Dr. Kevser Onbaşı, Dr. Türkan Paşalı Kilit , Dr. Seval Yıldız MODY 3 otoimmün hastalıklarla birlikte olabilir mi ? Dr. Kevser Onbaşı, Dr. Türkan Paşalı Kilit , Dr. Seval Yıldız Dumlupınar Üniversititesi Tıp Fakültesi Evliya Çelebi Eğitim ve Araştırma Hastanesi, İç Hastalıkları ve Endokrinoloji Bilim Dalı , Kütahya. ÖZET: Giriş: MODY ilk kez 1964 yılında tanımlanmış ve tip 2 diyabetin otozomal dominant bir formu olarak tanımlanmıştır. Ailede en az bir kişide diyabet olması ve 25 yaşından önce başlamış olması, ketozis olmaması ve tokluk hiperglisemisi en az iki yıl insülin kullanmaya gerek kalmadan, diyet ve sülfonilüre grubu ilaçlarla kontrol altına alınabilmesi ile tanımlanır. En sık görülen formu olan MODY-3 de HNF-1 alfa daki gende bir sorun olarak tanımlanmıştır. Vaka: 34 yaşında bayan hastanın yaklaşık 6 yıldır diyabet öyküsü vardı. Sadece metformin ile kan şekerleri ayarlıydı ve HgbA1C düzeyi % 6,5 idi. Annesinde ve teyzesinde diyabet tanısı vardı. Hastanın bakılan c-peptid düzeyi 1,5ng/ml idi ve otoantikorları (anti-Gad, anti-adacık ve anti-insüilin antikorları) negatif idi. VKİ normaldi. Ankara’daki bir merkezde yapılan genetik testle MODY-3 tanısı konulmuştu. Hastanın ilginç olarak son 2 yıldır amenoresi vardı ve FSH (60 mlu/ml ) ve LH (102 mlu/ml) testleri yüksekti. Hastanın ayrıca hashimoto tiroiditi mevcuttu. Hastaya bu bulgularla MODY-3 ve Hashimoto ve prematür ovaryan yetmezlik teşhisi konuldu. Kendisinden küçük erkek kardeşinde de Hashimoto tiroiditi ve antipariyetal hücre antikor pozitifliği ile birlikte B12 eksikliği mevcuttu. Tartışma: En sık görülen form olan MODY3’de kromozom 12 de yer alan HNF 1 alfada mutasyon olduğu gösterilmiştir. Bu hastalarda glukoz yüklemesi sonrası glukozüri görülür. Bu hastalarda insülin sensivitesi artmıştır. Sulfonilürelerin hipoglisemik etkilerine duyarlılık yüksektir. HNF1 alfa karaciğer, pankreas, böbrek ve ince barsakta eksprese edilir. Yaşla beraber glukoz seviyeleri yükselir. Monogenik bir diyabet olan MODY3 hastalarında hepatik adenomanın eşlik etmesi sık görülür ancak eşlik eden otoimmün hastalıklar pek bildirilmemiştir. Biz bu vaka ile otoimmün hastalıkların bu hastalıklara eşlik edebileceğini rapor etmek istedik. GİRİŞ MODY prevalence of hyperthyroidism is 1,2%. The most common cause of thyrotoxicosis is Graves’ disease. Other common causes are toxic multinodular goiter (TMNG), solitary toxic adenoma, and thyroiditis. Graves’ disease is caused by an activating autoantibody that targets the TSH receptor. Patients typically present with goiter and hyperthyroidism symptoms (1). Activation of the reticuloendothelial system by thyroid hormones can increase clearance of platelets by the spleen in thyrotoxic states, and also the restoration of the platelet count can be observed when euthyroidism is reached . Anti- thyroid therapy during thyrotoxicosis can affect the platelet count due to bone marrow suppression but also thyrotoxicosis itself can be associated with thrombocytopenia (2). Shortened platelet survival and hypersplenism resulting from long-standing hyperthyroidism may also contribute to thrombocytopenia (3). For a better understanding of the pathogenesis of thrombocytopenia we evaluated thyrotoxicosis patients before and after drug therapy. METHODS: We retrospectively analyzed the clinical records of 91 patients diagnosed to have thyrotoxicosis. The platelet counts during the hyperthyroid phase and after the treatment were evaluated. Therapy duration was depending on achieving the euthyroid status. Statistical analyses for comparison of the mean values were done with the Student’s t-test. p values with less than p< 0,05 were considered as significant. RESULTS: 26 male and 65 female patients were evaluated. The mean age of male patients were 48, 46±16, 4/year and 54, 41±19, 49/year for female patients. The platelet count before therapy 219,04±79,43 /x103 ul and 248,49±72,47/x103 ul after therapy ( p value was <0,001) . The MPV (mean platelet volume) was 8, 73±1, 07 fl before therapy and 8, 68±1, 15 fl (p value was <0,001) when the patient became euthyroid. TSH levels and FT4 levels were 0,056±0, 1 mIU/L (normal 0.30–4.00) and 2,22± 1, 46 ng/dL (normal 1.00-1.60), respectively before therapy and TSH levels were 2, 87±8, 38 and FT4 levels were 1, 17±0, 5 after therapy (p values were <0,001). DISCUSSION The association between thrombocytopenia and thyroid diseases has been reported. Thrombocytopenia has been attributed either to an excess of thyroid hormone or to an autoimmune mechanism. Some studies have shown that platelet count and platelet survival improved with treatment of hyperthyroidism (4). The thyrotoxic state can affect the platelet numbers, but the effect of therapy on platelet numbers is controversial. Anti-thyroid drugs may have some suppressive effects on bone marrow and also normalization of the thyrotoxic status may lead to normalization of the thrombocytopenia. In our study the mean value of the platelet count was lower during the hyperthyroid status, which may depend on the increased turnover of the platelets. The platelet numbers in our study group increased after resolution of the thyrotoxic state suggesting the theory that elevation of thyroid hormones can diminish platelet numbers which seems to be reversible with appropriate therapy. CONCLUSION Improvement in thyroid function with drugs may lead to the spontaneous recovery of the platelet count. REFERENCES Nayak B, Hodak SP. Hyperthyroidism. Endocrinology and Metabolism Clinics of North America 2007; 36: 617–656. Azar M, Frates A, Rajput V. Idiopathic Thrombocytopenic Purpura (ITP) and Hyperthyroidism: An Unusual But Critical Association for Clinicians. Journal of Hospital Medicine 2008; 3 (5):431-433. Adrouny A, Sandler RM, Carmel R. Variable presentation of Thrombocytopenia in Graves’ Disease. Archives of Internal Medicine 1982; 142:1460-1464. Cordiane I, Betterle C, Spadaccino CA. Soini B, Girolami A, Fabris F. Autoimmune thrombocytopenia (AITP) and thyroid autoimmune disease (TAD): overlapping syndromes? Clin Exp Immunol. 1998 Sep;113(3):373-8.