Lecture 13 - Thyroid Gland Flashcards
Desc. the structure and location of the thyroid gland.
- Below the thyroid cartilage, around front larynx and trachea
- 2 lobes joined by central isthmus
Desc. the embryological development of thyroid gland.
- First endocrine gland to develop
1. At 3-4 weeks of gestation, appears as an epithelial proliferation at base of tongue.
2. Migrates down thyroglossal duct
3. Duct subsequently degenerates
4. Thyroid gland reach final position over 2 weeks.
What are follicular cells arranged in and what is it filled with?
- Arranged in follicles
- Filled with colloid (thyroglobulin)
What is the difference between parathyroid and thyroid gland?
Thyroid Gland:
- Follicular cells secrete thyroid hormone
- Parafollicular cells secrete calcitonin
Parathyroid Gland:
- Principal/Chief cells secrete parathyroid hormone
Desc. the structure of T3 & T4. Give full name.
T3: Triiodothyronine
MIT (Monoiodotyrosine) + DIT (Diiodotyrosine)
T4: Tetraiodothyronine
DIT + DIT
Desc. the synthesis of T3 & T4
- Transport of iodide into the epithelial cells against concentration gradient.
- Synthesis of thyroglobulin
- Exocytosis of thyroglobulin into lumen of follicle
- Oxidation of iodide to produce iodinating species
- Iodination of side chains to form MIT (mono-iodotyrosine) and DIT.
- Coupling of DIT + MIT to form T3 & T4.
(soic)
What is the function of thyroid peroxidase
- Oxidation of iodide to iodine
- Iodination of thyroglobulin
- Coupling of MIT or DIT
How is iodine absorbed through the diet?
- Dietary iodine –> iodide before absorption
- Iodide taken up by cells that have ‘sodium-iodide symporter’
Where and why is T4 converted to T3?
- Converted in liver and kidneys
- T3 is biologically active
- Transported via thyroxine-binding globulin
Desc. the pathway of secretion of thyroid hormones
- Hypothalamus
TRH (Thyrotropin releasing hormone) - Anterior Pituitary (- feedback on TRH)
TSH (Thyroid stimulating hormone) - Thyroid gland (- on TRH + TSH)
T3+ T4
What is TSH and what are its functions?
- Glycoprotein hormone (a & b subunits, b is biologically active)
- Functions:
i. Iodide uptake
ii. Thyroglobulin synthesis
iii. Thyroglobulin iodination
Effects of thyroid hormone.
- Increase BMR + Heat production (except brain, spleen & testis)
- Increase no. & size of mitochondria
- Stimulate synthesis of enzymes in respiratory chain
2.⬆️ Lipolysis and b-oxidation of fatty acids
⬆️Gluconeogenesis & glycogenolysis
- Increase target cell effects to adrenaline
Increase no. of receptors
Specific effect of adrenaline on heart and nervous system
- Cardiovascular system: ⬆️ cardiac output, ⬆️ H.R, Vasodilation
- Nervous system: ⬆️ Myelination of nerves
Desc. mechanism of T3 & T4
- Diffuse across plasma membrane (lipid sol)
- Bind to specific high affinity receptors (T3 higher)
- Results in conformational change and unmasks the DNA binding domain
- Interaction of hormone-receptor complex w DNA ⬆️ rate of transcription
- ⬆️ protein synthesis, cell activity, demand for energy
Examples of thyroid hormone activated genes…
- PEPCK (Phosphoenolpyruvate carboxy kinase)
- Cytochrome oxidase
- Ca2+ ATPase
- Na+, K+ ATPase
What is goitre?
- Enlargement of the thyroid gland due to overstimulation
- May be present in hyper- or hypo-
Causes of hypothyroidism
- Thyroid gland failure
- TSH/TRH deficiency
- Inadequate iodine
- Autoimmune disease
- Post surgery
Symptoms of hypothyroidism
- Bradycardia (reduced responsiveness to catecholamines + heart muscle proteins)
- Muscle weakness
- Alopecia (due to reduced protein synthesis)
- Dry, flaky skin (due to reduced protein synthesis)
- Obesity
- Lethargy
- Intolerance to cold
- Slow reflexes
*Associated with low T3+ T4, ⬆️TSH
What is cretinism?
- Hypothyroidism in infants
- Mental and physical retardation
- Poor bone dev.
- Muscle weakness
What is myxedema?
- Hypothyroidism in adults
- Thick puffy skin, Muscle weakness, slow speech, mental deterioration
What is Hashimoto’s disease?
- Autoimmune disease that results in destruction of thyroid follicles. Form of hypothyroidism
- More common in women
- Goitre yes or X
Treatment for Hashimoto’s disease?
- Oral thyroid hormone
- Using T4, longer half life
- Usually single dose per day
What are the causes of hyperthyroidism?
- Graves’ disease (autoimmune)
- Toxic multinodular goitre
- Solitary toxic adenoma
- Drugs
- Excessive T4 or T3 therapy
Symptoms of hyperthyroidism
- Exophthalmos (bulging eyes)
- Weight loss
- Heat intolerance
- Irritability
- Tachycardia
What is Graves’ disease?
- Autoimmune disease resulting in hyperthyroidism
- Caused by production of thyroid stimulating immunoglobulin (TSI)
- TSI continuously stimulates thyroid hormone secretion outside of negative feedback control
*High T3+T4, low TSH
What is the isotope used for scanning of the thyroid using a gamma camera?
- Technetium-99m (half life= 1 day)
What are anti-thyroid drugs used for? Give an example of one.
- Treat overactive thyroid
- Carbamizole (pro-drug, after administration is converted/metabolised to smt else)
- Converted to methimazole
- Prevents thyroid peroxidase from coupling and iodinating tyrosines
What type of receptor do both T3 & T4 bind to to elicit a cellular response?
- Nuclear receptor
- Associated with a conformational change in the receptor that causes increase of transcription
Which protein serves to transport thyroid hormone (T3 & T4) in plasma?
- Mainly is thyroxine-binding globulin
- Proteins transthyretin and albumin
How is hypothyroidism treated?
Levothyroxine (Contains iodine)
A 44 year old female patient has a thyroid function test. Her plasma levels of free T3 and free T4 are within the normal range but her TSH is undetectable.
What term would best describe this finding?
- Subclinical hyperthyroidism (characterised with low or undetectable concentration of serum TSH with free triiodothyronine and free thyroxine levels within laboratory reference ranges)
Which drug can be associated with disrupted thyroid function?
- Amiodarone
- Sructurally similar to thyroxine and so can disrupt thyroid function (both hypo- and hyperthyroid effects have been reported with this drug).
What is the half life of T3 & T4 hormones?
- T3: 1 day
- T4: 5-7 days
What is the most common cause of goitre in the UK and globally?
- UK: Toxic multinodular goitre
- Global: Iodine deficiency
Why did the thyroid gland move up when the woman was asked to swallow?
- Because it is invested by the pre-tracheal fascia which holds the gland onto the larynx and the trachea.
What is another name for Hashimoto’s disease?
Chronic auto-immune thyroiditis
What is the mode of action of drugs that treat hypothyroidism?
e.g. levothyroxine
- Binds to thyroid hormone receptors on DNA to modulate gene transcription
- Increase rate of transcription
A patient with hypothyroidism presents with a palpable mass at the base of her neck in the midline. What is this sign called and how has it occurred in this patient?
- Goitre
- Increased TSH due to negative feedback of high T4 and T3. TSH has trophic effects on the gland that result in increased vascularity, increase in size and number of the follicle cells.
