Should patients on levothyroxine therapy be screened for pancreatic cancer? Pancreatic cancer and hypothyroidism

Should patients on levothyroxine therapy be screened for pancreatic cancer?

Pancreatic cancer and hypothyroidism


  • Ingrid Garajova a:1:{s:5:"en_US";s:28:"University Hospital of Parma";}
  • Rita Balsano
  • Matilde Coriano'
  • Fabio Gelsomino
  • Francesco Tovoli
  • Stefania De Lorenzo
  • Paolo Del Rio
  • Raffaele Dalla Valle
  • Matteo Ravaioli
  • Francesco Leonardi


pancreatic cancer, levothyroxine, hypothyroidism


Background: Pancreatic ductal adenocarcinoma is an aggressive disease with increasing incidence. Thyroid hormones play different roles in development and physiological processes of the entire digestive system, including pancreas. Therefore, many have hypothesized that thyroid hormone supplementation for hypothyroidism disorders might increase the risk of malignancy. Patients and methods: We conducted retrospective observational mono-centre study. The aim was to examine the prevalence of thyroid disorders among patients with pancreatic cancer. Moreover, we investigated the impact of thyroid hormone supplementation in pancreatic cancer patients’ outcome and the correlation with various clinicopathologic parameters. Results: A total of 92 consecutive pancreatic cancer patients were retrospectively reviewed: 18.5% patients had a history of hypothyroidism and all received a replacement hormone therapy with levothyroxine, in particular 20% in metastatic group and 11% in radically resected PDAC patients’ group. Nor in radically resected neither in metastatic group, we did not observe any statistically significant difference in outcome between the group with or without thyroid disorders. On multivariate analyses, cox proportional hazards model analysis showed that only the presence of perineural invasion was associated with a significantly higher hazard ratio for overall survival in metastatic PDAC patients (HR=2.7; 95%CI=1.029-6.925; p=0.009). Conclusions: We observed higher prevalence of thyroid disorders in PDAC patients. Further studies are warranted to explore the impact of levothyroxine therapy on outcome in PDAC patients.


McGuigan A, Kelly P, Turkington RC, Jones C, Coleman HG, McCain RS. Pancreatic cancer: A review of clinical diagnosis, epidemiology, treatment and outcomes. World Journal of Gastroenterology. 2018.

Tonini V, Zanni M. Pancreatic cancer in 2021: What you need to know to win. Vol. 27, World Journal of Gastroenterology. 2021.

Balsano R, Tommasi C, Garajova I. State of the art for metastatic pancreatic cancer treatment: Where are we now?*. Vol. 39, Anticancer Research. 2019.

Digiacomo G, Volta F, Garajova I, Balsano R, Cavazzoni A. Biological hallmarks and new therapeutic approaches for the treatment of pdac. Vol. 11, Life. 2021.

Brown AR, Simmen RCM, Simmen FA. The role of thyroid hormone signaling in the prevention of digestive system cancers. International Journal of Molecular Sciences. 2013.

Tang HY, Lin HY, Zhang S, Davis FB, Davis PJ. Thyroid hormone causes mitogen-activated protein kinase-dependent phosphorylation of the nuclear estrogen receptor. Endocrinology. 2004;145(7).

Pinto M, Soares P, Ribatti D. Thyroid hormone as a regulator of tumor induced angiogenesis. Vol. 301, Cancer Letters. 2011.

Sarosiek K, Gandhi A v., Saxena S, Kang CY, Chipitsyna GI, Yeo CJ, et al. Hypothyroidism in Pancreatic Cancer: Role of Exogenous Thyroid Hormone in Tumor Invasion - Preliminary Observations. Journal of Thyroid Research. 2016;2016.

Wu CC, Islam MM, Nguyen PA, Poly TN, Wang CH, Iqbal U, et al. Risk of cancer in long-term levothyroxine users: Retrospective population-based study. Cancer Science. 2021;112(6).

Pinto A, Glick M. Management of patients with thyroid disease: Oral health considerations. Journal of the American Dental Association. 2002;133(7).

Rennert G, Rennert HS, Pinchev M, Gruber SB. A case-control study of levothyroxine and the risk of colorectal cancer. J Natl Cancer Inst. 2010;102(8).

Kuijpens JLP, Nyklíčtek I, Louwman MWJ, Weetman TAP, Pop VJM, Coebergh JWW. Hypothyroidism might be related to breast cancer in post-menopausal women. Thyroid. 2005;15(11).

Goldman MB, Monson RR, Maloof F. Cancer Mortality in Women with Thyroid Disease. Cancer Research. 1990;50(8).

Bensenor IM, Olmos RD, Lotufo PA. Hypothyroidism in the elderly: Diagnosis and management. Vol. 7, Clinical Interventions in Aging. 2012.

Cappola AR, Fried LP, Arnold AM, Danese MD, Kuller LH, Burke GL, et al. Thyroid status, cardiovascular risk, and mortality in older adults. J Am Med Assoc. 2006;295(9).

Benseñor IM, Goulart AC, Lotufo PA, Menezes PR, Scazufca M. Prevalence of thyroid disorders among older people: results from the São Paulo Ageing & Health Study. Cadernos de Saúde Pública. 2011;27(1).

Kapdi CC, Wolfe JN. Breast Cancer: Relationship to Thyroid Supplements for Hypothyroidism. JAMA: The Journal of the American Medical Association. 1976;236(10).

U. C, G. B, M. R, A. F. Levothyroxine and lung cancer in females: The importance of oxidative stress. Reproductive Biology and Endocrinology. 2013;11(1).

Strzałka A, Hogendorf P, Skulimowski A, Spychalski M, Strzelczyk J, Durczynski A. Thyroid hormones concentration in portal and peripheral blood in patients with pancreatic cancer: Preliminary study. Cancer Biomarkers. 2020;29(3).

Aranda A, Martínez-Iglesias O, Ruiz-Llorente L, García-Carpizo V, Zambrano A. Thyroid receptor: roles in cancer. Vol. 20, Trends in Endocrinology and Metabolism. 2009.

Hercbergs A, Johnson RE, Ashur-Fabian O, Garfield DH, Davis PJ. Medically Induced Euthyroid Hypothyroxinemia May Extend Survival in Compassionate Need Cancer Patients: An Observational Study. The Oncologist. 2015;20(1).

Gasparini G, Pellegatta M, Crippa S, Lena MS, Belfiori G, Doglioni C, et al. Nerves and pancreatic cancer: New insights into a dangerous relationship. Cancers. 2019.

Crippa S, Pergolini I, Javed AA, Honselmann KC, Weiss MJ, di Salvo F, et al. Implications of Perineural Invasion on Disease Recurrence and Survival After Pancreatectomy for Pancreatic Head Ductal Adenocarcinoma. Annals of Surgery. 2020;







How to Cite

Garajova I, Balsano R, Coriano' M, Gelsomino F, Tovoli F, De Lorenzo S, et al. Should patients on levothyroxine therapy be screened for pancreatic cancer? Pancreatic cancer and hypothyroidism. Acta Biomed [Internet]. 2022 Dec. 16 [cited 2024 Jul. 18];93(6):e2022268. Available from: