Lecture 21. Thyroid Flashcards
What are the actions of thyroid hormone
- Promoting growth and development of fetus - especially CNS (b4 they have their own thyroid)
- Increase metabolic rate and heat production - increase oxygen requirements by brain/cvs
- Increases Cardiac output by increasing HR and SV, increases peripheral vasodilation and pulse pressure
- Increases metabolism of fat, glucose and proteins: to regulate body weight (lose weight) and provide substrate for Growth and development
What muscles is the thyroid deep to
Sternohyoid and sternothyroid muscles.
What are the two markers for differentiated thyroid cancer- persisting thyroid tissue and where are they made
- Calcitonin- made from c-cells that sit adjacent to thyroid follicles (lined by cuboidal epithelium)
- Thyroglobulin - made by thyroid follicular cells. Found within the colloid in the lumen of the follicle and circulates in blood in low levels
(also stores thyroid hormone)
Where does iodine come from and who needs it most
Dietary intake in Salt, fish, bread.
Women planning pregnancy need supplements
How is hyperthyroidism or remaining cancerous thyroid tissue treated
- For Hyper: TPO is inhibited by Carbimazole stopping thyroid peroxidase making the oxidised form of iodine needed for Thyroid hormone synthesis
- Radioactive iodine drink as the thyroid tissue actively transports one Iodide (I-) with 2 Na+ using the sodium iodide transporter storing up to 8000ug of iodide
What are the steps to making Thyroid hormone from iodine transport
- TRH released from hypothalamus acts on thyrotrophs in the ant pit to make TSH
- TSH allows transport of iodide (I-) from the blood through the sodium iodide transporter into thyroid follicular cell
- I- is transported to the follicle lumen by Pendrin
- Iodide ions are converted to an oxidised form of iodine (I2) by enzyme thyroid peroxidase (in presence in H2O2)
- Thyroglobulin (TG) synthesised in the thyroid follicular cell is secreted into the lumen
- Oxidised iodine attaches to the tyrosine in TG forming Monoiodo or Diodo tyrosine
- This goes on to form T3, Reverse T3 and T4 which stays attached to the TG and stored ->50days
- These are pinocytosed into thyroid follicular cell where proteases digest thyroglobulin and free T4, T3 and RT3 to be secreted -
- While doing this Iodine is also cleaved from any unused MIT and DIT for recycling by deiodinase enzyme
What are the differences and similarities between T4 and T3
T4 only made in thyroid gland. 20% of T3 made in thyroid and 80% of T3 comes from peripheral conversion of T4 by removal of iodine atom.
T3 is the active form of thyroid hormone. T4 is the main hormone in plasma
Both are metabolised by many organs, especially liver/kidneys
What is the H-P axis for regulation of thyroid hormone - including feedbacks
- Hypothalamus releases Thyrotropin releasing hormone (TRH) which signals to Ant pit
- Ant Pit releases Thyroid stimulating hormone (TSH) to act on thyroid
- Thyroid makes T3/T4 - more T3 by peripheral circulation. T3/4 bind to tissue receptors which have a and B subunits expressed variably in different tissues
- T3 gives negative feedback on the ant pit and hypothalamus - more important on pit.
Why is TSH important
TSH is most sensitive measurement from blood about T3/T4 levels in thyroid disease. Only when there is no Ant Pit or Hypothalamic disease is T4 measured
- In early pregnancy when b-HCG is high, due to similar a-subunit to TSH it can cause transient hyperthyroidism- have to determine if it is due to the hyperemesis gravidarum or coincidentally getting thyroid disease
Increases in TSH cause goitre
What does TSH do
uncontrolled up regulation in Graves disease due to autoantibodies
- Increases iodide into follicular lumen
- Increases blood flow => causing a bruit in the thyroid
- increases TG, TPO and H2O2
- Increases endocytosis and degradation of Tg to release more T4
After a thyroidectomy- in order to maintain a pre-op T3 level, how much T4 replacement (Thyroxine) do you need to give and how is this measured
More than required to get in the normal range of T4 (but not thyrotoxic) so some can be converted to T3 to replace the 20% lost from thyroidectomy.
It is measured in slightly suppressed (lower than normal) TSH plasma concentration
What are the symptoms (from history) and signs (from exam) of thyrotoxicosis: what are the levels of TSH, T4/T3
- Graves disease, multinodular goitre
High T4/3 so low TSH
Symptoms
- nervousness, increased sweating- T4 does symp
- weight loss, muscle weakness, increased heat DUE to
- increased basal metabolic rate - break down of proteins, carbs, fat
- Palpitations: T3 works directly on heart to increase cardiac contractililty
Signs
- Bruit- gd,
- tachycardia
- Goitre- not always
- Bulging eye signs - graves disease although not proportional to thyroid dysfunction
- Tremor
- Skin changes: thyroid dimopathy - on ant tibia
What is the main cause of 1’ hypothyroidism - problem with the thyroid
What is the possible effect on all organ systems and the symptoms seen
Treated with thyroid hormone
Hashimotos disease: autoantibodies to TPO trigger cell mediated immune response which gets thyroid destruction - reduce T4 formation-> high TSH.
There is slow adult onset of
-decreasing energy metabolism, lower basal metabolic rate = weight gain, hair loss and dry skin, tired
- lower body temperature
- decreased protein synthesis = oedema
What are the consequences of iodine deficiency
(acute iodine deficiency is protected against by large stores in the thyroid
Iodine is needed to make thyroid hormone.
Iodine deficiency leads to enlargement of the thyroid= endemic goitre
Severe low maternal iodine can lead to Cretinism of fetus- irreversible CNS damage.
What are all the causes of goitre
- Iodine deficiency
- Increased TSH stimulation of the thyroid due to Hashimotos, or Graves disease or HCG
- inflammation of the thyroid gland
