1103 - Histology and Functions of the Thyroid Flashcards
What is the embryology of the thyroid gland?
Begins as a tubular invagination from the root of the tongue (foramen cecum), growing downwards in front of the trachea and thyroid gland to its adult position. Distal end proliferates to form the gland, proximal end degenerates and disappears by 5-6weeks gestation.
Outline the structure of the thyroid
Thyroid consists of right and left lobes, joined by an isthmus. Around 50% have a pyramidal lobe, remnant of foramen cecum. The lobes have multiple lobules, each of which consists of 20-40 follicles. Thyroid is the only gland to store its hormone extracellularly.
What is function of C cells? What is the effect of their hormone?
Function is to produce calcitonin. Effect is theoretically to control osteoclasts, but in reality has little biological function in humans.
How is T4 synthesised? What stimulates release?
Iodine is converted to iodide in the gut. It is taken up in the thyroid where it links with pre-existing tyrosine residue of thyroglobulin to form monoiodotyrosine residue. Two of these come together to form diiodotyrosine. Two of these then come together to form thyroxine (T4). Each step is catalysed by Thyroid Peroxidase (TPO). If a mono links with a di, it makes T3 directly.
Release stimulated by TSH - Tg taken up by endocytosis, digested, and T3 and T4 released into circulation.
How is Thyroid hormone transported?
Predominantly by Thyroxin-binding globulin (TBG) - high affinity and low capacity.
TBPA has intermediate affinity and capacity for T4, but low capacity for T3
Albumin has high capacity but low affinity.
How is T4 converted to T3?
Deiodinases containing selenium convert T4 to T3 in the periphery.
D1 is principle agent - particularly in liver, kidneys, thyroid, and pituitary.
T3 is then deiodinased to DIT, metabolised by the liver and excreted in bile.
What is the mechanism of action of T3?
Enters the cell and interacts with the thyroid hormone receptor in the nucleus (similar to steroid receptor). The receptor then binds to thyroid hormone response element to modify gene transcription, and in the cytoplasm modifies translation/protein synthesis.
What are some genes targeted by thyroid hormone?
Genes for TSH (negative feedback), GH, myosin, Ig Heavy chain, and some lipogenic liver enzymes.
What are some nongenomic actions of Thyroid Hormone?
Alters solute transport (electrolytes and glucose), modifies kinase activity incl PKC, and modulates mitochondrial respiration and muscle contractility (including cardiac output).
What do T3 and T4 feed back onto?
T3 and T4 give negative feedback to both TSH and TRH.
What are the major types of thyroid disease?
Hypothyroidism (autoimmune/iodine deficiency) - Goitre
Hyperthyroidism (Grave’s Disease) - Goitre
Maldevelopment (congenital)
Nodules
Malignancy
What is the difference between hyperthyroidism and thyrotoxicosis?
Thyrotoxicosis is the clinical state caused by excess thyroid hormone production. Hyperthyroidism is the arbitrary definition of thyroid activity from thyroid function tests.
Briefly outline Hashimoto’s and Grave’s Disease
Hashimoto’s - Autoimmune disease targeting thyroid, resulting in destruction
Grave’s Disease - Antibodies generated that stimulate TSH receptor, causing hyperthyroidism.
What is the most common carcinoma of the thyroid?
Papillary carcinoma (80%) followed by follicular carcinoma (5-10%)
