From macrocytosis to incomplete autoimmune polyglandular syndrome type 2: a poorly known entity

Abstract

Dear Sir, We report a 41-year-old woman who was diagnosed with incomplete autoimmune polyendocrine syndrome type 2 (APS-2) during the work up of macrocytosis. The patient was admitted to our institution for 24 h observation after experiencing chest pain. Her physical examination did not reveal any pertinent findings. Laboratory examination including complete blood count and metabolic panel were normal except for MCV of 108.7 fl. After ruling out serious cardiac pathology, the work up for the macrocytosis was completed and revealed ovalocytes on the peripheral smear, TSH of 8.33 uIU mL−1 (0.3–5.0 uIU mL−1) and a vitamin B12 level of 150 pg mL−1 (193–982 pg mL−1). Further studies concerning her low TSH level showed a normal free T4 level and positive antithyroid peroxidase antibodies, consistent with the diagnosis of autoimmune thyroid disease. An esophagogastroduodenoscopy showed atrophic gastritis and anti-parietal cell antibodies were positive confirming the diagnosis of chronic atrophic gastritis. Based on these findings, an autoimmune process was suspected and further laboratory studies showed the presence of anti-adrenal cortex antibodies but there was no evidence of adrenal insufficiency based on her baseline serum cortisol, ACTH (adrenocorticotropic hormone) level and ACTH stimulation test. Patient was diagnosed with incomplete APS-2 and she was discharged on vitamin B12 and levothyroxine. Type 2 APS is characterized by the obligatory occurrence of autoimmune Addison’s disease (AD) in combination with thyroid autoimmune diseases (TAD) and/or with type 1 diabetes mellitus [1]. The simultaneous expression of the three major components of the disease is rarely found in clinical practice and represents only the ‘tip of the iceberg’. In fact, the spectrum of the disease is more variable and incomplete forms of the disease are more frequently encountered but unfortunately their importance is not well recognized. Incomplete APS-2 is considered when patients have AD with thyroid antibodies, islet-cell antibodies or glutamic acid decarboxylase antibodies, or TAD with adrenal cortex antibodies (ACA) or 21-hydroxylase antibodies (21-OH Abs), or type 1 diabetes mellitus with ACA or 21-OH Abs, or simple expression of these antibodies in asymptomatic patients [2]. Patients with positive antibodies are considered at high risk for developing clinical symptoms related to the endocrine gland affected [3]. Although, not all patients will develop a complete clinical overt syndrome, it remains important that all patients undergo further functional tests such as TSH, thyroid hormones, glucose tolerance test, and ACTH stimulation test. This approach will help to classify patients in tow categories. The first one is potential APS-2 with positive antibodies and normal functional test and the second one is subclinical APS-2 with positive antibodies and functional test [2]. From clinical point of view, the recognition of the incomplete form of the disease whether it is classified as potential or subclinical is crucial for further workup and follow up. As in our case, the early finding of macrocytosis and subsequently the atrophic gastritis with autoimmune thyroid disease lead to further workup to evaluate the involvement of other endocrine glands. Follow up of patients with positive antibody test and normal function of the relevant organ is highly advisable. Appropriate functional and morphological tests should be done every two to three years to prevent the outbreak of the ongoing autoimmune disease [3]. In summary, the early diagnosis of incomplete APS-2 will help us to start early treatment for the endocrine gland affected by the autoimmune process and it can be life saving by early recognition and management of another autoimmune endocrine disorder such as acute adrenal failure. None.