L11- Thyroid Gland Flashcards
(23 cards)
Structure (structure, cells withing, follicle and lobes
• Follicular structure of the thyroid gland
• C cells within the thyroid gland
(Parafollicular) – secrete calcitonin
- Human thyroid follicle – Thyroglobulin-filled follicular lumen (colloid)
- R +L Lobes anterolaterally on trachea – can have an extra lobe (Pyramidal lobe)
parathyroid tissues
four parathyroid glands and these are located on posterior surface of thyroid gland.
Parathyroid hormone production
Normal thyroid follicle (size and molecules within)
- Size and shape of epithelial cells and amount of thyroglobulin is dynamic
- Thyroglobulin contains sufficient iodide to supply thyroid hormones for 90 days
- ~ 300 µm
Regulation of function
- Control of TSH secretion from pituitary thyrotropes
- Anterior pituitary secretes:Thyroid Stimulating Hormone (TSH) also known as thyrotropin
o 15% carbohydrate (key determinant of bioactivity and half-life
o Half-life in serum approximately 1 hour/M.W. = 28 kD
o T3 activated/T4 inactivated
Thyroid stimulating hormone structure (alpha, beta and side chains)
- Alpha subunit is identical for all four glycoprotein hormones within a single species
- Beta subunit imparts a unique biological specificity to each hormone
- CHO side chains determine the STABILITY and BIOLOGICAL ACTIVITY of TSH
Effects of TSH on thyroid gland function (Low T3)
Low T3 > Pituitary thyrotropes (alpha and beta increase) > High TSH > Thyroid enlargement and increased activity
o Net Tg loss from lumen o High blood flow o Maximum cellular activity o Pseudopodia on apical cell surface – max extraction o Hyperthyroid: excess T4 secretion
Effects of TSH on thyroid gland function (High T3)
High T3 > Pituitary thyrotropes (alpha and beta decrease) > Low TSH > Thyroid regression and reduced activity
o Net Tg accumulation in lumen o Minimal blood flow o Minimal cellular activity o Minimal apical differentiation (pseudopodia) o Hypothyroid: very low T4 secretion o Hypothyroid
Synthesis of thyroid hormones T3 and T4 (transport and journey through secretory pathway)
- Iodide transport in the follicular cells
- Iodide is transported from the blood into the follicle lumen via NIS (secondary active transporter) and pendrin
Thyroglobulin production in the follicular cells – assembled from AA from ER – moves through Golgi and packed into vesicles – exocytosis and enters the thyroid follicular lumen
Formation and coupling of iodotyrosines in the thyroglobulin molecule (enzymes)
• Thyroid peroxidase (TPO) enzyme complex
o Oxidises Tg → Adds tyrosine → Conjugation (formation of T4 (90%)/T3(10%))
- Spans the apical membrane
- Responsible for iodination of thyroglobulin (Tg)
Formation of DIT or MIT via action of TPO
o Di-iodotyrosine (DIT) – 2 Iodides
o Mono-iodotyrosine (MIT) – 1 iodide
- In conditions of adequate iodide supply:
- Tg - DIT + DIT – Tg = T4
- In moderate iodide deficiency, or after TSH hyperstimulation:
- Tg - MIT + DIT – Tg = T3
Basolateral to apical transport
- T3 and T4 production in the follicular cells
- Apical to basolateral transport
- Tg and …. > Endocytosis > proteolysis – Tg can be recycled
Major binding proteins
- TBG (70%) + albimum bind to both T3 and T4
- TTR only binds T4
- Albumin bind T4 highest capacity > TTR > TBG (lowest
- TBG binds with highest affinity for T4, then TTR then albumin (Lowest)
D1 – converts T4 to T3 and T4 to rT3
D2 also convert T4 to T3
The Iodothyronines (Thyroid Hormones)
- Thyroxine (T4)
- Tri-iodothyronine (T3)
- Reverse T3 = inactive
Why does a goitre develop in severe iodine deficiency?
- Primary hypothyroidism
- Non-toxic goitre
- Endemic goitre
- Lack of idodine = reduction in active thyroid hormone T3 = stops release = PPG stop producing PPG producing TSH?
(a) hypothyroidism (thyroid hormone deficiency). (causes)
Potential causes:
o Inadequate dietary iodide
o Unresponsive thyroid (e.g. impaired TSH receptor function)
• Inhibition of NIS by goitrogens, e.g. cassava, cherries, almonds, cabbage (all rich in thiocyanate)
• Impaired conversion of T4 to T3 in target tissues
• Iatrogenic (e.g. surgery or radiotherapy)
Features and characteristics of hypothyroidism (8)
- Overweight
- Lethargy
- Dry, cool skin
- Myxedema
- Hair loss
- Intolerance of cold
- Slowed movement, speech and thought
- Sleepiness
Treatment of hypothyroidism (3)
- Restore iodide supply (possibly)
- Administer thyroxine tablets
- Administer triiodothyronine tablets (T3) – rare (patient has no TPO)
b) hyperthyroidism (thyroid hormone excess). (causes)
Potential causes:
o Hyperstimulated thyroid gland (TSH-secreting tumour in pituitary – RARE!)
o Autonomously-functioning thyroid (e.g. TSH receptor function even in ABSENCE of TSH)
o Autoimmune stimulation of thyroid by TSH-receptor antibodies (Graves’ Disease – MOST COMMON CAUSE)
Features and characteristics of hyperthyroidism
- Weight loss
- Thyroid enlargement (goitre) – sometimes
- Large appetite
- Hyperactive – high metabolic rate
- Warm, sweaty skin
- Protruding eyes (exopthalmos)
- Intolerance of heat
- Nervousness, tremor
- Osteoporosis due to bone resorption
- Angina, cardiac arrhythmias
Hyperthyroid Graves’ Disease (hyper)
- Antibodies attack fatty tissues at the back of the eye
* Tissue inflammation causes eyes to protrude
Treatment of hyperthyroidism(2)
- Surgical removal of thyroid gland
* Radioactive iodine treatment (e.g. 131I)
Hyperthyroidism – drug treatment (4)
- Thionamide drugs: Carbimazole (competitive inhibitor to TPO), propylthiouracil – the SCN (thiocyanate) grouping is essential
- Competitively inhibit thyroperoxidase enzymes
- Reduce iodination of tyrosine
- Reduce output of T4 and T3
Thionamide drugs: problems (6)
- Slow response; relapse common
- Often results in hypothyroidism
- May result in a goitre due to decreased feedback on TSH
- Skin rashes are common (5%)
- Agranulocytosis (0.3%) neutrophils<500 cells / µl
- Hepatic enzyme induction
