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

Year 2017, Volume: 39 Issue: 2, 40 - 44, 20.07.2017

Bengür Taşkıran Güven Barış Cansu

https://doi.org/10.20515/otd.308303

Abstract

Öz: 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.

Anahtar Kelimeler: eksenatid, ince iğne 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 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. 

Keywords: exenatide, fine
needle aspiration biopsy, calcitonin, thyroid cancer

Keywords

eksenatid, ince iğne aspirasyon biyopsisi, kalsitonin

References

• 1. Inzucchi SE, Bergenstal RM, Buse JB, et al. (2012). Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia, 55(6), 1577-1596.
• 2. Rosol TJ. (2013). On-target effects of GLP-1 receptor agonists on thyroid C-cells in rats and mice. ToxicolPathol, 41(2), 303-309.
• 3. Elashoff M, Matveyenko AV, Gier B, et al. (2011). Pancreatitis, pancreatic, and thyroid cancer with glucagon-like peptide-1-based therapies. Gastroenterology, 141(1),150-156.
• 4. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, Schuff KG, Sherman SI, Sosa JA, Steward DL, Tuttle RM, Wartofsky L. (2016) .2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid, 26(1),1-133.
• 5. American Thyroid Association GuidelinesTask Force, et al. (2009). Medullary thyroid cancer: management guidelines of the American Thyroid Association. Thyroid, 19(6), 565-612.
• 6. Diazzi C, Madeo B, Taliani E, Zirilli L, Romano S, Granata AR, De Santis MC, Simoni M, Cioni K, Carani C, Rochira V. (2013). The diagnostic value of calcitonin measurement in wash-out fluid from fine-needle aspiration of thyroid nodules in the diagnosis of medullary thyroid cancer. EndocrPract, 19(5),769-779.
• 7. Boi F, Maurelli I, Pinna G, Atzeni F, Piga M, Lai ML, Mariotti S. (2007). Calcitonin measurement in wash-out fluid from fine needle aspiration of neck masses in patients with primary and metastatic medullary thyroid carcinoma. J Clin Endocrinol Metab, 92(6), 2115-2118.
• 8. Knudsen LB, Madsen LW, Andersen S et al. (2010). Glucagon like peptide-1 receptor agonists activate rodent thyroid Ccells causing calcitonin release and C-cell proliferation. Endocrinology,151(4), 1473–1486.
• 9. Chiu WY, Shih SR, Tseng CH. (2012). A review on the association between glucagon-like peptide-1 receptor agonists and thyroid cancer. Exp Diabetes Res, 2012:924168.
• 10. Madsen LW, Knauf JA, Gotfredsen C, Pilling A, Sjögren I, Andersen S, Andersen L, de Boer AS, Manova K, Barlas A, Vundavalli S, Nyborg NC, Knudsen LB, Moelck AM, Fagin JA. (2012). GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation. Endocrinology, 153(3), 1538-1547.
• 11. Gier B, Butler PC, Lai CK, et al. (2012). Glucagon like peptide-1 receptor expression in the human thyroid gland. J Clin Endocrinol Metab, 97(1), 121-131.