Post on 29-Jul-2015
Cushing’s Disease/Syndrome
Humans vs. Dogs
Dylan Djani
Cushing’s - Definition
Hyperadrenocorticism Endocrinopathy / Endocrine syndrome (Cohan)
Characterized by hypercortisolemia Clinical signs Improper cortisol regulation
Affects humans, dogs, and horses (very rarely cats) 1-2 cases/1000 dogs/year (de Bruin et. al.) ~1-2 cases/million people/year More common in females than males
Cushing’s: Disease vs. Syndrome
Cushing’s Syndrome General signs and symptoms due to hyperadrenocorticism Non-specific cause
Cushing’s Disease Specific cause: pituitary adenoma Resulting in hyperadrenocorticism and hypercortisolemia
Referring to the same pathophysiologic process (Pluta and Burke)
Hypothalamic-Pituitary-Adrenal Axis(HPA Axis)
Note* CRF = CRH
Corticosteroids from adrenal cortex: Glucocorticoids (cortisol) Mineralocorticoids (aldosterone)
Cortisol release is triggered by stress(Bronstein)
Systemic effects are metabolic
Multiple levels of regulation Feedback loops Negative feedback on H and AP “Feedback inhibition”(Kooistra and Galac)
Source: http://upload.wikimedia.org/wikipedia/commons/a/ad/ACTH_Negative_Feedback.jpg
Cushing’s – EtiologyDisruption of Feedback Loops in HPA
Axis Tumors
Pituitary tumor (80-85% cases) Cushing’s disease; pituitary/ACTH-dependent Cushing’s Excess ACTH – does not respond to feedback (Bronstein)
Adrenal tumor (15-20% cases) Adrenal-dependent, pituitary/ACTH-independent
Cushing’s Excess cortisol – unaffected by presence of ACTH or lack
thereof
Prolonged exogenous corticosteroid administration Iatrogenic Associated with corticosteroid therapy (i.e. Addison’s
patients)
Cortisol – Main Functions
Stimulatory effects on:
Gluconeogenesis
Lipolysis
Protein/collagen degradation
Sodium/water retention
PTH release
Osteoclast activity
Inhibitory effects on:
Gonadotropin releaseFSH and LH
TSH and GH release
Gonadal steroidogenesis
Vitamin D and calcium intestinal reabsorption
Immune and inflammatory responses
STRESS RESPONSE
METABOLIC EFFECTS
HypercortisolemiaPathophysiologic Effects in Humans and
Dogs
Hyperglycemia and hyperlipidemia Insulin release & resistance Increased plasma osmolarity ADH release
Altered fat deposition Central trunk weight gain and peripheral weight loss
Muscle wasting and thinning of the skin
Stunted growth, loss of libido, and hypogonadism
Immunosuppression immunocompromised
Hypercalcuria and hypertension
Polyuria and polydipsia (more prominent in dogs)
Cushing’s Disease - Clinical Presentation Examples
Source: http://jama.jamanetwork.com/article.aspx?articleid=1104780 Source: personal photographs
Canine Cushing’s Disease - Thinning of Skin (ventral abdomen)
Source: http://www.dog-health-guide.org/image-files/dog_cushings_disease.jpg
Cushing’s: Humans vs. Dogs
Main Clinical Signs (de Bruin et. al.) Dogs: polyuria/polydipsia/polyphagia Humans: obesity and skin changes
Overwhelming rates of companion animal obesity
Polyphagia from cortisol excess is unique to dogs
Differences at the level of the kidney Species-specific physiologic implications of glucocorticoid
interactions with the ADH receptor Changes in ADH receptor sensitivity
Polyuria and PolydipsiaCanine Cushing’s
Vasopressin Interference (Feldman and Nelson)
Increased osmotic diuresis – hence polyuria Cushing’s is more “diabetogenic” in dogs
Main water sources for lowering plasma osmolarity in dogs Intracellular fluid compartment & dietary intake Intracellular fluid compartment is eventually depleted
Exacerbated thirst signaling – hence polydipsia From increased plasma osmolarity Additionally from body tissue dehydration
Less prominent of a feature in human Cushing’s
In conclusion…
Endocrinopathies are extremely complicated
Hormone dysregulation and lack of feedback have many systemic pathophysiologic effects
Each clinical sign can be traced back to one of the hormone’s proper physiologic functions occurring in excess
Bibliography
Overview of Hyperadrenocorticism by Mindy Cohan, VMD
Cushing’s Syndrome – Pathophysiology, Diagnosis, and Treatment by Bronstein
Cushing’s Syndrome and Cushing’s disease JAMA by Pluta and Burke
Cushing’s Disease in Dogs and Humans by de Bruin, et. al.
Canine and Feline Endocrinology and Reproduction by Feldman and Nelson
Recent Advances in the Diagnostics of Cushing’s Syndrome in Dogs by Kooistra and Galac
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A few thoughts medical students studying for USMLE Step 1 on online forums…