Given the ubiquity of statin use and prevalence of thyroid diseases, such as thyroid cancer, hyperthyroidism, and thyroiditis, understanding their association deserves further attention.
Objective:
To examine the association between statin use and thyroid cancer, thyrotoxicosis, goiter, and thyroiditis.
Methods:
Using Tricare data, 2 propensity score (PS)-matched cohorts of statin users and nonusers were formed: (1) a PS-matched general cohort (all patients aged 30-85 years) and (2) a PS-matched healthy cohort (excluded patients with cardiovascular diseases or severe comorbidities). Outcomes were thyroid cancer, thyrotoxicosis, goiter, and thyroiditis. Odds ratios (ORs) and 95% CIs of outcomes were estimated using conditional regression analysis.
Results:
Of 43 438 patients, the PS-matched general cohort matched 6342 statin users to 6342 nonusers. The OR of thyroid cancer was 0.62 (95% CI = 0.39-0.996). There was no significant difference between statin users and nonusers in risk of thyrotoxicosis (OR = 0.88; 95% CI = 0.71-1.09), goiter (OR = 0.9; 95% CI = 0.77-1.03), or thyroiditis (OR = 0.78; 95% CI = 0.53-1.15). In the PS-matched healthy cohort (3351 statin users to 3351 nonusers), there was no difference between statin users and nonusers in any outcome. Limitations of the study include its retrospective observational design and use of administrative codes in outcomes ascertainment.
Conclusion and Relevance:
This study did not demonstrate any association of statins with harmful effects on thyroid diseases, which offers assurance to clinicians and patients. Furthermore, statin use appears to be associated with a decreased risk of thyroid cancer, but more studies are needed.
KantorEDRehmCDHaasJSChanATGiovannucciEL.Trends in prescription drug use among adults in the United States from 1999-2012. JAMA. 2015;314:1818-1831. doi:10.1001/jama.2015.13766
2.
HungSHLinHCChungSD.Statin use and thyroid cancer: a population-based case-control study. Clin Endocrinol (Oxf). 2015;83:111-116. doi:10.1111/cen.12570
3.
FriedmanGDFlickEDUdaltsovaNChanJQuesenberryCPJrHabelLA.Screening statins for possible carcinogenic risk: up to 9 years of follow-up of 361 859 recipients. Pharmacoepidemiol Drug Saf. 2008;17:27-36. doi:10.1002/pds.1507
4.
SmithPFGrossmanSJGersonRJ, et al. Studies on the mechanism of simvastatin-induced thyroid hypertrophy and follicular cell adenoma in the rat. Toxicol Pathol. 1991;19:197-205. doi:10.1177/019262339101900301
5.
MascitelliLGoldsteinMR.Statin immunomodulation and thyroid cancer. Clin Endocrinol (Oxf). 2015;82:620. doi:10.1111/cen.12600
6.
CappelliCCastellanoMPirolaI, et al. Reduced thyroid volume and nodularity in dyslipidaemic patients on statin treatment. Clin Endocrinol (Oxf). 2008;68:16-21. doi:10.1111/j.1365-2265.2007.02982.x
7.
AydinKErsoz GulcelikNTuncelM, et al. Thyroid volumes and serum VEGF levels in dyslipidemic patients: effects of statin treatment. Turk J Med Sci. 2019;49:738-745. doi:10.3906/sag-1708-106
8.
ChonMGSukJHOhKH, et al. Influence of long-term statin use in type 2 diabetic patients on thyroid nodularity in iodine-sufficient area. Exp Clin Endocrinol Diabetes. 2011;119:497-501. doi:10.1055/s-0031-1283123
9.
DemirCAnilCBozkusY, et al. Do statins affect thyroid volume and nodule size in patients with hyperlipidemia in a region with mild-to-moderate iodine deficiency? A prospective study. Med Princ Pract. 2018;27:1-7. doi:10.1159/000486748
10.
ZhongWBWangCYChangTCLeeWS.Lovastatin induces apoptosis of anaplastic thyroid cancer cells via inhibition of protein geranylgeranylation and de novo protein synthesis. Endocrinology. 2003;144:3852-3859. doi:10.1210/en.2003-0098
11.
UrbichCDernbachEZeiherAMDimmelerS.Double-edged role of statins in angiogenesis signaling. Circ Res. 2002;90:737-744. doi:10.1161/01.res.0000014081.30867.f8
12.
ZhaoJXuCYaoJYuCLiaoLDongJ.Statins and thyroid carcinoma: a meta-analysis. Cell Physiol Biochem. 2018;47:1422-1431. doi:10.1159/000490832
13.
BifulcoMCiagliaE.Statin reduces orbitopathy risk in patients with Graves’ disease by modulating apoptosis and autophagy activities. Endocrine. 2016;53:649-650. doi:10.1007/s12020-015-0762-z
14.
RuchalaMSzczepanekEPuszczewiczMSosnowskiPSowinskiJ.Not a Graves’ situation. Am J Med. 2011;124:210-214. doi:10.1016/j.amjmed.2010.11.006
15.
YandellSDHarveyWCFernandesNJBarrPWFeldmanM.Radioiodine studies, low serum thyrotropin, and the influence of statin drugs. Thyroid. 2008;18:1039-1042. doi:10.1089/thy.2008.0129
16.
GulluSEmralRBastemirMParkesABLazarusJH.In vivo and in vitro effects of statins on lymphocytes in patients with Hashimoto’s thyroiditis. Eur J Endocrinol. 2005;153:41-48. doi:10.1530/eje.1.01941
17.
KrysiakRKowalczeKOkopienB.The effect of statin therapy on thyroid autoimmunity in patients with Hashimoto’s thyroiditis: a pilot study. Pharmacol Rep. 2016;68:429-433. doi:10.1016/j.pharep.2015.11.005
18.
KrysiakRSzkrobkaWOkopienB.Atorvastatin potentiates the effect of selenomethionine on thyroid autoimmunity in euthyroid women with Hashimoto’s thyroiditis. Curr Med Res Opin. 2019;35:675-681. doi:10.1080/03007995.2018.1541314
19.
StoneNJRobinsonJGLichtensteinAH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63(25, pt B):2889-2934. doi:10.1016/j.jacc.2013.11.002
20.
ElixhauserASteinerCPalmerL.Clinical Classifications Software (CCS) for ICD-9-CM. databases and related tools from the Healthcare Cost and Utilization Project (HCUP) Agency for Healthcare Research and Quality, 2012: appendix A. Accessed December 23, 2020. https://www.hcup-us.ahrq.gov/toolssoftware/ccs/ccs.jsp
21.
CowenMEDusseauDJTothBGGuisingerCZodetMWShyrY.Casemix adjustment of managed care claims data using the clinical classification for health policy research method. Med Care. 1998;36:1108-1113. doi:10.1097/00005650-199807000-00016
22.
DuffySElixhauserASommersJ. Diagnosis and Procedure Combinations in Hospital Inpatient Data. Agency for Health Care Policy and Research; 1996. AHCPR Publication No. 96-0047.
23.
ElixhauserAMcCarthyE. Clinical Classifications for Health Policy Research, Version 2: Hospital Inpatient Statistics. Agency for Health Care Policy and Research; 1996. AHCPR Publication No. 96 0017.
24.
ElixhauserASteinerCWhittingtonC. Clinical Classifications for Health Policy Research: Hospital Inpatient Statistics, 1995. Agency for Health Care Policy and Research; 1998. AHCPR Publication No. 98-0049.
25.
ElixhauserASteinerC. Healthcare Cost and Utilization Project (HCUP) Research Note. Agency for Health Care Policy and Research; 1999. AHCPR Publication No. 99-0034.
26.
MansiIFreiCRPughMJMakrisUMortensenEM.Statins and musculoskeletal conditions, arthropathies, and injuries. JAMA Intern Med. 2013;173:1-10. doi:10.1001/jamainternmed.2013.6184
27.
ThompsonDAMakaryMADormanTPronovostPJ.Clinical and economic outcomes of hospital acquired pneumonia in intra-abdominal surgery patients. Ann Surg. 2006;243:547-552. doi:10.1097/01.sla.0000207097.38963.3b
28.
LeuschenJMortensenEMFreiCRMansiEAPandayVMansiI.Association of statin use with cataracts: a propensity score-matched analysis. JAMA Ophthalmol. 2013;131:1427-1434. doi:10.1001/jamaophthalmol.2013.4575
29.
LiuMMcPeek HinzERMathenyME, et al. Comparative analysis of pharmacovigilance methods in the detection of adverse drug reactions using electronic medical records. J Am Med Inform Assoc. 2013;20:420-426. doi:10.1136/amiajnl-2012-001119
30.
RadleyDCGottliebDJFisherESTostesonAN.Comorbidity risk-adjustment strategies are comparable among persons with hip fracture. J Clin Epidemiol. 2008;61:580-587. doi:10.1016/j.jclinepi.2007.08.001
31.
AshASPosnerMASpeckmanJFrancoSYachtACBramwellL.Using claims data to examine mortality trends following hospitalization for heart attack in Medicare. Health Serv Res. 2003;38:1253-1262.
32.
AcharyaTHuangJTringaliSFreiCRMortensenEMMansiIA.Statin use and the risk of kidney disease with long-term follow-up (8.4-year study). Am J Cardiol. 2016;117:647-655. doi:10.1016/j.amjcard.2015.11.031
33.
MansiIFreiCRWangCPMortensenEM.Statins and new-onset diabetes mellitus and diabetic complications: a retrospective cohort study of US healthy adults. J Gen Intern Med. 2015;30:1599-1610. doi:10.1007/s11606-015-3335-1
34.
TrivediLUAlvarezCAMansiIA.Association of statin therapy with risk of epilepsy in 2 propensity score-matched cohorts. Ann Pharmacother. 2018;52:546-553. doi:10.1177/1060028018756650
35.
DeyoRACherkinDCCiolMA.Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol. 1992;45:613-619. doi:0895-4356(92)90133-8
36.
US Food and Drug Administration. FDA Drug Safety Communication: new restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Accessed March 16, 2015. http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm
37.
BenedettoUHeadSJAngeliniGDBlackstoneEH.Statistical primer: propensity score matching and its alternatives. Eur J Cardiothorac Surg. 2018;53:1112-1117. doi:10.1093/ejcts/ezy167
38.
LaezzaCFiorentinoLPisantiS, et al. Lovastatin induces apoptosis of k-ras-transformed thyroid cells via inhibition of ras farnesylation and by modulating redox state. J Mol Med (Berl). 2008;86:1341-1351. doi:10.1007/s00109-008-0396-1
39.
LibertiniSIacuzzoIFerraroA, et al. Lovastatin enhances the replication of the oncolytic adenovirus dl1520 and its antineoplastic activity against anaplastic thyroid carcinoma cells. Endocrinology. 2007;148:5186-5194. doi:10.1210/en.2007-0752
40.
WangCYShuiHAChangTC.In vivo evidence of duality effects for lovastatin in a nude mouse cancer model. Int J Cancer. 2010;126:578-582. doi:10.1002/ijc.24760
41.
GoldsteinMRMascitelliLPezzettaF.The double-edged sword of statin immunomodulation. Int J Cardiol. 2009;135:128-130.
Aschebrook-KilfoyBWardMHSabraMMDevesaSS.Thyroid cancer incidence patterns in the United States by histologic type, 1992-2006. Thyroid. 2011;21:125-134. doi:10.1089/thy.2010.0021
44.
HarachHRFranssilaKOWaseniusVM.Occult papillary carcinoma of the thyroid: a “normal” finding in Finland. A systematic autopsy study. Cancer. 1985;56:531-538. doi:10.1002/1097-0142(19850801)56:3<531::aid-cncr2820560321>3.0.co;2-3
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
