Thyroid

Describe follicular structure

Colloid in the centre

Follicular epithelium surrounds colloid

Some blood vessels present between follicles

What is thyroid hormone derived from

tyrosine

incorporates iodine

Forms of thyroid hormone

Precursor

* Thyroglobulin

Thyroid hormone

* T4
* T3

Describe synthesis of TH

1. Protein synthesis produces thyroglobulin and associated enzymes
2. Above transported and stored in colloid
3. Iodide co-transported into cell and colloid via transporter making it available to be added to thyroglobulin – makes T3 and T4
4. Thyroglobulin taken back into cell when needed
5. Enzymes separate T3 and T4 enzymes from backbone
6. T3 and T4 available for circulation

Which makes up most proportion - T3 or T4

T3 - 10%, T4 - 90%

T3 is more active and so most effects are due to it

Half life of T3 vs T4

T3 - 1 day

T4 - 6 days

Describe the hormonal pathways which regulate secretion of TH

1. Neuroendocrine cells secrete TRH into hypophyseal portal system
2. TRH goes into anterior lobe of pituitary gland where it binds to thyrotrophs where it stimulates TSH
3. TSH released into circulation and travels to thyroid gland
4. TSH causes synthesis and release of T3 and T4

Effect of sympathetics on TH release

activates it

How does TSH work?

1. Secreted from thyroid tropes within the anterior pituitary lobe
2. Bind to receptor on thyroid follicular epithelial cells
3. Stimulates functions of thyroid glands


1. Inc iodine uptake
2. Inc protein synthesis
3. Inc re-uptake of colloidal thyroglobulin
4. Increases size, number and secretory activity of thyroid cell
5. Increases synthesis and release of T3 and T4

3 physiological actions of thyroid hormone

* Growth
* Cardiovascular
* Basal metabolic rate

How does thyroid hormone contribute to growth?

* Thyroid hormone essential for normal growth in childhood
* Critical for CNS development

Effects of lacking T3/4 in late foetal/early neonatal period

Irreversible CNS development

* Reduction in neurone number
* Reduction in myelination

How does thyroid hormone contribute to cardiovascular?

* Increased manufacture and incorporation of B1 adrenergic receptors
* Increased responsiveness
* Sets heart sensitivity to Ad/Nad
* Long term sensitivity of cardiac cells is regulated by plasma levels of thyroid hormone

Define basal metabolic rate

Rate at which body uses energy to maintain vital functions whilst at rest

Changes in thyroid hormone can change basal metabolic rate

THis can be seen as…

This can be measured as…

* Increased oxidative metabolism
* Increased heat production

Increased thyroid hormone … basal metabolic rate

increases

Effects of increased basal metabolic rate

* Catabolic and anabolic reactions in pathways affecting fats, carbohydrates and proteins stimulated
* Enzyme and structural proteins synthesised
* More glucose made available to meet elevated metabolic demand
* Increased lipid metabolism

Action of TH on target cells

1. T3/T4 enter target cell
2. Most of T4 is converted to T3
3. T3 enters the nucleus and binds to the thyroid hormone receptor (THR)
4. Binding of THR to promoter elements activates gene transcription

How is T4 converted to T3

Removal of one iodine

What can hyperthyroidism be caused by

* Grave’s disease
* Tumours of follicular cells

Effects of hyperthyroidism

* Thyroid gland increases in size
* Hyperplasia
* Increased rate of TH secretion
* Increased metabolic rate

Symptoms of hyperthyroidism

* Weight loss
* Cardiovascular – inc. force and rate of contraction
* CNS – nervousness, irritability, sleeplessness
* Other – fatigue, heat intolerance, sweating, moist skin

Cause of Grave’s Disease

Caused by thyroid stimulating immunoglobulin

* Over-stimulation of the thyroid
* Increased T4/T3 synthesis and secretion
* Immunoglobulins also stimulate connective tissue → exophthalmos (bug eye)

Treatment of Grave’s disease

* Anti-thyroid drugs


* Thyroidectomy
* Radioactive iodine

What causes the thyroid gland enlargement?

* Thyroid gland stimulated


* Continued stimulation of T3/T4 formation
* Gland enlarges

Causes of hypothyroidism

* Iodine deficiency – can’t synthesis T3/T4
* Hashimoto’s disease – autoimmune destruction of thyroid cells

Effect of hypothyroidism

* Low metabolic rate

How does hypothyroidism actually manifest?

Low T4/T3 secretion

Symptoms of hypothyroidism

* Body weight – increase body weight, decreased appetite
* Cardiovascular – decreased cardiac output, decreased force of contraction, decreased rate of contraction
* CNS – mental sluggishness, fatigue, cognitive dysfunction in children
* Other – myxoedema, cold intolerance, goiter

Iodine deficiency and thyroid gland enlargement

* No T3/4 formation
* No feedback control of TSH
* High TSH
* Continued stimulation of thyroglobulin by TSH
* Gland enlarges up to 500g

Thyroid gland morphology - depending on TSH stimulation

When TSH stimulated

* Hypertrophy of follicle cells due to increased uptake of colloid for T3/T4 production
* Folloicles depleted and collapsed