Malfunctioning adrenals: how to diagnose them (Proceedings)

Regulation of Secretion of glucocorticoids - corticosterone and cortisol

• Hypothalamic-pituitary-adrenal (HPA) axis - classic endocrine feedback loop

• CRH (hypothalamus)

• ACTH (pituitary)

• Cortisol (adrenals)

• Cortisol negative feedback on CRH and ACTH release

Diseases of the Adrenal Cortex and how to diagnose them

• Hypoadrenocorticism

• primary disease - destruction of the adrenal cortex

• iatrogenic

• mitotane (Lysodren)

• trilostane (Vetoryl) – can also cause adrenal necrosis

• abrupt withdrawal of glucocorticoids

• bilateral adrenalectomy

• Diagnosis

• Decreased Na:K ratio - less than 25-27 consistent with addison's disease

• ACTH-stimulation test – definitive test

• normal pre 1-4  mcg/dl cortisol

• normal post 10-18 mcg/dl cortisol

• Addisons:  pre and post sample <1 mcg/dl of cortisol

• Low dose ACTH (5 mcg/kg cortrosyn) effective

• Resting cortisol levels

• 2 ug/dl or greater, probably not Addisons

• Hyperadrenocorticism

• Pathogenesis

• Primary disease

• adrenal tumor with overproduction of

• glucocorticoids

• approximately 15% of animals have this

• 50% carcinoma

• secrete cortisol as well as cortisol precursors

• usually unilateral; can be bilateral

• Secondary disease

• pituitary microadenomas that overproduce ACTH

• approximately 85% of animals have this

• pituitary-dependent hyperadrenocorticism (PDH)

• macroadenomas can cause neurologic signs

• iatrogenic - overuse of exogenous glucocorticoids

• PDH and adrenal tumors have been found in same animal

• Diagnostic screening tests – Cushing's yes/Cushing's no

• Urine cortisol:creatinine ratio

• Rationale:  gives cortisol estimation since last time dog urinated - so      usually get an estimate of plasma cortisol over several hours

• Procedure:  collect urine sample (preferably owners collect at home);    urine cortisol measured and compared to creatinine to normalize

• For urine concentration

• Interpretation  - if morning urine (really should be 3 on separate days)

• sample(s) less than 10 (or use your lab's reference ranges) then animal probably doesn't have Cushing's.  If ­> 10 then you need to do another screening test.  Very sensitive; not specific

• ACTH-stimulation test

• Rationale:  stimulate gland to determine hormonal reserve;

• If gland is hyperfunctioning you should get an exaggerated   response interpretation:          

• Normal pre 1-4  mcg/dl cortisol normal post 10-18 mcg/dl cortisol

• Gray area post sample (may/may not be hyperadrenocorticism)18-22 mcg/dl 

• Post > 22 mcg/dl think hyperadrenocorticism                                 

• Uses: 

• Test of choice for diagnosing iatrogenic hyperadrenocorticism                                                                       

• Screening test for hyperadrenocorticism – is a more specific test in animals with concurrent disease

• Monitoring lysodren therapy

• 60-75% sensitive

• 85-90% specific

• Low Dose Dexamethasone Suppression Test (LDDS)

• Rationale:  take advantage of the normal negative feedback mechanism in the HPA axis.  If you can't suppress  the system normally, then suspect hyperadrenocorticism

• Procedure:  

• Get baseline cortisol

• Give 0.01 mg/kg dexamethasone IV

• Get 4 and 8 hour post-injection cortisol samples

• Can use dexamethasone SP or dexamethasone in polyethylene glycol

3.  Interpretation: 

• Look at the 8 hour post-injection sample first; in a normal animal it should be below the normal range; the gray area in which you can't make a diagnosis is 1.0-1.4 ug/dl; greater than 1.4 mcg/dl is consistent with hyperadrenocorticism

• The 4 hr post-injection sample is used as a discriminating test (to tell whether there is an adrenal tumor or PDH)

4.  Advantages:

• More sensitive for diagnosis of hyperadrenocorticism  85-95% sensitive

• By getting the four hour sample, can also use as a discriminating test for hyperadrenocorticism (i.e. tell whether hyperadrenocorticism is due to a pituitary or adrenal tumor)

5.  Disadvantages:

• 8 hour test

• May be less specific in animals with concurrent disease (i.e. get false positives) 70-75% specific

6.  Uses:

• Screening test for hyperadrenocorticism

• Discriminating test for hyperadrencorticism    

• Discriminating Tests for Adrenal Function  (tests to differentiate pituitary- versus adrenal-dependent hyperadrenocorticism)

•  Low Dose Dexamethasone Suppression test – 4 hour sample

• Endogenous ACTH levels

• Measure on a single blood sample

• If  how – adrenal tumor

• If very high – PDH

• Significant overlap between normal and dogs with PDH  

• Ultrasound

• Look for adrenal tumors and contralateral adrenal atrophy

• Look for bilateral adrenal enlargement

• Look for potential metastatic disease

•  High Dose Dexamethasone Test (HDDST)-no longer recommended

ACTH-Stimulation Test

• Synthetic ACTH (cortrosyn)

• ACTH gel – compounded by compounding pharmacy (be careful)

• Cortrosyn

• 5 mcg/kg cortrosyn IV (or IM)

• adrenal hormone(s) that you want to measure before and 45-60 min after injection

• Can reconstitute and freeze cortorsyn in aliquots.  Stable for 6 months.

•  ACTH gel – trust your pharmacy

• 2.2 U/kg IM or check with your pharmacy

• Adrenal hormone(s) measured pre and 2 hours post injection

• Feline Adrenal Axis Testing

• LDDST – use 0.1 mg/kg of dexamethasone (instead of 0.01 mg/kg of dex for a dog); use the same criteria for diagnosing hyperadrenocorticism

• ACTH-stimulation test

• ug/kg synthetic ACTH IV

• Cortisol levels at 60 and 90 minutes

• Cortisol above 16 ug/dl (slightly lower than dogs) consistent with hyperadrenocorticism

• Low sensitivity (~50%)

•    Adrenal ultrasonography