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870    PART VI   Endocrine Disorders


            Oral Dexamethasone Suppression Test                       35
            An alternative at-home oral dexamethasone suppression test        Normal range
  VetBooks.ir  has been used for years at the University of Utrecht, The   30  Suggestive of Cushing’s        a
            Netherlands. This test relies entirely on results of UCCRs to
                                                                              Strongly suggestive
            establish the diagnosis of hyperadrenocorticism and to iden-
            tify PDH. The client is instructed to collect two urine samples   of Cushing’s
            from the dog on two consecutive mornings and to store them   25
            in the refrigerator. After collection of the second urine
            sample, the client should administer three doses of dexa-
            methasone (0.1 mg/kg/dose) to the dog orally at 8-hour    20                                      b
            intervals. Urine is collected on the morning of the third day,
            and all three samples are delivered to the veterinarian for   Plasma cortisol (µg/dL)
            measurement of UCCRs. The first two urine samples are     15
            used as the screening test to diagnose hyperadrenocorticism.
            Abnormal  values support hyperadrenocorticism;  normal                                            c
            values rule out the disease. If both values are abnormal, the   10
            average of the two values is used as the baseline value and
            compared with the third value obtained after dexamethasone                                        d
            administration. The dog is described as having responded to   5
            dexamethasone  (suppressed)  if  the  UCCR  result  from  the
            third  urine  sample  is  less  than  50%  of  the  baseline  value.                              e
            Dogs meeting this criterion have results consistent with   0
            PDH, whereas those that fail to demonstrate suppression       Pre-ACTH                 Post-ACTH
            could have either ADH or PDH.                                  cortisol                  cortisol
            Adrenocorticotropic Hormone                          FIG 50.14
                                                                 Interpretation of the adrenocorticotropic hormone (ACTH)
            Stimulation Test                                     stimulation test in dogs. Ideally, dogs with Cushing’s
            The ACTH stimulation test is the gold standard for diagnosis   syndrome have an increased post-ACTH administration
            of hypoadrenocorticism, for identification of iatrogenic   cortisol concentration (line a). Post-ACTH cortisol values that
            hyperadrenocorticism, and for monitoring of trilostane and   fall into the “gray zone” (line b) could be consistent with
            mitotane  treatment.  Because of  problems with sensitivity   Cushing’s syndrome or may result from the effects of
                                                                 concurrent illness or chronic stress. Post-ACTH cortisol values
            (PDH, 80%-83%; ADH, 57%-63%) and specificity (59%-   may also fall into the normal range in dogs with Cushing’s
            93%) and the cost of synthetic ACTH, the diagnostic useful-  syndrome. The absence of a response to ACTH stimulation
            ness of the ACTH stimulation test as a screening test for   is suggestive of adrenocortical neoplasia (lines c and d) or
            spontaneous hyperadrenocorticism is inferior to the LDDS   iatrogenic hyperadrenocorticism (lines d and e). History and
            test. We do not use the ACTH stimulation test when evaluat-  physical examination findings should differentiate between
            ing dogs for hyperadrenocorticism. Test results of ACTH   these possibilities.
            stimulation are commonly inconclusive, and clearly abnor-
            mal test results (>30 µg/dL [800 nmol/L]) occur in dogs that
            do not have hyperadrenocorticism. ACTH stimulation test   supportive of hyperadrenocorticism, as long as the clinical
            results do not distinguish between PDH and ADH.      findings and clinicopathologic data are strongly consistent
              The protocol for the ACTH stimulation test is given in   with the disease. An increased post-ACTH serum cortisol
            Table 50.2. Only synthetic ACTH should be used; the lyophi-  value does not by itself confirm a diagnosis of hyperadreno-
            lized and liquid solution synthetic ACTH products can be   corticism, especially if clinical features and clinicopathologic
            used interchangeably. We typically administer 5 µg of syn-  data are not consistent with the diagnosis.
            thetic ACTH/kg IV and obtain blood for serum cortisol   Post-ACTH serum cortisol concentrations that do not
            concentration immediately before and 1 hour after ACTH   increase to above the preadministration value suggest iatro-
            administration. The unused  reconstituted ACTH  can  be   genic hyperadrenocorticism or spontaneous hypoadreno-
            stored frozen at −20° C in plastic syringes for 6 months with   corticism, especially if the cortisol values are below the
            no adverse effects on bioactivity of the ACTH. We use four   normal baseline reference range (see Fig. 50.14). A history
            ranges of values for interpretation of the ACTH stimulation   of recent glucocorticoid administration and the clinical pre-
            test (Fig. 50.14). Post-ACTH serum cortisol values between   sentation of the dog can help differentiate iatrogenic hyper-
            6 and 18 µg/dL (150 and 500 nmol/L) are within the normal   adrenocorticism from spontaneous hypoadrenocorticism. In
            reference range, values of 5 µg/dL (150 nmol/L) and below   rare instances a dog with ADH will have a minimal cortisol
            are  suggestive  of  iatrogenic  hyperadrenocorticism,  values   response to ACTH; however, its pre-ACTH and post-ACTH
            between 18 and 24 µg/dL (500 and 650 nmol/L) are incon-  administration serum cortisol concentrations should be
            clusive, and values greater than 24 µg/dL (650 nmol/L) are   within or above the reference range.
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