Are there TSH (Thyroid-Stimulating Hormone) derangements in thyroid cancers, particularly in cold or hot nodules, and which type of thyroid cancer is associated with cold nodules?

TSH Derangement in Thyroid Cancers and Nodules

Higher TSH levels are associated with an increased risk of differentiated thyroid cancer, while autonomously functioning nodules (with suppressed TSH) have a lower risk of malignancy. Cold nodules are more commonly associated with thyroid cancer, particularly papillary thyroid carcinoma.

TSH Derangement in Thyroid Cancers

• Higher serum TSH concentrations are associated with increased risk for differentiated thyroid cancer in patients with nodular thyroid disease 1
• TSH is a trophic hormone that can stimulate the growth of cells derived from thyroid follicular epithelium, which is why TSH suppression is part of treatment for patients with papillary, follicular, or Hürthle cell carcinoma 2
• Patients with more aggressive thyroid tumors tend to have higher preoperative serum TSH concentrations, suggesting TSH may play a role in cancer progression 1
• For patients with known residual thyroid carcinoma or at high risk for recurrence, TSH levels should be maintained below 0.1 mU/L as part of treatment 2

TSH Derangement in Hot Nodules

• Hot nodules (hyperfunctioning) typically produce thyroid hormone autonomously, leading to suppressed TSH levels 3
• Autonomous thyroid function (TSH<0.4 mU/ml) is associated with a reduced risk of papillary thyroid carcinoma 1
• Hot nodules are rarely malignant, with only a small number of cases reported in the literature 4
• When evaluating thyroid nodules, if TSH is suppressed, a thyroid scan with 99Tc is recommended to distinguish between a solitary hot nodule, toxic multinodular goiter, or less commonly, thyroiditis or Graves' disease 3
• Molecular analysis of rare malignant hot nodules has not found mutations in the TSH receptor or G(s alpha) genes, suggesting other mechanisms are involved 4

TSH Derangement in Cold Nodules

• Cold nodules (hypofunctioning) do not show radiotracer uptake on scintigraphy and have a higher risk of malignancy compared to hot nodules 5
• While most cold nodules are benign, thyroid cancers typically present as cold nodules on radioiodine scintigraphy 5, 4
• In patients with cold nodules, TSH levels are typically normal or elevated 3
• Fine-needle aspiration (FNA) is recommended for cold nodules, especially if they are ≥1.0 cm, depending on clinical and sonographic risk factors 3

Thyroid Cancer Types Associated with Cold Nodules

• Papillary thyroid carcinoma, which accounts for approximately 80% of thyroid cancers, typically presents as a cold nodule 2, 5
• Follicular thyroid carcinoma (11% of thyroid cancers) also commonly presents as a cold nodule 2
• Hürthle cell carcinoma (3% of thyroid cancers) typically presents as a cold nodule 2
• Medullary thyroid carcinoma (4% of thyroid cancers) and anaplastic thyroid carcinoma (2% of thyroid cancers) also typically present as cold nodules 2

Diagnostic Approach for Thyroid Nodules

• TSH measurement should be performed as part of the initial workup for thyroid nodules 2
• Ultrasound of the thyroid and central neck is recommended for evaluation of thyroid nodules 2, 6
• If TSH is suppressed, a radionuclide scan is indicated to determine if the nodule is hyperfunctioning 6
• If TSH is normal or elevated, FNA is the appropriate next step for nodules ≥1.0 cm, depending on clinical and sonographic risk factors 3
• Scintigraphically cold nodules should be evaluated with FNA regardless of TSH levels 3

Clinical Implications

• Higher TSH levels should raise suspicion for malignancy in patients with thyroid nodules 1
• Patients with higher serum TSH concentrations and borderline cytological results may require more aggressive investigation and treatment 1
• TSH suppression therapy is an important part of treatment for differentiated thyroid cancer to prevent stimulation of residual cancer cells 2
• Routine monitoring of TSH levels is essential in the follow-up of patients with thyroid cancer 2