Thyroid Gland Flashcards
Anatomy of Thyroid Gland
The thyroid gland is located immediately below the larynx and anterior to the upper part of the trachea.
Weight is approximately 25g
It consists of 2 lateral lobes connected by a thyroid tissue called isthmus.
The isthmus usually overlies the region from the 2nd to the 4th tracheal cartilage.
What do the lobes of the thyroid contain?
The lobes of the thyroid contain follicles, the functional units of the thyroid gland.
What is interspersed between the follicles?
Interspersed between the follicles are C cells, which secrete calcitonin.
Thyroid Histology
Follicles consist of a layer of epithelium
Central cavities containing colloid
Major constituent of colloid is the large glycoprotein, thyroglobulin.
Follicular cells are TSH dependent.
What is needed for thyroid hormones?
Tyrosine and iodine are essential for thyroid hormones.
Both are taken up by the blood
Tyrosine is synthesised by the body (in the thyroglobulin)
Steps in Biosynthesis, storage and secretion of thyroid hormones
Thyroglobulin produced by the follicular cells are released into colloid in follicle lumen by exocytosis
Iodide (I-) uptake by follicular cells from the blood, oxidation (I) and transferred to colloid.
Attachments of iodine into tyrosine residues on thyroglobulin in colloid forming di-and-mono-iodotyrosine (DIT and MIT)
Coupling process between the iodinated tyrosine molecules to form T4 (2DIT) and T3 (DIT + MIT)
Secretion upon stimulation of T4 and T3 occurs by endocytosis, fusion with a lysosome, uncoupling of T4 and T3 and diffusion out of the follicular cell where it is released into the peripheral tissues.
Composition of T4 hormones
Approximately, 90% of the hormones released from the thyroid gland initially appear in the form of T4.
However, a majority of the T4 that is secreted from the thyroid gland is converted to T3.
What is T3?
T3 is formed from the monodeiodination of T4 in the thyroid and in peripheral tissues.
Which is more potent: T3 or T4
T3 is 4 times more potent in its biologic form than T4 and is the major hormone that interacts with the target cells.
What mediates conversion of T4 to T3?
Type 1 5’- deiodinase primarily in the liver and kidney mediates conversion of T4 to the bioactive T3.
Regulation of thyroid hormones
There is a higher centre of regulation in the hypothalamus. There’s release of TRH (thyrotrophin releasing hormone) which acts on the anterior pituitary gland which is stimulated to produce TSH (thyroid stimulating hormone) which then acts upon the thyroid gland. The thyroid gland is then stimulated to release thyroid hormones T3 and T4 which acts on target cells.
But as with all endocrine systems, there is this negative feedback whereby there is inhibition of both anterior pituitary and hypothalamus levels. Essentially means that the system is nicely and tightly regulated to maintain normal levels.
TSH: Mechanism of Action to stimulate thyroid hormone release
TSH receptors are members of the large family of G-protein coupled receptors.
The major second messenger is cAMP.
Growth and the nervous system
Effect on growth is manifested mainly in growing children
Thyroid hormone stimulates GH secretion and promotes GH effects.
Lack of thyroid hormone = growth retardation but can be reversed by thyroid replacement therapy unlike excess GH, excess thyroid hormone does not produce excessive growth
Important in promoting growth and development of the brain during fetal and postnatal life.
Thyroid hormone deficiency = mental retardation if therapy is not administered days or weeks after birth.
Role of thyroid hormones in metabolism
Metabolic rate and heart production:
Increase metabolic activities
Increases O2 consumption to metabolically active tissues
Basal metabolic rate (BMR) can increase by 60-100%
Since increase metabolism results in increase heat production, thyroid hormone effects is calorigenic (heat producer)
Intermediary metabolism:
Modulates rates of many specific reactions involved in fuel metabolism.
Symapthomimetic Effect
Sympathomimetic: any action similar to one produced by the sympathetic nervous system
Thyroid hormone increase target cell responsiveness to catecholamines (SNS and adrenal)
Thyroid hormones are permissive = increase production of specific catecholamine target cell receptors.
Thyroid Hormones and cardiovascular system
Increase the heart’s responsiveness to circulating catecholamines (permissive action above)
Increase heart rate and force of contraction = increase CO
In response to the heart load = peripheral vasodilation to eliminate generation of extra heat.
Metabolic Effects of Thyroid Hormones
Lipid metabolism
Carbohydrate metabolism
Growth
Development (foetal and postnatal)
Cardiovascular System
Nervous system
Reproductive system
Term used to describe deficient thyroid hormone
Hypothyroidism
Term used to describe excess thyroid hormones
Hyperthyroidism
Symptoms of T3/T4 deficiency
Symptoms:
Fatigue
Lethargy
Weakness
Cold Intolerance
Mental slowness
Depression
Dry skin
Constipation
Muscle cramps
Irregular menses
Infertility
Mild weight gain
Fluid retention
Hoarseness
Signs of hypothyroidism
Goitre (primary hypothyroidism)
Bradycardia
Non-pitting edema
Dry skin
Delayed relaxation
Hypertension
Slow speech
Slow movements
Voice hoarseness
Causes of Hypothyroidism
Autoimmune (Hashimoto’s) thyroiditis
Atrophic (commonly in elderly)
Iodine 131 treatment
Secondary to pituitary disease
Hypothyroidism: Laboratory Evaluation
Increased TSH is the most sensitive test (primary hypothyroidism)
Always measure unless you know the patient has defective TSH secretion (e.g. pituitary disease/secondary hypothyroidism)
Antibodies is hypothyroidism are associations not causal (high titres suggest Hashimoto’s thyroiditis)
Anti-thyroid peroxidase (TPO) and anti-thyroglobulin (Tg) antibodies (Hashimoto’s)
Hypothyroidism: Therapy
L-thyroxine (levothyroxine; T4)
Alleviate symptoms
Titrate T4 intake to normalise TSH (primary hypothyroidism) or free T4 (secondary and tertiary hypothyroidism).
