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54  Section 2  Endocrine Disease

            Table 7.2  Diagnostic tests that differentiate between PDH and ADH
  VetBooks.ir  Test        Components           Procedures                   Results



             Low‐dose      Dexamethasone sodium   Obtain blood samples:      ●   With LDDS, suppression to <50%
             dexamethasone   phosphate or       1)  Before administration     baseline in a dog with HAC confirms
             suppression   polyethylene glycol:  2)  4 h after administration  PDH.
                                          b
             (LDDS) a      0.01–0.015 mg/kg IV    3)  8 h after administration  ●   If no suppression with LDDS, cACTH
                           (dog), 0.10 mg/kg IV (cat)                         measurement or abdominal ultrasound is
             High‐dose     Dexamethasone sodium                               recommended.
             dexamethasone   phosphate:                                      ●   With LDDS or HDDS, lack of suppression
             suppression   0.1 mg/kg IV c                                     does not confirm AT (approximately 25%
             (HDDS) a      (dog), 1.0 mg/kg IV (cat)                          of dogs with PDH fail to suppress)
             Endogenous    cACTH                Collect blood into chilled, silicon‐  Normal or elevated concentrations are
             ACTH                               coated glass or plastic EDTA tubes.   consistent with PDH, suppressed values are
                                                Centrifuge within 15 min (ideally   consistent with AT
                                                cooled centrifuge).
                                                Transfer plasma to plastic tubes and
                                                freeze immediately; samples must
                                                stay frozen until analysis d
            a  LDDS and HDDS results cannot be considered 100% absolute; when imaging and endocrine test results conflict, the latter should be given
            preference.
            b  Calculate dose using parent compound.
            c  For HDDS, avoid the free alcohol form.
            d  Addition of the protease inhibitor aprotinin prevents ACTH degradation by plasma proteases and greatly facilitates sample handling. Check
            with your laboratory regarding suitability because, with some assays (i.e., Immulite), aprotinin introduces an artifactual decrease in results.
            AT, adrenal tumor; ATCH, adrenocorticotrophic hormone; cATCH, canine adrenocorticotrophic hormone; HAC, hyperadrenocorticism;
            IV, intravenous.

            tests should be performed to determine a definitive   administration (0.01 mg/kg IV). Diagnosis of HAC is
            diagnosis.                                        based on lack of suppression of cortisol concentration
             Several endocrine screening tests are available to arrive   eight hours after dexamethasone administration.
            at a diagnosis of HAC, including:
                                                              ACTH Stimulation
               low‐dose dexamethasone suppression (LDDS)
            ●                                                 Adrenocorticotropic hormone stimulation assesses
               ACTH stimulation
            ●                                                 adrenocortical reserve. Sensitivity of ACTH stimulation
               urine cortisol to creatinine ratio (UCCR).
            ●                                                 for all forms of spontaneous canine HAC ranges from
            Additional tests may be required to differentiate PDH   57% to 95%. In dogs with PDH, sensitivity is 80–83%.
            from other causes of hypercortisolemia, such as endog­  Specificity ranges from 59% to 93%.
            enous ACTH measurement and advanced imaging.        Due to greater purity and quality control, use of syn­
                                                              thetic ACTH is recommended. Use of compounded
            Initial Endocrine Screening                       ACTH is discouraged, especially when monitoring
            Low‐Dose Dexamethasone Suppression                patients on adrenolytic agents or adrenal enzyme block­
            Low‐dose dexamethasone suppression demonstrates   ers (see Synthetic versus Compounded ACTH).
            decreased pituitary sensitivity to negative feedback from
            glucocorticoids.                                  Indications  Adrenocorticotrophic hormone stimula­
                                                              tion is the gold standard for diagnosis of iatrogenic HAC
            Indications  Most consider LDDS the screening test of   and spontaneous Addison disease (hypoadrenocorti­
            choice for HAC unless the patient history suggests iatro­  cism). A diagnosis of HAC is based on finding an ele­
            genic HAC, in which case ACTH stimulation is preferred.  vated post‐ACTH cortisol concentration based on the
                                                              reference range established by the laboratory.
            Sensitivity/Specificity  In veterinary medicine, the
            reported  sensitivity  and  specificity  of  the  LDDS  test   Sensitivity/Specificity  Due  to its low sensitivity, it  is
            range from 85% to 100% and from 44% to 73%, respectively.  inferior to LDDS as a screening test for spontaneous
                                                              HAC. However, many clinicians still use ACTH stimula­
            Test Results  Blood samples are obtained (1) before, (2)   tion because of its convenient study duration of 60 min­
            four hours after, and (3) eight hours after dexamethasone   utes and relative effectiveness in the clinical setting,
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