THYROID PATHOLOGY detailing the management, definitions and treatment.

A summary of thyroid pathology, management and treatment prepared by Stephen Rwapembe, BSCN, mountains of the moon university.

1. THE THYROID PATHOLOGY AND PATHOPHYSIOLOGY BY GROUP ONE MEMBERS MUHUMUZA FRANCIS B 2022/U/MMU/BNSD/001 RWAPEMBE STEPHEN 2022/U/MMU/BNSD/003 BIGABWOMWE IVAN 2022/U/MMU/BNSD/008

2. Anatomy The thyroid gland is a butterfly shaped, vascular, red-brown endocrine gland situated in the midline of the anterior neck. Under normal circumstances, it extends from the level of the 5th  cervical vertebra  (C5) to the first thoracic vertebra (T1). On average, the gland weighs between 15 to 25 g, and is the largest of the endocrine glands. The irregular structure is encased in the pretracheal part of the  deep cervical fascia  . It is made up of a central isthmus that connects the right and left lobes of the organ inferomedially. Between the ages of 8 months to 15 years, the thyroid gland appears the same in both males and females. However, the gland is slightly heavier in females over the age of 15 than in male counterparts of similar age.  Each lobe is roughly conical in shape, with each apex pointing superolaterally and their bases inferomedially (between the 4th and 5th tracheal rings). At their widest point, each lobe measures about 3 cm in the transverse plane, and 2 cm in the anteroposterior dimension. The lobes are roughly 5 cm long. The isthmus lies above the 2nd or 3rd tracheal cartilages and measures 1.25 cm in both the transverse and vertical planes. In some individuals, there may be a third lobe of the thyroid gland known as the pyramidal lobe. It is also a conical structure that extends from the isthmus up to the hyoid bone. In some cases, it may also arise from the inferomedial aspect of either left or right lobes; but it is more commonly seen arising from the left lobe.

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4. THYROID SECRETIONS The thyroid gland synthesizes the hormones thyroxine (T4 ) (prohormone) and triiodothyronine (T3 ) (active hormone), iodine-containing amino acids that regulate the body’s metabolic rate. Once the thyroid gland releases T4 into bloodstream, it can convert to T3 through a process called deiodination. Triiodothyronine (T3): the thyroid produces lesser amounts of T3 than T4, but it has a much greater effect on the metabolism than T4. Reverse triiodothyronine (RT3): the thyroid makes very small amounts of RT3, which reverses the effects of T3. Calcitonin : This hormone helps regulate the amount of calcium in your blood.

5. Mechanism of Hormone release

6. Disorders of thyroid gland Hyperthyroidism (over reactive thyroid gland) Hypothyroidism (under reactive thyroid gland) Thyroid cancer Hypothyroidism Hypothyroidism (underactive thyroid) happens when the thyroid doesn’t produce and release enough thyroid hormones. This causes aspects of metabolism to slow down. It therefore r efer to a condition where the thyroid gland produces insufficient amounts of thyroid hormones—triiodothyronine (T3) and thyroxine (T4). These hormones play a crucial role in regulating metabolism, energy production, and various physiological functions. Hypothyroidism can result from various causes, including autoimmune diseases (such as Hashimoto's thyroiditis), iodine deficiency, surgical removal of the thyroid, or certain medications. Symptoms of hypothyroidism include fatigue, weight gain, sensitivity to cold, dry skin, hair loss, and cognitive impairment. Diagnosis typically involves blood tests measuring thyroid hormone levels and thyroid-stimulating hormone (TSH).

7. Causes of hypothyroidism include: Hashimoto’s disease, an autoimmune disease. Thyroiditis (inflammation of the thyroid). Iodine deficiency. A nonfunctioning thyroid gland (when the thyroid doesn’t work correctly from birth). Over-treatment of hyperthyroidism through medication. ) Thyroid gland removal. A benign (noncancerous) tumor in your pituitary gland.

8. Hashimoto's Thyroiditis (Autoimmune Hypothyroidism): Autoimmune destruction of the thyroid gland by the immune system's attack on thyroid tissue. Autoantibodies, such as thyroid peroxidase antibodies and thyroglobulin antibodies, target and damage thyroid follicular cells. This leads to a gradual reduction in thyroid hormone production and secretion, impacting receptors involved in thyroid hormone synthesis, including thyroid peroxidase (TPO) and thyroglobulin. Iodine Deficiency-Induced Hypothyroidism Inadequate dietary iodine hinders the thyroid's ability to produce sufficient thyroid hormones. Iodine is a crucial component in the synthesis of both T3 and T4. Insufficient iodine leads to decreased synthesis, causing hypothyroidism. The sodium-iodide symporter (NIS) is essential for transporting iodine into thyroid follicular cells, and iodination reactions involving enzymes like thyroid peroxidase (TPO) are critical for hormone synthesis.

9. Central Hypothyroidism (Secondary or Tertiary): Dysfunction of the pituitary gland (secondary) or hypothalamus (tertiary) disrupts the normal feedback loop regulating thyroid hormone production. Reduced secretion of thyroid-stimulating hormone (TSH) from the pituitary or thyrotropin -releasing hormone (TRH) from the hypothalamus results in decreased stimulation of the thyroid gland. Thyrotropin -releasing hormone (TRH) receptors in the hypothalamus, thyrotrope cells in the anterior pituitary responding to TRH, and thyroid follicular cells responding to TSH are critical receptors in this pathway. Post-Surgical Hypothyroidism After thyroid surgery, especially total thyroidectomy, the remaining thyroid tissue may not produce sufficient hormones. Surgical removal or damage to the thyroid can disrupt the synthesis and release of thyroid hormones, leading to hypothyroidism. This is particularly relevant when the entire thyroid gland is removed due to conditions like thyroid cancer or a large goiter. The disruption in hormone production involves the loss or impairment of thyroid follicular cells, which normally respond to regulatory signals such as TSH.

10. Drug-Induced Hypothyroidism: Certain medications, such as lithium, amiodarone , or some antithyroid drugs, can interfere with thyroid function. Lithium can inhibit thyroid hormone release, amiodarone can contain high levels of iodine and affect hormone synthesis, while antithyroid drugs can decrease hormone production. These drugs may act at different points in the thyroid hormone synthesis pathway, affecting receptors such as sodium-iodide symporter (NIS), thyroid peroxidase (TPO), or interfering with TSH receptor signaling.

11. Congenital Hypothyroidism Present from birth, congenital hypothyroidism can result from a developmental defect in the thyroid gland or its hormone synthesis pathways. It may also occur due to maternal thyroid dysfunction during pregnancy. Genetic mutations affecting various receptors and enzymes involved in thyroid hormone synthesis can contribute to congenital hypothyroidism, impacting processes such as iodine transport (NIS) and hormone synthesis (TPO).

12. Subclinical Hypothyroidism In subclinical hypothyroidism, the thyroid hormone levels are within the normal range, but TSH levels are slightly elevated. This condition may progress to overt hypothyroidism. The exact mechanisms leading to subclinical hypothyroidism can include autoimmune factors, mild iodine deficiency, or aging. The receptors involved are primarily those related to the feedback loop regulating TSH secretion, including the TSH receptor on thyrotrope cells in the anterior pituitary Radiation-Induced Hypothyroidism: Exposure to therapeutic radiation, particularly in the head and neck region, can damage the thyroid gland, leading to decreased hormone production. This can occur as a side effect of treatments for head and neck cancers or as a consequence of radiation therapy for other conditions. Radiation-induced damage affects thyroid follicular cells and can impact receptors such as sodium-iodide symporter (NIS) and thyroid peroxidase (TPO).

13. THE FUNCTIONAL TEST

14. SYSTEM BASED SIGNS AND SYMPTOMS

15. Graves' Disease: Autoantibodies, particularly thyroid-stimulating immunoglobulins (TSI), bind to the TSH receptors on thyroid follicular cells. This mimics the action of TSH, resulting in the overproduction and release of thyroid hormones. The autoimmune response also causes diffuse hyperplasia of thyroid follicles, leading to goiter.

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17. Other causes of hyperthyroidism Thyroid Toxic Adenoma (Plummer's Disease): A single thyroid nodule develops a genetic mutation that leads to unregulated thyroid hormone production. The mutated cells function independently of TSH control, causing the adenoma to release thyroid hormones continuously. Toxic Multinodular Goiter: Multiple thyroid nodules form, and some of these nodules acquire mutations that enable them to function autonomously, producing thyroid hormones. The combined effect of these hyper functional nodules contributes to an overall hyperthyroid state. Subacute Thyroiditis: Often triggered by a viral infection, inflammation damages thyroid follicles, causing the release of stored thyroid hormones into the bloodstream. This inflammation is usually self-limiting, leading to a transient hyperthyroid state followed by hypothyroidism and eventual recovery. Excessive Iodine Intake : Excessive iodine disrupts the synthesis and release of thyroid hormones. High iodine levels can inhibit thyroid hormone production, but paradoxically, it can also trigger the release of pre-formed thyroid hormones, leading to hyperthyroidism. Thyroid Storm: Occurs as an extreme manifestation of uncontrolled hyperthyroidism. Stressors, infections, or trauma can accelerate the release of thyroid hormones, overwhelming the body's normal regulatory mechanisms. This results in a life-threatening surge of thyroid hormones, affecting multiple organ systems. Osteoporosis: Prolonged hyperthyroidism disrupts the balance between bone formation and resorption. Elevated thyroid hormone levels stimulate osteoclast activity, leading to increased bone resorption and reduced bone mineral density, contributing to osteoporosis. Cardiac Complications :  Hyperthyroidism increases sympathetic nervous system activity, leading to an elevated heart rate, increased cardiac output, and heightened blood pressure. These changes can strain the cardiovascular system, contributing to conditions like atrial fibrillation and an increased risk of heart disease.

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20. Goiter It means thyroid enlargement Results from thyroid hormone hyposecretion d ue to iodine insufficiency If have goiter, patient may be Normothyroid Hypothyroid Hyperthyroid clinical types Endemic goiter --- from lack of iodine in diet (hypothyroid) Toxic goiter --- hyperthyroidism Prevention iodized salt Goitrogens --- from drugs (e.g. lithium) & foods (e.g. cabbage) that prevent T3 & T4 production

21. . Diffuse thyroid enlargement most commonly results from prolonged stimulation by TSH (or a TSH-like agent). Such stimulation may be the result of one of the causes of hypothyroidism ( e.g , TSH in Hashimoto thyroiditis) or hyperthyroidism. Iodine deficiency is the most common cause of goiter. A diet that contains less than 10 µg/d of iodine hinders the synthesis of thyroid hormone, resulting in an elevated TSH level and thyroid hypertrophy. The iodination of salt has eliminated this problem in much of the developed world.

22. . A goiter may also develop from the ingestion of goitrogens (factors that block thyroid hormone synthesis) either in food or in medication. Dietary goitrogens are found in vegetables of the Brassicaceae family ( eg , rutabagas, cabbage, turnips, cassava). A goitrogenic hydrocarbon has also been found in the water supply in some locations. Medications that act as goitrogens include thioamides and thiocyanates ( eg , propylthiouracil, methimazole, nitroprusside), sulfonylureas, and lithium. Lithium inhibits thyroid hormone release and perhaps also iodide organification . A congenital goiter associated with hypothyroidism (sporadic cretinism) may occur as a result of a defect in any of the steps of thyroid hormone synthesis.

23. Thyroid Carcinoma Thyroid carcinoma is the most common endocrine malignancy, Exposure to ionizing radiation, especially during childhood, is the most consistent causal factor. Papillary and follicular thyroid carcinomas are the most frequent and medullary and anaplastic thyroid carcinomas are less common. Most tumors are well differentiated. Most individuals with thyroid carcinoma have normal T3 and T4 levels and are therefore euthyroid. The cancer is typically discovered as a small thyroid nodule or metastatic tumor in the lungs, brain, or bone. Changes in voice and swallowing and difficulty breathing are related to tumor growth impinging on the trachea or esophagus.

24. References Ross, D. S. (2011). Hyperthyroidism: Diagnosis and Treatment. American Family Physician, 83(4), 363-370. Bahn, R. S., & Burch, H. B. (2014). Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid, 24(12), 1670-1751. Brent, G. A. (2008). Clinical practice. Graves' disease. New England Journal of Medicine, 358(24), 2594-2605.