Thyroid gland Flashcards
(21 cards)
What are the general functions of the thyroid?
- Developmental - Essential for normal development, especially CNS and bone
- Metabolic - Essential for normal metabolism of many body tissues
Describe the blood supply to the thyroid and its anatomy
Rich blood supply: More blood per unit weight than kidney
- Inferior thyroid artery from subclavian
- Superior thyroid artery from carotid
Butterfly shaped gland, divided into 2 lobes connected by isthmus, which crosses the midline of the upper trachea at the second and third tracheal rings
Positioned in anterior neck, C5-T1, posterior to sternothyroid and sternohyoid muscles, wrapping around cricoid cartilage and tracheal rings
Describe the histology of the thyroid gland
- Follicular (epithelial) cells - Arranged in layer round ‘colloid’, protein-rich storage material. Apical surfaces in contact with colloid, basal near capillary blood supply, b/w follicles
- Colloid (mainly thyroblobulin) - Where TH is stored, after being synthesised by activity of follicular cells
- C-cell (parafollicular cell) - Secrete calcitonin
What’s the difference between colloids and thyroglobulins?
The colloid is a substance found in the thyroid follicles, while thyroglobulin is a protein that makes up a significant portion of the colloid. Thyroglobulin is synthesised by follicular cells and secreted into the colloid, it’s the main component of the colloid.
The colloid acts as a reservoir for thyroid hormones, and thyroglobulin is the protein that holds these hormones.When thyroid hormones are needed, they are released from the thyroglobulin molecules in the colloid.
What type of receptors are thyroid hormone receptors? Describe them
Belong to nuclear receptor superfamily:
- Ligand-activated transcription factors
High affinity for T3:
- Activation requires dimerisation with another TR or retinoid X receptor (RXR)
- TRs encoded by 2 genes: TR alpha and TR beta
Transactivation domain at N-terminal - Interacts with other transcription factors to form complexes that alter transcription
DNA binding domain - Binds to sequences of promoter DNA (hormone response elements)
Ligand binding domain - Where dimerisation occurs
Describe the metabolic regulation of thyroid hormones
Relative levels of T3, T4 and inactive forms controlled in target tissues
3 iodothyronine selenodeiodinases, D1-3 (so trace element selenium is essential in diet):
- D2 increases T3
- D3 deceases T3
Deiodinases - Family of 3 enzymes that activate or inactivate TH.
Tissue-specifc expression of deiodinases can control generation of T3 at lvl of the target tissues
Regulate amount of T3 actually available to bind
At cellular lvl, D3 decreases TH action and D2 increases
Explain the hypothalmic-pituitary-thyroid axis
- Negative feeback control of thyroid hormone synthesis and secretion, via the hypothalamo-pituitary axis
- Hypothalamic neurosecretory cells release thyrotrophin-releasing hormone (TRH) into portal capillaries
- TRH stimulates thyrotrophs of anterior pituitary to secrete TSH
Increasing levels of T3/T4 inhibit release of TRH and TSH
What stimulates thyroid hormone synthesis and release?
TSH
- The active uptake of iodide appears to be main control point for hormone synthesis, stimulated by TSH
- When iodine is sufficient in body, production of H2O2 is step that limits synthesis of thyroid hormones; when iodine is lacking, under stimulation of high TSH, thyroid cells produce more H2O2, and accumulation of H2O2 gradally damages thyroid cells
What type of receptor is the TSH receptor?
- GPCR
- Main effects mediated via Gs and cAMP - PKA cascade
Describe the actions of TSH
- Increases iodine uptake
- Stimulates other reactions involved in TH synthesis (e.g. TPO)
- Stimulates uptake of colloid
- Induces growth of thyroid gland (which can lead to goitre)
What are the thyroid hormones derived from?
2 iodinated tyrosine molecules:
- T4 - Major form released to blood, less active (prohormone)
- T3 - Active form, converted in target cells
Explain how thyroid hormones are synthesised
- Active uptake of I- across basolateral membrane, against concentration and electrical gradient, by Na/I symporter. Stimulated by TSH
- Iodide efflux (diffusion) across apical membrane via pendrin
- At extracellular apical membrane, iodide oxidised by H2O2 to iodine, catalysted by thyroid peroxidase (TPO), and covalently bound to tyrosine residues within the thyroglobulin (TG) macromolecule
- Tyrosine residues may be iodinated in 1 (mono-iodotyrosine, MIT) or 2 (DIT) positions. Coupling of iodotyrosine residues (also catalysed by TPO) produces T4 (DIT-DIT) and a smaller amount of T3 (MIT-DIT)
Explain how thyroid hormones are released
- Under influence of TSH, colloid droplets consisting of thyroid hormones within thyroglobulin molecules are taken back up into follicular cells by pinocytosis
- Fusion of colloid droplets with lysosomes causes hydrolysis of thyroglobulin and release of T3 and T4
- Approx 10% T4 undergoes mono-deiodination to T3 before it’s secreted. Released iodide is reutilised. Several-fold more iodide is reused than is taken from the blood each day but in states of iodide excess there is loss from thyroid
- Secretion relies on membrane transporter (MCT8 recently discovered, but otherwise unknown)
How do the thyroid hormones exist in circulation?
- Over 99% bound to plasma protein
- Mainly thyroid-binding globulin (approx 70%), also transthyretin (10-20%), albumin (10-20%)
Describe the functions of thyroid hormone
- Increase metabolic rate
- Number + size of mitochondria, enzymes in metabolic chain, Na/K ATPase activity
- Positive inotropic and chronotropic effects on heart
- Synergises with SNS
- Energy metabolism
- Partially antagonises insulin signalling
- Gluconeogenesis, lipolysis
- Anabolic and catabolic effects, catabolic dominate at high concentrations
- Growth and development
Define euthyroid
Normal thyroid function
What is hyperthyroidism and hypothyroidism?
TH excess:
- Primary - Problem is thyroid gland itself. Negative feedback, increased lvls of T3 + T4 lead to decreased release of TRH and TSH
- Secondary - Problem is pituitary regulation - Increase TSH, increase T3 + T4, increased negative feedback decreased TRH
Hypothyroidism:
- TH deficiency - Negative feedback, decreased levels of T3 + T4 result in increased secretion of TRH and TSH
Define Goitre
Swelling in front of neck caused by enlarged thyroid gland
Describe Graves’ disease
Primary hyperthyroidism:
- Autoimmune
- High circulating TH, low TSH
- Weight loss, tachycardia, fatigue
- Diffuse goitre (TSH receptor stimulation)
- Opthalmopathy
Describe Hashimoto’s
Primary hypothyroidism:
- Autoimmune
- Low circulating TH, high TSH
- Lethargy, intolerance to cold
- Lack of growth and development
- Diffuse goitre
How can hyper/hypothyroidism be distinguished?
> Primary - thyroid gland problem
> Secondary - pituitary gland problem
