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

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616<br />

Chapter | 19 Adrenocortical Function<br />

TABLE 19-4 Plasma Corticoids (nmol/l) Following ACTH Stimulation<br />

Species<br />

ACTH Dose and<br />

Route<br />

Sampling<br />

Time<br />

Hormone Range (Mean SEM) Reference<br />

Dog 250 μ g I.V. 90min Cortisol 120–620 ( Meijer et al ., 1978c )<br />

Dog 5 μ g/kg I.V. 60min Cortisol 220–560 ( Behrend et al ., 2005 )<br />

Corticosterone 18–102 ( Behrend et al ., 2005 )<br />

Cat 125 μ g I.V. 60min Cortisol (274 19) ( Peterson and Kemppainen, 1993 )<br />

Horse 250 μ g I.V. 120min Cortisol 308–602 ( van der Kolk et al ., 2001 )<br />

Cattle 2IU/kg BW 0.75 60min Cortisol (145 27) ( Beerda et al ., 2004 )<br />

1989 ). It does not seem to be advisable to increase saliva<br />

flow by pilocarpine ( Blackshaw and Blackshaw, 1989 ). It<br />

has also been reported that in calves ( Fell and Shutt, 1986 )<br />

and goats ( Greenwood and Shutt, 1992 ), saliva can be aspirated<br />

from the side <strong>of</strong> the mouth with minimum restraint.<br />

5 . Cortisol in Milk<br />

Monitoring adrenocortical activity by measurements in<br />

milk may be <strong>of</strong> value in searching for stressors in the livestock<br />

industry ( Gygax et al ., 2006 ; Stephens, 1980 ). In a<br />

comparison <strong>of</strong> different milking systems, no differences<br />

in milk cortisol concentrations were found ( Gygax et al .,<br />

2006 ). The low concentrations indicate that in milk also<br />

the biologically active free fraction instead <strong>of</strong> the total cortisol<br />

fraction is measured.<br />

6 . Plasma ACTH<br />

Determinations <strong>of</strong> resting plasma ACTH concentrations are<br />

not useful in the diagnosis <strong>of</strong> hyperadrenocorticism because<br />

<strong>of</strong> the overlapping values for normal dogs and dogs with<br />

hyperadrenocorticism. Its value lies mainly in the differential<br />

diagnosis <strong>of</strong> hyperadrenocorticism (discussed later). In<br />

animals with primary adrenocortical failure, plasma ACTH<br />

concentrations are usually extremely high. However, in most<br />

cases such a determination is primarily <strong>of</strong> academic interest<br />

as the diagnosis can be made with the more practical ACTH<br />

stimulation test (see Section IV.C.1). Plasma ACTH measurements<br />

are useful when in doubt about a primary or secondary<br />

adrenocortical insufficiency ( Kooistra et al ., 1995 ).<br />

C . Dynamic Tests<br />

Apart from the above-described measurements <strong>of</strong> reflections<br />

<strong>of</strong> basal adrenocortical secretions, various maneuvers<br />

have been introduced to test the physiology <strong>of</strong> the hypothalamo-pituitary-adrenocortical<br />

axis. As in other areas <strong>of</strong><br />

endocrinology, stimulation tests are used when hyp<strong>of</strong>unction<br />

is suspected, and suppression tests are used when<br />

hyperfunction is suspected.<br />

1 . Tests <strong>of</strong> Adrenocortical Reserve<br />

The critical feature <strong>of</strong> the test is that a substantial increase in<br />

plasma (or urinary) corticoids must occur in response to ACTH<br />

if one is to prove the existence <strong>of</strong> adrenal reserve ( Table 19-4 ).<br />

One method is described in detail in Section IV.F.<br />

In veterinary medicine, ACTH stimulation has also been<br />

used to confirm adrenocortical hyperfunction. This is based<br />

on the assumption that hyperplastic adrenal cortices have<br />

abnormally large cortisol reserves. Indeed, hyperresponsiveness<br />

to ACTH or lysine-vasopressin ( Meijer et al ., 1978a )<br />

stimulation is found in pituitary-dependent hyperadrenocorticism,<br />

but there is considerable overlap with normal dogs.<br />

Over the years, several modifications/combinations <strong>of</strong> the<br />

ACTH stimulation test ( Eiler and Oliver, 1980 ; Eiler et al .,<br />

1984 ; Feldman, 1986 ) for the diagnosis <strong>of</strong> hyperadrenocorticism<br />

have been used, but it still appears to be a dynamic<br />

test with less diagnostic accuracy than the low-dose dexamethasone<br />

suppression test (LDDST) ( Behrend et al ., 2005 ;<br />

Feldman, 1986 ; Peterson, 1986 ). This seems to hold true for<br />

the horse as well ( Dybdal et al ., 1994 ), although the ACTH<br />

stimulation test is recommended for the diagnosis <strong>of</strong> equine<br />

hyperadrenocorticism ( Van der Kolk et al ., 1993 ). The value<br />

<strong>of</strong> the ACTH stimulation test lies in the diagnosis <strong>of</strong> hypoadrenocorticism<br />

(see Section IV.F). When used for the diagnosis<br />

<strong>of</strong> hyperadrenocorticism, the modification <strong>of</strong> a combination<br />

with a dexamethasone suppression test seems the least<br />

desirable, as doses <strong>of</strong> 0.1 mg <strong>of</strong> dexamethasone/kg can alter<br />

the results <strong>of</strong> the ACTH stimulation test for at least 3 days<br />

(Kemppainen et al ., 1989 ). Measurement <strong>of</strong> plasma corticosterone<br />

or 17 α -hydroxyprogesterone after ACTH stimulation<br />

is <strong>of</strong> little additive value as the changes measured are proportionate<br />

with changes in cortisol and may be high in dogs with<br />

nonadrenal neoplasia as well ( Behrend et al ., 2005 ).<br />

2 . Tests <strong>of</strong> Pituitary (ACTH) Reserve<br />

In animals with adrenals responsive to ACTH, administration<br />

<strong>of</strong> the 11 β -hydroxylase inhibitor metyrapone decreases cortisol<br />

secretion and consequently increases ACTH secretion.<br />

As a result, cortisol precursor synthesis increases, which can

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