Last updated on April 4, 2020 at 22:07
The thyroid gland consists of two lateral lobes connected by a thin isthmus, usually located below and anterior to the larynx. It develops from pharyngeal endoderm that descends from the base of the tongue to its normal position on the anterior neck. It normally weighs less than 30 g.
The gland is divided into lobules, each of which is composed by 20 to 40 thyroid follicles. These follicles are lined by cuboidal/low columnar epithelium, and the lumen of the follicles is filled with colloid. This colloid is mostly composed of thyroglobulin, the precursor protein for the active thyroid hormones T3 and T4. When stimulated by TSH the thyroid follicular cells will convert thyroglobulin in the colloid into T3 and T4, which are then released into the circulation. Thyroid hormones act on cells to increase their metabolism and to increase their sensitivity to catecholamines.
The thyroid is subject to many clinical diseases, like inflammation, hyperplasia, autoimmune disease and tumors. Due to its easily accessible anatomical location, these conditions are often easy to treat if necessary. In a worst case scenario the thyroid can be removed and thyroid hormone replacement therapy can be initiated.
Most clinically important thyroid disorders are 3-10 times more common in women. The population that is most frequently affected are young (20s) females.
Goiter, also called struma, refers to an enlargement of the thyroid gland. It is the most common clinical manifestation of thyroid disease. It can accompany hyperthyroidism (toxic goiter), hypothyroidism (hypothyroid goiter) and normothyroidism (non-toxic goiter). It can occur due to hyperplasia, thyroiditis or neoplasms.
The enlargement of the thyroid can come from increased stimulation by TSH. In conditions that cause hypothyroidism, like iodine deficiency and Hashimoto thyroiditis, the decreased level of thyroid hormone means decreased feedback inhibition of TSH, which causes more TSH to be secreted by the pituitary. TSH then stimulates hyperplasia of the thyroid, causing it to grow. Enlargement can also come from cysts or neoplastic processes.
We classify goiters based on the morphology. A goiter can be either diffuse or nodular. Diffuse goiters are those that are diffusely and symmetrically enlarged, while nodular goiters are those that are irregularly enlarged and form nodules. Nodular goiters can be either uninodular or multinodular.
Many things can cause goiter:
|Graves disease||Diffuse goiter||Toxic goiter|
|Hashimoto thyroiditis||Diffuse or nodular goiter||Hypothyroid goiter|
|Iodine deficiency||Diffuse goiter||Hypothyroid goiter|
|Non-toxic adenoma||Uninodular goiter||Non-toxic goiter|
|Toxic adenoma||Uninodular goiter||Toxic goiter|
|Non-toxic multinodular goiter||Multinodular goiter||Non-toxic goiter|
|Toxic multinodular goiter||Multinodular goiter||Toxic goiter|
Goiter is endemic in areas where the soil, water and food contain little iodine. Iodine deficiency is the most common cause of goiter worldwide, but not in the western countries, where autoimmune conditions like Hashimoto thyroiditis and Graves disease are more common causes.
Multinodular goiter is usually idiopathic and symptomless. Any long-standing diffuse goiter can develop into a multinodular one.
Goiters are most commonly asymptomatic, but they can compress the trachea and oesophagus, causing dyspnoea and dysphagia, respectively. Mostly the multinodular goiters cause compression symptoms. Diffuse goiters are usually around 150 g, while multinodular goiters may reach up to more than 500 g!
Hyperthyroidism and thyrotoxicosis
Thyrotoxicosis is the state where the level of circulating free T3 and T4 is elevated, causing hypermetabolism. It is most commonly caused by hyperthyroidism, which is the state where the thyroid is overactive. Because of this the two terms are often used interchangeably; however, hyperthyroidism isn’t the only cause of thyrotoxicosis, as it can also be caused by thyroid inflammation and tumors producing thyroid hormone.
The symptoms of thyrotoxicosis are related to the hypermetabolic state and to the overactivity of the sympathetic nervous system:
- Warm and flushed skin
- Heat intolerance
- Weight loss despite increased appetite
- Hypermotility of the gut, diarrhoea
- Palpitations and tachycardia
- Muscle weakness
Thyrotoxicosis can be caused by:
- Graves disease
- Toxic multinodular goiter
- Toxic adenoma
- Destruction of the thyroid gland – causes release of preformed thyroid hormone
- De Quervain thyroiditis (early phase)
- Hashimoto thyroiditis
- Drug-induced thyroiditis
- Ectopic thyroid hormone production (rare)
- Struma ovarii – an ovarian teratoma
Graves disease, sometimes called Basedow-Graves disease, is the most common cause of hyperthyroidism. It’s caused by the immune system forming IgG antibodies against the ligand-binding site on the TSH-receptor on the follicular cells. These anti-TSH antibodies activate the receptor and trick the follicular cells into believing they’re being stimulated by TSH.
Graves disease usually present with a triad of symptoms:
- Diffuse goiter
- Ophthalmopathy with or out without exophthalmos
- Thyroid dermopathy (Pretibial myxoedema)
Goiter results from the hyperplasia stimulated by the TSH receptor, but the anti-TSH antibodies also stimulate fibroblasts. They stimulate fibroblasts in the orbit, which produce fibrofatty tissue which causes the eyeballs to be pushed outwards (exophthalmos). The antibodies also stimulate fibroblasts in the skin, causing them to produce more glycosaminoglycans, causing thyroid dermopathy.
The name pretibial myxoedema is misleading and old, as it doesn’t always occur on the tibia and doesn’t really cause just oedema. True myxedema occurs only in hypothyroidism.
Inflammation of the thyroid
Thyroiditis is most frequently subacute (transient) or chronic, but acute inflammation exists as well.
Acute absceding thyroiditis is a very rare condition. It’s most commonly caused by haematogenous spread of a bacterial infection. It causes painful enlargement of the thyroid.
Hashimoto thyroiditis is the most common cause of chronic hypothyroidism in western countries. It’s an autoimmune condition characterised by CD8-mediated destruction of the thyroid parenchyme and the presence of anti-thyroglobulin and anti-thyroid peroxidase antibodies. The clinical manifestations are:
- Thyrotoxicosis – in the early phase, as the destroyed cells release preformed hormones
- Hypothyroidism – in the chronic phase, as the number of cells decreases
- Painless goiter
It’s associated with other autoimmune diseases and with HLA-DR5.
De Quervain thyroiditis, also called subacute granulomatous thyroiditis, is a transient, self-limiting disease that occurs some weeks after a viral upper respiratory tract infection. Granulomas are present in the thyroid, hence the name. The clinical manifestations are:
- Thyrotoxicosis – in the early phase
- Hypothyroidism – in the later phase
- Painful goiter
No treatment is usually required as it eventually undergoes spontaneous remission.
Subacute lymphocytic thyroiditis is a poorly understood condition that is associated with autoimmune diseases. It most frequently occurs in postpartum women, in which case it’s called postpartum thyroiditis. It causes painless goiter.
Riedel thyroiditis is a rare condition with unknown etiology. The thyroid parenchyme is replaced by fibrous tissue.
The thyroid gives rise to both benign and malignant tumors. The most common benign tumor 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. A small number of follicular adenomas produce thyroid hormones, in which case they’re called toxic adenomas. These 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.
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||Related gene mutations|
|Papillary carcinoma||Follicular cell||RET, NTRK1, BRAF|
|Follicular carcinoma||Follicular cell||RAS|
|Medullary carcinoma||Parafollicular cell (= C cells)||RET|
|Anaplastic carcinoma||Thyroid follicular cells||p53|
Thyroid carcinomas are usually discovered as nodular, painless goiters. The well-differentiated types are the most common, and these types rarely metastasize. If they do, it’s frequently to the cervical lymph nodes. The treatment for any type of thyroid carcinoma is total thyroidectomy.
Papillary carcinoma is the most frequent type by far as it accounts for 80% of all thyroid carcinomas. Medullary carcinomas are associated with multiple endocrine neoplasia type 2a and 2b (MEN-2). Anaplastic carcinoma is most frequent in elderly and is the most aggressive variant. It has an average 6 months survival.
The major risk factor predisposing to thyroid cancer is exposure to ionizing radiation 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 linked With follicular thyroid carcinoma.
42. Anterior lobe pituitary tumours and their consequences. Posterior lobe syndromes. Disorders associated with hypopituarism (Sheehan syndrome, chromophobic adenoma, empty sella syndrome, suprasellar tumours)
44. Pathology of the parathyroid glands (hyperplasia, adenoma, causes of hypoparathyreoidism). Multiple endocrine neoplasms