasone suppression as screening tests in canine hypera- drencorticism. J Am Vet Med Assoc 1983;182:506-510.
8. Feldman EC. Distinguishing dogs with functioning adrenocortical tumors from dogs with pituitary-dependent hy- peradrenocorticism. J Am Vet Med Assoc 1983;183:195-200.
9. Smith MC, Feldman EC. Plasma endogenous ACTH concentrations and plasma cortisol responses to synthetic ACTH and dexamethasone sodium phosphate in healthy cats. Am J Vet Res 1987;48:1719-1724.
10. Steel R, Torrie J. Principles and procedures of statistics. New York: McGraw-Hill Book Co, 1960;110-111.
11. Kirk GR, Boyer S, Hutcheson DP. Effects of o,p’-DDD on plasma cortisol levels and histology of the adrenal gland in the normal dog. J Am Anim Hosp Assoc 1974;10:179-182.
12. Kirk GR, Jensen HE. Toxic effects of o,p’ -DDD in the normal dog. J Am Anim Hosp Assoc 1975;11:765-768.
13. Lubberink AAME. Therapy for spontaneous hypera- drenocorticism. In Kirk RW ed. Current veterinary treatment VII. Philadelphia: WB Saunders Co, 1980;979-983.
14. Peterson ME. Hyperadrenocorticism. Vet Clin North Am Small Anim Pract 1984;14:731-749.
15. Kintzer PP, Peterson ME. Mitotane (o,p’-DDD) treat-
ment of cortison-secreting adrenocortical neoplasia. In: Kirk RW, ed. Current veterinary treatment X. Philadelphia: WB Saun- ders Co, 1989;1034-1037.
16. Feldman EC, Bruyette DS, Nelson RW, et al. Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism. J Am Vet Med Assoc 1990;197:71-78.
Book Review: Behavior Problems in Dogs, 2nd edition
Behavior Problems in Dogs, by William E. Campbell, “is aimed to helping all students of dog behavior.” The author draws on his many years of experience to present a practi- cal case-report approach to diagnosing and treating prob- lem behavior. Technical be- havioral terminology is not used. Although author’s ap- proach to the subject remains experiential as opposed to ex- perimental, this second edition reflects substantial revision of the book’s content and design since it was first published in 1975.
The book is divided into 15 chapters. The first 2 chap- ters profile “problem-prone” dogs, owners, and environ- ments. Chapter 3 provides tips on analyzing problem behav- ior. Chapters 4 and 5 address the relation of physiology and nutrition with behavior. Chap- ter 6 introduces the author’s praise exclusive-punishment excluded approach to correct- ing problem behavior. Methods of correcting specific types of problem behavior are covered in chapters 7 through 13. Chapter 14, new to the second edition, gives advice on intro- ducing babies and new pets into households with a dog already in residence. The book ends with a chapter on train- ing systems.
Formally trained veteri- nary behaviorists will fault the book in several areas. Although conditioned and uncondi- tioned reflexes are mentioned
in chapter 1, the author does not discuss the development and treatment of specific prob- lem behavior in the context of the principles of classical and operant conditioning, on which learning is based. An- other concern involves the author’s tendency to omit rele- vant aspects in his discussion. One example of this is the sec- tion in chapter 7 on behavior testing of puppies. Recent evi- dence indicates that tempera- ment testing of 6- to 8-week- old pups is not predictive of their behavior as mature dogs (Margaret S. Young, “Puppy selection and evaluation,” Pro- ceedings [Minnesota Veterinary Medical Association 89th An- nual Meeting] 1986). Addition- ally, in Campbell’s discussion of sexual mounting, he states that pups engage in this be- havior because it “feels good” and that the behavior in adults can be ascribed to one of sev- eral physiologic causes. How- ever, the author never men- tions that fact that mounting in dogs occurs more often in the social rather than sexual con- text.
Campbell’s section on neuroses and psychoses is con- fusing. These terms are usually applied to human mental ill- nesses. There are no means of direct assessment of a dog’s mental state. Finally, the book occasionally denounces well established methods for behav- ioral modification. For exam- ple, Campbell presents 2 explanations for the ineffec-
tiveness of desensitization as a treatment for storm phobias because of the difficulties en- countered in reproducing stim- uli to which the phobic dog responds (page 279). The au- thor’s point, though well taken, does not explain why the technique is widely ac- cepted as the most reliable method for treatment of ca- nine and human phobias (Eliz- abeth A. Shull-Selcer and Wayne Stagg, Veterinary Clinics of North America, Small Animal Practice [Philadelphia: WB Saunders Co, 1991] 353-368). Perhaps Campbell’s lack of success is attributable to “op- erator error.” Correct use of desensitization requires that there be absolutely no fear response in the dog during treatment sessions. Addition- ally, desensitization works best when combined with counter- conditioning, which is appar- ently not used by Campbell.
The book is written in a highly readable fashion. How- ever, the needs of the general veterinary practitioner would be better met in refereed books that are based on re- search, learning theory, and the principles of ethology as well as clinical experience .- [Behavior Problems in Dogs, 2nd edition. By William E. Camp- bell. 330 pages; illustrated. American Veterinary Publica- tions Inc, 5782 Thornwood Dr, Goleta, CA 93117. 1991. Price 5.00 shipping.]- JANE HILLSMAN