Describe the location of the thyroid gland
- Located in the neck anterior to the lower larynx and upper trachea
- It is inferior to the thyroid cartilage
There are two major cells in the thyroid gland, what are they?
- Follicular cells - Arranged into follicles separated by connective tissue. The follicle is spherical surrounded by the follicular cells surrounding a central space containing colloid (protein)
- Parafollicular (C-cells) - found in the connective tissues surrounding the follicle
The thyroid gland has a butterfly shape with two lateral lobes joined by a central ______
Two nerves lie in close proximity to the thyroid gland which are at risk during thyroid removal. What are they?
- Recurrent laryngeal
- External branch of the superior laryngeal
How vascularised is the thyroid gland?
Very 3 arteries/veins supplying it - (superior, middle and inferior thyroid)
What 3 hormones does the thyroid gland produce and from where?
Thyroxine (T3) and triiodothyronine (T4) from the follicular cells
Calcitonin - parafollicular cells
What amino acid is T3 and T4 derived from?
Outline the basic synthesis of T3 and T4 in thyroid follicles
- Transport of iodide into the follicular cells against a concentration gradient
- Synthesis of a tyrosine rich protein (thyroglobulin in follicular cells
- Secretion of thyroglobulin into the lumen of the follicle
- Oxidation of iodide to produce iodinating species
- iodination of the side chains of tyrosine residues in thyroglobulin to form MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
- Coupling of MIT and DIT = T3
- Coupling DIT with DIT = T4 - T3 & T4 residues are produced in the ratio of 1:10
Where is T3 and T4 stored?
Extracellular in the lumen of the follicle The amounts stored are considerable and would last for several months at normal rates of secretion
How is T3 and T4 secreted?
- Thyroglobulin (with iodinated side chains) taken into follicular cells by endocytosis
- Proteolytic cleavage of thyroglobulin releasing T3 and T4
- These diffuse from the follicular cells into the circulation
How are the levels of T3 and T4 secretion regulated?
- T3 and T4 secretion are under the control of the hypothalamus and anterior pituitary gland
- hypothalamus - Thyrotropin-releasing hormone (TRH)
- TRH influenced by levels of T3 and T4 (negative feedback)
- TRH travels in the HYPOTHALAMIC/PITUITARY PORTAL SYSTEM to stimulate the secretion of thyroid stimulating hormone (TSH)
- TSH released from the thyrotrophs in the anterior pituitary which travels in the blood to affect follicular cells of thyroid gland
List the hierarchy of T3 and T4 control
Thyrotropin-releasing hormone (TRH)
Thyroid stimulating hormone (TSH)
T3 andT4 release
(T3 and T4 negatively feedbacks on both TRH (long-loop inhibition) and TSH (short-loop inhibition ))
What stimulates the release or thyrotropin-releasing hormone?
- Fall in temperature
Where is thyroid stimulating hormone released from?
The thyrotropes in the anterior pituitary
Outline the actions of TSH
- TSH interacts with receptors on the surface of follicular cells and stimulates all aspects of of synthesis and secretion of T3 and T4
- TSH also exerts a trophic effect on the thyroid, increasing vascularity, size and number of follicle cells
- This is what leads to goitre
What effects do T3 and T4 have in the body?
- Increase the metabolic rate of tissues
- Stimulate glucose uptake
- Stimulates mobilisation and oxidation of fatty acids
- Stimulate protein metabolism
- important role in growth (see other question) The effects are generally catabolic leading to an increase in BMR, heat production and increased oxygen consumption
How are T3 and T4 carried in the blood?
- They are hydrophobic molecules and are transported bound to proteins:
Thyroxine binding globulin, pre-albumin and albumin Only a small amount left unbound
What effect does increased levels of oestrogen during pregnancy have on T3 and T4?
- Oestrogen increases the synthesis of thyroxine binding globulin
- Less T3 and T4 in solution
- Feeds back with increased levels of TRH and TSH
- Free T3 and T4 return to normal levels but the total amount in the blood is increased
Does T3 or T4 have a shorter half life?
T3 = 2 days
T4 = 8 days
What role does T3 and T4 play in growth?
The CNS is particularly sensitive:
- Development of cellular processes of nerve cells
- Hyperplasia of cortical neurones and myelination of nerve fibres (In the absence of thyroid hormones from birth to puberty the child remains mentally and physically retarded (CRETINISM)
- Directly effect bone mineralisation
- Increase synthesis of heart protein
In an adult, what does lack of thyroid hormone lead to?
- Poor concentration
- Poor memory
- Lack of initiative
Outline the mechanism of action for T3 and T4
- Cross the plasma membrane of target cells and interact with high affinity receptors located in the nucleus and possibly mitochondria
- The receptors have a 10-fold greater affinity for T3 than T4
- Binding unmasks the DNA binding domain
- When DNA binds, this increases the rate of transcription of specific genes that are translated into proteins
- Protein synthesis stimulates oxidative energy metabolism
Outline T4 to T3 conversion and describe why it is important
- Important mechanism for regulating the amount of active hormone in cells as T3 is 10 times more active
- Removal of T4's 5' iodide yield normal functioning T3
- Removal of T4 3' iodide yield an inactive reverse T3 (rT3) rT3 can bind to thyroid hormone receptors without stimulating them, but blocks the effect of T3
What is the most common form of hypothyroidism?
Hashimoto's disease Affecting around 1% of the population, mainly women
What is the pathology of Hashimoto's disease?
- An autoimmune disease
- Destruction of thyroid follicles OR
- Production of an antibody that blocks the TSH receptor on follicle cells preventing them from responding to TSH
How are sufferer's of Hashimoto's disease treated?
- Oral thyroxine
What are the possible signs and symptoms of hypothyroidism in adults?
- Cold intolerance
- Weight gain
- Tiredness and lethargy
- Neuromuscular system - weakness, muscle cramps and cerebellar ataxia (clumsiness of movement)
- Dry and flaky skin
- Voice is deep and husky
What is the most common form of hyperthyroidism?
Graves's Disease Affects 1% of population, mainly women
What is the pathology of Grave's disease?
- An autoimmune disease
- Thyroid stimulating immunoglobulin (TSI) antibodies produced
-TSI stimulate TSH receptors on follicle cells resulting in increased production and release of T3 and T4
- TSH levels fall due to the negative feedback loop
- TSH levels do not affect thyroid hormone release since stimulus is TSI
How is Grave's disease treated?
Inhibits the thyroid peroxide enzyme that prevents coupling and iodination of tyrosine residues on the thyroglobulin
- total removal of thyroid leaving parathyroid behind
What are the possible signs and symptoms of hyperthyroidism?
- Heat intolerance, increased oxygen consumption and increased BMR
- Weight loss
- Physical and mental hyperactivity
- Intestinal hyper mobility
- Skeletal and cardiac myopathy giving rise to tiredness, weakness and breathlessness
- Osteoporosis due to increased bone turnover and preferential resorption
What role does calcitonin have?
Reduces blood calcium levels by inhbiting the actions of osteoclasts
Opposite of parathyroid hormone
What is found in the lumen of follicles in the thyroid?
Thyroglobulin rich colloid
Why does T4 have a greater half life than T3
Higher affinity for transport proteins so remains in circulation for longer However T3 is more biologically active
Describe the structure of TSH
- Glycoprotein hormone
- 2 subunits (alpha, beta)
- Released in low amplitude pulses twice per day
- Circadian rhythm
Outline the differences you would expect to see in the blood test results of a patient with hyperthyroidism and one with hypothyroidism
Hyperthyroidism- high free T4, low TSH
Hypothyroidism- low free T4, high TSH