Thyroid Gland Pharmacology Flashcards
What is the Thyroid Gland
“butterfly” shaped gland at the base of the neck
releases two main classes of hormones
1. T3 (most active) and T4 thyroid hormones
2. cacitonin
Thyroid Hormone
- TRH (thyrotropin releasing hormone) - hypothalamus
- TSH (thyroid stimulating hormone) - anterior pituitary
- T3 and T4 exert negative feedback on both upstream glands
Physiological Effects of Thyroid Hormone
- increased basal metabolic rate
- sensitization to catecholamines (increased cardiac output, heart rate and breathing rate)
- important role in growth and development
‘apical’ side (follical lumen)
iodination and coupling of thyroglobulin happen here
intracellular
processing of thyroglobulin after in has been iodinated and coupled
‘basolateral’ side (bloodstream)
T4 and T3 are released here after being generated from thyroglobulin
Thyroid Hormone Receptor
-thyroid hormones ‘break the rules’
- is an intracellular type receptor- acts as transcription factor after binding of thyroid hormone
- T3 and T4 are not very lipid soluble and need to be taken up into cells by a transporter protein in order to reach their receptor
Mechanism of Action of Thyroid Hormone
- at rest, unbound thyroid hormone receptors can associate with response elements (TRE) and recruit co-repressors
- T3 and T4 are taken up via a transmembrane receptor and T4 is typically de-iodinated to form T3
- T3 binding in the nucleus causes recruitment of RXR to form a heterodimer with the thyroid hormone receptor
- recruitment of co-activators leads to enhanced transcription of target genes
Hypothyroidism ( what is it? causes? symptoms? )
deficient thyroid function (not enough release of thyroid hormone
causes:
- iodine deficiency (dietary)
-autoimmunity towards thyroid (hashimoto’s thyroiditis)
-innapropriate hormonal regulation (insufficient TRH or TSH)
- congenital defect
symptoms:
- fatigue
-weight gain
-hypersensitivity to cold
-bradycardia
Diagnosis and Treatment of Hypothyroidism
diagnosis: measurement of TSH is helpful to know whether hypothyroidism is primary or secondary
treatment; hormone replacement, most commonly with synthetic thyroxine (T4) - levothyroxine is extremely commonly prescribed
primary hypothyroidism
cause: defect in thyroid function
features: low T4 and T3, high TSH
secondary hypothyroidism
cause: central defect (poor function of anterior pituitary of hypothalamus
features: low T4 and T3, low TSH
Hyperthyroidism (what is it? causes? Symptoms?)
overactive thyroid function (excessive production of thyroid hormone
causes:
- Graves’ Diseases (stimulatory auto-antibodies against TSH receptor, these activate the receptor leading to excess thyroid hormone release)
- hyperplasia of the thyroid leading to excess thyroid hormone release
symptoms:
- sleep difficulty
-heat/temperature intolerance
-tachycardia
-weight loss
-tremor
Diagnosis and Treatment of Hyperthyroidism
diagnosis: measurement of TSH is helpful to determine underlying causes, also detection of anti-TSH receptor antibodies
treatment:
1. surgery
- approach: resection of part or all of thyroid, followed by hormone replacement
-drawback: danger of disrupting parathyroid glands, needs management for hypothyroidism)
- radioactive iodine treatment
- approach: iodine is concentrated within the thyroid, radiation leads to destruction of the thyroid
- drawbacks: should not be used in pregnancy, nursing (irreversible destruction of thyroid of infant) - anti-thyroid drugs (methimazole)
- approach: prevents several steps in T4/T3 synthesis
-drawbacks: diverse side effects - symptomatic treatment with beta-blockers
- approach: may help with issues such as tachycardia
- drawbacks: does not influence underlying cause of the disease
Graves’ Disease
cause: stimulation of thyroid by anti-TSH receptor antibodies
features: high T4 and T3, low TSH, detection of anti-TSH receptor antibodies, ‘bulging eyes’, exophtalmos
