21-22 Thyroid physiology Flashcards
Thyroid follicular cells secrete _________________into lumen of the follicles, and tyrosine residues of _______________(same) provides the substrate for thyroid hormone synthesis.
Thyroglobulin, a colloid material (TG)
Thyroid hormone is synthesized in _____________________ and stored in ______________/
Thyroid follicles; colloid
What are thyroid bruits?
When will it occur?
Bruits are vascular murmurs, which could be heard over a hyperactive thyroid gland with the sound of high turbulent flow
The first step of thyroid hormone synthesis is the ___________uptake into thyroid follicle cells by ______________.
iodine;
NIS (sodium-iodide transporter)
How does a sodium-iodide transporter work?
It works by bringing 2 Na+ in and thus 1 I- in as well
Which of the following steps require TPO (thyroid peroxidase)?
A. Iodine uptake by NIS
B. Oxidation of iodide (I-) into a reactive intermediate I*
C. Iodination of tyrosine residues of the thyroglobulin to form MIT and DIT (iodotyrosine)
D. Coupling of 2 iodotyrosines to form iodothyronine (MIT + DIT = T3, DIT + DIT = T4)
E. Endocytosis of thyroglobulin into follicular cells
F. Proteolysis of thyroglobulin in the lysosomes to release thyroid hormones
B,C,D only
Recycling of iodide from MIT and DIT requires dehalogenase.
What is the ratio of T4 to T3 release?
T4:T3 = 15:1
sometimes is 10:1
Name the 2 drugs that aim at TPO (thyroid peroxidase) as anti-thyroid drugs.
List their respective actions.
- Propylthiouracil: blocks iodination to from T4 and T3
- Carbimazole: metabolize to form methimazole, prevent TPO form coupling and iodinizing the tyrosine residues on thyroglobulin
Why will inhibition of hormone synthesis only produce a delay effect in lowering plasma levels?
Because there is a store of thyroid hormones in colloid material
What will happen to the levels of TSH, I- uptake and T3 and T4 when there is thyroiditis?
Thyroiditis (inflammation of the thyroid gland) may result in destructive thyrotoxicosis due to leakage of hormones
TSH decreases (-ve feedback)
I- uptake decreases
T3 and T4 levels increased
(thyroglobulin also increases)
Which of the followings are stimulatory effects of TSH?
A. Endocytosis B. Proteolysis C. Generation of H2O2 D. Synthesis of thyroglobulin E. Synthesis of TPO F. Synthesis of sodium-iodide transpoters
All of the above
Trophic effect of TSH on thyroid gland on prolonged stimulation will cause?
Hyperplasia and hypertrophy, resulting in Goitre, and increase thyroid blood flow (with vascular bruit)
What effect does dopamine and somatostatin has on thyroid hormone production?
It inhibits the release of hypothalamic neurons, TRH and therefore TSH
Describe the autoregulation of thyroid hormone production.
Iodide uptake is inversely related to intrathyroidal concentration of iodide.
Therefore expression of NIS is inhibited by high intrathyroidal [I-]
What is the Wolff-Chaikoff effect?
Thyroid hormone synthesis (organification) is blocked above a critical concentration of intrathyroid iodide.
(= high intrathyroidal [I-] will stop the following step: organification of iodine)
- intake of KI after nuclear accidents is an example
- high iodine intake > NIS raises the intrathyroidal I- above critical condition, leading to compounds that inhibits TPO
Which of the following about thyroid hormone secretion is false?
A. Thyroid hormone release is blocked by a pharmacological dose of iodide
B. Under the state of iodine deficiency, T3 is preferentially synthesized and secreted over T4
C. the increase in organification of iodine will affect the concentration of intrathyroid iodide by negative feedback.
D. The increase in concentration of intrathyroid iodide will affect the uptake of iodide by thyroid
C.
Should be Wolff-Chaikoff effect, in which increased concentration of intrathyroid iodide will inhibit the organification of iodine (which occurs after)
D is true, the autoregulation
What does it mean by Wolff-Chaikoff escape?
Normally, the effect is brought by high iodine intake causing NIS to raise the intrathyroidal I- above critical condition, so that compounds will inhibit TPO.
Escape means that there is a decrease in NIS expression, causing a decrease in iodine trapping
Why are children more susceptible to thyroid diseases?
They have higher chances of drinking contaminated milk and they have smaller thyroid glands
What will happen when there is a deficiency in iodide intake?
Goitre and possibly hypothyroidism
List 3 possibilities of having excess iodide in thyroid.
- Iodide-induced hyperthyroidism (increased substrate for hormone synthesis with no Wolff-Chaikoff block)
- Thyroiditis (autoimmunity)
- Hypothyroidism (from Wolff-Chaikoff effect with no escape)
Which of the following about T3 and T4 is/are false?
A. T3 is more potent than T4
B. Plasma concentration of T4 is several times higher than T3
C. 20% of T3 is obtained from 5’-deiodination of T4 in peripheral tissues, 80% is from thyroglobulin
D. T4 is inactivated to rT3 by 5-deiodination
E. Measurement of free T4 gives a good indication of T3 levels of blood
F. Alternative pathway of T4/T3 metabolism generates TETRAC and TRIAC (tiratricol) - a form of thyroid hormone metabolite with thyromimetric activity (25%-35%)
G. T4 is cleared more rapidly than T3
C and G
Should be reverse,
80% peripheral conversion
G: T3 is cleared more rapidly and gives greater fluctuations in plasma concentrations
Match the following
A. PTU, MMI
B. I-, SCN-, CIO-
C. I-, Li+
D. PTU, iopanoic acid, amiodarone: block K+ channels; propanolol: block beta 2, glucocorticoids
- Conversion of T4 to T3 by 5’-deiodination
- Thyroid hormone release
- Thyroid hormone synthesis
- Iodide uptake
A: 3 (inhibit TPO by antithyroid drugs like PTU, MMI, CBZ)
B: 4 (I-, SCN-, CIO- all block NIS to stop uptake of iodide)
C: 2 (pharmacological dose of KI and Li+ can block thyroid hormone release)
D: 1 block peripheral conversion of T4 to more potent T3
What are goitrogens?
They negatively affects thyroid hormone synthesis, release and metabolism.
With reduced negative feedback, there is elevated TSH that stimulates thyroid enlargement *goitre
Which of the followings are not possible causes of goitre? A. Autoimmune disease B. Iodine deficiency C. Goitrogens D. Thyroiditis
None of the above
A: Grave’s disease: thyroid stimulating immunoglobulins stimulate thyroid growth and hypersecretion of hormones, activating antibodies develop against the TSH receptor (bind to TSH, hypersecretion of hormones)
B, C: reduce -ve feedback > increase TSH
D: autoimmune disease as well, but unlike Grave’s, it will eventually cause hypothyroidism
