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B13. Nodular disease of the thyroid gland.

Thyroid nodule

Discovery of a thyroid nodule, a nodule in the thyroid gland, either by the patient or incidentally during physical examination, is a common presentation of thyroid neoplasms or cysts. 95% of thyroid nodules are benign.

Some thyroid tumours produce thyroid hormones, causing hyperthyroidism, in which case they’re called “toxic”.

Etiology

These are the most common causes of thyroid nodule:

  • Benign thyroid nodule
    • Follicular adenoma
    • Toxic adenoma
    • Thyroid cyst
  • Malignant thyroid nodule

The most common thyroid nodule is the follicular adenoma. Follicular adenomas are derived from the follicular epithelium. They’re solitary, well-circumscribed masses that may give rise to painless uninodular goiter.

Toxic adenomas are follicular adenomas which produce thyroid hormones. These toxic adenomas have acquired a gain-of-function mutation in the TSH receptor complex, allowing the follicular cells to be stimulated even in the absence of TSH. They’re common in iodine deficient regions, but very rare in iodine sufficient regions.

Multinodular goitre (MNG) is a complication of long-standing nodular goitre which occurs when multiple nodules develop. These nodules may be toxic (toxic multinodular goitre) or non-toxic (non-toxic multinodular goitre).

Diagnosis and evaluation

The following modalities are used in the evaluation of thyroid nodules:

When a new thyroid nodule is found, TSH should be measured, and the nodule should be examined with ultrasound. If the ultrasound shows features suspicious for malignancy, a fine needle aspiration biopsy (FNAB) is usually performed to determine the dignity, if the nodule is over a certain size. If the nodule is too small for FNAB, it’s monitored regularly.

If TSH is low, thyroid scintigraphy is performed to look for whether the nodule is hot (produces hormones) or cold (doesn’t). A single hot nodule is likely a toxic adenoma, while multiple hot nodules usually refers to a toxic multinodular goitre. Hot nodules are rarely malignant.

Treatment

Toxic adenoma and toxic multinodular goitre are treated with radioiodine therapy or surgical removal. Compensated toxic adenoma is managed with observation only.

Malignant cold nodules are treated with surgery. Benign cold nodules are treated with observation if < 3 cm, and surgery if > 3 cm.


Thyroid cancer

Thyroid cancer is rare and generally has a good prognosis. The incidence has increased markedly in the recent decades, but the mortality remains low. Thyroid cancer is rarely hyperfunctional, meaning that it rarely causes hyperthyroidism.

The differentiated types are the most common, and these types rarely metastasize and have a good prognosis. If they do metastasise, it’s frequently to the cervical lymph nodes. The treatment for any type of thyroid carcinoma is total thyroidectomy.

Etiology

The major risk factor predisposing to thyroid cancer is previous exposure to ionizing radiation at the area of the neck, especially during the first 2 decades of life. Therefore it’s not strange that the incidence of papillary carcinomas among children exposed to the chernobyl disaster was high. Dietary deficiency of iodine is also linked with follicular thyroid carcinoma.

Medullary carcinoma is associated with MEN2A and MEN2B.

Classification

We classify the malignant thyroid tumors according to their differentiation. Here they are in order from most to least common:

Tumor type Cell of origin
Differentiated
Papillary carcinoma Thyroid follicular cell (= epithelial cells)
Follicular carcinoma Thyroid follicular cell
Poorly differentiated
Medullary carcinoma Parafollicular cell (= C cells)
Anaplastic carcinoma Thyroid follicular cells

Papillary carcinoma is the most frequent type by far as it accounts for 80% of all thyroid carcinomas. It has a very good prognosis.

Medullary carcinomas are associated with multiple endocrine neoplasia type 2a and 2b (MEN-2). It has a poor prognosis.

Anaplastic carcinoma is most frequent in elderly. It’s one of the most aggressive cancers. It has an average 6 months survival.

The tumour marker for thyroid cancer is thyroglobulin, except for medullary carcinoma, for which calcitonin is the tumour marker.

Clinical features

Thyroid carcinomas are usually discovered as nodular, painless goiters. The nodule is fixed and rapidly growing, and may cause symptoms of compression of the trachea or oesophagus.

Diagnosis and evaluation

See evaluation of thyroid nodules.

Treatment

Thyroid cancer is treated with total or near-total thyroidectomy with or without neck dissection. For well-differentiated cancers, radioactive iodine ablation and TSH suppression therapy are used after the surgery. TSH is a growth factor and so suppression of it prevents tumour recurrence.

Poorly differentiated cancers respond to neither radioactive iodine ablation nor TSH suppression. Instead, poorly differentiated cancers are treated with adjuvant radiation and/or chemotherapy.

After total thyroidectomy, thyroid hormones must be substituted for life.