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Goitre and thyroid nodules Thyroid cancer Goitre and thyroid nodules A goitre is an enlarged thyroid gland and may be diffuse or nodular (consisting of a solitary or multiple nodules). Definitions When diffuse enlargement of the thyroid occurs in the absence of nodules and hyperthyroidism, it is referred to as a diffuse nontoxic goiter. This is sometimes called simple goiter, because of the absence of nodules, or colloid goiter, because of the presence of uniform follicles that are filled with colloid. Worldwide, diffuse goiter is most commonly caused by iodine deficiency and is termed endemic goiter when it affects >5% of the population. In nonendemic regions, sporadic goiter occurs, and the cause is usually unknown. Thyroid enlargement in teenagers is sometimes referred to as juvenile goiter. Differential diagnosis of goitre Thyrotoxic patients • Graves’ disease • Multinodular goitre • Solitary adenoma • Thyroiditis (subacute or painless) Hypothyroid patients • Hashimoto’s thyroiditis Euthyroid patients • Simple goitre (non - toxic) • Malignancy: thyroid carcinoma, lymphoma • Riedel’s thyroiditis Clinical presentations A mass in the neck noticed by the physician, the patient or relatives may be the only presenting complaint. Features in the history and examination that raise the suspicion of malignancy include: ● age < 20 or > 60 years ● recent rapid enlargement of a thyroid nodule ● local compressive symptoms: dysphagia, dyspnoea, hoarseness, stridor ● family history of thyroid cancer or multiple endocrine neoplasia (MEN) ● history of exposure to radiation ● lymphadenopathy. Thyroid examination Thyroid examination should include the following steps: • Inspection : ask the patient to swallow (the goitre moves upward). • Palpation : examine the goitre with the patient swallowing — the goitre moves upward. This may be lost in anaplastic carcinoma and Riedel ’ s thyroiditis (a rare chronic inflammatory disease of the thyroid gland characterized by a dense fibrosis replacing normal thyroid parenchyma, which results in a ‘woody’ goitre). Determine the size, whether the goitre is nodular or diffusely enlarged, soft or hard, or tender (e.g. in subacute thyroiditis or bleeding into a cyst) and the presence of lymph nodes. • Percussion of the upper mediastinum (dull in retrosternal goitre). • Auscultation : for a bruit (in hyperthyroidism) and inspiratory stridor (in cases of tracheal compression). • Determination of thyroid status (look for features of hypothyroidism or thyrotoxicosis). Investigations LABORATORY FINDINGS Thyroid function tests 1. TSH and free T4 (to exclude thyrotoxicosis and hypothyroidism) 2. Serum thyroglobulin levels are increased in both benign and malignant nodules, and can only be used in the follow - up of patients with treated differentiated (papillary and follicular) cancers. 3. Calcitonin should be measured when medullary cell carcinoma is suspected (usually after fine needle aspiration cytology results) 4. Respiratory flow-volume loop studies (to exclude tracheal obstruction) Investigations FINE NEEDLE ASPIRATION AND CYTOLOGY The cytologist’s report may be one of the following: • Non – diagnostic • Non - neoplastic (abundant colloid, features compatible with multinodular goitre or thyroiditis) • Follicular lesions: adenoma or carcinoma • Suspicious of malignancy • Diagnostic for malignancy. Ultrasound - guided fine needle aspiration should be performed where there is high suspicion of malignancy, suspicious ultrasound features, presence of cervical lymph nodes. Investigations IMAGING 1. Ultrasound of thyroid gland (There are no ultrasonographic findings that are specifi c for thyroid carcinoma. However, features that raise suspicion of malignancy include hypoechogenicity, irregular border, microcalcifications and increased colour Doppler flow). 2. Radioisotope uptake scan (should be performed in all patients with suppressed TSH) Malignant nodules are more likely to be cold (i.e. not to take up radioisotope). However, most (80%) cold nodules are benign (e.g. colloid nodules, haemorrhage, cysts or inflammatory lesions such as Hashimoto’s thyroiditis). Hot nodules are associated with a low incidence of thyroid cancer. However, the presence of hot nodules does not exclude malignancy. 3. Computed tomography (CT) or magnetic resonance imaging (MRI) of the neck and thoracic inlet (in cases of Clinical suspicion of a retrosternal goitre causing tracheal compression) Treatment of non-toxic goitre and thyroid nodules Following fine needle aspiration of thyroid nodules and cytological examination, all patients should be discussed at a specialist thyroid multidisciplinary meeting. • Patients with non - diagnostic cytology need repeat ultrasound - guided fine needle aspiration immediately. • Patients with suspicious or malignant cytology should be offered surgery. • Patients with benign cytology should be followed up clinically with palpation (and with ultrasound if a nodule is not easily palpable). Some guidelines recommend repeat fine needle aspiration after 6 months to reduce falsenegative rates. Surgery may also be offered in the presence of symptoms caused by local compression or significant cosmetic disfigurement. Thyroid cancer Thyroid cancer is the most common endocrine malignancy. Classification of thyroid carcinoma: • Papillary (70 – 80%) • Follicular (15%) • Anaplastic (5%) • Medullary (5 – 10%) • Lymphoma (5 – 10%) Main aetiology factors are: • Exposure to ionizing radiation • Genetic factors (genetic mutation) • Family history of thyroid cancer Papillary thyroid cancer Papillary thyroid cancer is the most common thyroid cancer. It is often multifocal. About 15 – 20% show local extra - thyroidal invasion. Papillary carcinomas metastasize via the lymphatics to the regional lymph nodes (clinically evident in about one third of patients at presentation) and distantly, for example to the lungs and bones (2 – 10% at diagnosis). Papillary carcinomas are typically unencapsulated. They are characterized by papillae consisting of one or two layers of tumour cells surrounding a fibrovascular core. The cells and nuclei are large, and their cytoplasm has a ‘ ground glass ’ appearance. Nucleoli are prominent, and the nuclei have clefts, grooves and ‘ holes ’ due to intranuclear cytoplasmic inclusions ( ‘ Orphan Annie eyes ’ ). About 50% of papillary carcinomas contain calcified psammoma bodies, the scarred remnants of tumour papillae that presumably infarcted. Follicular carcinoma This type of epithelium - derived thyroid carcinoma shows follicular differentiation and capsular or vascular invasion. The peak incidence of follicular carcinomas is between ages 40 and 60 years. Fine needle aspiration specimens may show microfollicles with varying nuclear atypia and little colloid. However, it is difficult to differentiate between benign follicular adenomas and malignant follicular carcinomas on cytology. The distinction between follicular adenoma and carcinoma can only be made through histological identification of capsule and/or vascular invasion. Follicular carcinomas may be minimally or widely invasive. Spread is more likely to be haematogenous (to lung and bones) than to regional lymph nodes. Hurthle cell carcinoma is a variant of follicular thyroid carcinoma and is characterized by the presence of oncocytic cells, which have an abundant oxyphillic cytoplasm (due to the accumulation of altered mitochondria) and round oval nuclei with prominent nucleoli. Anaplastic carcinoma Anaplastic thyroid carcinoma occurs more frequently in older patients (60 – 80 years of age). Patients usually present with a rapidly enlarging neck mass. The spread is haematogenous, and distant metastases are found in 15 – 50% of patients at initial disease presentation. Thyroid lymphoma Thyroid lymphoma may be part of a systemic disease or may primarily involve the thyroid gland. The risk of thyroid lymphoma is increased in patients with autoimmune thyroiditis. Treatment of papillary and follicular carcinoma Papillary and follicular carcinoma Treatment includes initial thyroidectomy, postoperative TSH suppression with thyroxine and, in high - risk patients, postoperative radio - iodine ablation. Surgery is the primary treatment and should be performed by an experienced thyroid surgeon to minimize the risk of hypoparathyroidism and recurrent laryngeal nerve injury. Total thyroidectomy is appropriate when the primary tumor is 1.0 cm or more, or if there is extra - thyroidal extension or metastasis. This aggressive initial surgical approach is associated with lower rates of local and regional recurrence and overall mortality. Lobectomy plus isthmusectomy may be appropriate for tumours of less than 1.0 cm confined to one lobe of the gland. Lymph node status should be assessed by neck ultrasound scans, and regional neck dissection is carried out in cases of central or lateral nodal involvement. Treatment of papillary and follicular carcinoma TSH suppression After initial surgery, all patients should receive thyroxine to prevent hypothyroidism and to minimize potential TSH stimulation of tumour growth. The dose of levothyroxine should be adjusted by 25 μ g every 6 weeks until the serum TSH is below 0.1 mU/L. Most patients require 175 – 200 μ g daily. A lower level of TSH suppression may be appropriate in those with heart disease or low bone mineral density. Treatment of papillary and follicular carcinoma Radio – iodine Thyroid follicular cells can take up radio – iodine (131 I), which causes cell death by the emission of beta rays. Postoperatively (at about 4 – 6 weeks), radio - iodine ablation is given to high - risk patients (those aged ≥ 45 years, tumours > 3 – 4 cm, aggressive histological variants, extra thyroidal disease with direct invasion or metastases). The need for radio iodine ablation in low - risk patients is controversial. Radio - iodine ablation destroys residual normal thyroid as well as microscopic malignant tissue and improves the specifi city of subsequent radio - iodine scans and serum thyroglobulin for detecting recurrent or metastatic cancer. Follow – up scanning with 123 I and further radio iodine treatment with 131 I in cases of positive uptake is done 6 – 12 months after initial radio - iodine and is repeated until the patient has a negative scan. Complications of radio - iodine include radiation thyroiditis, painless neck oedema, sialoadenitis, tumour haemorrhage or oedema, and nausea. An increased risk of secondary malignancies has been reported. Treatment of anaplastic thyroid carcinoma and thyroid lymphoma Anaplastic thyroid carcinoma The treatment of anaplastic thyroid carcinoma includes total thyroidectomy with lymph node clearance, chemotherapy (e.g. doxorubicin and cisplatin) and external beam irradiation. Thyroid lymphoma Disease limited to the thyroid is treated with radiotherapy.