Session 10 Flashcards
When is the thyroid gland visible and palpable?
- When it is enlarged (goitre)
Where is the thyroid gland located?
- In the neck in the front of the lower larynx and upper trachea
What else is near to the thyroid gland?
- 2 nerves (recurrent laryngeal and external branch of the superior laryngeal)
- Highly vascularised with 3 arteries and veins supplying and draining it (superior, middle and inferior thyroid arteries and veins)
What is the structure of the thyroid gland?
- Butterfly shape
- 2 lateral lobes connected by a central isthmus
- Usually 2-3 cm and 15-20g
What are the main cells types of the thyroid gland?
- Follicular (arranged in follicles separated by connective tissue)
- Parafollicular (C-cells) (found in the connective tissue)
What hormones are produced by the follicular cells of the the thyroid gland?
- Throxine (T4)
- Tri-idothyronine (T3)
- Small molecules derived from amino acid tyrosine with the addition of atoms of iodine
What hormone is produced by the parafollicular cells of the thyroid gland?
- Calcitonin
- Polypeptide hormone
How are T3 and T4 synthesised in the thyroid follicles?
- Transport of iodine into epithelial cells against a concentration gradient
- Synthesis of a tyrosine rich protein (thyroglobulin) in the epithelial cells
- Secretion by exocytosis of thyroglobulin into the lumen of the follicle
- Oxidation of iodine to produce an iodinating species
- Iondination of the side chains of tyrosine residues in the thyroglobulin to form MIRA (mono-iodotyrosine) and DIT (di-iodotyrosine)
- Coupling of DIT with MIT/DIT to form T3/T4 respectively within the thyroglobulin
- T3 and T4 residues are produced in the ratio of 1:10
How are T3 and T4 stored?
- Extracellularly in the lumen of the follicles as part of thyroglobulin molecules
How are T3 and T4 secreted?
- Thyroglobulin is take into epithelial cells by Endocytosis from the lumen of the follicles
- Thyroglobulin undergoes proteolytic cleavage to release T3 and T4
- T3 and T4 diffuse from the epithelial cells into the circulation
What controls T3 and T4 synthesis and secretion?
- Hypothalamus: releases Thyrotrophin-releasing hormone (TRH)
- Anterior pituitary gland: releases Thyroid Stimulating Hormone (stimulated by TRH) and affects follicular cells of thyroid gland
What is TRH secretion influenced by?
- Circulating levels of T3 and T4 (negative feedback)
- Stress (increases release)
- Temperature (fall increases release)
What is the structure of TSH?
- Glycoprotein consisting of 2 non-covalently linked subunits
When is TSH a released?
- Released in low-amplitude pulses
- Diurnal rhythm: higher levels at night, lower levels in the early morning
What are the actions of TSH on follicle cells and how?
- Interacts with cell surface receptors
- Stimulates synthesis and secretion of T3 and T4
- Has trophic effects on the cell -> increased vascularity, size and number of cells
- Can result in an enlarged thyroid (goitre) that may or may not be active
How are T3 and T4 transported?
- Are hydrophobic
- Transported in the blood bound to proteins (thyronine binding globulin, pre-albumin and albumin)
- Only a small amount is free in solution
- Free hormone is biologically active
- T3 has a shorter half-life and a higher free percentage than T4 as T3 has a slightly lower affinity for transport proteins
What happens to T3 and T4 levels during pregnancy?
- Oestrogens increase synthesis of thyronine binding globulin -> flat in T3 and T4 in the circulation as more is bound
- Fall in T3 and T4 removes inhibitory feedback in pituitary and hypothalamus -> secrete more TRH and TSH -> more T3 and T4 are secreted
- Amount of free T3 and T4 returns to normal, but total amount in the blood increases
What types of effects does T3 and T4 have in tissues?
- General effects on metabolic activity
- Specific effects
What general effects do T3 and T4 have on tissues?
- Increase metabolic rate
- Stimulate glucose uptake and metabolism
- Stimulates fatty acid mobilisation and oxidation
- Stimulates protein metabolism
- Metabolism effects are usually catabolic -> increase in BMR, heat production and oxygen consumption
How are T3 and T4 important in normal growth and development?
- Effects on physical growth related to metabolic effects on tissues
- Also specific effects eg bone mineralisation, and increased synthesis of heart muscle protein
What is T3 and T4 required for in the development of the CNS?
- Development of cellular processes of nerve cells
- Hyperplasia of cortical neurones
- Myelination of nerve fibres
What happens in relation to the CNS is the thyroid hormones are not present?
- Cretinism: mental and physical retardation if thyroid hormones are not present from birth to puberty
- Damage is irreversible a few weeks after birth if deficiency is not corrected (all newborns have their thyroid function checked after birth)
What is lack of thyroid hormones characterised by in adults?
- Poor concentration
- Poor memory
- Lack of initiative
What are the indirect actions of T3 and T4?
- Related to important interactions with other hormones and neurotransmitters
- Stimulate hormone and neurotransmitter receptor synthesis in a variety of tissues eg heart muscle, GI tract
- Increased responsiveness in these tissues to regulatory factors
- eg in heart muscle -> tachycardia; in the GI tract -> increased motility
With which hormones do T3 and T4 have a permissive role?
- FSH, LH and ovulation fails to occur in the absence of thyroid hormones
What is the mechanism of action for T3 and T4?
- Cross plasma membrane of target cells
- Interact with specific high affinity receptors in the nucleus and possibly mitochondria
- Receptors have a 10-fold greater affinity of T3 and T4
What happens when T3 binds to the hormone-binding domain of receptors?
- Conformational change in receptor that unmasks DNA-binding domain
- Interaction of hormone-receptor complex with DNA (nuclear or mitochondrial) increase the rate of transcription of specific genes that are then translated into protein
What does increased rate of protein synthesis do in target cells?
- Stimulates oxidative energy metabolism required for protein synthesis
- Also increases production of specific functional proteins -> increase cell activity and increased demand for energy
How can T4 be converted to T3?
- Removal of the 5’-iodide
Why is conversion of T4 to T3 important?
- Regulation of active hormone in cells as T3 has x10 activity of T4
What does the removal of 3’-iodide from T3 do?
- Produces inactive reverse T3 (rT3)
- Binds to thyroid hormone receptors without stimulating them and blocks the effect of T3
What are clinical problems caused by?
- Hyperthyroidism (too much physiologically active thyroid hormones)
- Hypothyroidism (to little physiologically active thyroid hormones)
What is the most common form of hypothyroidism?
- Hashimotos’ disease
- Autoimmune disease -> destruction of thyroid follicles or production of an antibody that blocks TSH receptor on follicle cells (prevents them responding to TSH)
- Treated with oral thyroxine
What are other causes of hypothyroidism?
- Post-surgery
- Radioactive iodine
- Anti-thyroid drugs
- Secondary (lack of TSH)
- Congenital
- Iodine deficiency
What is the most common form of hyperthyroidism?
- Grave’s disease
- Autoimmune disease -> antibodies that stimulate TSH receptors on follicle cells are produced -> increased production and release of T3 and T4
- Treated with carbimazole drug (inhibits thyroid peroxidase enzyme -> prevents coupling and iodination of tyrosine on thyroglobulin)
What are other causes of hyperthyroidism?
- Toxic (overproducing T3/T4) multi-nodular goitre
- Excessive T3/T4 therapy
- Excess iodine - amiodarone
- Thyroid carcinoma (99% don’t cause hyper/hypothyroidism)
- Ectopic thyroid tissue
What are the signs and symtoms of hypothyroidism in adults?
- Cold intolerance and reduced BMR
- Weight gain
- Tiredness and lethargy
- Bradycardia
- Neuromuscular system: weakness; muscle cramps; cerebellar ataxia (clumsiness of movement)
- Skin is dry and flaky
- Alopecia
- Voice is deep and husky
What are the signs and symptoms of hyperthyroidism?
- Heat intolerance; increased oxygen consumption and increased BMR
- Weight loss
- Physical and mental hyperactivity
- Tachycardia
- Intestinal hyper-mobility
- Skeletal and cardiac myopathy -> tiredness; weakness; breathlessness
- Osteoporosis due to Increased bone turnover and preferential resorption (osteoclasts > osteoblasts)
What happens to levels of free T4 and TSH in hypothyroidism?
- ⬇️ free T4
- ⬆️ TSH
What happens to levels of free T4 and TSH in hyperthyroidism?
- ⬆️ free T4
- ⬇️ TSH
