WOMEN IN CANCER THEMATIC REVIEW: Thyroid-stimulating hormone in thyroid cancer: does it matter?

Abstract

Differentiated thyroid cancer is the most common endocrine malignancy and the incidence is increasing rapidly worldwide. Appropriate diagnosis and post-treatment monitoring of patients with thyroid tumours are critical. Fine needle aspiration cytology remains the gold standard for diagnosing thyroid cancer, and although there have been significant refinements to this technique, diagnostic surgery is often required for patients suspected to have malignancy. Serum thyroid-stimulating hormone (TSH) is higher in patients with malignant thyroid nodules than in those with benign disease, and TSH is proportionally increased in more aggressive tumours. Importantly, we have shown that the pre-operative serum TSH concentration independently predicts the presence of malignancy in subjects presenting with thyroid nodules. Establishing the use of TSH measurements in algorithms identifying high-risk thyroid nodules in routine clinical practice represents an exciting, cost-efficient and non-invasive approach to optimise thyroid cancer diagnosis. Binding of TSH to receptors on thyrocytes stimulates a number of growth promoting pathways both in normal and malignant thyroid cells, and TSH suppression with high doses of levothyroxine is routinely used after thyroidectomy to prevent cancer recurrence, especially in high-risk tumours. This review examines the relationship between serum TSH and thyroid cancer and reflects on the clinical potential of TSH measurements in diagnosis and disease monitoring.

Fasting serum glucose, thyroid‐stimulating hormone, and thyroid hormones and risk of papillary thyroid cancer: A case‐control study

“…The main functions of TSH are regulation of thyroid hormones, facilitation of thyroid cell growth, excitation of the sodium iodide symporter, and adjustment of extrathyroidal effects. A study showed that long‐term high TSH levels leaded to hyperplasia and hypertrophy of the thyroid gland . A previous meta‐analysis of 28 studies suggested that an increased thyroid neoplasm risk was related to high TSH concentrations .…”

Risk of incident circulatory disease in patients treated for differentiated thyroid carcinoma with no history of cardiovascular disease

“…9,10 Importantly, there is mounting evidence that exogenous subclinical thyrotoxicosis as a result of TSH suppression therapy may be detrimental with regard to long-term cardiovascular health by impairing cardiac contractility and arterial elasticity, [11][12][13] exacerbating angina and inducing atrial fibrillation (AF) in high-risk patients. 14 The aforementioned mechanism via which detrimental cardiovascular impact may be observed in patients with DTC was not demonstrated in a study involving 366 patients with thyroid cancer. 15 In contrast, a more recent observational study reported a three-fold increased risk of cardiovascular mortality in 414 patients with DTC compared to matched controls and suggested that this increase was associated with lower serum TSH concentrations.…”

“…Importantly, there is mounting evidence that exogenous subclinical thyrotoxicosis as a result of TSH suppression therapy may be detrimental with regard to long‐term cardiovascular health by impairing cardiac contractility and arterial elasticity, exacerbating angina and inducing atrial fibrillation (AF) in high‐risk patients . Moreover, in preparation of adjuvant thyroid ablation therapy, when indicated, patients with DTC may also undergo a transient hypothyroid phase, in settings where recombinant human TSH is not used.…”

Targeting the TSH receptor in thyroid cancer

“…Additionally, chronic exposure to TSI has been associated with increased disease-specific mortality in thyroid cancer in some, but not all, studies (Belfiore et al 1990, Pellegriti et al 2013. Recently, multiple large cohort studies have found that increased levels of serum TSH are associated with increased subsequent risk of thyroid cancer (Nieto & Boelaert 2016). The largest study, recruiting 10,178 patients presenting with nodular thyroid disease for fine needle aspiration (FNA) biopsy, found an increasing odds ratio for papillary thyroid cancer (PTC) with incremental increases of TSH within the reference range of 0.4-3.4 IU/L (Fiore et al 2009).…”