111 Thyroid Disease—Benign
Benign thyroid disease can be analysed from three different aspects, which are often inter-related. These are non-toxic thyroid goitre (NTG), hypothyroidism and hyperthyroidism. Patients with NTG are the most important from a surgical standpoint as it is this group that is often referred to otorhinolaryngologists/head and neck surgeons by general practitioners for primary management. In the United Kingdom, it is estimated that up to 15% of the population have a goitre and that when using ultrasound up to 50% of women and 30% of men might have thyroid nodules. Although thyroid nodules are common, the incidence of thyroid cancer is relatively low (See Chapter 112). However, its incidence is increasing rapidly. It is therefore necessary that patients are adequately evaluated.
111.1 Classification of Goitre
1. Non-toxic goitre These may be both physiological and pathological. Physiological goitres include puberty, pregnancy and with the contraceptive pill. The causes of pathological goitres include iodine deficiency. Nodular goitre may be solitary or multi-nodular. The differential diagnosis of the solitary thyroid nodule (STN) includes colloid nodule, adenomatoid nodules, follicular adenoma, thyroid cyst or carcinoma. Multi-nodular goitre (MNG) is defined as an enlarged thyroid gland with multiple nodules of different size and consistency. It can be associated with iodine deficiency, which is endemic in patients living at high altitude such as the Alps or Himalayas. The majority of patients with MNG are euthyroid, and present with an asymptomatic enlargement of the thyroid gland or increasing symptoms of compression. Patients with hypothyroidism may or may not have a goitre. Hypothyroidism may be congenital or acquired. The former is usually due to congenital absence or atrophy of the thyroid and if untreated, it leads to cretinism. Rarely, it is associated with inherited dyshormonogenesis such as Pendred’s syndrome (which is the association of congenital hypothyroidism with high tone deafness). Acquired hypothyroidism is usually idiopathic or due to surgical ablation of the gland, post-treatment of thyrotoxicosis with radioiodine or Hashimoto’s (lymphocytic) thyroiditis. Treatment is with thyroid hormone replacement. The starting dose is usually T4 100 to 125 μg/d. In the presence of sub-clinical hypothyroidism (high thyroid-stimulating hormone (TSH) > 10 mU/1, normal free T4), patients should be treated with T4 (100 μg/d) if antibodies are positive, if there are convincing symptoms or a past history of radioiodine treatment.
2. Toxic goitre (hyperthyroidism) Patients with thyrotoxicosis usually either have Graves’ disease or a solitary toxic nodule. Graves’ disease is caused by circulating thyroid-stimulating immunoglobulins (IgGs) which bind to TSH receptors to increase thyroid hormone production. These IGs are usually associated with thyroid eye disease (thyroid ophthalmopathy), which is caused by a specific antibody named exophthalmos-producing substance (EPS). EPS targets retro-orbital tissue to cause oedema of fat and muscle. Graves’ disease may also be associated with signs of vitiligo, pre-tibial myxoedema, fatigue, atrial fibrillation, weight loss and other autoimmune disorders such as pernicious anaemia.
Hyperthyroidism is usually treated either medically using antithyroid drugs (carbimazole or propylthiouracil) or with radioiodine. About 50% of patients will relapse following medical treatment after 6 months. In these patients, together with those who have significant thyroid ophthalmopathy or those who request surgery, surgery either with a ‘near-total’ or ‘total’ thyroidectomy is an alternative option. Radio-iodine can also be used to treat large toxic MNG in the elderly and infirm, when good shrinkage is achievable. Patients who have solitary toxic nodules are usually best dealt with surgically.
Some patients who have had a MNG for a long time can develop thyrotoxicosis (Plummer’s disease). These patients are often elderly with co-existent morbidity such as ischaemic heart disease, and the rise in T4 is often associated with atrial fibrillation. Because of this, these patients usually have cardiac signs (and not eye signs) and are usually treated medically. Recurrent thyrotoxicosis is treated on its merits, but may require further treatment with either the same or another modality. Many patients (whatever their treatment) will be hypothyroid post-treatment and will be on long-term thyroxine replacement therapy.
Surgical thyroidectomy indications in hyperthyroidism are as follows:
• Failure to medical or radioiodine treatment.
• Suspected malignancy.
• Compression symptoms.
• Dysthyroid eye disease or thyroid ophthalmopathy.
• Patient choice.
• Allergy to iodine and amiodarone.
3. Inflammatory goitre—thyroiditis
a. Hashimoto’s thyroiditis This is an autoimmune disorder most common in middle-aged women. Antibodies are directed against thyroglobulin and/or microsomal peroxidase. They cause lymphocyte infiltration, atrophy and regeneration of the thyroid, and ultimately a goitre. The gland is usually firm, but rubbery. Initially, patients are hyperthyroid, but may become hypothyroid as the disease progresses. Once the diagnosis is made, patients should be treated with thyroxine suppression and have thyroid function tests once a year. Surgery may be required for an enlarged gland causing obstructive symptoms or when there is an indeterminate or suspicious fine-needle aspiration cytology (FNAC) result that necessitates definitive diagnosis. These patients are at a high risk of subsequently developing a thyroid lymphoma.
b. De Quervain’s thyroiditis This condition results as a consequence of acute viral infection. Etiological viruses include coxsackie virus, mumps and adenovirus. Some cases develop post-partum. This is a flu-like illness, and associated with diffuse swelling and tenderness of the gland. There is usually both a transient hyperthyroidism and production of autoantibodies. Treatment is with symptomatic non-steroidal anti-inflammatory drugs (NSAIDs), β-blockers and corticosteroids in severe cases.
c. Riedel’s thyroiditis This is a rare condition associated with a woody hard, sometimes tender, irregular thyroid gland which histologically shows marked fibrosis. This is thought by some to signify a fibrotic reaction to an underlying carcinoma or lymphoma.
4. Neoplastic goitre This can be a benign adenoma or malignant tumour. The overall risk of malignancy in a STN has been reported to be between 4 and 7% and in a MNG between 2 and 11%. This incidence can be even higher in endemic areas.
5. Miscellaneous goitres There are a number of other causes of an enlargement of the thyroid gland. These include tuberculosis, sarcoidosis, amyloid, HIV infection, drug-associated thyroiditis and radiation.
111.2 Clinical Assessment
Depending on the cause and duration of the goitre, patients may be euthyroid, hyperthyroid or hypothyroid. A drug history is important because some are goitrogens, for example, sulphonylureas. The goitre may produce discomfort on swallowing, dysphagia (implying oesophageal compression) or stridor (implying tracheal compression or involvement of the recurrent laryngeal nerve). It is important to confirm that the swelling moves with swallowing and to note its size, position and any intrathoracic or retrosternal involvement. The latter is suspected from dullness to percussion over the manubrium or the inability to find a plane between the goitre and the clavicle. The rest of the neck requires examination for the presence of lymph nodes, and the examination of the larynx with fibre-optic endoscopic nasolaryngoscopy is mandatory for the evaluation of vocal cord movement.
All patients with a goitre should have their thyroid function and thyroid antibody status checked. In addition, all euthyroid patients should have an ultrasound (US) guided with or without FNAC performed and a vocal cord check is advised in those with any voice change, difficulty in swallowing and breathing, and in those patients undergoing surgery. A chest X-ray is not usually required and flow loops are not helpful unless the patient has an incidental intrathoracic goitre. Serum calcium and calcitonin may be indicated when there is clinical suspicion of multiple endocrine neoplasia or medullary thyroid carcinoma.
• US is now part of the baseline assessment in patients with nodular goitres. It provides information about size, number of nodules and the status of the other lobe and neck. It will provide evidence of the characteristics of the nodules for being solid, cystic or mixed. Cystic nodules are rarely neoplastic. Hypoechoic nodules, micro-calcification, irregular margins, high vascularity and evidence of associated lymphadenopathies are all features of malignancy. It also aids the FNAC by decreasing the sample error and by increasing its accuracy.
• Radionuclide scintigraphy using Tc99 or I123 can be used to identify whether a nodule is ‘hot’ (takes up isotope) and therefore is functioning, or is ‘cold’ (and therefore not functioning). More than 90% of lesions identified with scintigraphy will not concentrate the radionuclide and therefore will appear ‘cold’. These clinically solitary non-functional nodules may represent an adenoma, carcinoma, a cyst or a dominant nodule in a non-palpable MNG. The likelihood of malignancy in a truly solitary cold nodule is between 10 and 20%. The rate of malignancy in truly functioning nodules (hot) is less than 5%. Scintigraphy is only used in the evaluation of thyroid nodules if there is evidence of hyperthyroidism.
• FNAC is safe, cheap and reliable with a diagnostic accuracy of approximately 90% and is therefore together with the US the initial investigation of choice for a STN. The diagnostic strategy for evaluating the thyroid nodule is shown below.
• Anatomical imaging with computed tomography (CT) scan with contrast is useful to assess patients with compression symptoms, suspicion of intrathoracic extension or malignancy. It is an excellent modality to evaluate the neck for nodes, the visceral compartment of the neck, the mediastinum and the chest.
Patients presenting with STN or non-toxic MNG should be managed by the following guidance from the British Thyroid Association (Fig. 111.1).