30 Thyroid Gland Pharmacology Flashcards
What are the two main classes of hormones released by the thyroid gland?
- Thyroid hormones
- T3 (triiodothyronine - Most Active) and T4 (thyroxine)
- T4 has higher levels circulating but not the most active
- Calcitonin
What are the three levels of control for thyroid hormone production?
- TRH (thyrotropin releasing hormone from the hypothalamus)
- TSH (thyroid stimulating hormone from the anterior pituitary)
- T3 and T4 exert negative feedback on both upstream glands
What are three powerful physiological effects of the thyroid hormone?
- Increased basal metabolic rate
- Sensitization to catecholamines (increased cardiac output, heart rate, breathing rate)
- Important role in growth and development
Thyroid hormones are made up of __________ from the precursor protein _______
Thyroid hormones are made up of 2 modified tyrosine molecules from the precursor protein thyroglobulin (tyrosine rich)
Tyrosines that make up thyroid hormones are _____________ and then _________
Tyrosines that make up thyroid hormones are enzymatically iodinated (1 or 2 iodines per ring) and then enzymatically coupled (2 linked rings)
TSH stimulation causes ______ to be endocytosed and processed followed by the release of ___ and ___
TSH stimulation causes precursor protein (thyroglobulin) to be endocytosed and processed followed by the release of T3 and T4 (T4 is predominant)
What happens at the apical side of the follicle lumen?
Iodination and coupling of thyroglobulin
What happens in the intracellular space of the thyroid follicle?
Processing of thyroglobulin after it has been iodinated and coupled
What happens on the basolateral side of the thyroid follicle (by the bloodstream)
Release of T4 and T3 after being generated from thyroglobulin
How does the thyroid gland accumulate and concentrate iodine from the bloodstream?
Using a Na+/I- co-transporter
The thyroid hormone receptor is an ________ type receptor - acts as a _________ after binding of thyroid hormone
The thyroid hormone receptor is an intracellular type receptor - acts as a transcription factor after binding of thyroid hormone
T3 and T4 are not very lipid soluble, so how do they reach their receptors?
Thyroid hormone receptors are intracellular. T3 and T4 don’t easily diffuse across the membrane
- need to be taken up into cells by a transporter protein in order to reach their receptors
At rest, unbound thyroid hormone receptors can associate with ________ and recruit ________
At rest, unbound thyroid hormone receptors can associate with response elements (TRE) and recruit co-repressors (weakens gene transcription)
What happens after T4 and T3 are taken up into the cell by a transmembrane receptor?
- T4 is typically de-iodinated to T3
- T3 binding in the nucleus causes recruitment of RXR (retinoic acid receptor) to form a heterodimer with the thyroid hormone receptor
- Recruitment of co-activators leads to enhanced transcription of target genes
What is hypothyroidism?
- Deficient thyroid fxn = insufficient release of thyroid hormone
Four common causes of hypothyroidism?
- iodine deficiency (dietary)
- Autoimmunity towards thyroid (Hashimoto’s thyroiditis)
- Congenital defect
- Inappropriate hormonal regulation (insufficient TSH or TRH)
What are common symptoms of Hypothyroidism?
- Fatigue
- Weight Gain
- Hypersensitivity to cold
- Bradycardia (reduced cardiac output)
What is the difference between primary and secondary hypothyroidism?
- Primary Hypothyroidism
- Caused by a defect in thyroid function
- Features: Low T4 and T3, High TSH
- Secondary Hypothyroidism
- Caused by Central defect (poor function of anterior pituitary or hypothalamus)
- Features: Low T4 and T3, Low TSH
What is hyperthyroidism?
Overactive thyroid fxn (excessive production of thyroid hormone)
What are two most common causes of Hyperthyroidism?
- Graves’ disease
- Stimulatory auto-antibodies against TSH receptor (ant pit)
- activate the receptor leading to excess thyroid hormone release
- Stimulatory auto-antibodies against TSH receptor (ant pit)
- Hyperplasia of the thyroid leading to excess thyroid hormone release (thyroid adenoma, goiter)
What are five common symptoms of hyperthyroidism?
- Sleep difficulty
- Heat (temperature) intolerance
- Tachycardia
- Weight loss
- Tremor
How does measuring TSH help determine the underlying cause of Hyperthyroidism?
- Graves’ disease
- Caused by stimulation of thyroid by anti-tsh receptor antibodies (stimulatory)
- Features: High T4 and T3, Low TSH
- Detection of anti-TSH receptor antibodies which cause bulging eyes (exophthalmos)
- Thyroid hyperplasia
- Caused by Thyroid adenoma or goiter
- Features High T4 and T3, Low TSH
- Secondary hyperthyroidism (uncommon)
- Caused by central defect (excessive production of TSH by ant pit)
- Features High T4 and T3, High TSH
What is the difference between Graves and Hashimotos thyroiditis?
- Graves:
- Autoimmune
- Antibodies (anti-TSH antibodies) cause stimulation of the TSH receptor
- Hashimotos
- Autoimmune
- Antibodies recognize other thyroid-specific proteins and lead to damage of the thyroid
What are four treatment approaches for hyperthyroidism?
- Surgery
- resection of part or all of the thyroid followed by hormone replacement
- Radioactive iodine tx
- Iodine (131I) is concentrated within the thyroid, radiation leads to destruction of the thyroid
- Anti-thyroid drugs (methimazole)
- Prevents several steps in T4/T3 synthesis
- Symptomatic tx with beta-blockers (short term)
- May help with issues such as tachycardia
What are thioamides? provide an example:
Thioamides (eg Methimazole) prevent iodination and coupling steps (mediated by thyroperoxidase enzyme)
- methimazole inhibits thyroperoxidase enzyme preventing iodination and coupling
