Abstract
ObjectiveThe increasing incidence of thyroid nodules demands identification of risk factors for malignant disease. Several studies suggested the association of higher TSH levels with cancer, but influence of 25-hydroxyvitamin D (25OHD) is controversial. This study aimed to identify the relationship of thyroid cancer with higher TSH levels and hypovitaminosis D and to evaluate their influence on prognostic characteristics of papillary thyroid carcinomas (PTC).MethodsWe retrospectively evaluated 433 patients submitted to thyroidectomy for thyroid nodules. Patients were categorized according to quartiles of TSH and 25OHD levels. Clinicopathological features were analyzed.ResultsSubjects with thyroid carcinomas were more frequently male and younger compared to those with benign disease. Their median TSH levels were higher and adjusted odds-ratio (OR) for cancer in the highest-quartile of TSH (> 2.4 mUI/mL) was 2.36 (1.36–4.09). Although vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases. Among 187 patients with PTC, analyses of prognostic features revealed increased risk of lymph nodes metastases for subjects with highest-quartile TSH levels (OR = 3.7, p = 0.029). Decreased 25OHD levels were not overtly associated with poor prognosis in PTC.ConclusionsIn this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, particularly favoring lymph nodes metastases. On the other hand, no association was found between 25OHD levels and thyroid carcinoma risk or prognosis, suggesting that serum 25OHD determination may not contribute to risk assessment workup of thyroid nodules.
Highlights
The widespread use of cervical imaging for purposes other than investigation of thyroid disease is responsible for the increasing incidence of thyroid nodules
Vitamin D deficiency/insufficiency was prevalent in our cohort (84%), no significant differences in 25OHD levels or quartile distribution were observed between benign and malignant cases
Decreased 25OHD levels were not overtly associated with poor prognosis in papillary thyroid carcinomas (PTC). In this cross-sectional cohort, higher TSH levels increased the risk of cancer in thyroid nodules and influenced its prognosis, favoring lymph nodes metastases
Summary
The widespread use of cervical imaging for purposes other than investigation of thyroid disease is responsible for the increasing incidence of thyroid nodules. Vitamin D nuclear receptors (VDR) have been identified in tissues not directly involved with bone and mineral metabolism, including the thyroid, and in several cancers, such as breast, prostate, colon, leukemia and thyroid carcinoma [4,5,6,7,8]. Cancer cells express CYP21B1, the enzyme involved in hydroxylation of 25OHD [9, 10]; in cancer tissues, calcitriol (1,25OHD) action could be enhanced by local synthesis, which, in turn, would depend on circulating 25OHD levels. Some observational and clinical studies suggested an association of vitamin D deficiency and cancer, especially breast, prostate, and colon cancer, and leukemia [22,23,24,25,26]. A few studies have analyzed the association of 25OHD deficiency and thyroid cancer with conflicting results [27,28,29,30]
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