Hyperadrenocorticism (Cushings) Flashcards
Define HAC
- HAC is chronic, excessive production or exposure to glucocorticoids
What are the three main types of HAC
1) ACTH-dependent/pituitary dependent
2) ACTH-independent HAC develops from functional adrenal tumours (ie. adrenal dependent)
3) Iatrogenic HAC arises from excessive or prolonged administration of exogenous glucocorticoids that lead to adrenal atrophy, suppressed ACTH levels and adrenocortical atrophy.
What is the most common type of HAC in cats?
- pituitary dependent (accounts for 80-85% of cases)
- pituitary gland secretes an excessive amount of ACTH which leads to bilateral adrenal gland hyperplasia and excessive production of glucocorticoids
how do cats develop DM with HAC?
> 76-80% cats with HAC have concurrent, poorly-regulated DM –> these cats often have insulin resistance and require large dosages of insulin
- glucocorticoids cause insulin resistance by inhibiting insulin-dependent glucose transport into skeletal muscle suppressing insulin secretion from pancreatic beta cells and increasing hepatic gluconeogenesis
how do glucocorticoids affect the immune system?
- decrease AB production, macrophage expression or inflammatory cytokines, T-cell activation, natural killer cell-mediated lysis of target cells, and mitogen-induced B cell proliferation
- reduced fibroblast and keratinocyte proliferation also occurs
- recurrent infections and delayed wound healing are common
Explain what an ACTH-stim test is
- assesses the adrenocortical reserve; gold standard for diagnosing iatrogenic HAC
- patients with HAC (in theory) have an exaggerated cortisol production in response to ACTH injection
- compared to other screening tests, ACTH stim test has low sensitivity (~60%)
- less affected by nonadrenal ilness
- less time consuming (pre, synacthen, 1h post)
explain what a low dose dex suppression test is
- the screening test of choice (unless iatrogenic HAC)
- low dose of dexamethasone inhibit ACTH secretion from the pituitary through a negative feedback loop, so cortisol secretion subsequently drops. Pituitary-adrenal axis in patients with HAC is resistant to feedback, and lack of suppression is the expected finding
- Serum/plasma cortisol concentration before, 4 and 8 hours post dex admin (0.01mg/kg IV)
- diagnosis of HAC is made from the 8hr sample
- results can be affected by nonadrenal illness
what results of a LDDST are consistent with pituitary dependent HAC?
1) 4h cortisol conc <50% of baseline cortisol conc and is less than cut off
2) 8hr cortisol conc <50% of baseline cortisol conc and is higher than cut off
what is the urine cortisol:creatinine ratio used for
- measurement of urinary cortisol level reflects cortisol secretion over several hours.
- since creatinine excretion is relatively constant when kidney function is stable, dividing urine cortisol by creatinine concentration negates the effect of urine volume in interpreting urine cortisol concentration
- single mid-stream free catch urine is collected in the morning (at least 2 days after last vet visit)
- low specificity - cannot be used to diagnose
what is a high dose dex suppression test useful for?
- can be used to differentiated functional adrenal tumours and pituitary dependent HAC
- dex dose 0.1mg/kg IV
- consistent with PDH: suppression of cortisol to either below lab cut off OR <50% of baseline at either 4 or 8 hrs
What is the metastatic rate for adrenocarcinoma in dogs?
14-50%
What are potential surgical considerations in unilateral adrenalectomies?
- large and infiltrative tumours (into kidney, body wall or caudal vena cava)
- thromboembolism
What are surgical recommendations when treating FAC?
- medical control of HAC prior to minimize complications (hypercortisolaemia + thromboemboli)
- adrenalectomy is performed once hypercortisolaemia is controlled but no later than 30 days after initiating medical treatment
what is the MOA of trilostane?
- synthetic steroid analogue that inhibits the adrenocortical enzyme 3-beta-hydroxysteroid dehydrogenase
- it blocks the production of progesterone and its end products (ie. cortisol and aldosterone)
- cannot ablate FAT as mitotane can
MOA of Mitotane
- chlorinated hydrocarbon with direct cytotoxic effects on the adrenal cortex (ie. adrenocorticolytic)
- mitotane causes selective necrosis of the zonae fasciculata and reticularis that secrete cortisol and sex hormones
- although zona glomerulosa is relatively resistant to the effects of mitotane, aldosterone secretion can be decreased
- dose dependent effect - destruction of tumour tissue vs. PDH control
