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Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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References<br />

619<br />

b . Performance<br />

In the morning, 0.01 mg dexamethasone per kg body<br />

weight is administered intravenously. Blood for cortisol<br />

measurements is collected immediately before and at 3 and<br />

8 h after dexamethasone administration.<br />

c . Interpretation<br />

A plasma cortisol concentration exceeding 40nmol/liter at<br />

8 h after dexamethasone administration can be regarded<br />

as diagnostic for hyperadrenocorticism with a diagnostic<br />

accuracy <strong>of</strong> 0.83 (95% confidence limits 0.76 to 0.88)<br />

( Rijnberk et al ., 1988 ). The measurements at 0 and 3 h<br />

are not needed for the diagnosis <strong>of</strong> hyperadrenocorticism<br />

but may be informative in the differential diagnosis. Quite<br />

commonly the high value at 8 h is preceded by a lower<br />

value at 3 h. Thus, at 8 h the pituitary-adrenocortical system<br />

escapes from the suppression by dexamethasone. If the<br />

value at 3 or 8 h is at least 50% lower than the basal value,<br />

the disease may be regarded as pituitary dependent.<br />

3 . High-Dose Dexamethasone Suppression Test<br />

a . Indication<br />

Differentiation between pituitary-dependent hyperadrenocorticism<br />

and hypercorticism arising from adrenocortical<br />

tumors is possible with the high-dose dexamethasone suppression<br />

test.<br />

b . Performance<br />

Blood for cortisol determination is collected immediately<br />

before and 3 to 4 h after administration <strong>of</strong> 0.1 mg dexamethasone<br />

per kg body weight.<br />

c . Interpretation<br />

If the plasma cortisol declines by more than 50%, the diagnosis<br />

<strong>of</strong> pituitary-dependent hyperadrenocorticism is justified.<br />

A decrease <strong>of</strong> less than 50% can be due either to an<br />

adrenocortical tumor or to dexamethasone-resistant pituitarydependent<br />

hyperadrenocorticism. Differentiation between<br />

these two forms requires additional tests (see Section IV.D).<br />

4 . Urinary Corticoid/Creatinine Ratios<br />

(with High-Dose Dexamethasone Test)<br />

a . Indication<br />

Determination <strong>of</strong> corticoid/creatinine ratios can be performed<br />

when hyperadrenocorticism is suspected.<br />

b . Performance<br />

The owner is asked to collect morning urine samples at<br />

set times (e.g., 7 A.M.) on 3 consecutive days. On the preceding<br />

evenings, the animal should have its last walk at<br />

identical times (e.g., 11 P.M.). After collection <strong>of</strong> the second<br />

urine sample, dexamethasone is administered orally.<br />

At 8-h intervals, the owner administers 0.1 mg dexamethasone<br />

per kg body weight.<br />

c . Interpretation<br />

Corticoid/creatinine ratios exceeding 10 10 6 can be<br />

regarded as compatible with hyperadrenocorticism with a<br />

diagnostic accuracy <strong>of</strong> 0.91 (95% confidence limits 0.85 to<br />

0.95) ( Rijnberk et al ., 1988 ). When the ratio <strong>of</strong> the third<br />

urine sample is 50% lower than the mean <strong>of</strong> the first two<br />

ratios, the diagnosis <strong>of</strong> a pituitary-dependent hyperadrenocorticism<br />

is justified. A lesser decrease may be due to<br />

either adrenocortical tumors or dexamethasone-resistant<br />

pituitary-dependent hyperadrenocorticism (for differentiation,<br />

see Section IV.D).<br />

d . Comment<br />

This test is now generally regarded as a sensitive screening<br />

test for the diagnosis <strong>of</strong> hyperadrenocorticism ( Feldman,<br />

1995 ). There has been some debate on its specificity<br />

( Feldman, 1992 ; Rijnberk and Teske, 1992 ), and recently<br />

it was stated that the test lacks specificity ( Feldman, 1995 ).<br />

Indeed as with other screening tests the specificity is not<br />

100% ( Kaplan et al ., 1995 ; Smiley and Peterson, 1993 ),<br />

and in conditions that are associated with increased adrenocortical<br />

function, such as hepatic encephalopathy<br />

( Rothuizen et al ., 1995 ), elevated ratios can be found.<br />

In this discussion, two points remain somewhat underexposed.<br />

First, a high sensitivity and not a high specificity<br />

is essential for a screening test. The predictive value <strong>of</strong><br />

a positive test result depends on the sensitivity <strong>of</strong> the test<br />

and also on the prevalence <strong>of</strong> the disease in the population<br />

studied. When the testing is limited to dogs suspected <strong>of</strong><br />

the disease, the population under study will have a high<br />

prevalence <strong>of</strong> disease, and as a result the predictive value<br />

<strong>of</strong> a positive test result will be high. Second, as always, the<br />

diagnostic accuracy <strong>of</strong> a test depends also on the quality <strong>of</strong><br />

the test procedure. In this respect, it should be mentioned<br />

that easily elevated C/C ratios can be obtained when the<br />

urines are collected under stressful conditions, such as in<br />

the hospital. This will increase the number <strong>of</strong> false-positive<br />

test results (i.e., lower the specificity).<br />

When C/C ratios are measured in a population suspected<br />

<strong>of</strong> hyperadrenocorticism, with urine collections at home,<br />

not only is the sensitivity <strong>of</strong> the test high, but also the specificity<br />

(0.77) is comparable to that <strong>of</strong> the low-dose dexamethasone<br />

suppression test (0.73) ( Rijnberk et al ., 1988 ).<br />

REFERENCES<br />

Ash , R. A. , Harvey , A. M. , and Tasker , S. ( 2005 ). J. Feline Med. Surg.<br />

7 , 173 .<br />

Balikian , H. M. ( 1971 ). Endocrinology 89 , 1309 .<br />

Beerda , B. , Kornalijnslijper , J. E. , van der Werf , J. T. , Noordhuizen-<br />

Stassen , E. N. , and Hopster , H. ( 2004 ). J. Dairy Sci. 87 , 2094 – 2102 .

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