Aşkın Güngüneş, Şenay Arıkan Durmaz, Dilek Oğuz, Selim Yalçın, Nesrin Turhan, Aydın Çifci

Akromegali ve pankreas adenokarsinomunun insidental birlikteliği olan nadir bir vaka; Olgu sunumu

Akromegali nadir bir endokrin hastalıktır. Akromegali, premalign tübüler adenom ve kolorektal kanser sıklığında artış ile ilişkili olup meme ve tiroid gibi diğer organ maligniteleriyle de ilişkili olabilir. Bu yazıda, tarafımızca akromegali ve pankreas adenokarsinom insidental birlikteliği ışığında nadir görülen bir vakanın bildirimi yapıldı.Elli iki yaşında erkek hasta, yaklaşık 2 yıl önce akromegali tanısı aldı. Tanı sonrası transsfenoidal cerrahi uygulandı. Cerrahi sonrası büyüme hormonu (GH) ve insülin benzeri büyüme faktörü (IGF-1) düzeyleri normale dönmeyen hastaya bu nedenle somatostatin analog tedavisi başlandı. Bu tedaviyi takiben IGF-1 değeri yaş ve cinsiyete göre normale döndü. Aynı hasta 3 ay önce karın ağrısı şikayeti ile polikliniğimize başvurdu. Abdomen bilgisayarlı tomografide (BT) pankreas kuyruk kesiminde 44x26 mm boyutlarında kitle lezyonu ve karaciğerde çok sayıda metastatik lezyon saptandı. Üst gastrointestinal sistem endoskopisi ve kolonoskopide sırasıyla eroziv gastrit ve kolonda polipler gözlendi. Pankreas kuyruğundaki kitle lezyonundan endoskopik ultrasonografi eşliğinde ince iğne aspirasyon biyopsisi yapıldı. Patolojik inceleme pankreas kaynaklı duktal adenokarsinom ile uyumlu idi. Akromegalisi olan hastalarda benign ve malign neoplazm riskinde artış olup bu durum dolaşımdaki artmış IGF-1 düzeyleri ile ilişkili olabilir. IGF-1, proliferatif ve anti-apoptotik etkinliğe sahiptir. Akromegali ve metastatik pankreatik tümör birlikteliği literatürde yer almakla birlikte oldukça nadirdir. Akromegali hastalarında pankreas adenokarsinomu ve diğer malign hastalıkların olabileceğini dikkate almak gerekir.

Anahtar Kelimeler:

Akromegali, duktal pankreas adenokarsinomu, GH ve IGF-1

A rare case with incidental coexistence of acromegaly and pancreatic adenocarcinoma; Case report

Acromegaly is a rare endocrine disease. Acromegalyis associated with an increased prevalence of colorectal cancer and pre-malignant tubularadenomas, and also may be associated with other organ malignancies such as breast and thyroid. In this article, were reported rare case in th elight of coexistence of acromegaly and incidental pancreatic adenocarcinoma.A52-year-old man who was diagnosed with acromegaly about two years ago.After diagnosis, transsphenoidal surgery was performed. After surgery serum growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels was not return to normal, therefore somatostatin analog treatment was started. After this treatment, serum IGF-1 concentration was normal for age and gender. He was admitted to out-patient clinic with abdominal pain3 month ago. 44x26 mm mass lesion in the tail of the pancreas and multiple metastatic lesions in the liver were detected on abdomen computed tomography (CT). Erosive gastritis and polyps in the colon were observed on upper gastrointestinal endoscopy and colonoscopy, respectively. Endoscopic ultrasound-guided fineneedle aspiration biopsy was performed to the mass lesions in the tail of the pancreas. Pathological examination was consistent with ductal adenocarcinoma arising from the pancreas. Thepatients with acromegaly have an increased risk of benign and malignant neoplasms, these situation may be related with increased circulating levels of IGF-1. IGF-1 have proliferative and anti-apoptotic activity. The coexistence of acromegaly and metastatic pancreatic tumor was present in the literature but it is quite rare. It is necessary to consider that pancreatic adenocarcinoma and other malignant diseases may present in acromegaly patients.

Keywords:

Acromegaly ductal pancreatic adenocarcinoma, GH, IGF-1,

PDF

___

CapatinaC, Wass JA. 60 years of Neuroendocrinology:Acromegaly. Journal of Endocrinology 2015; 226:141-160.(doi:10.1530/JOE-15-0109)
Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. European Journal of Endocrinology 2008;159: 89-95.(doi:10.1530/EJE-08-0267)
Sherlock M, Ayuk J, Tomlinson JW, et al. Mortality in patients with pituitary disease. Endocrine Reviews 2010;31:301-342.(doi:10.1210/er.2009-0033)
Ezzat S, Melmed S. Clinical review 18: are patients with acromegaly at increased risk for neoplasia? J Clin Endocrinol Metab 1991;72: 245–249.
Jenkins PJ, Besser M. Clinical perspective: acromegaly and cancer: a problem. J Clin Endocrinol Metab 2001; 86:2935-2941.
Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of Acromegaly: epidemiology, pathogenesis, and management. Endocrine Reviews 2004;25:102-152.
Loeper S, Ezzat S. Acromegaly: re-thinking the cancer risk. Reviews in Endocrine and Metabolic Disorders 2008; 9:41-58.
Melmed S. Acromegaly and cancer: not a problem? Journal of Clinical Endocrinology and Metabolism 2001 86: 2929-2934.
P. J. Jenkins, V. Frajese, A-M. Jones, et al. Insulin-Like Growth Factor I and the Development of Colorectal Neoplasia in Acromegaly. J Clin Endocrinol Metab. 2000 Sep;85(9):3218-21.
Boguszewski CL, Ayuk J. Management of endocrıne dısease: acromegaly and cancer: an old debate revısıted. Eur J Endocrinol. 2016 Apr 18. pii: EJE-16-0178. [Epubahead of print] PMID:27089890.
Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer Incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. Journal of Clinical Endocrinology and Metabolism 1998 83: 2730-2734.
Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. Journal of Clinical Endocrinology and Metabolism 2004 89: 667-674.
Kopchick JJ, List EO, Kelder B, Gosney ES, Berryman DE. Evaluation of growth hormone(GH) action in mice: discovery of GH receptor antagonists and clinical indications. Molecular and Cellular Endocrinology 2014 386:34-45. (doi:10.1016/j.mce.2013.09.004)
Clayton PE, Banerjee I, Murray PG, Renehan AG. Growth hormone, the insulin- like growth factor axis, insulin and cancer risk. Nature Reviews Endocrinology 2011 7: 11-24. (doi:10.1038/nrendo.2010.171)
Chi F, Wu R, Zeng YC, XingR, LiuY. Circulation insulin-like growth factor peptides and colorectal cancer risk: an updated systematic review and meta-analysis. Molecular Biology Reports 2013 40: 3583-3590.(doi:10.1007/s11033-012-2432-z)
Aguiar-Oliveira MH, Oliveira FT, Pereira RM, etal. Longevity in untreated congenital growth hormone deficiency due to a homozygous mutation in the GHRH receptor gene. Journal of Clinical Endocrinology and Metabolism 2010 95: 714-721.(doi:10.1210/jc.2009-1879)
Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer and diabetes in humans. ScienceTranslational Medicine 2011 3: 70ra13.(doi:10.1126/scitranslmed.3001845)
Petroff D, Tönjes A, Grussendorf M, et al. The incidence of cancer among acromegaly patients: results from the German Acromegaly Registry. Journal of Clinical Endocrinology and Metabolism 2015 100 3894-3902. (doi:10.1210/jc.2015-2372)
Mercado M, Gonzalez B, Vargas G,et al. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. Journal of Clinical Endocrinology and Metabolism. 2014 99:4438-4446.(doi:10.1210/jc.2014-2670)
Arosio M, Reimondo G, Malchiodi E, et al. Predictors of morbidity andmortality in acromegaly: an Italian survey. European Journal ofEndocrinology. 2012 167: 189-198.
Creutzfeldt W, Arnold R, Creutzfeldt C, Feurle G, Ketterer H. Gastrin and G-cells in the antral mucosa of patients with pernicious anaemia, acromegaly and hyperparathyroidism and in a Zollinger-Ellison tumour of the pancreas. Eur J Clin Invest. 1971 Sep;1(6):461-79.
Gallagher EJ, LeRoith D. Epidemiology and molecular mechanisms tying obesity, diabetes, and the metabolic syndrome with cancer. Diabetes Care 2013 36: Supp l2: S 233-9.(doi:10.2337/dcS13-2001)
Ezzat S, Ezrin C, Yamashita S, Melmed S. Recurrent acromegaly resulting from ectopic growth hormone gene expression by metastatic pancreatic tumor.Cancer. 1993 Jan 1;71(1):66-70.
Klöppel G, Maillet B. Classification and Staging of pancreatic Nonendocrine Tumors. Radiologic Clinics of North America 1989;27/1: 105-11.
Lillemoe KD. Current management of pancreatic carcinoma. Ann Surg 1995; 221: 133-148.
Vezeridis MP, Wanebo HJ. Pancreatic cancer in 1994: Diagnosis and treatment. R I Med 1994; 77: 115-118.
Warshaw AL, Fernandez-Del Castillo C. Pancreatic carcinoma. N Engl J Med 1992; 326: 455-464.
Norell SE, Ahlbom A, Erwald R, et al. Diet and pancreatic cancer: A case control study. Am J Epidemiol 1986; 124: 894-903.
Gold EB. Epidemiology of and risk factors for pancreatic cancer. Surg Clin North Am 1995; 75: 819-843.
Lowenfels AB, Maisonneuve P, Cavallini G, et al. Pancreatitis and the risk of pancreatic cancer. N Engl J Med 1993; 328: 1433-1437.
Hahn SA, Kern SE. Molecular genetics of exocrine pancreatic neoplasms. Surg Clin North Am 1995; 75: 857-869.
Barton CM, Staddon SL, Hall PA, et al. Abnormalities of the p53 tumour suppressor gene in human pancreatic cancer. Br J Cancer 1991; 64: 1076-1082.
Sakorafas GH, Tsiotou AG. Genetic basis of cancer of the pancreas: Diagnosis of therapeutic applications. Eur J Surg 1994; 160: 529-534.
Enrique Rozengurt, James Sinnett-Smith, KrisztinaKisfalvi. Crosstalk between Insulin/Insulin-likeGrowth Factor-1 Receptors and G Protein-Coupled Receptor Signaling Systems: A Novel Target for the Antidiabetic Drug Metformin in Pancreatic Cancer. Clin Cancer Res 2010;16:2505-2511.
Chong CR, Chabner BA. Mysterious Metformin. Oncologist 2009;14: 1178–81.
Li D, Yeung S-CJ, Hassan MM, Konopleva M, Abbruzzese JL. Anti- diabetic therapies affect risk of pancreatic cancer. Gastroenterology 2009;137:482–8.