Malfunctioning adrenals: how to diagnose them (Proceedings)


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

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
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