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Often these abnormal growths of thyroid tissue are located at the edge of the thyroid gland and can be felt as a lump in the throat. When they are large, they can sometimes be seen as a lump in the front of the neck.
Sometimes a thyroid nodule presents as a fluid-filled cavity called a thyroid cyst. Often, solid components are mixed with the fluid. Thyroid cysts most commonly result from degenerating thyroid adenomas, which are benign, but they occasionally contain malignant solid components.
Thyroid nodules are nodules (raised areas of tissue or fluid) which commonly arise within an otherwise normal thyroid gland. They may be hyperplasia or a thyroid neoplasm, but only a small percentage of the latter are thyroid cancers. Small, asymptomatic nodules are common, and many people who have them are unaware of them. But nodules that grow larger or produce symptoms may eventually need medical care. Goitres may have nodules or be diffuse.
A cold nodule is a thyroid nodule that does not produce thyroid hormone. On a radioactive iodine uptake test a cold nodule takes up less radioactive material than the surrounding thyroid tissue. A cold nodule may be malignant or benign. On scintigraphy cold nodules do not show but are easily shown on ultrasound. Figure 1 illustrates the basic anatomy of the thyroid gland. The case shown in Figure 4 shows a cold nodule quite emphasized representation of the thyroid. The investigation was carried out due to a goiter rating of 3. Striking was the discrepancy between the magnification sonographically depicted the thyroid lobe and the findings in the scintigraphy; the lower part of the right lobe and the lateral part of the left missing in the bone scan, although demonstrably thyroid tissue is present there sonographically. This imperfective representation for thyroid tissue is the characteristic of "cold node".
Symptoms of toxic multinodular goitre are similar to that of hyperthyroidism, including:
- heat intolerance
- muscle weakness/wasting
- hyperactivity
- fatigue
- tremor
- irritability
- weight loss
- osteoporosis
- increased appetite
- non-painful goitre (swelling of the thyroid gland)
- tachycardia (high heart rate - above 100 beats per minute at rest in adults)
Symptoms of the condition vary with type: hypo- vs. hyperthyroidism, which are further described below.
Possible symptoms of hypothyroidism are:
Possible symptoms of hyperthyroidism are:Note: certain symptoms and physical changes can be seen in both hypothyroidism and hyperthyroidism —fatigue, fine / thinning hair, menstrual cycle irregularities, muscle weakness / aches (myalgia), and different forms of myxedema.
Thyroid cancers are mainly papillary, follicular, medullary or anaplastic thyroid cancer. Most patients are 25 to 65 years of age when first diagnosed; women are more affected than men. Nearly 80 percent of thyroid cancer is papillary and about 15 percent is follicular; both types grow slowly and can be cured if caught early. Medullary thyroid cancer makes up about 3 percent of this cancer. It grows slowly and can be controlled if caught early. Anaplastic is the most deadly and makes up around 2 percent. This type grows quickly and is hard to control. The classification is determined by looking at the sample of cells under a microscope and by which type of thyroid cell is present.
Other thyroid malignancies include thyroid lymphoma, various types of thyroid sarcoma, smooth muscle tumors, teratoma, squamous cell thyroid carcinoma and other rare types of tumors.
Most often the first symptom of thyroid cancer is a nodule in the thyroid region of the neck. However, many adults have small nodules in their thyroids, but typically under 5% of these nodules are found to be cancerous. Sometimes the first sign is an enlarged lymph node. Later symptoms that can be present are pain in the anterior region of the neck and changes in voice due to an involvement of the recurrent laryngeal nerve.
Thyroid cancer is usually found in a euthyroid patient, but symptoms of hyperthyroidism or hypothyroidism may be associated with a large or metastatic well-differentiated tumor.
Thyroid nodules are of particular concern when they are found in those under the age of 20. The presentation of benign nodules at this age is less likely, and thus the potential for malignancy is far greater.
Thyroid adenoma is a benign neoplasm of the thyroid. Thyroid nodules are very common and around 80 percent of adults will have at least one by the time they reach 70 years of age. Approximately 90 to 95 percent of all nodules are found to be benign.
Colloid nodules are usually small enough to be undetectable without an ultrasound or other imaging techniques. They usually produce no symptoms, so patients are unlikely to notice them until their size makes them easier to detect. Like other thyroid nodules, they are usually first noticed in a routine physical examination.
Toxic multinodular goiter (also known as toxic nodular goiter, or Plummer's disease) is a multinodular goiter associated with hyperthyroidism.
It is a common cause of hyperthyroidism in which there is excess production of thyroid hormones from functionally autonomous thyroid nodules, which do not require stimulation from thyroid stimulating hormone (TSH).
Toxic multinodular goiter is the second most common cause of hyperthyroidism (after Graves' disease) in the developed world, whereas iodine deficiency is the most common cause of hypothyroidism in developing-world countries where the population is iodine-deficient. (Decreased iodine leads to decreased thyroid hormone.) However, iodine deficiency can cause goitre (thyroid enlargement); within a goitre, nodules can develop. Risk factors for toxic multinodular goiter include individuals over 60 years of age and being female.
Almost all thyroid adenomas are follicular adenomas. Follicular adenomas can be described as "cold", "warm" or "hot" depending on their level of function. Histopathologically, follicular adenomas can be classified according to their cellular architecture and relative amounts of cellularity and colloid into the following types:
- Fetal (microfollicular) - these have the potential for microinvasion. These consist of small, closely packed follicles lined with epithelium.
- colloid (macrofollicular) - these do "not" have any potential for microinvasion
- embryonal (atypical) - have the potential for microinvasion.
- Hürthle cell adenoma (oxyphil or oncocytic tumor) - have the potential for microinvasion.
- Hyalinizing trabecular adenoma
Papillary adenomas are very rare.
The major clinical symptom of metastatic medullary thyroid carcinoma is diarrhea; occasionally a patient will have flushing episodes. Both occur particularly with liver metastasis, and either symptom may be the first manifestation of the disease. The flushing that occurs in medullary thyroid carcinoma is indistinguishable from that associated with carcinoid syndrome. In MTC, the flushing, diarrhea, and itching (pruritis) are all caused by elevated levels of calcitonin gene products (calcitonin or calcitonin gene-related peptide). Alternatively, the flushing and diarrhea observed in carcinoid syndrome is caused by elevated levels of circulating serotonin.
Medullary thyroid carcinoma may also produce a thyroid nodule and enlarged cervical lymph nodes.
Sites of spread of medullary thyroid carcinoma include local lymph nodes in the neck, lymph nodes in the central portion of the chest (mediastinum), liver, lung, and bone. Spread to other sites such as skin or brain occurs but is uncommon.
The first signs of a parathyroid adenoma and the resulting primary hyperparathyroidism can include bone fractures and urinary calculi such as kidney stones.
Oftentimes parathyroid adenoma is not diagnosed until found on standard blood-tests that reveal high calcium content in the blood, it can appear in urine tests as well. Patients may not be experiencing any noticeable symptoms but could be producing excessive amounts of calcium and eventually experience problems later in life if untreated. However, patients can experience common symptoms that can range from joint, muscle, and abdominal pain to slight discomfort. Additionally patients might be experiencing feelings of depression due to the hormonal imbalance. Constipation and exhaustion can also be experienced as a result of the irregularity in the bloodstream. There is also a potential that the kidneys could be damaged with the excess of calcium in the blood.
Colloid nodules, also known as adenomatous nodules or colloid nodular goiter are benign, noncancerous enlargement of thyroid tissue. Although they may grow large, and there may be more than one, they are not malignant and they will not spread beyond the thyroid gland. Colloid nodules are the most common kind of thyroid nodule.
A thyroid adenoma may be clinically silent ("cold" or "warm" adenoma), or it may be a functional tumor, producing excessive thyroid hormone ("hot" adenoma). In this case, it may result in symptomatic hyperthyroidism, and may be referred to as a toxic thyroid adenoma.
Thyroid disease is a medical condition that affects the function of the thyroid gland (the endocrine organ found at the front of the neck that produces thyroid hormones). The symptoms of thyroid disease vary depending on the type. There are four general types: 1) hypothyroidism (low function) caused by not having enough thyroid hormones; 2) hyperthyroidism (high function) caused by having too much thyroid hormones; 3) structural abnormalities, most commonly an enlargement of the thyroid gland; and 4) tumors which can be benign or cancerous. It is also possible to have abnormal thyroid function tests without any clinical symptoms. Common hypothyroid symptoms include fatigue, low energy, weight gain, inability to tolerate the cold, slow heart rate, dry skin and constipation. Common hyperthyroid symptoms include irritability, weight loss, fast heartbeat, heat intolerance, diarrhea, and enlargement of the thyroid. In both hypothyroidism and hyperthyroidism, there may be swelling of a part of the neck, which is also known as goiter.
Diagnosis can often be made through laboratory tests. The first is thyroid-stimulating hormone (TSH), which is generally below normal in hyperthyroidism and above normal in hypothyroidism. The other useful laboratory test is non-protein-bound thyroxine or free T4. Total and free triiodothyronine (T3) levels are less commonly used. Anti-thyroid autoantibodies can also be used, where elevated anti-thyroglobulin and anti-thyroid peroxidase antibodies are commonly found in hypothyroidism from Hashimoto's thyroiditis and TSH-receptor antibodies are found in hyperthyroidism caused by Graves' disease. Procedures such as ultrasound, biopsy and a radioiodine scanning and uptake study may also be used to help with the diagnosis.
Treatment of thyroid disease varies based on the disorder. Levothyroxine is the mainstay of treatment for people with hypothyroidism, while people with hyperthyroidism caused by Graves' disease can be managed with iodine therapy, antithyroid medication, or surgical removal of the thyroid gland. Thyroid surgery may also be performed to remove a thyroid nodule or lobe for biopsy, or if there is a goiter that is unsightly or obstructs nearby structures.
Hypothyroidism affects 3-10% percent of adults, with a higher incidence in women and the elderly. An estimated one-third of the world's population currently lives in areas of low dietary iodine levels, making iodine-deficiency the most common cause of hypothyroidism and endemic goiter. In regions of severe iodine deficiency, the prevalence of goiter is as high as 80%. In areas where iodine-deficiency is not found, the most common type of hypothyroidism is an autoimmune subtype called Hashimoto's thyroiditis, with a prevalence of 1-2%. As for hyperthyroidism, Graves' disease, another autoimmune condition, is the most common type with a prevalence of 0.5% in males and 3% in females. Although thyroid nodules are common, thyroid cancer is rare. Thyroid cancer accounts for less than 1% of all cancer in the UK, though it is the most common endocrine tumor and makes up greater than 90% of all cancers of the endocrine glands.
A goitre, associated with hypothyroidism or hyperthyroidism, may be present with symptoms of the underlying disorder. For hyperthyroidism, the most common symptoms are associated with adrenergic stimulation: tachycardia, palpitations, nervousness, tremor, increased blood pressure and heat intolerance. Clinical manifestations are often related to hypermetabolism, (increased metabolism), excessive thyroid hormone, an increase in oxygen consumption, metabolic changes in protein metabolism, immunologic stimulation of diffuse goitre, and ocular changes (exophthalmos). Hypothyroid individuals may have weight gain despite poor appetite, cold intolerance, constipation and lethargy. However, these symptoms are often non-specific and make diagnosis difficult.
Regarding morphology, goitres may be classified either as the growth pattern or as the size of the growth :
- Growth pattern:
- Uninodular goitre: one thyroid nodule; can be either an inactive or a toxic nodule.
- Multinodular goitre: multiple nodules; can likewise be inactive or toxic, the latter is called toxic multinodular goitre and associated with hyperthyroidism; thyroid cancer is identified in 13.7% of the patients operated for multinodular goitre. These nodules grow up at varying rates and secrete thyroid hormone autonomously, thereby suppressing TSH-dependent growth and function in the rest of gland.
- Diffuse goitre: the whole thyroid appearing to be enlarged due to hyperplasia.
- Size:
- Class I (palpation goitre): in normal posture of the head, it cannot be seen; it is only found by palpation.
- Class II: the goitre is palpable and can be easily seen.
- Class III: the goitre is very large and is retrosternal; pressure results in compression marks.
Thyroid cancers can be classified according to their histopathological characteristics. The following variants can be distinguished (distribution over various subtypes may show regional variation):
- Papillary thyroid cancer (75% to 85% of cases) – often in young females – excellent prognosis. May occur in women with familial adenomatous polyposis and in patients with Cowden syndrome.
- Newly reclassified variant: noninvasive follicular thyroid neoplasm with papillary-like nuclear features is considered an indolent tumor of limited biologic potential.
- Follicular thyroid cancer (10% to 20% of cases) – occasionally seen in patients with Cowden syndrome
- Medullary thyroid cancer (5% to 8% of cases) – cancer of the parafollicular cells, often part of multiple endocrine neoplasia type 2.
- Poorly differentiated thyroid cancer
- Anaplastic thyroid cancer (less than 5% of cases) is not responsive to treatment and can cause pressure symptoms.
- Others
- Thyroid lymphoma
- Squamous cell thyroid carcinoma
- Sarcoma of thyroid
The follicular and papillary types together can be classified as "differentiated thyroid cancer". These types have a more favorable prognosis than the medullary and undifferentiated types.
- Papillary microcarcinoma is a subset of papillary thyroid cancer defined as measuring less than or equal to 1 cm. The highest incidence of papillary thyroid microcarcinoma in autopsy series was reported by Harach et al. in 1985, who found 36 of 101 consecutive autopsies were found to have an incidental microcarcinoma. Michael Pakdaman et al. report the highest incidence in a retrospective surgical series at 49.9% of 860 cases. Management strategies for incidental papillary microcarcinoma on ultrasound (and confirmed on FNAB) range from total thyroidectomy with radioactive iodine ablation to observation alone. Harach et al. suggest using the term "occult papillary tumor" to avoid giving patients distress over having cancer. It was Woolner et al. who first arbitrarily coined the term "occult papillary carcinoma" in 1960, to describe papillary carcinomas ≤ 1.5 cm in diameter.
A parathyroid adenoma is a benign tumor of the parathyroid gland. It generally causes hyperparathyroidism; there are very few reports of parathyroid adenomas that were not associated with hyperparathyroidism.
A human being usually has four parathyroid glands located on the back surface of the thyroid in the neck. The parathyroids secrete parathyroid hormone (PTH), which increases the concentration of calcium in the blood by inducing the bones to release calcium into the blood and the kidneys to reabsorb it from the urine into the blood. When a parathyroid adenoma causes hyperparathyroidism, more parathyroid hormone is secreted, causing the calcium concentration of the blood to rise, resulting in hypercalcemia.
Medullary thyroid cancer (MTC) is a form of thyroid carcinoma which originates from the parafollicular cells (C cells), which produce the hormone calcitonin.
Medullary tumors are the third most common of all thyroid cancers. They make up about 3% of all thyroid cancer cases.
Approximately 25% of medullary thyroid cancer is genetic in nature, caused by a mutation in the RET proto-oncogene. This form is classified as familial MTC. When MTC occurs by itself it is termed sporadic MTC. When it coexists with tumors of the parathyroid gland and medullary component of the adrenal glands (pheochromocytoma) it is called multiple endocrine neoplasia type 2 (MEN2).It was first characterized in 1959.
An "ectopic thyroid", also called "accessory thyroid gland", is a form of thyroid dysgenesis in which an entire or parts of the thyroid located in another part of the body than what is the usual case. A completely ectopic thyroid gland may be located anywhere along the path of the descent of the thyroid during its embryological development, although it is most commonly located at the base of the tongue, just posterior to the foramen cecum of the tongue. In this location, an aberrant or ectopic thyroid gland is known as a "lingual thyroid". If the thyroid fails to descend to even higher degree, then the resulting final resting point of the thyroid gland may be high in the neck, such as just below the hyoid bone. Parts of ectopic thyroid tissue ("accessory thyroid tissue") can also occur, and arises from remnants of the thyroglossal duct, and may appear anywhere along its original length. Accessory thyroid tissue may be functional, but is generally insufficient for normal function if the main thyroid gland is entirely removed.
Lingual thyroid is 4-7 times more common in females, with symptoms developing during puberty, pregnancy or menopause. Lingual thyroid may be asymptomatic, or give symptoms such as dysphagia (difficulty swallowing), dysphonia (difficulty talking) and dyspnea (difficulty breathing).
Hyperthyroidism may be asymptomatic or present with significant symptoms. Some of the symptoms of hyperthyroidism include nervousness, irritability, increased perspiration, heart racing, hand tremors, anxiety, difficulty sleeping, thinning of the skin, fine brittle hair, and muscular weakness—especially in the upper arms and thighs. More frequent bowel movements may occur, and diarrhea is common. Weight loss, sometimes significant, may occur despite a good appetite (though 10% of people with a hyperactive thyroid experience weight gain), vomiting may occur, and, for women, menstrual flow may lighten and menstrual periods may occur less often, or with longer cycles than usual.
Thyroid hormone is critical to normal function of cells. In excess, it both overstimulates metabolism and exacerbates the effect of the sympathetic nervous system, causing "speeding up" of various body systems and symptoms resembling an overdose of epinephrine (adrenaline). These include fast heart beat and symptoms of palpitations, nervous system tremor such as of the hands and anxiety symptoms, digestive system hypermotility, unintended weight loss, and (in "lipid panel" blood tests) a lower and sometimes unusually low serum cholesterol.
Major clinical signs include weight loss (often accompanied by an increased appetite), anxiety, heat intolerance, hair loss (especially of the outer third of the eyebrows), muscle aches, weakness, fatigue, hyperactivity, irritability, high blood sugar, excessive urination, excessive thirst, delirium, tremor, pretibial myxedema (in Graves' disease), emotional lability, and sweating. Panic attacks, inability to concentrate, and memory problems may also occur. Psychosis and paranoia, common during thyroid storm, are rare with milder hyperthyroidism. Many persons will experience complete remission of symptoms 1 to 2 months after a euthyroid state is obtained, with a marked reduction in anxiety, sense of exhaustion, irritability, and depression. Some individuals may have an increased rate of anxiety or persistence of affective and cognitive symptoms for several months to up to 10 years after a euthyroid state is established. In addition, those with hyperthyroidism may present with a variety of physical symptoms such as palpitations and abnormal heart rhythms (the notable ones being atrial fibrillation), shortness of breath (dyspnea), loss of libido, amenorrhea, nausea, vomiting, diarrhea, gynecomastia and feminization. Long term untreated hyperthyroidism can lead to osteoporosis. These classical symptoms may not be present often in the elderly.
Neurological manifestations can include tremors, chorea, myopathy, and in some susceptible individuals (in particular of Asian descent) periodic paralysis. An association between thyroid disease and myasthenia gravis has been recognized. The thyroid disease, in this condition, is autoimmune in nature and approximately 5% of patients with myasthenia gravis also have hyperthyroidism. Myasthenia gravis rarely improves after thyroid treatment and the relationship between the two entities is not well understood.
In Graves' disease, ophthalmopathy may cause the eyes to look enlarged because the eye muscles swell and push the eye forward. Sometimes, one or both eyes may bulge. Some have swelling of the front of the neck from an enlarged thyroid gland (a goiter).
Minor ocular (eye) signs, which may be present in any type of hyperthyroidism, are eyelid retraction ("stare"), extraocular muscle weakness, and lid-lag. In hyperthyroid "stare" (Dalrymple sign) the eyelids are retracted upward more than normal (the normal position is at the superior corneoscleral limbus, where the "white" of the eye begins at the upper border of the iris). Extraocular muscle weakness may present with double vision. In lid-lag (von Graefe's sign), when the patient tracks an object downward with their eyes, the eyelid fails to follow the downward moving iris, and the same type of upper globe exposure which is seen with lid retraction occurs, temporarily. These signs disappear with treatment of the hyperthyroidism.
Neither of these ocular signs should be confused with exophthalmos (protrusion of the eyeball), which occurs specifically and uniquely in hyperthyroidism caused by Graves' disease (note that not all exophthalmos is caused by Graves' disease, but when present with hyperthyroidism is diagnostic of Graves' disease). This forward protrusion of the eyes is due to immune-mediated inflammation in the retro-orbital (eye socket) fat. Exophthalmos, when present, may exacerbate hyperthyroid lid-lag and stare.
There are many different signs and symptoms for thyroiditis, none of which are exclusively limited to this disease. Many of the signs imitate symptoms of other diseases, so thyroiditis can sometimes be difficult to diagnose. Common hypothyroid symptoms manifest when thyroid cell damage is slow and chronic, and may include fatigue, weight gain, feeling "fuzzy headed", depression, dry skin, and constipation. Other, rarer symptoms include swelling of the legs, vague aches and pains, decreased concentration and so on. When conditions become more severe, depending on the type of thyroiditis, one may start to see puffiness around the eyes, slowing of the heart rate, a drop in body temperature, or even incipient heart failure. On the other hand, if the thyroid cell damage is acute, the thyroid hormone within the gland leaks out into the bloodstream causing symptoms of thyrotoxicosis, which is similar to those of hyperthyroidism. These symptoms include weight loss, irritability, anxiety, insomnia, fast heart rate, and fatigue. Elevated levels of thyroid hormone in the bloodstream cause both conditions, but thyrotoxicosis is the term used with thyroiditis since the thyroid gland is not overactive, as in the case of hyperthyroidism.
Thyroid storm is a severe form of thyrotoxicosis characterized by rapid and often irregular heart beat, high temperature, vomiting, diarrhea, and mental agitation. Symptoms may be unusual in the young, old, or pregnant. It is a medical emergency and requires hospital care to control the symptoms rapidly. Even with treatment, death occurs in 20% to 50%.