Thyroid Gland Flashcards
Give a brief overview of thyroid function.
- essential for normal development, especially the CNS and bone
- essential for normal metabolism of many body tissues
What are the functions of the different cells in the thyroid?
- Follicular cells synthesise and secrete thyroid hormone.
- Colloid is where TH is stored.
- C-cells secrete calcitonin - to reduce plasma Ca2+
Thyroid hormones are derived from two iodinated tyrosine molecules.
Describe two thyroid hormones learnt.
T4: major form released to blood, less active (prohormone)
T3: active form, converted in target cells
What are the steps to TH synthesis? PART 1
- Active uptake of I- across the basolateral membrane, against the concentration gradient. Done by the Na/I symporter, and stimulated by TSH.
- Iodide efflux (by diffusion) then occurs across the apical membrane via pendrin exchanger
What are the steps to TH synthesis? PART 2
- At the extracellular apical membrane, iodide is oxidised to iodine and covalently bind to tyrosine residues within thyroglobulin (TG) macromolecules.
- Requires TPO and H2O2.
What are the steps to TH synthesis? PART 3
- Tyrosine residues may be iodinated in one (mono-iodotyrosine, MIT) or two (DIT) positions.
- Coupling of iodotyrosine residues produces T4 (DIT-DIT) and a smaller amount of T3 (DIT-MIT). Catalysed by TPO
What are the steps to TH release? PART 1
- Under influence of TSH, colloid droplets consisting of thyroid hormones within TG molecules are taken back up into the follicular cells by pinocytosis.
- Fusion of the colloid droplets with the lysosomes causes hydrolysis of TG and release of T3 and T4.
How do thyroid hormones circulate?
- Bound to plasma proteins.
- Mainly TBG (~70%), transthyretin (10-20%) and albumin (10-20%).
How do thyroid hormones act on target tissues? PART 1
- TH receptors (TRs).
- Belong to the nuclear receptor superfamily - high affinity for T3
- Ligand-activated transcription factors.
How do thyroid hormones act on target tissues? PART 2
- Activation requires dimerisation with another TR or a retinoid X receptor (RXR).
- TRs are encoded by two genes: TR α and TR β.
Describe the metabolic regulation of THs.
- Done by selenodeiodinases, abbreviated to D1-3.
- Used selenium as their trace element, so it is essential in the diet.
- Regulate the amount of T3 available to bind with the receptor.
Outline the functions of the selenodeiodinases.
- Activate by converting T4 to T3 (D2)
- Inactivate by converting T3 to T2 (D3)
- Inactivate by converting T4 to rT3 (D3).
What are some ways TH increases metabolic rate?
- affects number and size of mitochondria, enzymes, Na/K ATPase activity, etc.
- positive inotropic and chronotropic effects on the heart
- synergises with the sympathetic nervous system
What are some ways TH is involved in energy metabolism?
- antagonises insulin signalling
- gluconeogenesis, lipolysis
Describe how TH moves across the membrane.
- HYPOTHESIS: TH diffused across the cell membrane to work.
- TRUTH: TH transporters are required to allow TH across membrane e.g MCT8.
What genetic mutation is MCT8 linked to?
Allan-Herndon-Dudley Syndrome
Describe the role of the hypothalamic-pituitary-thyroid axis.
- Negative feedback control of thyroid hormone synthesis and secretion
- Hypothalamic neurosecretory cells release TRH into the portal capillaries.
- TRH stimulates thyrotrophs of the anterior pituitary to secrete TSH.
What happens with high levels of T4 and T3?
- Release of TSH and TRH are turned down.
Describe congenital hypothyroidism.
- Inadequate thyroid hormone production in neonates.
- Occur because of anatomic defects in gland, an inborn error of thyroid metabolism, or iodine deficiency.
How is congenital hypothyroidism investigated and treated in neonates?
- Preventable with a simple neonatal heel prick before testing for TSH levels.
- Possible congenital hypothyroidism if the levels of TSH are high.
Describe the TSH receptor and its actions.
- G-protein coupled receptor
- Done through Adenylate Cyclase (αGs and the cAMP-PKA cascade).
- Leads to iodide uptake, the transcription of NIS (Na+/I- symporter), TG and TPO, etc.
What are the actions of TSH?
- increases iodine uptake
- stimulates other reactions involved in TH synthesis (eg. TPO)
- stimulates uptake of colloid
- induces growth of the thyroid gland (which can lead to goitre)
Define hyperthyroidism.
- Occurs when there is TH excess.
- Primary - problem with the thyroid gland
- Secondary - problem with pituitary regulation
Define hypothyroidism.
TH deficiency
Describe Grave’s Disease.
- Common cause of primary hyperthyroidism.
- Autoimmune disease characterised by high levels of circulating TH/ low levels of TSH.
- Antibodies are directed to the TSH receptor - work as pharmacological agonists, so we end up with unregulated overproduction of TH.
What are the symptoms of Grave’s Disease?
- Weight loss (due to the increased metabolism)
- Tachycardia
- Fatigue
- Diffuse goitre (due to TSH receptor stimulation)
- Ophthalmopathy (an inflammatory disorder of the orbit and periorbital tissues).
Describe Hashimoto’s Disease.
- Cause of hypothyroidism.
- Autoimmune disease characterised by low levels of circulating TH/high levels of TSH.
- Antibodies cause thyroid destruction and dysfunction.
What are the symptoms of Hashimoto’s Disease?
- Lethargy
- Weight gain
- Lack of growth and development
- Diffuse goitre.
What are the 2 main branches that supply the thyroid?
- Inferior thyroid artery - subclavian
- Superior thyroid artery - carotid
What is reverse T3?
- Iodinated on a different side
- Inactive
What 2 factors stimulate the hypothalamus to produce TH?
- Stress
- Cold
Why is high TSH and high TRH indicative of HYPOthyroidism?
→ If thyroid isn’t producing T3 or T4
→ There is no negative feedback
→ TRH and TSH concentration are high
What is the diagnosis for low TRH and low TSH but high T4 and T3?
Primary hyperthyroidism
What is the diagnosis for high TRH & TSH but low T4 and T3?
Primary hypothyroidism
What is the diagnosis for low TRH, high TSH and high T4 and T3?
Secondary hyperthyroidism
