Thyroid Gland

Question 1

Describe the location of the thyroid gland

Answer 1

• Below thyroid cartilage (Adams apple), just above supersternal notch
• Lies against and around front larynx and trachea

Question 2

Explain the appearance of thyroid gland

Answer 2

• Butterfly shape with 2 lobes joined by isthmus

- Isthmus extends from 2nd and 3rd rings of the trachea

Question 3

Describe the structure of the thyroid gland

Answer 3

• Follicular cells arranged in spheres called thyroid follicles which are separated by connective tissue
  
  • Follicles filled with colloid, a deposit of thyroglobulin
  • Colloid is extracellular even through it is inside the follicle
• Parafollicular cells produce calcitonin (calcium homeostasis) and found in connective tissue

Question 4

How is radiography on the thyroid performed

Answer 4

• Radiography done through thyroid uptake and scan or MRI

- Technetium-99 (sometimes iodine) taken orally and used for isotope scanning

Question 5

What are the hormones produced in the thyroid gland

Answer 5

• Follicular cells produce thyroxine and T3

- Parafollicular cells produce calcitonin

Question 6

Explain the process of T3&T4 synthesis in follicular cells

Answer 6

1. Iodide enters through iodide trap against concentration gradient
2. Amino acids synthesise thyroglobulin on basal surface of epithelium
3. Thyroglobulin undergoes exocytosis and secreted into lumen of follicle
4. Oxidation of iodide produce iodinating species
5. Iodination of side chains of tyrosine residues in thyroglobulin form MIT (mono-iodotyrosine) and DIT (di-iodotyrosine)
6. Coupling of DIT with MIT or DIT to form T3 & T4 respectively within thyroglobulin
7. Thyroxine or T3 reuptake through pinocytosis and proteolytic cleavage of thyroglobulin occurs to release T3 & T4 into plasma

Question 7

How are T3 and T4 stored

Answer 7

Stored extracellularly in lumen of follicles as part of thyroglobulin molecules (before pinocytosis)

Question 8

What is the role of thyroid peroxidase

Answer 8

• Thyroid peroxidase - regulates 3 iodine reactions
  
  • Oxidation of iodide to iodine (requires presence of hydrogen peroxide)
  • Addition of iodine to tyrosine acceptor residues on the protein thyroglobulin
  • Coupling of MIT and DIT to generate thyroid hormones within the thyroglobulin protein

Question 9

Is T3 or T4 secreted more

Answer 9

• Most T4 is converted to T3 outside thyroid (mostly in liver and kidney)
• 90% of thyroid hormone secreted is T4
• Biological activity of T3 is 4 times that of T4

Question 10

How is thyroid hormone secretion controlled

Answer 10

• Hypothalamus releases thyrotropin releasing hormone (TRH) which stimulates anterior pituitary to produce thyroid stimulating hormone (TSH)
• Thyroid hormones effect virtually every cell in the body by effecting cellular differentiation and development or effect metabolic pathways
• The entire pathway is controlled through negative feedback
  
  • Depends on circulating volume of T3 and T4, stress (increases release), temperature (fall in temp increases release)

Question 11

Explain the structure and role of TSH

Answer 11

• Glycoprotein hormone consisting of alpha and beta subunit covalently bound
  
  • Alpha subunit also present in FSH and LH, but beta subunit provides unique biological activity
• G protein receptor activation by TSH resulting in iodide uptake and oxidation
  
  • Results in thyroid hormone synthesis and release
    
    • TSH induces second messenger pathways

Question 12

How are thyroid hormones transported in the blood

Answer 12

• Lipid soluble hormones - need protein to transport in blood
• Thyroxine binding globulin, pre-albumin and albumin transport thyroid hormone

Question 13

What happens to T3 and T4 plasma levels in response to oestrogen

Answer 13

• Oestrogens increase synthesis of thyroxine binding globulin during pregnancy - produces fall in free T3 and T4 in circulation as more is bound
  
  • Removes inhibitory feedback - more TRH and TSH produced
    
    • Free T3 and T4 returns to normal but total amount in blood increased

Question 14

Explain the effects thyroid hormones have on the body

Answer 14

• Increase in basal metabolic rate and heat production
  
  • In most tissues (except testes, brain and spleen)
  • Increase size and number of mitochondria
  • Stimulating synthesis of enzymes in respiratory chain
• Stimulation of metabolic pathways
  
  • Lipid metabolism - stimulates lipolysis and ß-oxidation of fatty acids
  • Carbohydrate metabolism - stimulate uptake of glucose in cells, gluconeogenesis and glycogenolysis
• Important in normal growth and development
  
  • Affect bone mineralisation - physical growth
  • Synthesis of heart muscle protein
• Sympathomimetic effects
  
  • Promote effects of sympathetic nervous system
  • Increase target cell receptors of adrenaline and noradrenaline
• Tissue specific effects
  
  • Cardiovascular system - increase heart’s responsiveness to adrenaline
    
    • Increase cardiac output and peripheral vasodilation to carry extra head to body surface
  • Nervous system - essential for both development and adult function
    
    • Increase myelination of nerves and development of neurons
      - Mental retardation due to lack of development of nervous system

Question 15

Explain the mechanism of action of T3 and T4

Answer 15

• T3 and T4 cross plasma membrane and interact with specific receptors in nucleus and mitochondria
• Nuclear receptors
• 10 fold greater affinity for T3 than T4
• Function as hormone-activated transcription factors
• When thyroid hormone binds, complex promotes gene expression rather than repress (when DNA bound)
• New protein facilitate net effects of hormone

Question 16

Explain Hashimoto’s disease including treatment

Answer 16

• Hypothyroidism disease
• Autoimmune disease resulting in destruction of thyroid follicles or production of antibody that blocks TSH receptor on follicular cells preventing them to respond to TSH
  
  • Goitre may or may not be present
  • 5 times more common in women than in men
• Treatment of hypothyroidism - oral thyroxine (adjust dose to normalise serum TSH)

Question 17

Explain Graves’ disease including treatment

Answer 17

• Autoimmune disease resulting in hyperthyroidism
• Caused by production of thyroid stimulating immunoglobulin (TSI)
• Stimulates TSH receptors on follicle cells to produce T3 and T4
• TSH levels fall due to negative feedback, however does not affect thyroid hormone secretion since stimulus due to TSI
• Treatment - Carbimazole
  
  • Pro-drug - converted to methimazole and prevents thyroid peroxidase from coupling and iodinating tyrosine on thyroglobulin, reducing T4 production
  • Delayed effect to allow iodine store to diminish

Question 18

What are signs and symptoms of hypothyroidism

Answer 18

• Tired, feeling slowed down, lethargy
• Memory problems, depression, psychosis
• Weight gain
• Cold intolerance
• Bradycardia
• Dry and flaky skin
• Gruff / croaky voice
• Hair loss - particularly on outer third of eyebrows
• Symptoms of carpal tunnel syndrome
• Muscle weakness and cramps
• Constipation
• Menorrhagia - causes menstruation
• Non-pitting oedema - myxoedema
• Peaches and cream face
• Cretinism in infants - dwarfed stature, mental deficiency, muscle weakness, weak pulse
• Myxedema - thick puffy skin, muscle weakness , slow speech, mental deterioration

Question 19

What are signs and symptoms of hyperthyroidism

Answer 19

• Overactivity, tiredness
• Nervousness, anxiety, insomnia
• Shaking, trembling
• Heat intolerance, increased oxygen consumption
• Increased sweating - sweaty hands
• Palpitations
• Weight loss
• Tachycardia
• Intestinal hyper-mobility
• Amenorrhea - decrease in menstruation
• Osteoporosis - due to increased bone turnover and preferential resorption
• Proximal myopathy - cannot get up chair
• Lid lag, staring eyes - overstimulation of sympathetic portion of smooth muscle of eyelid

Question 20

Explain goitre including its causes

Answer 20

• Enlargement of thyroid
• Most common cause due to iodine deficiency
  
  • Reduced thyroxine levels increases TSH, leading to generalised thyroid enlargement
  • Can cause hypothyroidism in severe circumstances
  • Iodine deficient areas mainly mountainous
  • If iodine deficient in pregnancy and hypothyroid, then the foetus is also iodine deficient
    - Leads to mental retardation, cretinism, abnormal gait