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

614
Chapter | 19 Adrenocortical Function
IV . ASSESSMENT OF ADRENOCORTICAL
FUNCTION
A . Routine Laboratory Diagnostics
In both hypoadrenocorticism and hyperadrenocorticism,
there are a number of abnormal laboratory findings that are
more common than in other diseases. Many of these abnormalities
can be derived from the above-described action of
glucocorticoids and mineralocorticoids (Section II.F). The
essentials are summarized here.
In primary hypoadrenocorticism, the decreased aldosterone
production results in hyponatremia and hyperkalemia.
The associated hypovolemia leads to prerenal uremia. In
hyperadrenocorticism, the classic hematological abnormality
is eosinopenia, which may be associated with lymphopenia
and occasionally with leukocytosis and erythrocytosis.
A common biochemical abnormality is the elevated plasma
concentration of alkaline phosphatase ( Eckersall and Nash,
1983 ) that may occur in conjunction with mild elevation of
alanine aminotransferase (ALT). In addition, hyperglycemia,
hyperlipidemia, and low thyroxine concentrations may
be observed. Urine-specific gravity is usually low, and in
5% to 10% of cases glucosuria is found.
Of these abnormalities, the elevated alkaline phosphatase
(AP) concentration is the most common laboratory
abnormality in dogs with corticosteroid excess (either exogenous
or endogenous). This increase is due to the induction
of a specific isoenzyme, which has greater heat stability at
65 ° C than other AP-isoenzymes ( Teske et al ., 1986 ) and
is therefore easily measured by a routine laboratory procedure.
An abnormally elevated AP-65 ° C value may point
to hyperadrenocorticism, but it is unsuitable as a diagnostic
test because of its low specificity ( Teske et al ., 1989 ). The
low thyroxine (T4) concentrations in plasma, which may
be observed in hyperadrenocorticism, seem to be a consequence
of altered transport, distribution, and metabolism of
T 4 rather than the result of hyposecretion ( Rijnberk, 1996 ).
There may be other conditions causing these abnormalities,
however, and some cases do not present with typical
routine laboratory characteristics. Therefore, a detailed
understanding of the specific laboratory tests commonly
used to investigate adrenocortical function is essential. In
addition, the spontaneous forms of hyperadrenocorticism
may arise from pituitary ACTH overproduction or from
autonomously hypersecreting adrenocortical tumors. Each
of these requires a different mode of treatment, and therefore
insight into the tests used in the differential diagnosis
is of prime importance.
B . Tests of Basal Adrenocortical Function
The availability of highly specific radioimmunoassays has
greatly enhanced and simplified assessment of adrenocortical
function. Some of the older (chemical) methods, which
are now seldom used, are mentioned briefly. Methods in
common use are described in more detail, which applies
especially to the dynamic tests, part of which is used in the
differential diagnosis (Section IV.C).
1 . Cortisol Production Rate
In the radionuclide dilution method, the rate of cortisol
production is determined through administration of radiolabeled
cortisol and isolation of cortisol metabolites from
urine that is collected over at least 24h. The specific activities
of labeled cortisol and tetrahydrocortisol (THF) or
tetrahydrocortisone (THE) are compared. Some preliminary
work ( Rijnberk et al ., 1968b ) indicated that this test
worked for the dog and might potentially be very useful.
However, the laborious character of the procedure rules out
general availability.
2 . Plasma Corticoids
Plasma corticoid concentrations are subject to considerable
variation owing to the pulsatile nature of the secretion,
physiological variation (see Section II.G) , and
alterations in transport proteins ( Meyer and Rothuizen,
1994 ). Therefore, single determinations are regarded of little
diagnostic value in assessing hypo- or hyperadrenocorticism.
Nevertheless, in a considerable percentage of cases,
resting values outside the reference ranges may be found.
It has been demonstrated recently that calculation of the
ratio of plasma cortisol:ACTH concentrations in hypoadrenocorticism
did not show an overlap with values of healthy
control dogs ( Javadi et al ., 2006 ). There are few data on
sex and breed differences, and they are not dealt with in
Table 19-2 . Nevertheless there is evidence that they should
be taken into account ( Frank et al ., 2003a ). In dogs, circulating
cortisol concentrations do not differ between males
and females, but in small dogs higher values are found
than in large breed dogs ( Reimers et al ., 1990 ), and neutered
males may have lower plasma cortisol concentrations
in comparison to intact males ( Frank et al ., 2003b ). Also
in pigs, breed-specific basal plasma cortisol concentrations
exist ( Sutherland et al ., 2006 ).
3 . Urinary Corticoids
With measurements of urinary corticoids or their metabolites,
an integrated reflection of corticoid production over
a period of time is obtained, thereby adjusting for the
fluctuations in the plasma levels. Indeed, in dogs measurements
of 17-hydroxycorticosteroids in 24-hour urine
samples were found to have a high discriminatory power
( Table 19-3 ; Rijnberk et al ., 1968a ). However, the method
has been abandoned because of the complicated and timeconsuming
chemical analysis, in combination with the difficulty
of accurate collection of 24-hour urine samples.