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Pituitary‐Dependent Hyperadrenocorticism in Dogs and Cats

David S. Bruyette, DVM, DACVIM (SAIM)
Anivive Lifesciences, Long Beach, CA, USA

Etiology/Pathophysiology carcinoma on the basis of proliferation indices (p53
and Epidemiology immunoreactivity, MIB‐I Index, mitotic activity) and the
absence/presence of metastases.
Pituitary‐dependent hyperadrenocorticism (PDH), also More comprehensive molecular classification systems
known as Cushing disease, is a common endocrine dis­ based on relevant gene expression have not been system­
order in older dogs though relatively uncommon in cats. atically used to further characterize pituitary tumors.
This disorder is caused by a pituitary adenoma (PA) that Similar work to classify canine pituitary tumors both
secretes inappropriate amounts of adrenocorticotropic morphologically and functionally is currently under way.
hormone (ACTH), which results in bilateral adrenal
hyperplasia and disorderly and excessive production of Prevalence
cortisol by the adrenal gland.
Humans
In humans, PAs are common tumors, with an overall prev­
Classification alence in the general US population estimated at 16.7%.
Basics of Classification ● Corticotroph adenomas, comprising functional
As with all central nervous system tumors, the Tumor– (ACTH‐PAs) and silent corticotroph adenomas, rep­
Node–Metastasis (TNM) system used by the World resent approximately 10–15% of all PAs.
Health Organization does not apply. Current classifica­ ● Functional ACTH‐PAs are the most common cause of
tion systems for PAs in veterinary patients are based pri­ Cushing syndrome (hypercortisolemia from any
marily on secretory characteristics of the tumor. However, source), accounting for an estimated 70% of all cases.
in humans, PAs are currently classified based upon: ● Prevalence of Cushing disease is estimated to be 1.2–
tumor size and degree of invasiveness (Box 7.1) 2.4 per 1 million people, and affects approximately
●
tumor endocrine activity (hormone secretion) 12 000 people in the US. This number, however, may
●
be much higher, given that Cushing disease is fre­
or functional classification based on immunohisto­ quently misdiagnosed and diagnosis is often delayed.
logic findings such as ACTH, thyroid‐stimulating hor­
mone (TSH), follicle‐stimulating hormone (FSH), etc. Dogs
immunostaining. Functional ACTH‐PAs have a reported incidence of 0.2%
In both humans and animals, pituitary corticotroph in all dogs (1–2 cases/1000 dogs/year), with approxi­
adenomas that are responsible for Cushing disease (i.e., mately 100 000 dogs affected yearly in the US. PDH
PDH) are classified as functional ACTH‐secreting PAs accounts for approximately 85–90% of cases of hyper­
(ACTH‐PAs). adrenocorticism, with the remainder of cases resulting
from functional adrenal tumors, meal/food‐induced
Further Classification cases, occult or atypical disease.
The World Health Organization classification system for Meal‐ or food‐induced Cushing syndrome is thought to
PAs in humans has been refined to include designations occur as the result of a congenital defect resulting in the
for benign adenoma, atypical adenoma, and pituitary aberrant expression of the gastric inhibitory polypeptide

Clinical Small Animal Internal Medicine Volume I, First Edition. Edited by David S. Bruyette.
© 2020 John Wiley & Sons, Inc. Published 2020 by John Wiley & Sons, Inc.
Companion website: www.wiley.com/go/bruyette/clinical