Hypothyroidism & hyperthyroidism Flashcards
What are the 2 types of thyroid hormone?
Triiodothyronin (T3)
Thyroxine (T4)
How are thyroid hormones produced?
- The follicular cells apical surface surrounds a central lumen filled with viscous fluid (colloid)
- Basolateral surface is in contact with the blood stream
- Inorganic iodide ions from blood enter the follicular cells (+2 Na ions) through sodium iodide symporter
- Iodide ion passes into the colloid through pendrin protein
- Colloid contains thyroglobulin (precursor of thyroid hormone)
- In the colloid, inorganic iodide undergoes oxidation using thyroid peroxidase to become organic iodide which binds to tyrosinne in thyroglobulin (iodination)
- Some tyrosine molcules bind to 1 iodine atom = monoiodotyrosine (MIT)
- Some tyrosine molecules bind to 2 iodine atoms = Diiodotyrosine (DIT)
- MIT and DIT couple together using thyroid peroxidase to form T3 and T4
Which thyroid hormone is the more active form?
T3 (shorter half life)
T4 is produced in greater amounts but converted into T3 once inside their target cell (5-deiodinase enzyme)
How do thyroid hormones travel around the blood stream?
T3 and T4 travel mostly bound to thyroxine binding globulin (TBG) to their target cell
Is thyroid disease more prevalent in men or women? Is hypo or hyper thyroidism more common?
Women are 5-10x more likely to get thyroid disease
Hypothyroidism is more common (5%) Hyper (2.5%)
How is thyroid hormone level controlled in normal physiology? What is the effect of thyroid hormone in the body once inside cells?
- Hypothalamus detects low blood levels of thyroid hormones and releases thyrotropin releasing hormone (TRH)
- TRH travels to the anterior pituitary which stimulates the release of thyroid stimulating hormone (TSH)
- TSH stimulates the thyroid gland to produce thyroid hormones (T3 and T4) in the follicular cells which convert thyroglobulin (protein found in follicular cells) into iodine containing hormones (T3 & T4)
- T3 and T4 enter the blood stream and bind to circulating plasma proteins and only a fraction of T3 (0.5%) and T4 (0.02%) will travel unbound in the blood and picked up by cells
- Once inside the cell, T4 is mostly converted to T3 (which can take it’s effect)
- T3 serves to speed up basal cell metabolic rate making the cell produce more proteins and burn more energy (fats and sugar)
- T3 also increases cardiac output, stimulates bone resorption and activates the SNS
What are the 3 types of hypothyroidism?
- Primary - thyroid gland not producing enough thyroid hormone
- Secondary - failure of the pituitary gland to secrete thyroid stimulating hormone (TSH). This is usually caused by a tumor in the region of the pituitary.
- Tertiary - Hypothalamus doesn’t produce enough TRH
Causes of primary hypothyroidism (4)
- Iodine deficiencies most common cause in LOW income countries (they do not fortify foods with iodine)
- Hashimotos thyroiditis is the most common cause in DEVELOPED countries (autoimmune disorder where T cells, antithyroid peroxidase and antithyroglobulin infiltrate the thyroid gland)
- Post treatment for hyperthyroidism (surgery removing parts of thyroid or radioiodine therapy which damages follicular cells)
- Congenital hypothyroidism (newborns thyroid either doesn’t develop normally or there is a defect in the thyroid and it can’t produce thyroid hormones)
Causes of secondary hypothyroidism (2)
- Tumour on anterior. pituitary (compressing pituitary and preventing production of TSH
- Damage to hypothalamus (tumours or trauma = less thyrotrophin releasing hormone)
Symptoms of hypothyroidism
- Weight gain (lower metabolic rate)
- Cold sensitivity (body isn’t producing as much heat)
- Slower HR (decrease SNS)
- Brain fog (decreased SNS)
- Lethargy (decreased SNS)
- Constipation (decreased SNS)
- Myxoedema - swelling of soft tissues like tongue
- Goitre (hashimoto’s thyroiditis in acute phase)
- Myxedema coma in severe uncontrolled hypothyroidism (confusion and hypothermia)
In children / babies
- Excessive sleeping
- Delayed physical growth and height
Diagnosing hypothyroidism
- Blood levels of TSH, T3, T4
- T3 and T4 will be low in all cases by TSH levels will vary depending on cause
Primary cause = TSH high
Secondary cause = TSH low
Treatment of hypothyroidism
Using thyroid hormone analogues to replace body with normal levels of thyroid hormone
If iodine def = food rich in iodine (fish, meat, eggs)
Liothyronine (T3 replacement)
- shorter acting but more potent
- drug of choice in myxedema
- severe side effects of hyperthyroidism
- contraindicated in those with heart conditions
Levothyroxine (T4 replacement)
- less potent but longer acting
- 6-8 wks for therapy to take effect
- Treatment of choice for long term management
- Treatment of choice in pregnancy (increase dose in pregnancy as TBG increase due to oestrogen increase)
- Less severe side effects but lower dose for elderly and those with heart disease
How does TSH suppressive therapy work?
- Some thyroid cancers or thyroid nodules are TSH sensitive.
- We can use synthetic thyroid hormones to suppress the hypothalamus producing TRH which then suppresses the anterior pituitary from producing TSH
- Liothyronine can be used to prevent the growth of thyroid nodules
- Levothyroxine can be used to prevent the return of thyroid cancer
- This type of treatment should be avoided because it carries a high risk of adverse side effects such as AF, stroke, osteoporosis and fractures.
- It might be recommended in those with history of thyroid cancer with significant risk of it reoccuring
Side effects of long term treatment with synthetic thyroid hormones and contraindications of use
- Thyroid hormones stimulate bone resorption and bone remodelling and therefore, long term treatment with thyroid hormones can cause osteoporosis
- Thyroid hormones can also worsen glycaemic control in those with diabetes
- Thyroid hormones should not be used to treat obesity or cause weight loss
- Not to be used in those with uncorrected adrenal insuffiency.
- This is because thyroid hormones increase hepatic metabolism of glucocorticoids.
- In adrenal insufficiency, adrenal glands are unable to increase glucocorticoid production and compensate for increased turnover which can precipitate an adrenal crisis
