A. THYROID GLAND AND HORMONES Flashcards
where is the thyroid gland
under Adam’s apple around trachea
what are the 3 thyroid hormones
- thyroxine (T4)
- tri-iodothyronine (T3)
- calcitonin
where is calcitonin produced and what is its role
(‘calcium reducing’)
- by parafollicular ‘C’ cells
- to reduce plasma calcium levels
what is parathyroid hormone
- secreted by parathyroid glands which are 4 small glands located on posterior surface of thyroid gland
- increase plasma calcium levels
what is T4 and T3 made of
- tyrosine and iodine
- T4 = 2x di-iodotyrosine
- T3 = 1x mono-iodotyrosine and 1x di-iodotyrosine
what is the role of thyroid peroxidase
- catalyses iodination and coupling of MIT and DIT
what is reverse tri-iodothyronine (rT3)
- biologically inactive
- antagonist at T3 receptors
- made of MIT and DIT but different 3D structure to T3
proportions of T4, T3, rT3 in body
- 90-95% T4
- 5-10% T3
activity of TRH
- tropic: regulates TH production/release
activity of TSH
- tropic: regulates TH production/release
- trophic: maintains integrity of thyroid gland
how do thyroid hormones act in the circulation
- they are highly lipophilic
- highly bound to plasma proteins hence biologically inert
- <0.1% T4 & <1.0% T3 is in unbound (free) form
why measure free T4/T3 for thyroid function
- as 99.9% not readily availible
how is T4 converted to T3
- deiodinase enzymes in periphery which remove iodine
- T3 is 4-5x more potent than T4
- T4 functions largely as a pro-hormone
- T3 is principal active hormone
actions of thyroid hormones
- increase metabolism in body in nearly all tissues as most have thyroid receptors
- increased metabolism of CHOs, proteins, fats
- so increased oxygen consumption and heat production
i.e. increase basal metabolic rate = basic rate at which cells function at rest - stimulate growth and development
- good for young children - up regulate expression of B-ARs so promote CV effects
what is a goitre
- enlargement of thyroid gland
what is a diffuse goitre
- whole of thyroid gland
- occurs when there is overstimulation of thyroid gland by TSH or TSI
what is a nodular goitre
- discrete area clearly different from surrounding thyroid gland eg- a thyroid tumour
- effects on surrounding cells
hypothyroidism caused by primary failure of thyroid gland
- 90% primary cases caused by this
- Hashimoto’s thyroiditis
- autoimmune disease caused by an overactive immune response against substances/tissues normally present in body
- decreased T3 and T4
- increased TSH (ie trophic activity)
- goitre present
hypothyroidism secondary to hypothalamic or anterior pituitary failure
- decreased T3 and T4
- decreased TSH (ie less trophic activity)
- no goitre
- shrinkage of thyroid gland seen
hypothyroidism due to lack of dietary iodine
- decreased T3 and T4
- increased TSH
- goitre present: simple, non-toxic
what else can cause hypothyroidism
- drug induced (e.g. anti-thyroid drugs, lithium, amiodarone)
- radioactive iodine therapy, surgery
- thyroid hormone resistance
how does hypothyroidism affect metabolism
REDUCTION in metabolic activity
- decreased BP
- decreased body core temperature
- decreased sweating
- cold intolerance
- decreased appetite
- weight gain due to low metabolism
- constipation
how does hypothyroidism affect CNS
SLOWING DOWN
- depression
- confusion
- poor memory
- difficulty concentrating
- cretinism (perinatal): dwarfism and mental retardation
how does hypothyroidism affect CVS (resting)
- decreased HEART RATE
- decreased arterial blood pressure
what other effects does hypothyroidism have
- growth deficiency (childhood)
- dry skin
- hoarse voice
- menstrual problems
*every newborn tested for TSH and T4 within 5 days of birth
diagnosis of hypothyroidism
Thyroid function test
- primary: decreased T3 and T4, increased TSH
- secondary (usually pituitary disease): decreased T3 and T4, decreased TSH
- if suspect Hashimoto’s, test for thyroid antibodies
- anti-microsomal (TPO), anti-thyroglobulin antibodies
what is the goal when treating hypothyroidism
- euthyroid state
1st drug treatment for hypothyroidism
Levothyroxine (T4)
- drug of choice
- orally active
- once a day (long half-life)
what cautions need to be taken with levothyroxine
- can switch up metabolism in body and increase expression of B-ARs
- may worsen or uncover angina
- angina: give beta-blocker to decrease B-AR enhanced activity
- baseline ECG with initial dosage
2nd drug treatment for hypothyroidism
Liothyronine (T3)
- max effect 24h, disappear 24 - 48h
- not used routinely, rapid onset can induce heart
failure due to higher potency
- used in severe hypothyroid states when rapid response is desired (IV)
what is thyrotoxicosis
- toxic levels of T3 and T4
hyperthyroidism caused by abnormal levels of thyroid-stimulating immunoglobulins
- Graves’ disease
- increased T3 and T4
- decreased TSH
- goitre present due to TSIs
hyperthyroidism secondary to excess hypothalamic or anterior pituitary secretion
- increased T3 and T4
- increased TSH due to increased TRH or tumour
- goitre present due to increase in trophic activity
hyperthyroidism caused by a hyper-secreting thyroid tumour
- increased T3 and T4
- decreased TSH
- goitre present: toxic, multinodular, toxic adenoma
other causes of hyperthyroidism
- latrogenic (eg - amiodarone, lithium)
what is the most common cause of hyperthyroidism
- 90% of cases
- f:m 10:1
- autoimmune: TSIs bind to TSH receptors on thyroid gland and activate the thyroid gland to produce and release thyroid hormones
symptoms of Graves’ disease
- nervousness
- palpitations
- weight loss
- tremor
- sweating
- heat intolerance
- goitre
- exophthalmos: distinct for only Graves’
protrusion of both eyes (30% have)
how does hyperthyroidism affect metabolism
INCREASE in metabolic activity
- increased BP
- increase BMR
- increased body core temperature
- increased sweating
- heat intolerance
- increased appetite
- weight loss due to high metabolism (body burning CHOs, fat and proteins to heat)
- diarrhoea
how does hyperthyroidism affect CNS
INCREASE in neuronal function
- anxiety
- emotional
- irritable
- restless
- tremor
how does hyperthyroidism affect CVS
enhancement of B-AR responses so sympathetic nervous system activity enhanced
- increased heart rate
- increased arterial BP
- palpitations
what other effects does hyperthyroidism have
- growth acceleration (childhood)
diagnosis of hyperthyroidism
Thyroid function test
- increased T3 and T4
- decreased TSH (Graves’ disease/ tumour)
- radioactive isotope scan to show regions of thyroid gland
- presence of thyroid autoantibodies - autoimmune condition
what is the goal of hyperthyroidism treatment
- euthyroid state
- symptomatic relief from increased sympathetic activity
what are anti-thyroid drugs are used for hyperthyroidism
Thionamides
- Carbimazole and propylthiouracil
- if sensitivity to carbimazole, use propylthiouracil
how do carbimazole and propylthiouracil work
- decrease production of thyroid hormones, by inhibiting iodination and coupling processes (via TPO)
- PTU also blocks T4 to T3 deiodination
- several weeks for clinical response to occur (due to colloid stores)
- usually for 12-18 months, but ~50% relapse rate
- will become hypothyroidic
when to use propylthiouracil
carbimazole:
- rashes & pruritus are common (2-25%)
- RARE complication (0.1-1.2%) – neutropenia and agranulocytosis (bone marrow suppression)
- reversible
what should you use whilst waiting for anti-thryoid drugs to bring about a clinical response
- non-selective beta-blockers
- reduce actions of catecholamines
- rapid symptomatic relief of tremor, palpitations, anxiety (within 4 days)
dose titration approach with anti-thyroid drugs
- where only anti-thyroid drugs are used
- doses are adjusted to achieve normalisation of thyroid hormone production
- 12-18 months
- lower rate of side effects but both are equally effective
block and replace approach with anti-thyroid drugs
- where anti-thyroid drugs are given with thyroxine
replacement - 6-12 months
hyperthyroidism treatment with radioactive iodine (131I)
- taken up into thyroid gland and destroys cells with high energy beta-emission
- first-line for older patients with nodular goitres
and hyperthyroidism - used when thyrotoxicosis recurs after anti-thyroid drug therapy
- given as single drink or capsule
- max effect 2-4 months after due to slow destruction of thyroid follicular cells
- hypothyroidism may result if too many cells destroyed
hyperthyroidism treatment with a thyroidectomy (partial)
- not frequently used
- used when severe thyrotoxicosis associated
with a large goitre or concern about tumour
development - used when there are obstructive symptoms (breathing and swallowing)
- hypothyroidism may result
