Özgün MAKALE, During Exenatide THERAPY, BENGÜR TAŞKIRAN, GÜVEN BARIŞ CANSU

Eksenatid Tedavisinde Tiroid İnce İğne Aspirasyon Biyopsisi ve Kalsitonin Yıkamanın Yeri

Tiroid kanseri riski ve GLP-1 analogları arasındaki ilişkinin net olmaması nedeniyle bu hastalarda tiroid nodüllerine nasıl yaklaşılacağı konusu açık değildir. Bu çalışmada eksenatid kullanan tip 2 DM'li hastalarda tiroid hastalığı varlığı, nodül gelişimi ve tiroid ince iğne aspirasyon biyopsisinde kalsitonin yıkama sonuçlarının gözden geçirilmesi amaçlandı. 2011-2014 yılları arasında günde 2 defa 5-10 mcg eksenatid subkutan kullanan ve öncesinde bilinen tiroid kanseri öyküsü bulunmayan hastaların tıbbi verileri geriye dönük incelendi. Ultrason, tiroid ince iğne aspirasyon biyopsisi, serum kalsitonin düzeyleri ve biyopsi sırasında kalsitonin yıkama yapılmış olan, ortalama yaşı 53.88±8.77, 66'sı kadın olan toplam 77 tip 2 DM'li hasta çalışmaya dahil edildi. Ultrasonda kuşkulu özelliği olan (mikrokalsifikasyon, sınır düzensizliği, artmış nodüler kanlanma) nodüllerden ve >=1 cm nodüllerden 22 gauge kalınlığında iğne ucu takılı 10 cc.lik enjektörler yardımıyla örnekleme yapıldı. Örnekler lamlara yayıldıktan sonra iğnenin hubında kalan materyal 1 cc izotonikle yıkanarak ependorflara konan yıkama örneklerinde ve serumda kalsitonin düzeyleri kemiluminisan immün assay (CLIA) yöntemiyle ölçüldü. Genel hasta popülasyonunda 1-24 ay olan eksenatid kullanım süresi boyunca yapılmış olan serum kalsitonin ölçümleri bir hasta dışında normaldi. Bazal ölçümü bulunmayan, ilk kez tedavinin 5. ayında yapılan serum kalsitonin ölçümü 482 pg/ml çıkan bu hastaya medüller tiroid kanseri öntanısı ile biyopsi ve operasyon planlanırken takipten kayboldu. Yirmidört hastadan toplam 32 adet ince iğne aspirasyon biyopsisi yapıldı (22 benin, 4 tanısal olmayan, 3 Hürthle hücreli lezyon, 1 önemi bilinmeyen atipi, 1 papiller tiroid kanseri kuşkulu, 1 sonuç kayıp). Operasyona yönlendirilen vakaların 3'ünde mikro papiller tiroid kanseri saptandı. Hiç birinde medüller tiroid kanseri veya C hücre hiperplazisi belirlenmedi. Biyopsi yıkama sıvılarında kalsitonin ölçümü normaldi. Tip 2 DM hastalarında kısa-orta vadede eksenatid kullanımında medüller tiroid kanseri ve C hücre hiperplazisi yoktur. Eksenatid-tiroid kanseri ilişkisi muğlak olduğundan eksenatid tedavisi öncesi hastalara ultrason yapılarak standart nodüllere yaklaşım ile değerlendirilmesinin uygun olduğunu düşünüyoruz.

Role of Thyroid Fine Needle Aspiration Biopsy and Calcitonin Wash-Out During Exenatide Therapy

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 Hürthle 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.

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