The Thyroid Gland Flashcards
what are the two classes of thyroid function?
developmental and metabolic
what is developmental thyroid function?
essential for normal development, especially in CNS and bone during early life
what is metabolic thyroid function?
essential for normal metabolism of many body tissues and in cardiovascular function
what is congenital hypothyroidism?
condition of thyroid hormone deficiency present at birth
what is congenital hypothyroidism associated with?
retarded growth and learning impairment, linked to iodine deficiency so avoiding by monitoring idoine levels during pregnancy
what is thyroid hormone controlled by?
hypothalamic-pituitary axis
how is thyroid hormone released?
thyroid gland is stimulated by its stimulating hormone released from anterior pituitary gland (TSH)
euthyroid
thyroid function in normal range
hypothyroid
thyroid function below normal
hyperthyroid
thyroid function above normal
what are the two types of hypo/hyper thyroidism?
primary and secondary
what is primary hypo/hyper thyroidism?
the problem is with the thyroid gland itself
what is secondary hypo/hyper thyroidism?
the problem is with the pituitary regulation of the thyroid gland
what is the anatomy of the thyroid gland?
there are two lobes and sometimes a third pyramidal lobe. rich blood supply (more blood per unit weight than kidneys).
what vessels supply the thyroid gland?
supplied by inferior thryoid artry from thyroicervical trunk of subclavian artery and superior thyoid artery as branch of external carotid artery
what is the functional unit of thyroid tissue?
the follicle
what does a follicle consist of?
a mass of colloid (protein rich storage material containing hormones available for release). the colloid is surrounded by a single layer of follicular cells
what do the follicular cells do?
they synthesise thyroid hormones and release into colloid and also take them back up from colloid when there is need for release
what is there between the follicles?
capillaries, with the basal membrane of follicular cells facing the capillary and apical membrane facing the colloid
what are C-cells?
they secrete calcitonin involved in calcium regulation
what are thryoid hormones derived from?
joining of two iodinated tyrosine molecules
what are the two thyroid hormones?
T4 and T3
what is T4?
thyroxine (4 iodines)
what is T3?
triiodothyronine (3 iodines)
what is reverse T3?
iodines in the opposite arrangement, this is inactive
which thyroid hormone is more active?
T3 is more active at the thyroid receptor but T4 is the major form released into the blood
what does the basolateral membrane face?
the blood
what does the apical membrane face?
the colloid
what is the process of TH release?
uptake of iodine occurs against conc gradient. (high in follicular cell and low in plasma) so actively transported (secondary active transport mechanism)
how is the iodine actively transported?
sodium gradient generated by Na+/K+ ATPase used to transport iodide into follicular cell via Na+/I- symporter
what happens to the iodide once it is inside the cell?
diffuses out via apical membrane and iodide is oxidised to iodine
what enzyme oxidises iodide into iodine?
thyroid peroxidase (TPO)
what is thyroglobulin?
large protein synthesised in follicular cell containing lots of tyrosine residues, used in oxidation of iodide to iodine
what does thyroid peroxidase do?
oxidises iodide to iodine then iodinates tyrosine residues (covalently bonds iodine to them). if it iodinates them in one place you get mono-iodotyrosine (MIT), two places gives di-iodotyrosine (DIT)
what is MIT?
mono-iodotyrosine
what is DIT?
di-iodotyrosine (DIT)
how is thyroid hormone released?
endocytosis/pinocytosis occurs into the follicular cell, then there is combining of colloid droplet with lysosomes and via lysosomal enzymes, the T3/T4 units are frees from protein stores as well as hydrolysis of thyroglobulin
what happens if you combine MIT and DIT?
you get T3
what happen if you combine DIT and DIT?
you get T4
how is some of the iodine recycled in the cell?
by diodinising enzymes (DEHAL-1)
how are T3 and T4 released into the circulation?
via transporters
why do T3/T4 exist in plasma bound to thyroid-binding globulin?
they are lipophilic
which thyroid hormone is more present in circulation?
T4
which thyroid hormone is more important?
T3 as its the free thyroid hormone to stimulate receptors
what are relative levels of T3 and T4 controlled by?
three iodothyronine selenodeiodinases D1-3 so selenium is important in diet
what do the D1-3 enzymes do?
de-iodinate the thyroid hormones converting T4 to T3 or convert T3 to an inactive form
How can levels of T3 be increased?
Convert T4 to T3
How can levels of T3 be decreased?
Convert T3 to an inactive form
What type of receptor is the thyroid hormone receptor?
nuclear (in the nucleas of the cell)
what are the implications of thyroid hormones receptors being nuclear?
the thyroid hormones need to enter the cell via specific thyroid hormone transporters
how can T3 be upregulated?
convert T4 into T3 by D2 as T3 is more active
How does D1 de-iodinate?
removed an iodine from the 5 and 5’ position
how does D2 de-iodinate?
removes only from the 5’ position
how does D3 de-iodinate?
removes from the position 5
what type of feedback control regulates thyroid synthesis and secretion?
negative feedback via the hypothalamo-pituitary axis
how is the thyroid gland stimulated?
hypothalamus releases TRH which causes anterioir pituitiary to secrete TSH which then releases T3/T4 from the thyroid gland. Via negative feeback, increasing levels of T3/T4 causes TRH/TSH to shut off
what type of molecule is TSH?
glycoprotein with its receptor being a surface transmembrane receptor
what type of receptor is the TSH receptor?
GPCR (G protein couples receptor)
What are the actions of TSH?
- increase iodide uptake by increasing sodium-iodide symporter
- stimulates uptake of colloid
- induces growth of thyroid gland
what leads to a goitre?
lack of T3/T4 synthesis so no more -ve feedback so there is increased release of TSH and TRH
what are nuclear receptors?
ligand-activated transcription factors with higher affinity for T3
what genes code for TH receptors?
TR alpha and TR beta
how are TH receptors activated?
must be dimerised with another T3 receptor or retinoic acid receptor . there are certain domains on the receptor which bind to the hormone and bind to the DNA
what happens when the ligand binds T3?
combination of the receptor and cofactors present results in an activating effect
what must TH do to access the nuclear receptor?
cross the cell membrane via transporters as they are NOT lipophilic
what is MCT8?
transporter. mutations in gene discovered to underlie an X-linked condition, Allan-herndon-Dudley Syndrome
how can you regulate TH?
increase via selective activation of the D1-D3 diodinases to up/down regulate TH in a tissue specific manner
what are the functions of TH?
- increase metabolic rate
- positive inotropic and chronotropic effect on heart
- role in growth and development
what is primary hyperthyroidism?
thyroid gland is overproducing TH, would negatively feedback onto the hypothalamus and pituitary gland leading to decrease in TRH/TSH
what is wrong with thyroid gland in primary hypothyroidism?
thyroid gland isnt producing enough TH so there is absence of negative feeback. TSH/TRH increased
what is secondary hyperthyroidism caused by?
tumour effecting the thyrotrophs. there would be increased synthesis and secretion of TSH so levels increase. T3/T4 will increase and negative feeback still there but working at a higher level. So high TSH and T3/T4 indicate secondary.
what is Grave’s disease?
auto-immune disease as it is primary hyperthyroidism so high levels of TH and low TSH
symptoms of Graves disease
weight loss, tachycardia, fatigue. Diffuse goitre and opthalmopathy
pathology of Graves disease
Its due to stimulating auto-antibodies. Normally the TSH receptor binds TSH and TH synthesis/secretion is stimulated in the normal way. There is then also negative feedback on levels of TSH. Auto-antibodies get generated by the body and bind to TSH receptors as agonists. So the receptor is permanently activated
what is Hashimoto’s?
autoimmune disease characterised by low circulating TH but high TSH
symptoms of Hashimoto’s?
lack of TH activity therefore lethargy and intolerance to the cold. Lack of growth and development and diffuse goitre.
