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CHAPTER 48   Disorders of the Thyroid Gland   775



            Blood vessel                                                              FIG 48.7
                                                                                      Intracellular metabolism of free
  VetBooks.ir             Free T  (<1%)           T –plasma protein (>99%)            5′- or 5-monodeiodinase,
                                                                                      T 4  to either T 3  or reverse T 3  by
                              4
                                                   4
                                                                                      respectively. Intracellular T 3
                                                                                      formed from monodeiodination
                                                                                      of free T 4  can interact with T 3
                                           5′–D                                       receptors on the cell membrane,
                                 Free T 4           T 3                               mitochondria, or nucleus of the
                                                                                      cell and stimulate the physiologic
                                     5–D                                              actions of thyroid hormone or
                                                                                      bind to cytoplasmic binding
                                                                                      proteins (CBP). The latter form an
                                         T –CBP                                       intracellular storage pool for T 3 .
                                          3
                                                                                      (From Feldman EC, Nelson RW:
                                   rT 3
                                                                                      Canine and feline endocrinology
                                                                                      and reproduction, ed 3, St Louis,
                                                                                      2004, WB Saunders.)




            active, exerts negative feedback inhibition on pituitary TSH   study, discrepancies, both overestimation and underestima-
            secretion (see  Fig. 48.1), and is capable of entering cells   tion of the T 4  concentration, between the in house ELISA
            throughout the body (Fig. 48.7). Within the cell, fT 4  is deio-  and RIA results were detected (Lurye et al., 2002). In con-
            dinated to form either T 3  or rT 3 , depending on the metabolic   trast, serum T 4  concentrations determined in dogs and cats
            demands of the tissues at that particular time. T 3  is prefer-  by RIA, chemiluminescent enzyme immunoassay, and a
            entially produced during normal metabolic states; rT 3  is bio-  point-of-care ELISA provided similar and consistent results
            logically inactive and produced during periods of illness or   (Kemppainen and Birchfield, 2006).
            excessive endogenous catabolism. T 3  is believed to be the   For most laboratories, the lower limit of the reference
            primary hormone that induces physiologic effects.    range for serum T 4  in dogs is approximately 0.8 to 1.0 µg/dL
              All serum T 4 , both protein bound and free, comes from   (10-13 nmol/L), although in some breeds the normal range
            the thyroid gland. Therefore tests that measure serum total   may extend to as low as 0.5 µg/dL (6 nmol/L) (see the dis-
            and fT 4  concentrations, in conjunction with the serum TSH   cussion of breed variations, p. 781).
            concentration, are currently recommended for assessment of   Theoretically, interpretation of baseline serum T 4  concen-
            thyroid gland function in dogs suspected of having hypothy-  tration should be straightforward in that dogs with hypo-
            roidism. Serum T 3  concentration is a poor gauge of thyroid   thyroidism should have values below the reference range.
            gland function because of its predominant location within   Unfortunately, the serum T 4  concentration range in healthy
            cells and the minimal amount secreted by the thyroid gland   dogs overlaps with that in hypothyroid dogs, and the serum
            in comparison with the amount of T 4  secreted (Fig. 48.8).   T 4  concentration can be suppressed below the reference
            Thus measurement of serum T 3 , free T 3 , and rT 3  concentra-  range in euthyroid dogs by a variety of factors, most notably
            tion is not recommended for assessment of thyroid gland   nonthyroidal illness and medications (Table 48.2). Clinicians
            function in dogs.                                    often find  it difficult  to judge the  effects that extraneous
                                                                 factors, especially concurrent illness, have on serum T 4  con-
            Baseline Serum T 4  Concentration                    centration. Because these variables can suppress a baseline
            The baseline serum T 4  concentration is the sum of protein-  serum T 4  concentration to less than 0.5 µg/dL in a euthy-
            bound and free levels circulating in the blood. Measurement   roid dog, and because hypothyroid dogs in early stages of
            of serum T 4  concentration can serve as the initial screening   the disease may have a serum T 4  concentration near the
            test for hypothyroidism or can be part of a thyroid panel   lower end of the reference range, the serum T 4  concentration
            containing T 4 , fT 4 , TSH, an antibody test for lymphocytic   should be used to confirm normal thyroid gland function,
            thyroiditis, or some combination of these tests (Box 48.4).  not hypothyroidism per se. A serum T 4  concentration in the
              Most reference laboratories use radioimmunoassay (RIA)   reference range, especially a value in the upper half of the
            or, more commonly, chemiluminescent immunoassays for   reference range, establishes normal thyroid gland function.
            measuring serum T 4  in dogs and cats. Point-of-care enzyme-  The exception is seen in a very small number (<2%) of hypo-
            linked immunosorbent assays (ELISAs) for measuring serum   thyroid dogs with lymphocytic thyroiditis that have serum
            T 4  are also available; are economical, quick, and easy to   T 4   autoantibodies  that  may  interfere  with  the assay  used
            perform; and allow the clinician to make recommendations   to measure T 4 . A serum T 4  concentration below the lower
            the same day the dog (or cat) is evaluated. Studies evaluating   limit of the reference range is consistent with hypothyroid-
            one point-of-care ELISA (Snap T 4  test kit and VetTest Snap   ism,  especially  if  the  T 4   concentration  is  less  than  0.5 µg/
            Reader, IDDEX laboratories) have been conflicting. In one   dL and all other findings are consistent with the diagnosis.
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