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.

3. ..

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.

6. Mechanism of Hormone release

7. 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 refer 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).

8. 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.

9. 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.

10. 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.

11. 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.

12. 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).

13. 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).

14. THE FUNCTIONAL TEST

17. SYSTEM BASED SIGNS AND SYMPTOMS

25. 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.

26. ………

27. 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.

36. ……

37. ……..

38. Goiter
• It means thyroid enlargement
• Results from thyroid hormone hyposecretion due 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

40. .
• 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.

41. .
• 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.

42. 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.

43. References
1. Ross, D. S. (2011). Hyperthyroidism: Diagnosis and Treatment. American Family Physician, 83(4), 363-370.
2. 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.
3. Brent, G. A. (2008). Clinical practice. Graves' disease. New England Journal of Medicine, 358(24), 2594-
2605.