The Difference in Thyroid Stimulating Hormone Levels between Differentiated Carcinoma and Benign Enlargement

THIEME Original Research The Difference in Thyroid Stimulating Hormone Levels between Differentiated Carcinoma and Benign Enlargement Bambang Udji Djoko Rianto1 Anton Sony Wibowo1 1 Ear Nose Throat Head and Head Neck Surgery Department, Faculty of Medicine, Universitas Gadjah Mada/Dr. Sardjito GH Yogyakarta, Indonesia Camelia Herdini1 Address for correspondence Bambang Udji Djoko Rianto, MSc, PhD, Nose Throat Head and Head Neck Surgery Department Faculty of Medicine, Universitas Gadjah Mada/Dr. Sardjito GH, Jalan Farmako Yogyakarta, Indonesia (e-mail: ). Int Arch Otorhinolaryngol 2020;24(1):e73–e79. Abstract Keywords ► thyroid stimulating hormone ► thyroid adenoma ► thyroid carcinoma ► thyrotropin ► thyroid neoplasms Introduction Papillary and follicular thyroid carcinoma are common head and neck cancers. This cancer expresses a thyroid stimulating hormone (TSH) receptor that plays a role as a cancer stimulant substance. This hormone has a diagnostic value in the management of thyroid carcinoma. Objective The present study aimed to determine the difference in TSH levels between differentiated thyroid carcinoma and benign thyroid enlargement. Methods The present research design was a case-control study. The subjects were patients with thyroid enlargement who underwent thyroidectomies at the Dr. Sardjito General Hospital, Yogyakarta, Indonesia. Thyroid stimulating hormone levels were measured before the thyroidectomies. The inclusion criteria for the case group were: 1) differentiated thyroid carcinoma, and 2) complete data; while the inclusion criteria for the control group were: 1) benign thyroid enlargement, and 2) complete data. The exclusion criteria for both groups were: 1) patients suffering from thyroid hormone disorders requiring therapy before thyroidectomy surgery, 2) patients receiving thyroid suppression therapy before the thyroidectomy was performed, and 3) patients suffering from severe chronic diseases such as renal insufficiency, and severe liver disease. Results There were 40 post-thyroidectomy case group patients and 40 post-thyroidectomy control group patients. There were statistically significant differences in TSH levels between the groups with differentiated thyroid carcinoma and benign thyroid enlargement (p ¼ 0.001; odds ratio [OR] ¼ 8.42; 95% confidence interval [CI]: 3.19–36.50). Conclusion Based on these results, it can be concluded that there were significant differences in TSH levels between the groups with differentiated thyroid carcinoma and benign thyroid enlargement. Introduction Thyroid stimulating hormone (TSH) has a crucial role for the growth and the progression of differentiated carcinoma in the thyroid.1,2 Considered a potentially treatable but commonly fatal cancer with increasing incidence due to its slow- received March 26, 2018 accepted May 8, 2019 DOI https://doi.org/ 10.1055/s-0039-1692406. ISSN 1809-9777. acting nature and tendency for metastasis, patients often present late for treatment, resulting in poor outcomes. Measurements of receptor levels and their effect on signaling pathways have been shown to be effective for accurate diagnosis, but prognoses remain challenging due to many factors. Although TSH levels may be normal, the malignancy Copyright © 2020 by Thieme Revinter Publicações Ltda, Rio de Janeiro, Brazil e73 e74 The Difference in Thyroid Stimulating Hormone Levels risk of thyroid nodules will increase if TSH levels are above the average range of the population.3 Thyroid stimulating hormone receptors (TSHRs) are essential in the metabolism of the thyroid hormone, and control the functions and growth of the main thyroid cells. A number of thyroid diseases, most notably hyperthyroidism, are associated with mutations in the TSHRs. Recent research has found that while genetic and epigenetic alterations in the TSHRs are not the direct cause of carcinogenesis, they significantly influence and contribute to tumor growth, which involves several oncogenes.4,5 A study by Fiore et al confirmed the link between TSH and thyroid cancer, and discussed the relevant research of the recent decades, which included subjects diagnosed on cytology in a large series of patients submitted to fine needle aspiration biopsy of thyroid nodules, after validating cytology in a series of 3,406 nodules from 3,004 patients who underwent surgery. The relationship between serum TSH levels and risk of papillary thyroid cancer (PTC) was further analyzed in 10,178 patients with a clinical diagnosis of nodular goitre and with a cytological diagnosis of PTC (n ¼ 497) and of benign nodular thyroid disease (n ¼ 9,681). Serum TSH was significantly higher in PTC (median: 1.10 mIU/L; interquartile range (IR): 0.70–1.70 mIU/L) than in patients with benign nodular thyroid disease (median: 0.70 mIU/L; IR: 0.30–1.20 mIU/L). The frequency of PTC was directly correlated to serum TSH levels, being the lowest in patients with subnormal TSH values (51 of 2,024; 2.5%), and the highest in patients with TSH values between 1.6 and 3.4 mIU/L (152 of 1,665; 9.1%). This observation is relevant on clinical grounds to define the risk of PTC in patients with nodular thyroid disease. Thyroid stimulating hormone concentrations were significantly higher in patients with differentiated thyroid cancer (2.08  2.1 mIU/L) than in patients with benign thyroid disease (1.36  1.62 mIU/L). There was a direct relationship between increment of tumor size and increased TSH levels.6 False negative diagnoses and conflicting reports have contributed to the debate about thyroid oncogenesis and the association of thyroid disease with TSH levels. One study of 41 patients with thyroid gland disorders, whose age ranged from 14 to 80 years old, and with controls aged between 29 and 66 years old, found that there was no significant difference between the TSH concentration and free T4 (fT4) values between the control and the thyroid disorder groups (p > 0.05).7 The insignificant results may have been due to the small sample size or to other environmental factors. Clinical thyroid diseases can be classified as euthyroid, hypothyroid, and hyperthyroid, according to the functional status. Thyroid functions are normal in a considerable number of patients with thyroid cancer. Measurement of highly sensitive thyrotropin (TSH) in serum plays the main role in the diagnosis of thyroid dysfunctions and has a predictive value for thyroid malignancies. While there are many factors that contribute to the carcinogenesis of the thyroid gland, TSH is considered a key cancer growth factor for thyroid cancer.8,9 International Archives of Otorhinolaryngology Vol. 24 No. 1/2020 Rianto et al. The impact of vascular invasion on the prognosis is still a matter of debate, as some researchers further subdivide the diagnosis into angioinvasive and nonangioinvasive tumors. Age > 45 years old, gender, extrathyroid invasion, greater tumor size, and the presence of distant metastasis at presentation are recognized ris (...truncated)