Assessment of corticosteroid-induced alkaline phosphatase isoenzyme as a screening test for hyperadrenocorticism in dogs

Philip F. Solter From the Departments of Pathobiology and Clinical Medicine (Solter, Hoffmann, Hungerford, Dorner), College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Dr, Urbana, IL 61801 and the Department of Medicine, Animal Medical Center, 510 E 62nd St, New York, NY 10021 (Peterson).

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Walter E. Hoffmann From the Departments of Pathobiology and Clinical Medicine (Solter, Hoffmann, Hungerford, Dorner), College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Dr, Urbana, IL 61801 and the Department of Medicine, Animal Medical Center, 510 E 62nd St, New York, NY 10021 (Peterson).

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Laura L. Hungerford From the Departments of Pathobiology and Clinical Medicine (Solter, Hoffmann, Hungerford, Dorner), College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Dr, Urbana, IL 61801 and the Department of Medicine, Animal Medical Center, 510 E 62nd St, New York, NY 10021 (Peterson).

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Mark E. Peterson From the Departments of Pathobiology and Clinical Medicine (Solter, Hoffmann, Hungerford, Dorner), College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Dr, Urbana, IL 61801 and the Department of Medicine, Animal Medical Center, 510 E 62nd St, New York, NY 10021 (Peterson).

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Joseph L. Dorner From the Departments of Pathobiology and Clinical Medicine (Solter, Hoffmann, Hungerford, Dorner), College of Veterinary Medicine, University of Illinois, 1008 W Hazelwood Dr, Urbana, IL 61801 and the Department of Medicine, Animal Medical Center, 510 E 62nd St, New York, NY 10021 (Peterson).

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Abstract

Quantitative determination of the corticosteroid-induced isoenzyme of alkaline phosphatase (cap) was evaluated as a screening test for hyperadrenocorticism (hac) in dogs. A series of 40 dogs with hac (cap range, 96 to 14,872 U/L), 30 clinically normal dogs (cap range, 0 to 38 U/L), and 80 dogs with various diseases (non-hac) and without history of exogenous glucocorticoid exposure for a minimum of 60 days (cap range, 0 to 1163 U/L) were used to evaluate the test. Sensitivity and specificity of cap was calculated at various cutoff points for absolute cap activity and for cap activity expressed as a percentage of total alkaline phosphatase activity. A cutoff point of 90 U/L was selected as optimal for use of this assay as a screening test for hac. A prevalence survey then was done of all canine serum samples submitted to our diagnostic laboratory over a 3-month period, to calculate the predictive values of a positive and a negative test result in a clinical population and to determine the relative frequency and magnitude of cap activity in dogs that had received glucocorticoids. The predictive values of a positive and a negative test result at the 90 U/L cutoff value were 21.43% (95% confidence limits, 8.3 to 40.95%) and 100% (95% confidence limit > 96%), respectively. It was concluded that cap isoenzyme activity, determined by routine biochemical analysis by an automated levamisole-inhibition assay, could function as a screening test for hac, however, (the predictive value of a positive test result was too low to recommend the assay as a diagnostic test. The cap activity was > 90 U/L in 52% of dogs receiving glucocorticoids, emphasizing the importance of treatment history in the use of this test. To help eliminate possible workup bias, an additional set of serum samples from 30 dogs diagnosed as having hac at a second institution also were analyzed. Sensitivity of the assay in this sample group, using the 90 U/L cutoff value, was 83.3% (95% confidence limits, 65.3 to 94.4%), suggesting that test sensitivity may vary, depending on the institution in which the assay is used and the selection of cases for diagnostic workup.

Abstract

Quantitative determination of the corticosteroid-induced isoenzyme of alkaline phosphatase (cap) was evaluated as a screening test for hyperadrenocorticism (hac) in dogs. A series of 40 dogs with hac (cap range, 96 to 14,872 U/L), 30 clinically normal dogs (cap range, 0 to 38 U/L), and 80 dogs with various diseases (non-hac) and without history of exogenous glucocorticoid exposure for a minimum of 60 days (cap range, 0 to 1163 U/L) were used to evaluate the test. Sensitivity and specificity of cap was calculated at various cutoff points for absolute cap activity and for cap activity expressed as a percentage of total alkaline phosphatase activity. A cutoff point of 90 U/L was selected as optimal for use of this assay as a screening test for hac. A prevalence survey then was done of all canine serum samples submitted to our diagnostic laboratory over a 3-month period, to calculate the predictive values of a positive and a negative test result in a clinical population and to determine the relative frequency and magnitude of cap activity in dogs that had received glucocorticoids. The predictive values of a positive and a negative test result at the 90 U/L cutoff value were 21.43% (95% confidence limits, 8.3 to 40.95%) and 100% (95% confidence limit > 96%), respectively. It was concluded that cap isoenzyme activity, determined by routine biochemical analysis by an automated levamisole-inhibition assay, could function as a screening test for hac, however, (the predictive value of a positive test result was too low to recommend the assay as a diagnostic test. The cap activity was > 90 U/L in 52% of dogs receiving glucocorticoids, emphasizing the importance of treatment history in the use of this test. To help eliminate possible workup bias, an additional set of serum samples from 30 dogs diagnosed as having hac at a second institution also were analyzed. Sensitivity of the assay in this sample group, using the 90 U/L cutoff value, was 83.3% (95% confidence limits, 65.3 to 94.4%), suggesting that test sensitivity may vary, depending on the institution in which the assay is used and the selection of cases for diagnostic workup.

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