Eksenatid Tedavisinde Tiroid İnce İğne Aspirasyon Biyopsisi ve Kalsitonin Yıkamanın Yeri Role of Thyroid Fine Needle Aspiration Biopsy and Calcitonin Wash-Out During Exenatide Therapy

Oz: Tiroid kanseri riski ve GLP-1 analoglari arasindaki iliskinin net olmamasi nedeniyle bu hastalarda tiroid nodullerine nasil yaklasilacagi konusu acik degildir. Bu calismada eksenatid kullanan tip 2 DM’li hastalarda tiroid hastaligi varligi, nodul gelisimi ve tiroid ince igne aspirasyon biyopsisinde kalsitonin yikama sonuclarinin gozden gecirilmesi amaclandi. 2011-2014 yillari arasinda gunde 2 defa 5-10 mcg eksenatid subkutan kullanan ve oncesinde bilinen tiroid kanseri oykusu bulunmayan hastalarin tibbi verileri geriye donuk incelendi. Ultrason, tiroid ince igne aspirasyon biyopsisi, serum kalsitonin duzeyleri ve biyopsi sirasinda kalsitonin yikama yapilmis olan, ortalama yasi 53.88±8.77, 66’si kadin olan toplam 77 tip 2 DM’li hasta calismaya dahil edildi. Ultrasonda kuskulu ozelligi olan (mikrokalsifikasyon, sinir duzensizligi, artmis noduler kanlanma) nodullerden ve ≥1 cm nodullerden 22 gauge kalinliginda igne ucu takili 10 cc.lik enjektorler yardimiyla ornekleme yapildi. Ornekler lamlara yayildiktan sonra ignenin hub inda kalan materyal 1 cc izotonikle yikanarak ependorflara konan yikama orneklerinde ve serumda kalsitonin duzeyleri kemiluminisan immun assay (CLIA) yontemiyle olculdu. Genel hasta populasyonunda 1-24 ay olan eksenatid kullanim suresi boyunca yapilmis olan serum kalsitonin olcumleri bir hasta disinda normaldi. Bazal olcumu bulunmayan, ilk kez tedavinin 5. ayinda yapilan serum kalsitonin olcumu 482 pg/ml cikan bu hastaya meduller tiroid kanseri ontanisi ile biyopsi ve operasyon planlanirken takipten kayboldu. Yirmidort hastadan toplam 32 adet ince igne aspirasyon biyopsisi yapildi (22 benin, 4 tanisal olmayan, 3 Hurthle hucreli lezyon, 1 onemi bilinmeyen atipi, 1 papiller tiroid kanseri kuskulu, 1 sonuc kayip). Operasyona yonlendirilen vakalarin 3’unde mikro papiller tiroid kanseri saptandi. Hic birinde meduller tiroid kanseri veya C hucre hiperplazisi belirlenmedi. Biyopsi yikama sivilarinda kalsitonin olcumu normaldi. Tip 2 DM hastalarinda kisa-orta vadede eksenatid kullaniminda meduller tiroid kanseri ve C hucre hiperplazisi yoktur. Eksenatid-tiroid kanseri iliskisi muglak oldugundan eksenatid tedavisi oncesi hastalara ultrason yapilarak standart nodullere yaklasim ile degerlendirilmesinin uygun oldugunu dusunuyoruz. Anahtar Kelimeler: eksenatid, ince igne aspirasyon biyopsisi, kalsitonin, tiroid kanseri . Abstract: Management of thyroid nodules during exenatide therapy is not settled because of inconsistent data about relation between thyroid cancer and GLP-1 analogues. In this study we aimed to evaluate thyroid disease, nodule formation, and calcitonin wash-out of fine needle aspiration biopsy samples in patients with type 2 DM. Data of patients treated with exenatide 5-10 mcg bid for type 2 DM between 2010 to 2014 were retrospectively evaluated. There was no history of thyroid cancer prior to therapy. Seventy seven patients (66 female, 11 male) aged 53.88±8.77 years with documented ultrasound, thyroid fine needle aspiration biopsy, serum calcitonin, and calcitonin in wash-out fluid of biopsy results were included to the study. Fine needle aspiration biopsy was performed in patients having nodules ≥1 cm in size and/or nodules with suspicious features (microcalcification, irregular border, increased vascularity in nodules). Twenty-two gauged needles attached to 10 cc syringes were used for sampling. After smearing, the needle hub is washed with 1 cc saline. Both serum and wash-out samples were studied for calcitonin using chemiluminescence assay (CLIA).  During 1-24 months of therapy serum calcitonin measurements were all normal except in one patient. The patient had no calcitonin measurement and family and personal history of medullary thyroid cancer prior to therapy. At the 5th month of therapy serum calcitonin was measured and found 482 pg/ml. While we were scheduling biopsy and thyroidectomy for a suspicious medullary thyroid cancer, the patient had a traffic accident and was lost for follow-up. Twenty-four patients had 32 fine needle biopsy in total (22 benign, 4 nondiagnostic, 3 Hurthle cell lesion, 1 atypia of unknown significance, 1 suspicious for papillary thyroid cancer, 1 missing result). Three had micro papillary thyroid cancer among those were referred to surgery. None of the patients who underwent biopsy and/or surgery had medullary thyroid cancer and C cell hyperplasia. Calcitonin in wash-out fluid of biopsies were normal. Medullary thyroid cancer and C cell hyperplasia are not evident in short-midterm exenatide therapy in type 2 DM. Since exenatide-thyroid cancer relation has not settled yet, we suggest a baseline ultrasound examination prior to exenatide therapy and manage in a same manner as standard approach.  Keywords: exenatide, fine needle aspiration biopsy, calcitonin, thyroid cancer