Page 84 - Clinical Small Animal Internal Medicine

52 Section 2 Endocrine Disease

gene expression related to ACTH production and secre­ Box 7.3 Common clinical signs of PDH in dogs and cats
VetBooks.ir tion and the negative feedback by glucocorticoids in Polyuria and polydipsia
canine corticotroph adenoma was evaluated in pituitary
Polyphagia
tumors in 10 dogs with Cushing disease. The results dem­
onstrated increased ACTH production and resistance to Abdominal distension
negative feedback by glucocorticoids in canine cortico­ Bilaterally symmetric endocrine alopecia
troph adenomas. Panting
Hypertension
Therapeutic Role of EGFR Urinary tract infections
Since tumors in dogs and humans express epidermal Additional dermatologic signs:
growth factor receptor (EGFR), in another study we – Thin skin
examined whether EGFR might provide a therapeutic – Pyoderma
target for Cushing disease. – Calcinosis cutis
In cell cultures from surgically resected human and
●
canine corticotroph tumors, blocking EGFR also sup­
pressed expression of proopiomelanocortin (POMC), Box 7.4 Common laboratory findings of PDH
the ACTH precursor.
In mouse corticotroph EGFR transfectants, ACTH Hematologic abnormalities
●
secretion was enhanced and POMC promoter activity “Stress” leukogram (uncommon in cats):
was increased. – Neutrophilic leukocytosis
– Lymphopenia
In mice, blocking EGFR activity with gefitinib, an EGFR – Eosinopenia
tyrosine kinase inhibitor:
Mild thrombocytosis
attenuated POMC expression Mild erythrocytosis
●
inhibited corticotroph tumor cell proliferation and
●
induced apoptosis Serum biochemical abnormalities
decreased both tumor size and corticosterone levels
● Increased serum alkaline phosphatase
reversed signs of hypercortisolemia, including ele­
● Milder increased in alanine aminotransferase
vated glucose levels and excess omental fat. Hypercholesterolemia
These study results indicate that inhibiting EGFR signal­ Hypertriglyceridemia
ing may be a novel strategy for treating Cushing disease. Hyperglycemia
Urinalysis

History and Clinical Signs Decreased urine specific gravity <1.018
Proteinuria
Urinary tract infection (even in absence of pyuria and
Clinical signs, as well as laboratory abnormalities, seen bacteriuria)
in patients with PDH are secondary to the effects of ster­
oid excess, well recognized, and similar in scope to those
seen with exogenous glucocorticoid supplementation
(Boxes 7.3 and 7.4). and is felt to be due to steroid‐induced stimulation of
The clinical signs of polyuria and polydipsia occur as ventilator centers in the brainstem. Pyoderma and uri­
the result of excessive cortisol interfering with pituitary nary tract infections reflect the immunosuppressive
release of antidiuretic hormone (ADH) or the binding effects of glucocorticoids. The mechanism(s) behind
of ADH to receptors in the renal tubules. Abdominal the steroid induction of calcinosis cutis is poorly under­
distension and thinning of skin occur due to the cata­ stood although the condition does occur with both iat­
bolic effects of cortisol on tissues such as muscle and rogenic and spontaneous hyperadrenocorticism and
connective tissue. Hepatomegaly steroid‐induced vacu­ the condition can take months to resolve following res­
olar hepatopathy also contributes to the “pot‐bellied” olution of hyperadrenocorticism or withdrawal of the
appearance. The endocrine alopecia mirrors the known exogenous steroid.
distribution of sex hormone receptors in the skin Awareness of PDH has increased over time, resulting
with endocrine alopecias often sparing the head and in the presentation of patients with only mild clinical
extremities. Panting occurs in both dogs and humans signs, clinical signs affecting only one organ system (e.g.,