Adrenal disease tests

Measurement of a single serum or plasma cortisol concentration by obtaining a blood sample at any time of day.

Comments
• Resting cortisol is not a screening test for Cushing’s syndrome
• Resting cortisol can be used as a screening test to rule out hypoadrenocorticism; a low value cannot prove the presence of hypoadrenocorticism and should be followed by an ACTH stimulation test for confirmation of the disease.
• For all tests, cut-off values have to be established by each laboratory.
• Measurement of cortisol using in-house assays is discouraged and use of reference laboratories is encouraged
• In the clinical setting in which tubes may be underfilled, use of EDTA-plasma significantly increases the measured concentration of cortisol.

Measurement of urinary corticoid (cortisol and its metabolites) excretion. The ratio is calulated by dividing urinary corticoid concentration by urinary creatinine concentration.

Comments
• The sample used should be the first morning urine sample.
• The UCCR is, at best, a poor screening test for Cushing’s syndrome, as its sensitivity can be below 70% depending on the assay employed.
• ALIVE recommends that the urine be collected at home > 2 days after a visit to a veterinary clinic or stressful event.
• The UCCR should never be considered as an effective test for the diagnosis of Cushing’s syndrome as its specificity is less than 70%
• For all tests, cut-off values have to be established by each laboratory.

Defined as the determination of UCCR on two consecutive days followed by administration of oral dexamethasone (0.1 mg/kg q8h) on day 2 and a collection of a third sample for a UCCR on the third day.

Comments
• The UCCR dexamethasone suppression test is a screening and differentiating test.
• The samples used should be the first morning urine samples.
• ALIVE recommends the urine be collected at home > 2 days after a visit to a veterinary clinic or stressful event.
• For all tests, cut-off values have to be established by each laboratory.

Dexamethasone (0.01 mg/kg in dogs and 0.1 mg/kg in cats) is injected intravenously and serum/ plasma cortisol measured before injection and 4 and 8 hours thereafter.

Comments
• The LDDST can be a screening and differentiating test.
• Despite the existence of alternative dosage and timing recommendations, ALIVE encourages the future use of the above protocol for standardisation and comparability purposes.
• For all tests, cut-off values have to be established by each laboratory.
• Measurement of cortisol by in-house assays is discouraged and use of reference laboratories is encouraged
• In the clinical setting in which tubes may be underfilled, use of EDTA-plasma significantly increases the measured concentration of cortisol.

Dexamethasone (0.1 mg/kg in dogs and 1.0 mg/kg in cats) is injected intraveneously and serum/ plasma cortisol measured before injection and 4 and 8 hours thereafter.

Comments
• The HDDST can be a differentiating test, although it cannot prove the existence of ADH.
• Despite the existence of alternative dosage and timing recommendations, ALIVE encourages the future use of the above protocol for standardisation and comparability purposes.
• For all tests, cut-off values have to be established by each laboratory.
• Measurement of cortisol by in-house assays is discouraged and use of reference laboratories is encouraged
• In the clinical setting in which tubes may be underfilled, use of EDTA-plasma significantly increases the measured concentration of cortisol.

The ACTH stimulation test is performed with synthetic ACTH given (preferred dose 5 microgram/kg in dogs and 125 microgram/cat) and serum/ plasma cortisol concentrations are measured before and 60 minutes (dogs) or 60 and 90 minutes (cats) after ACTH administration.

Comments
• The ACTH stimulation test is a screening test for hypoadrenocorticism and naturally-occurring Cushing’s syndrome and the only test that can document iatrogenic Cushing’s syndrome.
• Intravenous use of the synthetic ACTH is considered standard; though intramuscular use has also been shown to be effective; for standardisation and comparability purposes, ALIVE recommends intravenous administration, where possible
• Several synthetic ACTH preparations exist with tetracosactide and cosyntropin being the most frequently used; ALIVE recommends the use of preparations with sufficient evidence base for efficacy.
• Several dosages of synthetic ACTH are being used; ALIVE recommends the use of a minimum of 5 microgram/kg (dogs) intravenously.
• Several timings for post-ACTH sampling have been reported (including several additional samples for cats); ALIVE recommends the above 60 minutes in dogs and, at least, 60 minutes and 90 minutes in cats, for standardisation and comparability purposes.
• Measurement of cortisol by in-house assays is discouraged and use of reference laboratories is encouraged.
• In the clinical setting in which tubes may be underfilled, use of EDTA-plasma significantly increases the measured concentration of cortisol.

A single EDTA-plasma sample is collected for measurement of endogenous ACTH.

Comments
• Measurement of eACTH is a differentiating test and cannot be used as a screening test.
• As eACTH is a fragile hormone, sampling and transport recommendations must be closely followed.
• For all tests, cut-off values have to be established by each laboratory.
• Measurement of eACTH by a reference laboratory enrolled in an external quality assurance program is encouraged.

maging of the adrenal glands can be used as a differentiating test in the context of Cushing’s syndrome. The dorsoventral measurement of the caudal pole thickness of either adrenal gland in a sagittal plane is the best dimension for evaluating size.

Comments
• A single reference interval for a normal measurement is not appropriate; body size must be taken into consideration.
• This is not a screening test; therefore, the finding of normal adrenal glands does not exclude Cushing’s syndrome.
• Finding enlarged adrenal glands without a clinical suspicion of Cushing’s syndrome and positive endocrine testing does not constitute a diagnosis of Cushing’s syndrome.
• ACTH-dependent forms usually present with bilateral symmetrical adrenomegaly, but adrenal asymmetry may also occur.
• Adrenal asymmetry, contralateral atrophy or destruction of the normal tissue architecture are suggestive of ACTH-independent Cushing’s.
• Vascular invasion and possible liver metastasis suggest malignancy.

CT or MRI can be used to image the pituitary. Use of contrast enhancement or a dynamic study increases the sensitivity of the techniques.

Comments:
• The finding of an apparently normal pituitary on CT and/or MRI does not exclude the possibility of a pituitary tumour.
• This is not a screening test; therefore, the finding of an enlarged pituitary without a clinical suspicion of Cushing’s syndrome and positive endocrine testing does not constitute a diagnosis of Cushing’s syndrome either.

Not enough evidence-based data are currently available to recommend routine use of these tests to diagnose Cushing’s syndrome.