The thyroid gland Flashcards
Where is the thyroid gland located?
What shape and size is it?
The thyroid gland lies across trachea at base of larynx
Butterfly shaped. One of the larger endocrine glands - but neither palpable or visible in health
What does the thyroid gland produce?
Synthesises the Thyroid hormones - of which there are 2 physiologically active forms
These are:
T3 - triiodothyronine
T4 - thyroxine
Describe the structure of the thyroid gland
Contains 2 main cell types:
- C (clear) cells - secrete calcitonin (Ca2+ regulating hormone)
- Follicular cells - support thyroid hormone synthesis and surround hollow follicles
Thyroid follicles:
- Spherical structures lined by follicular cells
- Centre is filled with colloid
Identify the different cells n shit in the thyroid gland
What is colloid?
Sticky glycoprotein matrix - which contains 2-3 months supply of Thyroid hormones
Describe the function of Follicular cells
Manufacture the enzymes that synthesize thyroid hormones and also thyroglobulin - a large protein, rich in tyrosine residues
The enzymes and thyroglobulin are packaged into vesicles and exported from the follicular cells into the colloid
It also moves iodine into the colloid from the blood through active transport
Where do we get our iodide and tyrosine
Diet
How is iodide moved into the colloid from the blood?
Iodide enters the follicular cells from the plasma via a Na+/I- transporter (symport). The coupling to Na+ enables the follicular cells to take up iodide against a concentration gradient
Iodide is then transported into the colloid via the pendrin transporter
What are the thyroid peroxidases?
These are the enzymes that follicular cells exocytose into the colloid along with thyroglobulin
Part of the thyroid hormone production pathway…
They catalyse:
- the oxidation of Iodide to iodine
- The addition of iodine^ to tyrosine residues on the thyroglobulin molecule
What molecules are produced through the addition of iodine in the colloid?
Addition of 1st iodine = MIT (monoiodotyrosine)
Addition of 2nd iodine = DIT (diiodotyrosine)
MIT & DIT can then undergo conjugation reactions:
-
MIT + DIT = T3 (triiodothyronine)
- 3 iodines
-
DIT + DIT = T4 (thyroxine)
- 4 iodines
- aka tetraiodothyronine
Describe the thyroid hormones in terms of tyrosines and iodines
Triiodothyronine
- 2 tyrosines + 3 iodines
Thyroxine
- 2 tyrosines + 4 iodines
Once synthesised - thyroid hormones are stored in the colloid
How is there release triggered?
In response to Thyroid-stimulating hormone - there is uptake of colloid into follicular cells
Within the cells they form vesicles which contain proteolytic enzymes that cut the thyroglobulin to release thyroid hormones.
How do T3 and T4 get into the blood?
Both T3 and T4 are lipid-soluble and so pass across the follicular cell membrane into the plasma
Once in plasma - they bind to plasma proteins, mainly thyroxine-binding globulin
Are there any transporters involved in the movement of thyroid hormones into the blood?
They are lipid soluble so dont need transporter proteins
however
Transporter proteins may also be involved in this process as rare mutations in this protein cause major disruption to TH balance
Movement of TH from colloid to plasma is under the influence of a)______________ released from the b)_________.
c)____________ stimulates the follicular cells to d)_________ colloidal thyroglobulin. When not stimulated, the thyroid hormones are stored in the colloid
Movement of TH from colloid to plasma is under the influence of TSH released from the pituitary. TSH stimulates the follicular cells to endocytose colloidal thyroglobulin. When not stimulated, the thyroid hormones are stored in the colloid
a) Thyroid-stimulating hormone
b) Pituitary gland
c) TSH
d) Endocytose
How do the thyroid hormones circulate?
99.8% of T3 and T4 circulates in plasma bound to plasma protein
Thyroxine Binding Globulin (TBG) has particularly high affinity for T4 releasing it only slowly into the plasma
Only free Thyroid hormones can do anything
What is the inhibitory effect of thyroid hormones in the blood?
Free T4 & T3 exerts an inhibitor effect of TSH and TRH
Compare the levels of T3 and T4 in the blood
Most TH circulates in the form of protein bound T4 ~100nmoles/l, while T3 is only ~2.3nmoles/l
This means about 50x more Thyroxine exists in the blood than T3
However - 90% of TH binding to TH receptors inside cells is T3
Why is T3 more physiologically active than T4?
TH receptor has a much higher affinity for T3 than T4
What is the fate of Thyroxine T4?
T4 is deiodinated to T3 by deiodinase enzymes.
Around half the T4 is deiodinated in plasma, the remaining fraction being deiodinated inside target cells
The level of deiodinase activity can be altered at different times in different tissues to suit demand
We know free TH has an inhibitory effect on TRH and TSH
What stimulates production of TRH in the hypothalamus?
There is a continuous secretion of TRH from the hypothalamus to keep stable hormone levels
However - Cold, exercise and pregnancy stimulate TRH production
What hormones inhibit TSH?
Somatostatin (GHIH) - inhibits TSH
Glucocorticoids - inhibits TSH & conversion of T4 to T3
Describe the effect of thyroid hormone action on target cells
TH bind to nuclear receptors in target cells, where they change transcription and translation to alter protein synthesis.
General actions of Thyroid hormones:
- Increase metabolic rate & thermogenesis
- Increase hepatic gluconeogenesis
- net increase in proteolysis
- net increase in lipolysis
- stimulates GH receptor expression
- brain development in utero
How do thyroid hormones alter metabolic rate?
Increase metabolic rate & thermogenesis
They do so typically through promoting futile cycles of simultaneous catabolism and anabolism.
One of the effects of thyroid hormones is to increase hepatic gluconeogenesis
What is the effect of this on blood glucose?
no effect on BG providing pancreas is releasing adequate insulin
(therefore not a counter-regulatory hormone)
What is the importance of thyroid hormones in growth?
critical for growth (lack of TH results in retarded growth)
stimulates GH receptor expression
Why risk is associated with low maternal iodine levels?
Low iodine levels impact thyroid production
Iodine essential for brain development in utero
Maternal iodine deficiency can cause congenital hypothyroidism
What are the causes of hyperthyroidism?
Graves disease (common)
Thyroid adenoma (rare)
What happens in graves disease?
Antibodies produced that bind mimic TSH and continually activate the thyroid gland.
Increased release of TH switches off TSH release from anterior pituitary so [TSH]plasma very low.
Thyroid gland may be 2-3x normal size due to hyperplasia. Hyperactivity of cells also apparent.
What are the symptoms of Hyperthyroidism?
Weight loss
- Increased metabolic rate
- Increased protein catabolism
Heat intolerance
Muscle weakness/loss
Hyperexcitable reflexes
Psychological disturbances
What are the signs of hyperthyroidism?
Neck swelling (goitre)
Hyperexcitable reflexes
Tachycardia (elevated cardio function)
Psychological disturbance
What are the causes of hypothyroidism?
Hashimoto’s disease - autoimmune attack of thyroid gland
Dietary iodine deficiency
Idiopathic - may have links to thyroiditis
What are the symptoms of hypothyroidism?
Weight gain
Cold intolerance
Fatigued state with slow speech/reflexes
Dry hair/hair loss
Puffiness appearing on face
What are the signs of hypothyroidism?
Neck swelling (goitre)
Brittle nails
Thin skin
Dry hair
Puffy face (facies)
Bradycardia / weak pulse
What is Goitre?
Thyroid gland swelling which can happen with either hypo or hyperthyroidism
caused by increased trophic action of TSH on thyroid follicular cells (hypothyroidism) or over-activity as a result of autoimmune disease (Graves Disease)
What would be the difference between hypothyroidism caused by a thyroid lesion or caused by pituitary lesion?
Thyroid lesion - High [TSH] but low [TH]
Pituitary (2ndary) lesion - Low [TSH], low [TH]
