thyroid Flashcards
What is the function of the Thyroid?
Hypothalamic regulation of hormones
What does TRH stand for?
Thyrotropin Releasing Hormone
tri-peptide
What does TSH stand for?
Thyroid Stimulating Hormone
What is TSH and what is it composed of?
pituitary dimeric glycoprotein (~30,000 MW) composed of an alpha and beta subunit.
The alpha subunit of TSH, FSH and hCg is identical what makes them different?
Beta subunits differ and confer biological specificity
What is the role of TSH?
TSH binds to a G protein-coupled receptor on thyroid follicle epithelial cells which activates both:
Adenylate cyclase => cAMP/PKA-dependent pathway
Phospholipase C => PI turnover => DAG and IP3
Describe what Thyroid follicles look like
Hollow spheres of epithelial cells. Lumen filled with a gelatinous colloid consisting of a large protein called THYROGLOBULIN
Describe the synthesis if thyroid hormones? (5)
Thyroglobulin synthesized by thyroid follicular cells and exocytosed into the lumen.
Thyroglobulin contains high content of tyrosine
Iodide is actively taken up from the blood into follicular cells and transported into the lumen
In the lumen, the enzyme thyroid peroxidase converts iodide to free iodine
Iodine atoms incorporated into tyrosine residues (still part of thyroglobulin molecule!)
What is a mono-iodotyrosine (MIT)?
one iodine per tyrosine
What is a di-iodotyrosine (DIT)?
two iodines per tyrosine
Can coupling occur between iodinated tyrosine residues?
DIT + DIT=> T4 or thyroxine
MIT + DIT => T3 or Triiodothyronine
Occurs under oxidising conditions.
(2 MITs do not couple)
Describe the process of releasing thyroid hormone (4)
Follicular cells take up a portion of the colloid in the lumen (endocytosis)
Lysosomal enzymes in the follicular cells break down the iodinated thyroglobulin liberating ‘free’ T3 and T4.
T4 and T3 diffuse through the plasma membrane of the follicular cells into the blood
Inactive MIT and DIT are rapidly deiodinated and the released iodine is recycle back to lumen for further use
What is the function of TGB? (4)
Thyroxine-binding globulin
T3 and T4 circulate bound to TBG (and albumin) as they have poor solubility in water – very little free T3/T4
TBG prevents urinary secretion of T3 & T4
TBG buffers against acute changes in thyroid function
T3/T4 must dissociate from TBG to exert biological effect
T3 vs T4 (3)
Which is secreted more?
Which is more potent?
Which is the active form?
90% is T4 10% is T3
T3 is 4 fold more potent than T4
Most of the secreted T4 is activated by peripheral target tissues by the removal of one iodine to yield T3
Which receptor do T3 and T4 bind to?
hormone-responsive transcription factor
What are the 4 effects of thyroid hormone?
- Increases basal metabolic rate (BMR)
Raised O2 consumption, CO2 production, heat production - Cardiovascular system
Increases heart rate and force of contraction - Nervous system
Increases activity of sympathetic nervous system
Enhances the sensitivity to catecholamines - Growth and maturation (essential)
Embryo development
CNS development
Linear growth (promotes effects of growth hormone)
What % of people have a disease associated with thyroid dysfunction?
2%
What is Goitre?
hypertrophy of thyroid gland caused by excessive stimulation by TSH
Can be associated with certain forms of hypo- or hyperthyroidism (depending upon whether or not TSH levels are elevated)
Often associated with autoimmune disease
What is Hypothyroidism?
lack of thyroid hormone
What are the symptoms of hypothyroidism in adults?
weight gain, cold intolerance, lethargy, depression, puffiness of skin and muscles (myxedema), sluggish reflexes, muscular weakness, reduced pulse rate and cardiac output
What are the symptoms of hypothyroidism in children?
Fetal brain damage which may be irreversible!
shortness, obesity, mental retardation
What is the treatment of hypothyroidism?
Lifelong replacement therapy with T4. Levothyroxine (identical to natural T4)
(adult ~150mg/day). Normally given on an empty stomach as absorbed better.
Unless due to chronic dietary iodine deficiency in which case give increased/supplementary iodine in diet
Can T3 (Liothyronine) be used?
Can be given - has a shorter half life but is faster acting
What are some causes of hypothyroidism? (5)
Primary failure of thyroid gland (low T3/T4, high TSH, goitre)
Secondary due to anterior pituitary failure (low T3/T4, low TSH and/or TRH, no goitre)
Tertiary due to hypothalamic failure (very rare) (same symptoms as above)
Primary due to autoimmune damage to gland (Hashimoto’s thyroiditis) (low T3/T4, high TSH, goitre)
Primary due to chronic lack of dietary iodine (low T3/T4, high TSH, goitre)
What is hyperthyroidism?
excess thyroid hormone ~2% women
What are the features of hyperthyroidism?
weight loss, nervousness, heat intolerance, high cardiac output, hand tremors, eyeball protrusion(‘exophthalmos’)
Give an example of a form of hyperthyroidism?
Graves disease ~ 50% of all cases
Due to thyroid-stimulating antibodies that mimic TSH!
(high T3/T4, low TSH, goitre)
protruding eyeballs
What other types of hyperthyroidism are there? (2)
Primary due to hypersecreting thyroid tumour
(high T3/T4, low TSH, no goitre)
Secondary due to excess hypothalamic or anterior pituitary secretion (high T3/T4, high TRH and/or TSH, goitre)
Treatment options for hyperthyroidism? (3)
- “Anti-thyroid drugs”
- surgical ressection of thyroid
- thyroid ablation using radioactive iodine
How do anti thyroid drugs work?
that interfere with thyroid hormone synthesis. These block the thyroid peroxidase enzyme thus preventing the iodination of thyroglobulin
Examples of drugs used for hyperthyroidism?
- Carbimazole - prodrug that is converted to active form Methimazole
- Propylthiouracil is given in a block replacement stratergy with Levothyroxine
Also given if Carbimazole is not tolerated
What problems can arise with use of hyperthyroid drugs?
Long term use = thyroid hypertrophy goitre
Carbimazole can cause rashes
also can cause suppression in bone marrow. normally presents as a sore throat/mouth ulcers and fever
How to diagnose thyroid disease?
- Thyroid function tests
Measure TSH and Thyroid hormones by immunoassay
How to diagnose pituitary malfunction?
Using TSH stimulation test
TRH administered and TSH measured from samples at 0,20 and 60 mins. Note difference in response i.e. no response in secondary and slow response in tertiary hypothyrodism
