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               14

               Canine Autoimmune Polyglandular Syndromes

               Deborah Greco, DVM, PhD, DACVIM (SAIM)
               Desert Veterinary Specialists, Palm Desert, CA, USA



               Many endocrine disorders, such as lymphocytic thyroid­  to a decrease in suppressor T cell activity. Approximately
               itis, hypoadrenocorticism, and type 1 diabetes mellitus,   45% of all human patients with idiopathic (autoimmune)
               have an autoimmune basis. When endocrine immune    adrenal insufficiency will develop one or more additional
               disorders occur in the same individual, they are known   endocrinopathies (usually hypothyroidism).
               as autoimmune polyglandular syndromes (APS). These   The  genetics  of  APS  has  been  studied  extensively  in
               syndromes (APS) can be further divided into APS type 1   human beings. APS 2 is inherited as an autosomal domi­
               (diabetes   mellitus, ectodermal mucositis, etc.), APS type   nant  trait in  humans  associated  with the  presence of
               2 (hypoadrenocorticism, hypothyroidism, etc.), and APS   human leukocyte antigens (HLA). In families where this
               type 3 (liver cirrhosis plus endocrinopathies). The com­  syndrome has been documented in several individuals,
               bination of hypoadrenocorticism and hypothyroidism is   the inheritance of major histocompatibility loci haplo­
               called Schmidt syndrome after the pathologist who   type correlates most strongly with the disease. Many
               described concurrence of these two diseases in human   individuals with this haplotype have circulating organ‐
               beings. Autoimmune polyglandular syndrome type 2 is   specific autoantibodies directed against cytochrome
               the only one that has been described in dogs.      P450 without clinical signs of disease. Recently, one study
                                                                  found that a higher proportion of dogs with hypoadreno­
                                                                  corticism were P450scc autoantibody   positive when
                 Etiology and Pathophysiology                     compared to hospital controls (24% vs 1%). Lymphocytic
                                                                  and plasmacytic destruction of the affected endocrine
               Polyendocrine gland failure or autoimmune polyglan­  glands may be documented histologically.
               dular syndrome, the most common form of which is APS   Hypoadrenocorticism is the most common initial endo­
               type 2, has been well documented in humans. Autoimmune   crinopathy observed in polyendocrine gland failure in
               polyglandular syndrome type 2 is defined as the occur­  dogs and is usually followed by the development of hypo­
               rence of two or more of the following disorders in the   thyroidism. However, type 1 diabetes combined with
               same individual: adrenal insufficiency, primary hypothy­  immune‐mediated thyroid disease (Hashimoto  thyroiditis)
               roidism, type 1 diabetes mellitus (DM), primary hypog­  is also a common combination of immune endocrinopa­
               onadism (premature ovarian failure, immune‐mediated   thies in humans and has been described in dogs. Studies
               orchitis), myasthenia gravis, megaesophagus, immune‐  show that 45–50% of humans with adrenal insufficiency
               mediated hemolytic anemia (IMHA), immune‐mediated   associated with polyendocrine gland failure (onset 20–30
               thrombocytopenia (ITP), hypoparathyroidism, hypopitu­  years) develop a second endocrinopathy. The most com­
               itarism, and celiac disease.                       mon   second endocrinopathy, primary hypothyroidism,
                 Circulating organ‐specific autoantibodies are com­  develops 10–20 years after the first endocrinopathy.
               monly present in APS type 2. Environmental factors   In a retrospective of 225 cases of canine hypoad­
                 combined with an HLA‐associated genetic predisposi­  renocorticism, 4% of the dogs (n = 9) also suffered from
               tion are thought to trigger the process. Cell‐mediated   hypothyroidism,  two dogs had  concurrent  IDDM and
               immune abnormalities in the type 2 syndrome include   hypoadrenocorticism, and one had concurrent hypoad­
               defects and alterations of cell surface markers, but the   renocorticism, hypothyroidism, IDDM, and hypopar­
               most consistent abnormality is a functional defect leading   athyroidism. Another retrospective of 45 dogs with


               Clinical Small Animal Internal Medicine Volume I, First Edition. Edited by David S. Bruyette.
               © 2020 John Wiley & Sons, Inc. Published 2020 by John Wiley & Sons, Inc.
               Companion website: www.wiley.com/go/bruyette/clinical
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