Thyroid Function - Human Structure and Function 1
Learning Outcomes
- Outline the steps in the manufacture of thyroid hormones
- Describe the structural and functional differences between T3 and T4
- Outline the cellular mechanisms of action of T3 and T4
- Explain how the hypothalamus and pituitary regulate circulating levels of thyroid hormones
- Describe how thyroid hormones are transported in the plasma
- Describe the metabolic effects of thyroid hormones
- Describe the systemic effects of thyroid hormones
- Relate the normal effects of thyroid hormones to the abnormalities seen with deficient and excess production
Where is the thyroid gland located?
Inferior to the larynx and superior to the trachea
Isthmus joins the two lobes
Brown because of the iodine necessary for thyroid hormone
Lumpy because of the lobes

What is the thyroid gland made up of, and what are these filled with?
What are these lined by?
What other types of cells are present?
Comprised of lobules of spherical follicles that are filled with colloid
Lined by cubboidal epithelial cells
C cell / parafollicular cell - these produce calcitonin

What is the primary constituent of colloid?
Thyroglobulin
2-3 month supply of thyroid hormone within the colloid within follicle within lobule within lobe

What are the thyroid hormones?
T3 and T4
Tyrosine residues incorporated – means that these are AMINE hormones
What are the basic 'ingredients' for thyroid hormone synthesis?
tyrosine & iodine
(can't make iodine in the body - can get it from shellfish etc)
Salt is ionised to make sure thyroid hormone can be produced

Outline the steps in the synthesis of T4 and T3
I + tyrosine => monoiodotyrosine (MIT)
MIT + I => diiodotyrosine (DIT)
DIT + DIT => thryoxine(T4)
DIT + MIT => triiodothyronine (T3)
Outline the steps in the synthesis and secretion of thyroid hormone
- Iodine is cotransported with Na+ from the capillary
- Diffusion across the follicle cell
- Iodine is oxidised and attached to rings of tyrosines in thyroglobulin (in the lumen of the follicle - colloid) Iodising agent HYDROGEN PEROXIDE. Enzyme catalysing oxidation of iodide to iodine = thyroid peroxidase.
- The iodinated ring of one MIT or DIT is added to a DIT at another spot (in the lumen of the follicle- colloid)
- Endocytosis of thyroglobulin contains T3 and T4
- Lysosomal enzymes release T3 and T4 from TG
- T3 and T4 moves back out into the interstitial fluid

What does T4 need to be converted into to exert its full biological activity?
What percentage is T4?
T3
90%
Give examples of organs that have cells with their own deiodinases
Liver and Kidney
How is T3 and T4 transported in the blood?
What is it bound to?
- What is the majority of T4 bound to?
- What is the majority of T3 bound to?
Almost 100% is bound - 0.02% isn't, but can still carry out a lot of biological effects
Thyroid Binding Globulin TBG
Thyroid Binding Prealbumin TBPA
Thyroid Binding Albumin TBA
- TBG
- TBA

Intracellular Actions of Thyroid Hormones
Outline these
Increases the number of mitochondria and their efficiency
Then also binds to nuclear receptors. Protein synthesis, enzyme activity altered. (increased sodium potassium ATPases). Acts like steroid hormones through Hormone Receptor Complex. Can exert genomic effects and non-genomic effects.

Thyroid hormones affect all cells in the body - describe the metabolic actions of T3 and T4.
- Increase O2 consumption - increased mitochondria
- Increase BMR
- Calorigenic effect
- Carbohydrate metabolism:
- increased absorption of glucose from GIT, increased insulin secretion, increased gluconeogenesis
- glucose oxidation, glycogen degradation (hypersecretion)
- Lipid metabolism:
- lipolysis - increases circulating FFA levels, accelerates FFA oxidation
- decrease cholesterol, triglycerides & phospholipids in plasma (hypersecretion)
- Protein metabolism:
- protein synthesis
- breakdown (hypersecretion)
- increased absorption of glucose from GIT, increased insulin secretion, increased gluconeogenesis
- glucose oxidation, glycogen degradation (hypersecretion)
- lipolysis - increases circulating FFA levels, accelerates FFA oxidation
- decrease cholesterol, triglycerides & phospholipids in plasma (hypersecretion)
- protein synthesis
- breakdown (hypersecretion)
Na K ATPase is increased
Systemic effects of Thyroid Hormones
Give examples of how the following are effected
- Heart
- Lungs
- GIT
- Reproductive
- Musculoskeletal
- Nervous System
-
increase HR, CO, SBP and decrease DBP
Increased blood flow to skin
-
increase ventilation rate
-
Increases appetite
Increases secretion digestive juices
Increases GIT motility
-
Essential for normal reproduction and lactation
-
promotes normal body growth and maturation of skeleton
promotes normal function and development of muscles
-
promotes normal neuronal development in feotus and infant (developmental)
promotes normal neuronal function in adult - increases synaptic activity
enhances effects of sympathetic nervous system – sympathomimetic: upregulates B1 adrenergic R in heartR
increase HR, CO, SBP and decrease DBP
Increased blood flow to skin
increase ventilation rate
Increases appetite
Increases secretion digestive juices
Increases GIT motility
Essential for normal reproduction and lactation
promotes normal body growth and maturation of skeleton
promotes normal function and development of muscles
promotes normal neuronal development in feotus and infant (developmental)
promotes normal neuronal function in adult - increases synaptic activity
enhances effects of sympathetic nervous system – sympathomimetic: upregulates B1 adrenergic R in heartR
What regulates circulating levels of thyroid hormones?
The Hypothalamus and Pituitary

The hypothalamus & pituitary regulate circulating levels of thyroid hormones
- What are the inputs?
- Negative
- Positive
- Where do they act?
- What does the Hypothalamus release?
- What does the ANT Pituitary Release?
- What does the Thyroid Gland release?
- What is the effect of T3 and T4?
- What does increased levels of T3 and T4 in the blood cause?
- Inputs
- Stress - less TH in blood to reduce stress on heart
- Cold
- Upon the hypothalamus
- TRH
- TSH
- T3 and T4
- Increase BMR, protein synthesis, and sympathetic tone
- Negative feedback loop
- Stress - less TH in blood to reduce stress on heart
- Cold
TSH action on the thyroid gland
What actions does TSH have on..,
- Iodide trapping and binding
- T3 and T4 Synthesis
- Thyroglobulin secretion into colloid
- Colloid endocytosis into follicular cells
- Size and Number of Follicular Cells
- Blood Flow at Thyroid
- Increase
- Stimulation
- Promotion
- Promotion
- Increased
- Increase
What are the actions of TSH on the Thyroid Gland?
- Increase in iodide trapping and binding
- Stimulation of T3 and T4 synthesis
- Promotion of thyroglobulin secretion into colloid
- Promotion of colloid endocytosis into follicular cells
- Increased size and number of follicular cells
- Increase in blood flow at thyroid
Abnormalities of Thyroid Function
Hypothyroidism
- What is Primary Hypothyroidism?
- What is Secondary Hypothyroidism?
- What is Tertiary Hypothyroidism?
-
problem within the thyroid gland itself - failure of thyroid gland to respond to TSH
-
deficient TSH production - thyroid atrophy
-
deficient TSH production due to deficient TRH secretion
problem within the thyroid gland itself - failure of thyroid gland to respond to TSH
deficient TSH production - thyroid atrophy
deficient TSH production due to deficient TRH secretion
Abnormalities of Thyroid Function
Primary Hypothyroidism
- What is it?
- Give 4 causes
- What are the TSH levels as a result, and why?
- What happens to the thyroid gland itself?
-
problem within the thyroid gland - failure of thyroid gland to respond to TSH
-
Thyroiditis eg. Hashimoto’s Disease => targets thyroid peroxidase enzyme and the thyroglobulin itself. (Autoimmune disease)
Severe iodide deficiency
Severe deficiency of one or more synthesis enzymes
Removal or destruction of thyroid gland
-
Elevated TSH levels – reduced negative feedback
-
Thyroid enlarges – goitre formation
problem within the thyroid gland - failure of thyroid gland to respond to TSH
Thyroiditis eg. Hashimoto’s Disease => targets thyroid peroxidase enzyme and the thyroglobulin itself. (Autoimmune disease)
Severe iodide deficiency
Severe deficiency of one or more synthesis enzymes
Removal or destruction of thyroid gland
Elevated TSH levels – reduced negative feedback
Thyroid enlarges – goitre formation
Developmental consequences of hypothyroidism
Give two examples
- Congenital Hypothyroidism
- early diagnosis is essential - blood tests for all newborns
- Adult Cretinism
- Brain, bone and other development
- early diagnosis is essential - blood tests for all newborns
- Brain, bone and other development

Hyperthyroidism or thyrotoxicosis
What are the three main causes?
What is the commonest cause?
-
Autoimmune disease – Grave’s Disease
-
Thyroid adenoma
-
Inappropriate TSH secretion (rare)
Autoimmune disease – Grave’s Disease
Thyroid adenoma
Inappropriate TSH secretion (rare)
Grave's Disease
What is the commonest cause of hyperthyroidism?
Grave's Disease
Outline the Pathogenesis of Grave's Disease
Antibody Producing Cells
Thyroid Stimulating Antibodies
THYROID
Excess T3 and T4 (and very low TSH via feedback to the pituitary)
Hyperthyroidism
Give two key clinical features of Grave's Disease
Toxic Goitre
Exophthalmos

Give signs and symptoms of Hyperthyroidism: increased T3 and T4 secretion
- Increased BMR
- Weight Loss with good appetite
- Anxiety, physical restlessness, mental excitability
- Hair loss
- Tachycardia, palpitations, AF
- Warm sweaty skin, heat intolerance
- Diarhoea
- Exopthalamos in Grave's Disease (MPS behind eyes)
- Fast tendon reflexes
- Muscle weakness
- Fine tremor
- Eye staring - eyelids up
- UNTREATED = Thyrotoxic storm - high temperature

Give signs and symptoms of Hypothyroidism: decreased T3 and T4 secretion
- Decreased BMR
- Weight gain, anorexia
- Depression, psychosis, mental slowness, lethargy
- Dry skin, brittle hair
- Bradycardia
- Cold skin, prone to hypothermia
- Constipation
- Slow tendon reflexes
- Muscle weakness
- Muscle stiffness
- Voice deep and slow
- UNTREATED = Myxoedema Coma - Hypothermia
What is a sign of untreated
- Hyperthyroidism?
- Hypothyroidism?
-
THYROTOXIC STORM - High temperature
-
MYXOEDEMA COMA – Hypothermia
THYROTOXIC STORM - High temperature
MYXOEDEMA COMA – Hypothermia
The hypothalamic-pituitary thyroidal axis is affected by thyroid disorders
Outline how release rate of T4, TSH and TRH are affected in the following:
- Primary Hypothyroidism
- Pituitary Hypothyroidism (2ry)
- Hypothalamic Hypothyroidism (3ry)
- Grave's Disease
- Decreased, Increased, Increased
- Decreased, Decreased, Increased
- Decreased, Decreased, Decreased
- Increased, Decreased, Decreased

Why is this knowledge important for dentists?
Oral Manifestations of Thyroid Gland Disorders are common
Hyperthyroidism: We must restrict the use of adrenaline and avoid severe stress situations and the spread of infectious foci. In patients treated with propylthiouracil, a complete blood count is usually recommended. NSAIDs and aspirin should be used with caution. Treatment should be discontinued if signs or symptoms of a thyrotoxic crisis develop
Hypothyroidism: a complete blood count before performing dental treatment is recommended. We must restrict the use of adrenaline and avoid oral infection and central nervous depressant drugs. We should know the drug interactions of thyroxine. If myxedematous coma develops, we will only carry out emergency dental treatment.
