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Questions and Answers
What is the energy source for Iodide ion uptake into thyroid follicle cells?
Which enzyme catalyzes the oxidation of iodide and its incorporation into tyrosine residues of thyroglobulin?
How are surplus Monoiodotyrosine (MIT) and Diiodotyrosine (DIT) handled in thyroid physiology?
What is the main thyroid hormone secreted into the bloodstream?
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How does iodide incorporation into thyroglobulin differ from other hormones in terms of storage?
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What is the ratio of plasma total [T4] to plasma total [T3]?
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Which autoimmune thyroid disorder results in hyperthyroidism?
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What is the most common autoimmune disease affecting the thyroid?
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Which thyroid disorder is associated with hypoactive thyroid?
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What is the cause of Graves` disease?
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Which gender is more prone to autoimmune thyroid disorders?
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Which hormone is considered the active form of thyroid hormones?
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What is the primary symptom of hyperthyroidism (thyrotoxicosis)?
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Which enzyme is primarily responsible for converting T4 to T3?
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What effect does 5'-deiodination of the outer ring in peripheral tissues have on T4?
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Which condition can be caused by drugs that decrease plasma protein binding of T4?
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Which of the following is produced by the gene DIO2?
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In which tissues is Dio1 primarily expressed?
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What are the three main hormones secreted by the thyroid gland?
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Which thyroid hormone circulates in the blood mostly bound to thyroxine-binding globulin (TBG)?
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What is the main function of thyroid hormones like T3 and T4?
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Which is the functional unit of the thyroid gland?
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What is synthesized and glycosylated inside the follicle cell of the thyroid gland?
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Which phenomenon involves the conversion of circulating T4 to T3 in a tissue-specific manner?
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What is the mechanism of action of thiourylenes?
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Which thiourylene has an additional effect of reducing the de-iodination of T4 to T3?
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What is the pharmacokinetics of methimazole's prodrug, carbimazole?
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What are the most dangerous unwanted effects of thiourylenes?
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Which thiourylene is preferred over methimazole in acute thyroid storm treatment?
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What is the incidence of neutropenia and agranulocytosis due to thiourylene therapy?
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Study Notes
Thyroid Physiology
- I- uptake by the follicle cell is rapid (within seconds) and occurs against a concentration gradient (25:1) via a Na+/I- symporter (NIS) and pendrin (PDS), an I-/Cl- antiporter.
- I- oxidation and incorporation into TG-incorporated Tyr residues (I- organification) is catalyzed by thyroperoxidase (TPO), which uses hydrogen peroxide (H2O2) as the oxidizing agent.
Thyroid Hormone Synthesis and Secretion
- The iodinated Tyr residues of TG serve as a large store of thyroid hormones within the gland, with a relatively slow turnover.
- TG is taken up into the follicle cell by endocytosis, followed by lysosomal proteolysis, which releases T4 and T3 to be secreted into the blood.
- Surplus MIT and DIT, released together with T4 and T3, are scavenged, and their I- is removed enzymatically (via deiodinases, Dios) and reused.
Thyroid Hormone Metabolism
- Plasma total [T4] is approximately 50 times higher than plasma total [T3].
- Although both T4 and T3 are secreted by the thyroid, metabolism of T4 by 5'-deiodination of the outer ring in peripheral tissues accounts for approximately 80% of circulating T3.
- 5'-deiodination of the inner ring produces the metabolically inactive 3,3',5'-triiodothyronine (reverse T3, rT3).
Iodothyronine Deiodinases
- There are three iodothyronine deiodinases, produced by the genes DIO1, DIO2, and DIO3: Dio1 & Dio2 convert T4 to T3.
- Dio1 is a plasma membrane protein expressed primarily in the liver, kidney, thyroid, and pituitary.
- Dio2 is primarily in the CNS, brown adipose tissue, thyroid, and at low levels in skeletal muscle and heart.
Thyroid Disorders
- Autoimmune thyroid disease is the most common autoimmune disease.
- Two main types of autoimmune thyroid disorders: Graves' disease and Hashimoto's thyroiditis.
- Both are caused by thyroid autoantibody production (usually against TSHR) and involve immune damage to the gland itself.
- Graves' disease results in thyrotoxicosis (hyperthyroidism), while Hashimoto's thyroiditis leads to hypoactive thyroid (hypothyroidism).
- Thyroid dysfunction in both is associated with typical gross enlargement of the gland (goiter).
Hyperthyroidism
- Excessive thyroid hormone secretion and activity resulting in high metabolic rate, increased skin temperature and sweating, and heat intolerance.
- Nervousness, tremor, tachycardia, and increased appetite associated with weight loss occur.
- Two common subtypes: exophthalmic or diffuse toxic goiter (Graves' disease) and toxic nodular goiter.
Graves' Disease
- Organ-specific autoimmune disease caused by activating (agonistic) anti-TSH receptor autoantibodies, increasing T4 secretion.
Thyroid Hormone Regulation
- The thyroid gland secretes three main hormones: thyroxine (T4), tri-iodothyronine (T3), and calcitonin (involved in the control of plasma [Ca2+], used to treat osteoporosis and other metabolic bone diseases).
- Both T3 and T4 circulate in the blood tightly bound (>99%) to plasma proteins, mainly thyroxine-binding globulin (TBG).
- The majority (~85%) of the secreted thyroid hormones is T4.
- Circulating T4 is converted to T3 (3-5-fold more active than T4) in a tissue-specific manner.
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Description
Test your knowledge on thyroid physiology and drugs used in treating thyroid disorders with this quiz. Learn about the hormones secreted by the thyroid gland, their functions, and the drugs commonly prescribed for thyroid conditions.
