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

IV. Assessment of Adrenocortical Function
617
TABLE 19-5 Upper Reference Values for Plasma Cortisol Concentrations (nmol/l) after
Low-Dose Dexamethasone Suppression Test
Species Dose and Route Sampling Time Cortisol Reference
Dog 10 μ g/kg I.V. 8h 40 ( Meijer et al ., 1979 )
Dog 15 μ g/kg im 2, 4, 6, 8h 28 ( Peterson, 1986 )
Cat 10 μ g/kg I.V. 8h 36 ( Smith and Feldman, 1987 )
Cat 15 μ g/kg im 8h 14 ( Peterson and Graves, 1988 )
Horse 40 μ g/kg I.V. 15h 30 ( Dybdal et al ., 1994 )
be measured as urinary 17-hydroxycorticosteroids. Although
effective in the dog ( Siegel, 1968 ), the cumbersome procedure
has prohibited wider use in veterinary medicine. At
present, pituitary ACTH reserve is tested by use of physiological
suprapituitary stimuli (i.e., vasopressin or CRH) (see
Chapter 18) . Such tests are mainly useful in the differential
diagnosis, whereby it should be noted that vasopressin is the
least useful for this purpose, as it can exert a direct stimulatory
effect on cortisol release by adrenocortical tumors
( Van Wijk et al ., 1994 ).
3 . Tests of Pituitary-Adrenocortical Suppressibility
The integrity of the feedback system can be tested by giving
a potent glucocorticoid and judging suppression of
ACTH secretion by measuring either steroids excreted in
urine or plasma cortisol levels. A potent glucocorticoid
such as dexamethasone is used so that the administered
compound may be given in such small amounts as not to
contribute significantly to the steroids to be analyzed. In
pituitary-dependent hyperadrenocorticism, there is loss of
normal sensitivity to suppression, and as a result higher
values are found than in normal individuals following
dexamethasone administration ( Table 19-5 ).
In the dog, the most frequently used test is still the lowdose
dexamethasone suppression test (LDDST) ( Meijer
et al ., 1978a ). In this test, 0.01 mg of dexamethasone/kg of
body weight is administered intravenously, and a plasma
sample for cortisol determination is taken after 8 h. In
healthy dogs at this time the plasma cortisol concentrations
are still depressed ( Kemppainen and Sartin, 1984b ).
This test is described in detail in Section IV.F. Others
recommend intramuscular administration of 0.015 mg
of dexamethasone/kg and the collection of plasma samples
for cortisol determination 2, 4, 6, and 8 h after injection
( Peterson, 1984 ). Although not necessary for the
diagnosis, the results of a 3- or 4-h sample may be informative
for differential diagnosis (see Sections IV.D
and IV.F).
D . Tests for Differential Diagnosis
In animals with primary hypoadrenocorticism, the physical
and biochemical features are very much determined by the
electrolyte disturbances caused by the insufficient mineralocorticoid
secretion. In secondary hypoadrenocorticism,
mineralocorticoid secretion is practically unchanged, and
the presenting signs are usually completely different. Thus,
only rarely is there a need for additional tests to distinguish
between these two forms of hypoadrenocorticism. However,
when doubt exists about the background of the hyporesponsiveness
to exogenous ACTH, plasma ACTH concentrations
should be measured (see also Section IV.B.6) or the pituitary
should be tested for ACTH reserve (see Section IV.C).
For hyperadrenocorticism, the situation is completely
different. Once the diagnosis of hyperadrenocorticism
has been made by either a basal test or a dynamic test, it
is necessary to distinguish between pituitary-dependent
hyperadrenocorticism and hyperadrenocorticism arising
from an adrenocortical tumor. In principle, these forms of
the disease require different modes of treatment. Probably
owing to the additional secretion of steroids with mineralocorticoid
activity by adrenocortical tumors, a higher
incidence of hypokalemia is found than in animals with
pituitary-dependent hyperadrenocorticism ( Meijer, 1980 ).
However, this sign is not specific enough to allow differentiation
between the two forms. As there are no further signs
that may be helpful to distinguish the two entities, specific
tests are needed. The two most helpful procedures are the
measurement of basal plasma ACTH levels and the highdose
dexamethasone suppression test (HDDST). A test of
pituitary ACTH reserve may also be helpful.
Normal to high plasma ACTH concentrations ( 40 pg/
ml) in hyperadrenocorticoid dogs usually indicate ACTH
excess of pituitary origin. Low to undetectable concentrations
of ACTH are found in dogs with hyperadrenocorticism
arising from an adrenocortical tumor in which the feedback
control of pituitary ACTH secretion is undisturbed. ACTH
concentration may not be low when both disease entities