Hi :) In this post we'll be having a look at the physiology of the thyroid gland. We'll discuss the anatomical structure of the thyroid and how this relates to its function. We'll also discuss the actions of thyroid hormones as well as their synthesis and how this is regulated. We'll finish off by discussing hypo- and hyperthyroidism as well as the euthyroid sick syndrome.
Structure
The thyroid gland (or "thyroid" for short) is the largest pure endocrine gland in the body and in most animals it is present as two separate lobes on either side of the trachea just below the larynx. The thyroid can be palpated but only in abnormal situations.
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| Histological Section of the Thyroid Gland Source |
As we can see in the diagram above, the functional unit of the thyroid is the follicle (1) which is made up of follicle cells (2). 20-40 follicles are separated by septa to form lobules. Inside the follicle is the proteinaceous colloid which contains thyroglobulin molecules (which are produced by the follicle cells and are precursors to the thyroid hormones) and iodine. Parafollicular cells are also present and these are the source of calcitonin.
Thyroid Hormone Synthesis
There are two thyroid hormones: thyoxine (T4) and triiodothyronine (T3) with T3 being the most active. These hormones work to increase the animal's basal metabolic rate.
The synthesis of these hormones cannot be done without the presence of iodine. T3 has three iodine atoms attached to its molecule while T4 has four. These hormones are also derivatives of the amino acid 'tyrosine'. Synthesis involves several steps:
- Thyroglobulin is synthesised in the endoplasmic reticulum and golgi apparatus and is discharged into the lumen of the follicle.
- Meanwhile iodide is actively transported into the follicle cell by the Na+/I- symporter. Iodide is oxidised (it loses an electron) to produce iodine by an enzyme called thyroid peroxidase.
- In the colloid, iodine is attached to tyrosine to form diiodotyrosine (DIT) and monoiodotyrosine (MIT). DIT is composed of a tyrosine molecule with two iodines attached. MIT is composed of a tyrosine molecule with one iodine attached. DIT and MIT are linked together to form T3 and T4. Two DITs are linked to form T4 while one MIT and one DIT are linked to form T3.
- The thyroglobulin colloid is endocytosed (it enters the cell) to form a lysosome.
- Here, enzymes cleave T3 and T4 from the thyroglobulin colloid.
- The hormones then diffuse into the blood.
Regulation
The synthesis of these hormones is regulated by thyroid stimulating hormone (TSH). The release of TSH is regulated by the thyrotropin-releasing hormone (TRH) which is released from the hypothalamus. The secretion of TSH is regulated by a long loop negative feedback mechanism. High levels of thyroid hormones in the blood depress the release of TSH and TRH. This in turn causes less thyroid hormone to be released. Low levels or circulating thyroid hormones, cold and stress increase the secretion of TRH from the hypothalamus.
Actions of the Thyroid Hormones
Although T4 is the major hormone secreted by the follicle cells, T3 is the most active form of the hormone and most T3 is formed through the conversion of T4 by tissues. Because T4 is lipid soluble, it binds to intracellular receptors in the nucleus where it is deiodonated (it loses an iodine) by deiodinases. T3 binds to a specific nuclear thyroid hormone receptor (TR) which then binds to DNA and modulates gene transcription and protein synthesis. T3 has a higher affinity for TR than T4 which is why it is more active. T3 effects the basal metabolic rate, growth and development, and reproduction.
Basal Metabolic Rate (BMR)
As mentioned earlier, T3 increases the BMR of all tissues. It does this by increasing heat production as a result of the increased consumption of oxygen as well as ATP hydrolysis. It also increases cardiac output by increasing heart rate as well as the rate and depth of respiration. It also has effects on metabolism, including:
- Stimulation of Carbohydrate Metabolism:
- increases metabolic enzymes, glycogenolysis and gluconeogenesis.
- increases rate of reabsorption of glucose from gut.
- Stimulation of Fat Metabolism:
- Stimulates lipolysis which increases plasma free fatty acid concentrations.
- Decreased plasma concentration of cholesterol due to conversion into bile acids.
- Stimulation of Protein Metabolism
- Stimulation of protein turnover.
Basically, anything which will increase blood glucose levels.
Growth and Development
The thyroid hormones are essential for normal growth and development and are required for the release of growth hormone. Inadequate amounts of thyroid hormone may result in cretinism during foetal development. It is also required for the maturation of surfactant producing cells in the lungs (see this post.). Thyroid hormones are also needed for the maintenance of the Central Nervous System.
Reproduction
Iodine deficient animals (which will subsequently have low levels of thyroid hormones) display: high rates of abortion, excessive still births, weak young, delayed puberty, irregular oestrus patterns and impaired spermatogenesis.
Hyperthyroidism
Hyperthyroidism refers to the abnormally increased levels of circulating T4 and T3. In animals it is the most frequently diagnosed endocrine disorder of middle-aged to older cats (about 12-13 years old). The main cause is a benign adenoma which is hyperplasia of the thyroid gland. This results in excess production of the thyroid hormones which has several effects on the body.
Metabolically, an increased BMR causes stimulation of metabolism and heat production. This results in chronic caloric and nutritional inadequacy as well as net protein degradation causing muscle wasting. Thus clinical signs include: Weight loss despite an increased appetite.
Hyperthyroidism also causes increased circulatory demands leading to high cardiac output (CO) and cardiac hypertrophy. This is a result of direct thyroid hormone activity as well as increased sensitivity to catecholamines and sympathetic nervous system activity. Cardiovascular clinical signs include tachycardia (this increases CO) and cardiac murmur (as a result of hypertrophy).
This condition may also affect the animal's behaviour, making it hyperactive, nervous and aggressive. Unkempt, matted hair and alopecia as well as palpable goitre (enlarged thyroid gland) may also be noticed.
Hypothyroidism
This refers to a condition in which a decreased production of T3 and T4 exists. There are two types:
- Primary Hypothyroidism: this is due to the irreversible loss of the thyroid gland and iodine deficiency. This is the most common form.
- Central Hypothyroidism: this is because of disorders of the pituitary gland or hypothalamus. This type is very rare.
Hypothyroidism is most often seen in dogs and has an excellent long term prognosis and is easily treatable.
Most clinical signs are related to a reduction in BMR. Metabolic features of the condition include lethargy, weight gain with no change in appetite, exercise intolerance and intolerance to cold. Hypothyroidism also affects the skin by causing scaling, alopecia, secondary infections and hyperpigmentation. In addition, neuromuscular features include generalised weakness as well as laryngeal paralysis or megaoesophagus.
Euthyroid Sick Syndrome
This occurs during illness and fasting when a decrease in T3 or T4 occurs (but TSH levels remain normal). This appears to be beneficial because it lowers BMR and hence the consumption of oxygen by tissues. The thyroid is normal in this condition and it results from a nonthyroidal illness. It is important to differentiate this syndrome when attempting to diagnose hypothyroidism.
That's it for this post, see you next time :)
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