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7  Pituitary-Dependent Hyperadrenocorticism in Dogs and Cats  55

               especially when combined with abdominal ultrasound   Evaluation of Pituitary–Adrenal Axis
  VetBooks.ir  evaluation  and  interpreted  in light  of  the history  and   the following circumstances.
                                                                  Evaluation of the pituitary–adrenal axis is indicated in
               physical examination.

                                                                  ●   Patients with clinical signs and laboratory findings
               Synthetic vs Compounded ACTH  Synthetic polypeptides,   consistent with PDH and in whom nonadrenal illness
               such as Cortrosyn® (cosyntropin) or Synacthen® (tetra­  has been ruled out or is well controlled.
               cosactrin), contain the biologically active first 24 amino   ●   Patients in whom an adrenal/pituitary mass or bilat­
               acids of ACTH; however, their potencies have not been   eral adrenal hyperplasia has been discovered in con­
               compared.                                            junction with compatible clinical signs.
                 In several studies, after administration of cosyntropin   ●   Patients with an incidentally discovered adrenal mass,
               (5 μg/kg or 250 μg/dog IV or IM), peak cortisol concen­  with adrenalectomy being considered.
               trations  occurred at 60–90  minutes.  After administra­  ●   Diabetic dogs with insulin resistance.
               tion of 5 μg/kg IV, no difference was detected between
               60‐ and 90‐minute cortisol concentrations. Cosyntropin
               can be reconstituted, divided into aliquots in plastic   Differentiating PDH from ADH: Laboratory Analysis
               syringes, and frozen at –20 °C for six months. Whether   Given that PDH and adrenal‐dependent hyperadreno­
               tetracosactrin can be frozen has not been investigated;   corticism (ADH) are the most common forms of HAC,
               according to the manufacturer, store it at temperatures   and that their treatment options and prognoses differ, it
               from 2 to 8 °C.                                    is important to recommend additional testing to deter­
                 Compounded ACTH products have been evaluated     mine the exact etiology of HAC. Several diagnostic
               in healthy dogs. Sixty minutes after administration,   modalities are commonly used to differentiate between
               cortisol  concentrations  were  similar  among  four   PDH and ADH.
                 compounded products (2.2 U/kg IM) and cosyntropin   ●   Endogenous ACTH
               (5 μg/kg IV). However, at later times, cortisol concen­  ●   Dexamethasone suppression
               trations varied considerably with the compounded   ●   Dexamethasone suppression with UCCR
               products.
                                                                  Endogenous ACTH
               Urine Cortisol to Creatinine Ratio                 Canine ACTH is secreted from the pituitary gland
               The UCCR provides an integrated reflection of cortisol   in  an episodic, pulsatile fashion in both healthy
               production, adjusting for fluctuations in blood concen­  dogs  and those with PDH. A circadian rhythm has
               trations. Determination of basal UCCRs can be per­  not  been  convincingly demonstrated, although one
               formed alone or in tandem with other endocrine testing.  study reported higher plasma concentrations of canine
                                                                  ACTH (cACTH) in the late afternoon than in the
               Indications  The UCCR can be used as a screening test   morning.
               for hypercortisolemia, although a single positive result
               should not be overinterpreted. Adding oral dexametha­  Indications  Concentrations of cACTH do  not differ
               sone  suppression to  UCCR  testing  (see  later) has the   between healthy dogs and those with PDH, and its
               advantage of potentially demonstrating both increased   measurement is not useful to screen for HAC. However,
               cortisol production and decreased sensitivity to gluco­  measurement of cACTH is the most accurate stand‐
               corticoid feedback.                                alone biochemical test for differentiating PDH from
                                                                  adrenocortical tumor (AT), but the sensitivity of the
               Sensitivity/Specificity  When a single, random urine   assay differs with methodology. Normal or elevated
               sample is collected in veterinary hospitals, reported sen­  concentrations of cACTH are consistent with PDH
               sitivity and specificity of UCCR for diagnosis of HAC   while suppressed values are consistent with AT.
               range from 75% to 100% and 20% to 25%, respectively. In
               some dogs, there is considerable day‐to‐day variation in   Sensitivity/Specificity  The most common problem with
               UCCR results.                                      the cACTH assay is poor sensitivity. The largest study of
                 However, in dogs with physical and biochemical   cACTH in dogs with HAC used a two‐site solid‐phase
               changes consistent with HAC, when two basal UCCRs   chemiluminescent immunometric assay (Immulite 2000
               were above the cut‐off level:
                                                                  Immunoassay System for ACTH; healthcare.siemens.
                  sensitivity was 99%; 95% confidence interval 94–100%  com) and showed excellent discrimination between
               ●
                  specificity was 77%; 95% confidence interval 64–87%.  PDH and AT.
               ●
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