Association of Thyroid Diseases with Primary Extra-Thyroidal Malignancies in Women: Results of a Cross-Sectional Study of 6,386 Patients

Abstract

We here analyzed the prevalence of extra-thyroidal malignancies (EM) in 6,386 female patients affected by different thyroid disease (TD). At first, an age-matched analysis of EM in all patients was performed. We then evaluated EM prevalence in four TD diagnostic categories: non-nodular TD (n = 2,159); solitary nodule (n = 905); multinodular TD (n = 2,871); differentiated thyroid cancers (n = 451). Finally, patients were grouped based on the absence (n = 3,820) or presence of anti-thyroglobulin (TgAb) and/or anti-thyroperoxidase (TPOAb) (n = 2,369), or anti-Thyroid Stmulating Hormone (TSH) receptor autoantibodies (n = 197). A total of 673 EM were recorded. EM prevalence in TD patients was higher compared to the general population (Odds Ratio, OR 3.21) and the most frequent EM was breast cancer (OR 3.94), followed by colorectal (OR 2.18), melanoma (OR 6.71), hematological (OR 8.57), uterus (OR 2.52), kidney (OR 3.40) and ovary (OR 2.62) neoplasms. Age-matched analysis demonstrated that the risk of EM was maximal at age 0–44 yr (OR 11.28), remaining lower, but significantly higher that in the general population, in the 45–59 and 60–74 year age range. Breast and hematological malignancies showed an increased OR in all TD, while other cancers associated with specific TD. An increased OR for melanoma, breast and hematological malignancies was observed in both TPOAb and/or TgAb autoantibody negative and positive patients, while colorectal, uterus, kidney and ovary cancers showed an increased OR only in thyroid autoantibody negative patients. In conclusions, women affected by both benign and malignant TD, especially at a younger age and in absence of thyroid autoimmunity, have an increased risk of developing primary EM, thus requiring a careful follow-up and surveillance.

Synchronous papillary thyroid cancer and non-Hodgkin lymphoma

“…DTC was associated with significantly higher risk (OR 12.2), most pronounced in the age 0 to 44 (OR 23.8). [ 2 ] We found only 2 reports in the English literature reporting simultaneous DTC and NHL. Rizkallah et al [ 3 ] reported similar case, whereas Singh et al [ 4 ] published recently a case with triple malignancies—laringeal cancer, DTC, and NHL.…”

“…Several studies, as cited by Prinzi et al, [ 2 ] attempted to explain the link between DTC and extra-thyroid malignancy implicating that “the long-term carcinogenic effects of specific cancer treatments might be responsible for a second cancer.” However, in our case there were synchronous occurrence of 2 malignancies and the most plausible explanation is the presence of yet unidentified molecular link or presence of general vulnerability carrying a higher risk for malignant transformation.…”

Hormone signaling pathways as treatment targets in renal cell cancer (Review)

“…Patients with thyroid disease (TD) and abnormal TSH levels, including on-nodular TD, solitary nodules, multinodular TD, thyroid cancers [with either the presence or absence of anti-thyroglobulin (TgAb)], and anti-thyroid peroxidase (TPOAb) or anti-thyroid-stimulating hormone (TSH) receptor autoantibodies, are at higher risk of developing kidney cancer (OR=3.40) compared to the general population (51). whereas, hypothyroidism is associated with longer progression-free survival (PFS) in sunitinib and sorafenib treatments (25,28).…”

Triiodothyronine regulates cell growth and survival in renal cell cancer

“…In molecular research, disturbances in the 3,5,3'-triiodotyronine (T3) signaling pathway were described as a possible trigger in RCC (4). In clinical reports, an increased risk of kidney cancer was reported in women with a history of hypothyroidism with myxedema, thyrotoxicosis (5) or multinodular thyroid disease (6). The molecular background of coincidence or codependence of renal cell cancer and thyroid disease is elusive.…”