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Goitre Thyroid Nodules and Cancer

Goitre, Thyroid Nodules and Cancer
The term goitre refers to enlargement of the thyroid gland. Up to 15% of the UK population have a goitre on ultrasound (although most are not palpable), and 5% have a discrete thyroid nodule. Thyroid malignancy is rare, but should be considered in any patient presenting with a thyroid lump.

Diffuse goitre
The most common cause of diffuse goitre worldwide is iodine deficiency (endemic goitre), occurring in land-locked areas including Africa, the Himalayas and the Andes. In the UK, diffuse thyroid swelling is idiopathic (simple goitre) or autoimmune (Figure 14.1a). A tender diffuse goitre with systemic symptoms suggests a viral thyroiditis. Riedel’s thyroiditis is a rare condition characterised by thyroid fibrosis.

Multinodular goitre
This occurs in up to 40% of the population, the frequency increasing with age. Patients with nodular thyroid disease are euthyroid, frankly hyperthyroid (toxic nodular goitre) or have subclinical hyperthyroidism (autonomous thyroid function) (Figure 14.1b). If TSH is suppressed and fT4 is normal, fT3 should be checked to exclude T3-toxicosis. Patients may rarely present with compressive symptoms of stridor and dysphagia, which can require thyroidectomy. If there is inferior extension into the thorax (retrosternal goitre), surgery is more difficult and may require a thoracotomy.

Solitary thyroid nodule
Malignancy should be excluded in this situation although the vast majority of nodules will turn out to be benign. Rapid enlargement, lymphadenopathy, extremes of age, family history of thyroid cancer, hoarse voice and previous neck irradiation are worrying features (Figure 14.1c). Sudden painful enlargement suggests haemorrhage within a thyroid cyst. The presence of a hard, fixed, craggy mass with lymphadenopathy is concerning. Benign lesions are smooth and mobile with no lymphadenopathy. Solitary thyroid nodules can cause hyperthyroidism so clinical and biochemical assessment of thyroid status is important.
Fine needle aspiration (FNA) is the first line investigation of a thyroid nodule, either by palpation or under ultrasound guidance. Cytology may reveal a clearly benign or malignant lesion. If the FNA result is inadequate or indeterminate, it should be repeated. The Thy classification system ensures consistent reporting of cytology and will establish which nodules require surgery.
Serum fT4, fT3, TSH and thyroid antibodies should be checked. Thyroid ultrasound must be performed by a dedicated thyroid radiologist, as radiological characteristics can help predict the likelihood of malignancy.
Toxic nodular goitres are managed with anti-thyroid medication, RAI or surgery. Indications for surgery in non-toxic nodular thyroid disease includes compressive symptoms, cosmetic issues or suspicion of malignancy.

Thyroid cancer
Differentiated thyroid cancer
Thyroid cancer is rare, comprising 0.5–1% of all malignancies. Differentiated thyroid cancer is the most common type, and is papillary or follicular. The prognosis of differentiated thyroid cancer is good if detected early and managed appropriately. Papillary thyroid cancer is usually obvious after FNA cytology. Follicular carcinoma can be difficult to distinguish from benign follicular adenoma on FNA, and requires a hemi-thyroidectomy for histological confirmation.
Anaplastic cancer, Hürthle cells and lymphoma
Anaplastic carcinoma is rare, making up 5% of thyroid cancer. It occurs in elderly patients and is a highly aggressive and invasive tumour carrying a poor prognosis. Cytology may reveal Hürthle cells, which are derived from follicular epithelium; surgical removal may be necessary to distinguish benign from malignant lesions. Rarely, FNA reveals thyroid lymphoma, which requires haematology referral and chemotherapy.
Medullary thyroid cancer
Medullary thyroid cancer (MTC) is a rare neuroendocrine tumour arising from the calcitonin-secreting C-cells of the thyroid. C-cell hyperplasia is a precursor to MTC. MTC can be associated with a mutation in the RET oncogene as part of multiple endocrine neoplasia type 2 (MEN-2). Familial isolated MTC, which is also associated with RET mutations, can also occur in the absence of MEN-2. Detection of a RET mutation has major implications for family screening; prophylactic thyroidectomy is indicated in children carrying the mutation. Serum calcitonin is a tumour marker in MTC, and high levels can lead to symptoms including flushing, sweating and diarrhoea.

Management of differentiated thyroid cancer
The first line treatment of papillary or follicular thyroid cancer is surgery. A hemi-thyroidectomy is initially performed. If the lesion is >4 cm or there are any adverse histological features, the remaining thyroid lobe is removed (complete thyroidectomy). Such patients are deemed high risk and are given ablative RAI therapy, using higher doses than those used for benign hyperthyroidism. Ablation of all thyroid tissue leads to undetectable thyroglobulin levels, which is used as a tumour marker. Iodine uptake scans can be used to localise any residual or recurrent thyroid tissue. During follow-up, thyroxine is given in higher doses than for primary hypothyroidism, to suppress TSH, beca s can be a driver for residual or recurrent tumour growth.