Describe the basic anatomy including the division into component parts, the normal size shape, position and character
Discuss the physiology of the thyroid
Describe the common diseases of the thyroid including thyroid cancer, hyperthyroidism, hypothyroidism, and thyroiditis
Describe the commonly used modalities for thyroid imaging, particularly in ultrasound and nuclear medicine
The thyroid is one of the largest endocrine glands. It is located immediately inferior to the larynx and thyroid cartilage, or the ‘Adam’s apple’, and anterior to and on each side of the trachea. It is an essential part of the endocrine system.
The structure of the thyroid is characterized by its highly vascular nature, bilobed, butterfly-shape, location in the neck, and its upward movement on swallowing due to its attachments to the laryngo-skeleton. It is comprised of a large number of follicles, each filled with its secretion called colloid. The follicles are lined with thyroid hormone secreting follicular epithelial cells, and surrounded by calcitonin secreting parafollicular cells (C cells), and a dense network of capillaries. It is the only endocrine organ in which the products produced are stored in an extracellular location.
As an endocrine organ, the function of the thyroid is to synthesize and secrete hormones into the blood stream. It secretes thyroxine (T4), triiodothyronine (T3) and calcitonin. The thyroxine and triiodothyronine are involved in the basal metabolic rate (oxygen consumption at rest) and are produced by the follicular cells. The calcitonin is produced by the parafollicular cells or C cells. Calcitonin reduces serum calcium, opposing the effects of parathyroid hormone. Thus, through release of these hormones the thyroid plays an important role in regulating both metabolic rate and calcium metabolism.
Common diseases of the thyroid include hyper- and hypothyroidism, thyroiditis, and cancer of the thyroid.
Thorough assessment of a patient’s family history, geographical history, and physical symptoms are key first clinical steps in diagnosing thyroid disease, since some of the disorders are hereditary, some related to iodine content in the soil where people live and grow their own crops, and some to radiation exposure. Laboratory tests for serum levels of thyroid-stimulating hormone (TSH) and nuclear scintigraphy, a tissue-specific imaging technology, are also useful in confirming cases of under or over active thyroid. Diagnosis of thyroid cancer requires additional measures, including ultrasound imaging and needle biopsy.
Treatment for hyperthyroidism includes medication, radioisotope therapy, and surgery. While hypothyroidism is easily treated with a lifelong regimen of hormone replacement therapy, Grave’s disease, an autoimmune hyperthyroid state is treated with antithyroid medication, radioactive iodine and surgery, and thyroid cancer almost always involves surgery.
As A Biological Unit
The thyroid, like any organ, is simultaneously a distinct biological unit, the sum of many smaller biological units, but also part of a larger physiological whole. As such, it is an indispensable component of the endocrine system and the body.
The elements of any organ are rooted in its structure and function, and the module defines the principle elements that govern these two disciplines in the thyroid. Structure is described most commonly by the size, shape, position, character and parts of the organ and also by the elements that connect the organ to other structures including the blood vessels nerves and lymphatics.
The thyroid is but one part of the endocrine system, yet a very central one. Basal metabolic rate, the fire that keeps the body warm and functioning, is an essential component of body function. Without the thyroid, metabolism would be at a standstill. Fortunately, its main function is executed through one type of hormone that can easily be replaced.
These principles are true to the thyroid and true to all the organs of the body. These principles are innately obvious but dogged attention to principles when issues become complex is key to solving the complex problems. The “devil” therefore from this vantage point is in the principles and also of course in the “detail”.
Units to Unity
One cell is no cell, and one organ is no organ. This implies that although the individual parts are important, they are nothing unless they combine forces to form something bigger and more powerful than the individual parts.
The cells as separate biological units need to combine forces in order to produce hormones in sufficient quantity in order to be effective. A thyroid cell isolated in the abdominal cavity producing T3 has no functional effect, no matter how hard it works and no matter how talented it is. A genius artist painting in isolation that he or she puts in the closet has no value to the community, and as such cannot “sell” the “goods”, and as such cannot survive.
The organization of the cells into acini, groups of cells that are factories of production, allow the cells to build strength in numbers and cohesive effort. The factories of acini in turn need to combine forces to form lobules, and the lobules in turn need to form lobes and eventually form the organ that has the power of number to be effective. As each unit builds, the organization gets bigger and stronger and as long as everybody pulls their weight, and has their eye on the bigger picture (welfare of the body at large) health and orderly pleasurable living can proceed. One part of the puzzle still needs to be added however in order for this to work – links and connections of the organ to the bigger whole.
Links and Connections
The factories of production need to have input from the outside as to how hard to work, how much to produce and where and how to get the product to the end user. This is executed through connections to the transport systems including the circulatory and lymphatic systems but also the control systems that include endocrine and nervous systems. Circulatory connections deliver raw products, transport processed products, and remove waste. Hormonal connections via the neurohormonal axis of the pituitary and chemical receptors on and in the cells connect it to the chemical milieu of the body and allow the thyroid to have its finger on the pulse meeting supply with demand via feedback mechanisms.
Dependence and Independence
In summary the “units to unity” concept, together with the “links and connections” concept allow the thyroid to be unique in its own right, but allows it to participate in the bigger whole, fulfilling a function for the body at large and allowing it to be personally enriched by its contributions. This “independence/dependence” balance is a key concept to all the biological units from each cell in the body to the societies in which we live.
Time, Growth and Aging
Thyroid development begins in the fetus at three to four weeks of gestation. The precursors consisting of epithelial cells arise from endoderm proliferate from the base of the pharynx. From this moment, the cells of the thyroid are subjected to the forces of time. Over the next several weeks this cell mass migrates to the base of the neck. Shortly thereafter, at eight weeks of gestation the pituitary begins to release thyroid stimulating hormone, prompting the thyroid to begin production of colloid and thyroxine by week ten.
The thyroid ages well, but function does decrease over time and often is the cause of morbidity in the elderly.
The space assigned to the thyroid in the neck has no obvious rationale. It is a thermostat and for this it may be centrally located and near the brain – the main controlling centre of the body.
It lies on the anterior side of the neck against and around the trachea and extends posteriorly to the esophagus and carotid sheath. Longitudinally it stretches from just below the laryngeal prominence, or Adam’s apple, to the fifth or sixth tracheal ring. Owing to this position, any significant swelling of the thyroid, such as that caused by hyperthyroidism or iodine deficiency, is easily visible and palpable.
The forces that govern thyroid function are primarily chemical. Like most endocrine organs, the thyroid produces and releases hormones according to negative feedback inhibition loops. For example, low levels of thyroxine prompt the pituitary gland to release TSH. This, in turn, causes the thyroid to release thyroid hormones. As the levels of thyroid hormone increase, TSH is inhibited, which results in a decrease in thyroid hormone production. It is a continual balance of supply and demand and checks and balances.
The involvement of calcitonin abides by the same principles but relate specifically to calcium metabolism.
Thyroid function is also regulated by nervous pathways, specifically the sympathetic nervous system. The sympathetic system and thyroid have very similar effects on the body though the nervous system is more rapid in reacting while thyroid hormone is in the background and slower in response. It may be said that the sound one may hear at the height of the fight or flight response may be likened to a screech, while the sounds of the thyroid hormone may be likened to a hum.
History of the Thyroid
Diagnosis of body disorder in early civilization was easiest performed on superficial structures. It is thought for example, that dental disease was recognized and surgically treated in civilizations as early as Indus Valley Civilization of Pakistan as far back as 7000 BC (Coppa). The thyroid is a superficial structure but not normally seen nor felt. However, goiter has been and is a very common entity in many parts of the world particularly in mountainous areas where soil erosion has washed iodine from the soil and as a result, people who live in the mountains and subsist on their own agriculture are at risk for this entity. Not only has it been a problem for the people of the mountains but also for the fetuses that depended on maternal intake for the iodine. Hence, cretinism went hand in hand with goiter disease of the mountain people.
Diminished iodine intake results in increased size of the gland by hyperplasia as it attempts to maintain a normal level of thyroxine in the blood. This disease thus creates a prominent and sometimes huge and deforming thyroid mass, defined by some ancients as “elephant of the throat”. The goiter was easily recognized and diagnosed as abnormal and the unsightly appearance necessitated attempts at solving the problem.
The Chinese emperor Shen Nungs prescribed the use of seaweed for the treatment of goiter as early as 2700 BC. It is remarkable that this civilization was aware of a real therapeutic advantage of seaweed, which we now know, like many products of the sea, are high in iodine content. It is one of the first diseases that not only was recognized as the treatment had an effective biochemical component. This is truly remarkable.
Here are some other interesting points in history:
Robert James Graves an Irish doctor published his accounts on exophthalmic goiter associated with palpitations and the entity now called Grave’s disease was established.
Edward Calvin Kendall isolated “thyroxine” as the active principle of the thyroid gland.
Thyroxine became available in the 1920’s. Three tons of animal thyroid yielded 33 grams of thyroxin and it was thus an expensive but necessary drug.
Sir Charles Harrington a British scientist was able to synthesize thyroxine
Hiroshima “Little Boy” August 6 1945 and “Fat Man”Nagasaki August 1945 resulted in exposure of large populations to radiation and resulted in an increase in papillary carcinoma and frequency depended on age at exposure and distance from the radiation source.
Rosalind Pitt-Rivers worked under Sir Charles Harington. She subsequently went on to work with her Canadian post doctoral fellow Jack Gross and synthesized tri-iodothyronine which was biologically more active than thyroxine.
1986 April 26th
Chernobyl is small town located in the Ukraine region of the former Soviet Union where the worst nuclear accident occurred when a reactor exploded and released radiation into the atmosphere which by some estimates were 100 greater than Hiroshima The radiation and particularly radioactive iodine became incorporated into the plants and water and people were contaminated by ingestion particularly of milk. One of the main consequences was an increase in thyroid carcinoma in children some of whom were not yet born estimates as a 10 times increase.
Parts of the Thyroid
The thyroid consists of two lobes, a right lobe and left lobe, connected by the isthmus. Sometimes a pyramidal lobe projects from the isthmus or from one of the lobes, which is a normal variant.
The superior poles diverge laterally, are almost cigar-shaped and usually differ slightly in size and shape. Sometimes there may be marked difference in size usually with the right lobe being larger than the left. The lobes are divided into lobules by connective tissue elements that emanate from the fibrous capsule. Each lobule consists of 20-30 follicles.
The isthmus originates from a Greek term which means a narrow neck of land bordered on two sides by water and usually connecting two larger areas of land. It is variably sized, and infrequently absent. The cricoid cartilage is its landmark and it may be encountered during tracheotomy and cognizance of this fact must be considered requiring it to be elevated, depressed or divided during the procedure.
At the histological level the unit of the thyroid is the lobule. Each lobule consists of 20-30 follicles.
The thyroid is brownish-red in color, is a highly vascular gland and is composed of multiple lobules separated by thin septations. Each lobule consists of 20-40 follicles and supplied by an intralobular artery.
The thyroid is characterized by three main histological features: colloid containing follicles, follicular epithelium, and parafollicular cells.
The follicles secrete thyroxine and triiodothyronine. The follicles are spherical cavities which contain colloid, a viscous secretion rich gel, primarily a storage for thyroglobulin, which is the precursor for T3 and T4. The colloid serves as a reservoir for raw materials and also as storage for the hormones themselves. The follicles range in size from 50-500 microns but average about 200 microns in diameter. There is sufficient storage of thyroid hormone for about 100 days.
Each follicle is lined by a single layer of follicular epithelial cells, collectively termed the follicular epithelium, whose morphology ranges from cuboid when inactive to columnar when active. These cells trap iodine from the bloodstream and use it to synthesize thyroxine and triiodothyronine from the glycoprotein thyroglobulin. If not needed immediately these hormones remain stored in thyroglobulin and are secreted along with colloid into the follicles. When serum levels of thyroxine and triiodothyronine drop too low, colloid is absorbed back into the thyroid cells where thyroglobulin is cleaved and the hormones are released through the base of the cell into the surrounding capillaries.
Parafollicular cells or C cells surround the follicular epithelium and follicles and synthesize calcitonin, which help regulate calcium metabolism in conjunction with the parathyroid glands.
The thyroid is one of the largest endocrine organs in the body, but on the other hand is small compared to most other organs. It weighs about 15- 35 grams measuring approximately 4-5 cm long, 2-2.5 cm wide and 1 -2 cm thick, in the average adult. The isthmus is 2-6mm in A-P diameter and is up to 20 mm in width.
The size of the thyroid changes with age. At birth is weighs 2-3 grams, reaches 10-15 gms at puberty and becomes full size by age 25 when it weighs 15-35 gms.
The weight of the gland varies with age, sex, functional status, iodine intake, and geographic location. The thyroid tends to be larger in women and also larger during the menstrual cycle and pregnancy.
From a clinical standpoint, size is an especially important structural characteristic of the thyroid. The gland is not usually palpable on clinical examination. If palpable, it is abnormal.
The enlarged gland may reflect hyperthyroidism, hypothyroidism or a nodular euthyroid gland, and further biochemical and imaging evaluation is necessary.
Fortunately, thyroid size is easily measured with ultrasound, which is a safe and relatively inexpensive tool. Linear measurements are the standard for most evaluations, but measurements that portray a volume or mass are also possible using conventional imaging techniques.
Size: Imaging the Normal Gland
Size: Imaging of Goiters
A goiter implies a large gland. It may be caused by a diffusely enlarged gland, by multiple nodules or sometimes by a single large nodule.
Size: Mass in a Lobe Causing a Goiter
Goiter Caused by Large Hemorrhagic Cyst
The thyroid is a butterfly-shaped gland with two lobes each an inverted cone. Together their shape varies from an H to a U shape in the coronal plane. It is also U-shaped or horseshoe-shaped in the axial projection.
The thyroid gland gets its name from the Greek word for shield given its shape and the shape of the thyroid cartilage on which it rests. In some patients a pyramidal lobe extends cranially from the isthmus representing residual thyroglossal duct tissue that assumes thyroid character.
The shape of the thyroid cannot be observed through clinical examination; however, the “thyroid neck check,” which requires a patient to observe his/her neck for asymmetrical bulges while swallowing, may reveal irregularities in its shape.
Shape: In the Transverse or Axial Projection
The thyroid lies on the anterior side of the neck, against and around the trachea, and reaches posteriorly to touch the esophagus. It is anchored to the laryngo-skeleton, and thus swallowing causes it to move up as the pharynx rises. It lies just below the cricoid cartilage. The cricoid cartilage is the landmark for the isthmus cartilage.
Relationships – Applied Anatomy
Anatomical relationships of the thyroid gland have clinical relevance; the recurrent laryngeal nerves lie in a groove between the lateral edges of the thyroid and the trachea behind the gland. In addition there are two pairs of parathyroid glands that are usually located in the back of the thyroid in the upper and middle portion of the lobes, but may be located within the gland.
The right recurrent laryngeal nerve originates from the vagus nerve, and after looping around the subclavian artery, it ascends behind the right lobe of the thyroid.
The left recurrent laryngeal nerve comes from the left vagus nerve, and after looping posteriorly around the aortic arch, it and ascends in the tracheoesophageal groove posterior to the left lobe of the thyroid.
The thyroid is also draped around the trachea and the esophagus posteriorly. All these structures can be affected by thyroid diseases like thyroid enlargement causing compression, or thyroid malignancies causing invasion. Surgical interventions may result in injury to these organs due to their close proximity.
What does it look and feel like?
The thyroid is a brownish-red in color, soft to the feel.
The imaging characteristics of the thyroid are far more revealing. These characteristics are most easily observed using ultrasound.
The normal gland though small is well seen due to its slightly higher density compared to surrounding tissues as a result of its iodine content. There are differences in the density of the thyroid on CT based on geography and differences in dietary iodine uptake.
There is no difference in density between male and female though the density of the thyroid decreases with age.
The thyroid is well supplied with blood from the superior thyroid artery, inferior thyroid artery and sometimes also from the thyroid ima artery. Blood flow through the thyroid is high at about 5mls/g/minute which is about the same volume of blood flow to the brain
The superior thyroid artery is a paired vessel and a branch of the external carotid artery and travels superiorly and anteriorly in the carotid triangle.
The inferior thyroid artery is also a paired vessel and a branch of the thyrocervical trunk which originates off the subclavian artery. It ascends in front of the vertebral artery. The recurrent laryngeal nerve is closely related to the inferior thyroid artery. The nerve may pass anterior, posterior, or through the branches of the inferior thyroid artery. It is of concern during thyroid surgery and damage to the nerve can cause hoarseness.
The superior and inferior thyroid arteries anastomose with each other through consistent collateral pathways.
The thyroid ima artery is a single artery that is present in only 4-10% of patients and supplies the inferior aspect of the thyroid. It ascends anterior to the trachea and is of concern when tracheotomies have to be placed.
In the early days of surgery the high mortality was related to post operative bleeding due to the highly vascular nature of the organ.
Blood Supply: Superior Thyroid Artery
Blood drains from the thyroid via the superior, middle and inferior thyroid veins.
The superior thyroid vein runs with the superior thyroid artery. Each superior thyroid vein drains to ipsilateral internal jugular vein.
The middle veins also drain into the jugular veins bilaterally.
The inferior thyroid vein on the left drains into the brachiocephalic vein. The inferior thyroid vein on the right may drain into a right sided innominate vein (if present) or into the left sided brachiocephalic vein. Sometimes a common vein called the thyroid ima vein drains the left and right inferior veins via a common channel.
The thyroid is surrounded by a rich network of lymphatics. There are approximately 300 lymph nodes in the neck, and flow is in all directions including across the midline, superiorly and inferiorly.
The cervical lymph nodes have muscular and bony/cartilagenous landmarks extending from the ear superiorly to the clavicle inferiorly. The bony/cartilage landmarks starting superiorly include the inferior margin of the mandible, the hyoid bone, the cricoid cartilage and the clavicle. The muscles include the digastric muscle sternocleidomastoid and finally the trapezius. The internal jugular vein is a central landmark for a large number of the cervical nodes.
Lymphatic Drainage: Applied Biology
The thyroid receives innervation from both the sympathetic and parasympathetic nervous systems, which are subsets of the autonomic nervous system.
Sympathetic input is supplied by the superior cervical ganglion and the cervicothoracic ganglion. The superior cervical ganglion lies posterior to the sheath of the internal carotid artery and internal jugular vein.
The parasympathetic input is supplied by the superior laryngeal nerve and the recurrent laryngeal nerve.
It is doubtful that they play a significant role in controlling thyroid metabolism and their exact role is unclear.
The thyroid contains a true, thin fibrous capsule of connective tissue that sends septa to divide the thyroid into lobules. There is also a false external capsule formed by a sheath of pretracheal fascia.
Support of the Gland
The thyroid gland is fixed firmly to the laryngo-skeleton accounting for its upward movement during swallowing.
The thyroid gland is covered by a part of the middle layer of deep cervical fascia, which anchors the thyroid to the laryngo-skeleton. In addition, there are suspensory ligaments extending from the superior aspect of each lobe to the cricoid and thyroid cartilages. The posterior aspect of the gland is fixed to the side of the cricoid cartilage, and the first two tracheal rings by the ligament of Berry (also known as the posterior suspensory ligament). It is this latter ligament that causes the thyroid to elevate during deglutition allowing the clinician to distinguish between the thyroid and a lymph node (Lee).
Growth and Aging
The thyroid loses volume with aging and in fact metabolism gradually slows beginning around age 20. However functionally, aging only affects the thyroid in minor ways with a slight decrease in T3 levels. Disease of the thyroid such as autoimmune disorders, become more prevalent with age.
The incidence of thyroid nodules increases with age.
50% of 50 year olds will have at least one thyroid nodule.
60% of 60 year olds will have at least one thyroid nodule.
70% of 70 year olds will have at least one thyroid nodule.
The thyroid gland is the first endocrine gland to develop in the embryonic stage at approximately the 24th day of gestation as an outpouching at the base of the tongue in the foramen cecum on the median surface of the developing pharyngeal floor. It takes its origin from the medial anlage which derives from the floor of the foregut. The medial anlage forms the major portion of the thyroid. The thyroid gland grows and descends anterior to the trachea. As it descends it remains attached to the thyroglossal duct which normally degenerates. The thyroid gland reaches its final position in the seventh gestational week overlying the second to fourth tracheal rings. Thereafter it grows laterally to form two lobes.
If the caudal end of the thyroglossal duct persists it becomes the pyramidal process, which is considered a normal variant.
Function of the Thyroid
The primary function of the thyroid is in regulating the body’s metabolism and to produce and secrete the metabolic hormones, thyroxine (T4) and triiodothyronine (T3), as directed by the pituitary and other control pathways within the endocrine system. This process may be broken down into four sections: Receiving, Processing, Export, and Control.
Synthesis of the thyroid hormones thyroxine and triiodothyronine requires a steady supply of iodine, a chemical element found in nature and supplied by diet in most developed countries.
The average adult must consume 50 mg of iodine per year to maintain proper thyroid function. Approximately four fifths of that ingested iodine is excreted by the kidneys, but the remaining one fifth, ~10 mg per year, is selectively gathered by thyroid cells and used to produce mass quantities of thyroxine and triiodothyronine.
This process, commonly referred to as iodine trapping, occurs through the action of a large number of iodide pumps located in the basal membrane of each follicular epithelial cell. In response to endocrine activation these pumps transport free iodide from the bloodstream to the interior of the cell, concentrating it to a level up to 250 times that found in the blood.
Once inside the cell this free iodide sequentially binds to tyrosine sites in thyroglobulin, a glycoprotein produced by follicular epithelial cells and the precursor to the hormones.
When the supply of thyroxine and triiodothyronine in the blood becomes depleted a cascade of endocrine signaling is initiated that induces the pinocytotic uptake of colloid and thyroglobulin by follicular epithelial cells.
Inside the cell thyroglobulin is digested by a series of enzymes, simultaneously releasing thyroid hormone and cleaving iodine to be reused for further hormone synthesis. Thyroxine and triiodothyronine, now freed, diffuse through the base of the thyroid cell and into the surrounding capillaries where they are transported to tissues throughout the body.
Regulation of the synthesis and secretion of thyroid hormone occurs through a negative feedback inhibition pathway in the endocrine system.
When the concentration of thyroxine and triiodothyronine in the blood dips below a certain level, thyrotropin-releasing hormone (TRH) is released from the hypothalamus, resulting in subsequent release of thyroid stimulating hormone (TSH) from the anterior pituitary gland. Receptors on the base of each follicular epithelial cell bind to TSH, activating intracellular cAMP pathways that initiate a series of stimulatory effects in each thyroid cell. These effects include increased proteolysis of thyroglobulin resulting in the release thyroxine and triiodothyronine, increased activity of iodine pumps, increased iodination of tyrosine, increased size and secretory activity of existing thyroid cells, and proliferation of new thyroid cells. While proteolysis of thyroglobulin occurs almost immediately, the majority of the effect of TSH require days or weeks to occur, resulting in a well-choreographed effort to increase and stabilize basal metabolic rate. Once the rate of secretion of the thyroid increases to 1.75 times its normal rate, thyroid hormone acts directly on the anterior pituitary gland to inhibit further secretion of TSH. As a result, thyroid secretion gradually decreases and the concentration of thyroxine and triiodothyronine in the blood is kept constant.
Calcitonin is the second hormone secreted by the thyroid. It is a non iodized hormone secreted by the parafollicular cells or so called C cells and responds to elevated serum calcium by diminishing bone resorption and thus, diminishing calcium release. It also increases urinary calcium excretion. Overall, therefore it serves to decrease serum calcium.
Diseases of the thyroid are common. The common structural changes include nodules and enlargement, and the common diseases that affect the thyroid include hypothyroidism, thyrotoxicosis, multinodular goiter, and thyroid cancer.
Absence or diminished function and iodine deficiency in the fetus, newborns, and young children, leads to devastating physical and mental retardation, or cretinism. Screening programs particularly in high risk regions has virtually eliminated the disease. In the adult, hypothyroidism results in disruption of normal metabolic function and, when severe can be life-threatening. While normal metabolic functioning is entirely salvageable through hormone replacement therapy, normal mental development in children once afflicted with cretinism is not, and permanent developmental delay both physically and mentally results.
Disease: Thyroid Cancer
Thyroid cancer is a malignant condition usually with no known cause, but sometimes associated with radiation exposure and in patients who are genetically predisposed.
Structurally, the disease usually manifests with a non functioning thyroid nodule. Lymphadenopathy is present in later stages of the disease.
Types of thyroid cancer
Papillary Carcinoma (75-85%)
Follicular Carcinoma (10-20%)
Medullary Carcinoma (5%)
Anaplastic Carcinoma (<3%) Other – squamous type, lymphoma
Clinically, the patient usually presents with a nodule. Causes for concern include age of the patient with younger patients being more likely to have malignant disease. Family history of thyroid cancer and excessive radiation exposure, particularly if exposure during childhood (Hiroshima, Nagasaki, Chernobyl, treatment for lymphoma) are other significant risk factors.
Clinically, concern is initially raised if a nodule is palpated.
Imaging is best performed by ultrasound examination, and concerns for malignancy are raised when there are microcalcifications, thick irregular halo or irregular margins of the mass, or the mass is longer than wide. Malignant lesions are usually hypoechoic and often hypervascular in the central matrix. Fine needle aspiration under ultrasound guidance is performed on any lesion with concerning ultrasound characteristics or in a patient with a high clinical suspicion of thyroid cancer.
The diagnosis is suggested or confirmed by pathologic examination.
Treatments include thyroidectomy or lobectomy. Radioactive iodine 131 is used in patients with papillary and follicular cancer for ablation of residual thyroid tissue after surgery but also for carcinoma that shows uptake of iodine.
Hyperthyroidism is a result of an over production of thyroid thyroxine (T4) and triiodothyronine (T3) by the thyroid gland.
Hyperthyroidism can be caused by several different pathologies including Grave’s disease (the most common cause), toxic adenoma, toxic multinodular goiter, thyroiditis, and drugs.
Hyperthyroidism results in a clinical syndrome caused by increased levels of metabolically active free T3 and T4 in the bloodstream. Symptoms typically include tachycardia, agitation, tremors, hyperreflexia, heat intolerance and weight loss. The clinical syndrome of hyperthyroidism, when pronounced, is called thyrotoxicosis.
At its most dangerous, elevated thyroid hormone concentration can cause thyroid storm. This condition is a medical emergency and is accompanied by fever and change in mental status.
Structural changes of hyperthyroidism depend on the underlying cause, but include diffuse hypertrophy of the entire gland (as in Graves’ disease) or a single hyperactive toxic nodule.
Functional changes define the disease and consist of increased production of thyroid hormones despite negative feedback.
Clinically, patients will present with thyrotoxicosis, a large constellation of symptoms which include tremor, weight loss, insomnia, heat intolerance and irritability.
Imaging modalities to diagnose hyperthyroidism mainly include thyroid ultrasound and thyroid scintigraphy. Ultrasound can be used to distinguish between multinodular goiter, single nodule, and diffuse hypertrophy. Thyroid scintigraphy with radioiodine tracer uptake can show either localized increased uptake, such as in a “hot” or toxic nodule, or diffuse increased uptake, as in Grave’s disease.
Although imaging is available, diagnosis is best made with laboratory tests showing both a decreased TSH level and an increased circulating level of T3 and T4.
Treatment depends on the cause of hyperthyroidism, but includes medications that inhibit thyroid hormone production (methimazole and PTU), and medications that block the increased metabolic effect of the hormones, such as beta blockers. Some cases are best treated with radioisotope (Iodine-131) ablation of the gland. Surgical thyroidectomy is the least common treatment.
Hypothyroidism is a disease state in which there is an underproduction of thyroid hormones (T3 and T4) by the thyroid gland.
Hypothyroidism can be caused by infection, trauma, autoimmune disease, or nutritional deficiency.
Thyroid gland dysfunction results in a decreased level of circulating T3 and T4, despite increased TSH.
Structural changes will depend on the cause of hypothyroidism, ranging from enlarged inflammatory gland of Hashimoto’s thyroiditis to an atrophic or absent thyroid gland.
Functional changes define the disease and result in decreased levels of production and circulation free thyroid hormones.
Clinically, a decreased level of thyroid hormones will present with a constellation of symptoms including fatigue, cold intolerance, constipation, depression, and weight gain.
Imaging modalities are not typically used to diagnose hypothyroidism.
Diagnosis is best made with laboratory studies showing high levels of TSH with inappropriate corresponding low levels of circulating T3 and T4.
Treatment for hypothyroidism is replacement of the deficient levels thyroid hormones with synthetic forms such as synthetic T4 (Levothyroxine) or combination T4 and T3 replacement. Treatment adequacy is determined by monitoring TSH levels to ensure adequate physiologic levels are achieved and maintained.
Hashimoto’s thyroiditis is an autoimmune disorder that leads to antibody mediated destruction of thyroid gland.
The most common causative antibodies responsible for Hashimoto’s thyroiditis are anti- thyroid peroxidase (anti-TPO), anti-thyroglobulin (anti-Tg), and anti-TSH receptors.
The immune destruction of the thyroid follicular cells results in glandular destruction and hypothyroidism.
Structural histopathological changes of Hashimoto’s include lymphocytic cell infiltration, fibrotic change, and formation of lymphoid follicles that replace the normal glandular tissue. Structural changes can range from an enlarged goiter to atrophy of the thyroid gland.
Clinically, patients suffering from the disease may have transiently increased thyroid hormone release during initial destruction of the thyroid follicles, but in general the disease is characterized by a hypothyroid state with a non-functioning thyroid gland. Classically, Hashimoto’s will present with insidious onset of hypothyroidism progressing over months to years.
These symptoms include fatigue, constipation, weight gain, cold intolerance, menstrual irregularities.
Imaging is not particularly useful for the diagnosis, but sonographic features of Hashimoto’s thyroiditis are evident and suggestive. Radioactive iodine scans may show a generalized decreased iodine uptake at later stages of the disease.
Treatment for Hashimoto’s thyroiditis is based on thyroid hormone replacement, most often with levothyroxine (synthetic T4).
Diagnosis of Thyroid Diseases
For the clinician the approach to diseases of the thyroid is in determining the functional status of the thyroid and whether the patient appears euthyroid, hypothyroid or hyperthyroid. Although the thyroid is superficial it is not normally palpable, but when palpable it is abnormal. Confirmation that it is the thyroid that is palpable is achieved by establishing that moves up with swallowing.
Blood tests measure thyroxine and TSH that enable evaluation of autonomous function, hyperproduction and hypoproduction.
Ultrasound is the study of choice for the morphological evaluation of the thyroid.
It is used initially to evaluate the size of the gland and the presence and nature of nodules. It is also helpful in defining nodules that may require biopsy and used to follow the patient with nodules or the patient who is at risk for cancer. Lastly, it is used as a guide for biopsy when indicated.
The approach to the nodule is quite a difficult imaging problem particularly when there are multiple nodules and the decision to biopsy requires intense analysis of each of the nodules. In the past, the main criterion for biopsy was size and nodules that were greater than 1 cm were biopsied. Currently, important criteria include nodules that are profoundly hypoechoic, contain microcalcifications, have an irregular halo or irregular or lobulated border, or show obvious invasive properties (Kim, Hoang).
Lesser criteria include inner vascularity or a nodule that has a longitudinal dimension greater than the transverse dimension.
Benign disease includes cystic disease without complexity and nodules that have echogenic foci that have ring down artifact suggesting colloid concretions (Hoang). Pathology reports divide findings into either non diagnostic material or diagnostic material. Non diagnostic material is due to inadequate material, while diagnostic material may be categorized as malignant, indeterminate, or benign.
Diagnosis of Thyroid Diseases: Nuclear Medicine
Nuclear medicine is used to determine the overall functional activity of the thyroid or a nodule and specifically to determine whether the thyroid or the nodule is hyperactive (hot) normal, or hypoactive (warm) or inactive (cold).
Imaging can be performed using radioactive iodine or pertechnitate. In the past, radioactive iodine (I) 131 was utilized but because of the relatively high dose to the thyroid it has been mostly supplanted by I 123 and pertechnitate imaging. I 131 emits a beta particle that has a long half life and therefore subjects the thyroid to larger amounts of radiation. In addition, contaminants such as I 124 and I 125 are present and serve to increase the radiation dose. I 131 is given to patients with known thyroid cancer after surgery in order to ablate remnant thyroid gland or any remaining thyroid cancer that is able to take up the iodine.
The thyroid organifies orally administered iodine and therefore imaging can only be done once the iodine is incorporated which is approximately 24 hours later. Intravenous pertechnetate requires a 20 minute wait before the thyroid can be imaged and is relatively inexpensive. However, it is not used for imaging cancer because of low uptake by cancer cells and therefore cannot be used to evaluate for metastases.
A hot gland indicates an overactive thyroid and a cold gland indicates underactivity.
When a nodule is” hot” the chances of malignancy are low. The risk of cancer in a solitary cold nodule is 15-40%.
Diagnosis of Thyroid Diseases: Computed Tomography (CT)
CT scan is helpful in patients who have large goiters and the effect on structures such as the airway need to be evaluated. It is also helpful in establishing regional nodal disease and distant metastases, particularly small lung metastases. However, these are not mainstream concerns in thyroid evaluation and the role is limited.
Diagnosis of Thyroid Diseases: Magnetic Resonance Imaging (MRI)
MRI has limited utility in routine thyroid imaging.
The thyroid gland is a large gland by endocrine standards, but is small compared to most other organs in the body. For such a small organ it has a rather important responsibility to control the basic metabolic rate of the body. Structurally its shape is unique, and its superficial position makes it easy to examine both clinically and with imaging. Functionally its ability to store its products in an extracellular location is unique among endocrine organs.
The diagnosis of the hyperactive and hypoactive gland is fairly straightforward by evaluating serum T4 and T3, and TSH. Ultrasound is the workhorse for structural evaluation while nuclear medicine is the imaging workhorse of functional evaluation. The great affinity of the thyroid for iodine is used for targeted therapy as well, when functional, unwanted thyroid requires ablation with radioactive iodine 131. Its close relationship to the recurrent laryngeal nerves, esophagus and parathyroids requires meticulous technique in surgery.