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

III. Adrenocortical Diseases
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an influence at the level of the pituitary and the adrenals
( Gaillard, 1994 ).
III . ADRENOCORTICAL DISEASES
As this chapter is not meant to cope with clinical and
pathological details, discussion of adrenocortical diseases
is confined to definitions, short statements on occurrence
in species, and referral to key references. In textbooks on
endocrine diseases of companion animals ( Drazner, 1994 ;
Feldman and Nelson, 2004 ; Rijnberk, 1996 ), the adrenocortical
diseases of the dog and the cat are described in
detail.
A . Hypoadrenocorticism
Adrenocortical hypofunction includes all conditions in
which the secretion of adrenal steroid hormones falls
below the requirements of the animal. It may be divided
into two categories:
1. Primary hypoadrenocorticism or Addison’s disease
is the result of deficiency of both glucocorticoid and mineralocorticoid
secretion from the adrenal cortices (primary
adrenocortical failure). “ Idiopathic ” or immune-mediated
atrophy ( Schaer et al ., 1986 ) of all zones is the most frequently
observed histopathological lesion, although the
lymphocytic adrenalitis may be confined to the zona fasciculata
and zona reticularis ( Kooistra et al ., 1995 ). It is
well known in the dog and rare in the cat ( Peterson and
Randolph, 1989 ).
2. Secondary hypoadrenocorticism is the result of
pituitary ACTH deficiency, causing decreased glucocorticoid
secretion. Because of the almost unaltered aldosterone
secretion, it will usually remain unnoticed. It is observed
occasionally in dogs with pituitary insufficiency resulting
from pituitary cystic lesions leading to an empty sella or as a
result of a compressive nonfunctioning (endocrine inactive)
pituitary macroadenoma.
Animals receiving long-term corticosteroid treatment,
despite physical and biochemical hyperadrenocorticoid
changes, develop secondary adrenocortical insufficiency
because of prolonged hypothalamo-pituitary suppression.
Atrophy of the two inner zones of the adrenal cortex results
from the loss of endogenous ACTH stimulation. This is
observed in the species in which corticosteroid therapy is
common practice such as the dog ( Greco and Behrend,
1995 ; Rijnberk, 1996 ) and the horse ( Hoffsis and Murdock,
1970 ; Toutain and Brandon, 1983 ). It has also been observed
in dogs and cats treated with progestagens, owing to the glucocorticoid
activity that is intrinsic to these drugs ( Chastain
et al ., 1981 ; Mansfield et al ., 1986 ; Middleton et al ., 1987 ;
Selman et al ., 1994 ).
B . Hyperadrenocorticism
In principle, the adrenal cortex of animals might, as in
humans, give rise to three distinct clinical syndromes of
hyperfunction: mineralocorticoid excess or hyperaldosteronism
(Conn’s syndrome), glucocorticoid excess or hypercortisolism
(Cushing’s syndrome), and androgen excess
(adrenogenital syndrome).
Hypercortisolism is common in the dog though rare in
the cat and the horse. In about 15% of hyperadrenocorticoid
dogs, the disease is due to a primary adrenocortical tumor
(ACTH independent). The excessive secretion of cortisol
by these tumors may either be autonomous or associated
with aberrant expression of ectopic or overexpression
of eutopic adrenocortical receptors ( Lacroix et al ., 2001 ).
For example, the expression of ectopic receptors for gastric
inhibitory polypeptide may result in “ food-dependent
hypercortisolism. ” In the other 85% of cases, the (ACTHdependent)
hypercortisolism is associated with a pituitary
lesion, producing excess ACTH. The pituitary corticotroph
adenomas may reside in either the anterior lobe or the intermediate
lobe ( Kemppainen and Peterson, 1994 ; Peterson
et al ., 1982 ). In rare cases, Cushing’s syndrome may also
be due to ectopic secretion of ACTH by a neuroendocrine
tumor outside the pituitary gland ( Galac et al ., 2005 ). In
cats, hypercortisolism (Cushing’s syndrome) is usually concurrent
with diabetes mellitus and may be either primary
adrenocortical or pituitary dependent ( Meij et al ., 2001,
2004 ; Meijer et al ., 1978b ; Peterson and Randolph, 1989 ).
Primary hyperaldosteronism in cats may be due to an
adrenocortical tumor ( Ash et al ., 2005 ; Flood et al ., 1999 ;
Mackay et al ., 1999 ; Moore et al ., 2000 ; Rijnberk et al .,
2001 ) or to bilateral hyperplasia of zona glomerulosa tissue
(Javadi et al ., 2005 ). Prominent clinical features in cats with
hyperaldosteronism are hypokalemia, episodic weakness,
cervical ventroflexion, arterial hypertension, and vision loss
resulting from retinal detachment. The nontumorous form
of primary hyperaldosteronism in cats is associated with
progressive renal disease ( Javadi et al ., 2005 ).
In the horse, hypercortisolism (Cushing’s syndrome)
originates almost invariably in the intermediate lobe of
the pituitary ( Orth et al ., 1982 ). In domestic ferrets, hyperadrenocorticism
is quite common and it is primarily associated
with adrenocortical tumor or nodular adrenocortical
hyperplasia ( Rosenthal et al ., 1993 ). Domestic ferrets with
hyperadrenocorticism have no detectable abnormalities in
plasma concentrations of ACTH or α-MSH (Schoemaker
et al ., 2002a ) and increased urinary corticoid/creatinine
ratios resistant to dexamethasone suppression ( Schoemaker
et al ., 2004 ), both indicating ACTH-independent hyperadrenocorticism.
Positive staining was found with the LH receptor
antibody in hyperplastic or neoplastic adrenal glands of
hyperadrenocorticoid ferrets supporting the hypothesis that
gonadotropic hormones play a role in the pathogenesis of
hyperadrenocorticism in ferrets ( Schoemaker et al ., 2002b ).