Influence of Long-term Statin use in Type 2 Diabetic Patients on Thyroid Nodularity in Iodine-sufficient Area

 

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Abstract

Objective:

Statins have marked beneficial effects on lipid profile, but also have pleiotropic actions. A previous study in an iodine-deficient area suggested that statin use is associated with reduced thyroid volume and nodularity. We performed this study to investigate how long-term statin use in type 2 diabetic patients affects thyroid nodularity in iodine-sufficient area.

Methods:

We recruited euthyroid type 2 diabetic patients, receiving statin therapy continuously for at least 5 years (statin group) and, age and sex matched statin-naive type 2 diabetic patients (control group). Subjects with past history of cancer, thyroid disease or treatment with lithium or amiodarone; family history of thyroid cancer; palpable goiter or thyroid nodule, and/or positive thyroperoxidase antibody were excluded. The prevalence, number, and volume of thyroid nodules, size of thyroid were evaluated in all subjects by high resolution ultrasound.

Results:

Prevalence of non-palpable thyroid nodules of statin group (n=70) and control group (n=98) were 51 and 53% , respectively. There was no difference of prevalence, number, and volume of non-palpable thyroid nodules and size of thyroid between statin and control group. But, the patients aged between 60 and 65 years from statin group showed lower prevalence of non-palpable thyroid nodules than the patients with same age interval from control group (4 out of 12 patients, 33% , statin group; 19 out of 27 patients, 70% , control group; P=0.04).

Conclusions:

Long-term statin use in elderly type 2 diabetic patients was associated with lesser prevalence of thyroid nodules in an iodine-sufficient area. Our data might support a possible antiproliferative effect of statins on thyroid in old type 2 diabetic patients. But, the effect was not as strong as that in an iodine-deficient area and further studies with enough numbers of subjects and revised design will be needed.

• References

• 1 Ayturk S, Gursoy A, Kut A et al. Metabolic syndrome and its components are associated with increased thyroid volume and nodule prevalence in a mild-to-moderate iodine-deficient area. Eur J Endocrinol 2009; 161: 599-605
  CrossrefPubMedGoogle Scholar
• 2 Baigent C, Keech A, Kearney PM et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins: Lancet 2005; 366: 1267-1278
  PubMed
• 3 Belfiore A, La Rosa GL, Padova G et al. The frequency of cold thyroid nodules and thyroid malignancies in patients from an iodine-deficient area. Cancer 1987; 60: 3096-3102
  CrossrefPubMedGoogle Scholar
• 4 Burgess JR. Temporal trends for thyroid carcinoma in Australia: an increasing incidence of papillary thyroid carcinoma (1982–1997): Thyroid 2002; 12: 141-149
  PubMed
• 5 Cappelli C, Castellano M, Pirola I et al. Reduced thyroid volume and nodularity in dyslipidaemic patients on statin treatment. Clin Endocrinol (Oxf) 2008; 68: 16-21
  CrossrefPubMedGoogle Scholar
• 6 Caraglia M, Budillon A, Tagliaferri P et al. Isoprenylation of intracellular proteins as a new target for the therapy of human neoplasms: preclinical and clinical implications. Curr Drug Targets 2005; 6: 301-323
  CrossrefPubMedGoogle Scholar
• 7 Colhoun HM, Betteridge DJ, Durrington PN et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet 2004; 364: 685-696
  CrossrefPubMedGoogle Scholar
• 8 Dale KM, Coleman CI, Henyan NN et al. Statins and cancer risk: a meta-analysis. JAMA 2006; 295: 74-80
  CrossrefPubMedGoogle Scholar
• 9 de BB, McLean E, Andersson M et al. Iodine deficiency in 2007: global progress since 2003. Food Nutr Bull 2008; 29: 195-202
  PubMedGoogle Scholar
• 10 Downward J. Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer 2003; 3: 11-22
  CrossrefPubMedGoogle Scholar
• 11 El-Serag HB, Hampel H, Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence. Clin Gastroenterol Hepatol 2006; 4: 369-380
  CrossrefPubMedGoogle Scholar
• 12 Friberg E, Orsini N, Mantzoros CS et al. Diabetes mellitus and risk of endometrial cancer: a meta-analysis. Diabetologia 2007; 50: 1365-1374
  CrossrefPubMedGoogle Scholar
• 13 Gonyeau MJ, Yuen DW. A clinical review of statins and cancer: helpful or harmful?. Pharmacotherapy 2010; 30: 177-194
  CrossrefPubMedGoogle Scholar
• 14 Huxley R, Ansary-Moghaddam A, Berrington de GA et al. Type-II diabetes and pancreatic cancer: a meta-analysis of 36 studies. Br J Cancer 2005; 92: 2076-2083
  CrossrefPubMedGoogle Scholar
• 15 Kim KW, Park YJ, Kim EH et al. Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto’s thyroiditis. Head Neck 2010; DOI: 10.1002/hed.21518.
  PubMedGoogle Scholar
• 16 Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006; 6: 292-306
  CrossrefPubMedGoogle Scholar
• 17 Laezza C, Fiorentino L, Pisanti S et al. Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state. J Mol Med 2008; 86: 1341-1351
  CrossrefPubMedGoogle Scholar
• 18 Laezza C, Mazziotti G, Fiorentino L et al. HMG-CoA reductase inhibitors inhibit rat propylthiouracil-induced goiter by modulating the ras-MAPK pathway. J Mol Med 2006; 84: 967-973
  CrossrefPubMedGoogle Scholar
• 19 Larsson SC, Mantzoros CS, Wolk A. Diabetes mellitus and risk of breast cancer: a meta-analysis. Int J Cancer 2007; 121: 856-862
  CrossrefPubMedGoogle Scholar
• 20 Larsson SC, Orsini N, Wolk A. Diabetes mellitus and risk of colorectal cancer: a meta-analysis. J Natl Cancer Inst 2005; 97: 1679-1687
  CrossrefPubMedGoogle Scholar
• 21 Development Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2010. URL http://www.R-project.org
  Google Scholar
• 22 Sacks FM, Pfeffer MA, Moye LA et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators: N Engl J Med 1996; 335: 1001-1009
  PubMedGoogle Scholar
• 23 Sever PS, Poulter NR, Dahlof B et al. Reduction in cardiovascular events with atorvastatin in 2 532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial – lipid-lowering arm (ASCOT-LLA). Diabetes Care 2005; 28: 1151-1157
  CrossrefPubMedGoogle Scholar
• 24 Sipahi I, Debanne SM, Rowland DY et al. Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol 2010; 11: 627-636
  CrossrefPubMedGoogle Scholar
• 25 Suk JH, Kim TY, Kim MK et al. Prevalence of Ultrasonographically-Detected Thyroid Nodules in Adults without Previous History of Thyroid Disease. J Korean Endocr Soc 2006; 21: 389-393
  CrossrefPubMedGoogle Scholar
• 26 Vaughan CJ, Murphy MB, Buckley BM. Statins do more than just lower cholesterol. Lancet 1996; 348: 1079-1082
  CrossrefPubMedGoogle Scholar
• 27 Wang CY, Zhong WB, Chang TC et al. Lovastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, induces apoptosis and differentiation in human anaplastic thyroid carcinoma cells. J Clin Endocrinol Metab 2003; 88: 3021-3026
  CrossrefPubMedGoogle Scholar
• 28 Williams ED, Doniach I, Bjarnason O et al. Thyroid cancer in an iodide rich area: a histopathological study. Cancer 1977; 39: 215-222
  CrossrefPubMedGoogle Scholar
• 29 Zhong WB, Wang CY, Chang TC et al. Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis. Endocrinology 2003; 144: 3852-3859
  CrossrefPubMedGoogle Scholar
• 30 Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet 2008; 372: 1251-1262
  CrossrefPubMedGoogle Scholar