Thyroid Gland Flashcards

1
Q

Describe the location of the thyroid gland

A
  • Below thyroid cartilage (Adams apple), just above supersternal notch
  • Lies against and around front larynx and trachea
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2
Q

Explain the appearance of thyroid gland

A
  • Butterfly shape with 2 lobes joined by isthmus

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

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3
Q

Describe the structure of the thyroid gland

A
  • 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
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4
Q

How is radiography on the thyroid performed

A
  • Radiography done through thyroid uptake and scan or MRI

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

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5
Q

What are the hormones produced in the thyroid gland

A
  • Follicular cells produce thyroxine and T3

- Parafollicular cells produce calcitonin

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6
Q

Explain the process of T3&T4 synthesis in follicular cells

A
  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
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7
Q

How are T3 and T4 stored

A

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

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8
Q

What is the role of thyroid peroxidase

A
  • 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
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9
Q

Is T3 or T4 secreted more

A
  • 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
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10
Q

How is thyroid hormone secretion controlled

A
  • 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)
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11
Q

Explain the structure and role of TSH

A
  • 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
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12
Q

How are thyroid hormones transported in the blood

A
  • Lipid soluble hormones - need protein to transport in blood
  • Thyroxine binding globulin, pre-albumin and albumin transport thyroid hormone
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13
Q

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

A
  • 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
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14
Q

Explain the effects thyroid hormones have on the body

A
  • 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
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15
Q

Explain the mechanism of action of T3 and T4

A
  • 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
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16
Q

Explain Hashimoto’s disease including treatment

A
  • 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)
17
Q

Explain Graves’ disease including treatment

A
  • 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
18
Q

What are signs and symptoms of hypothyroidism

A
  • 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
19
Q

What are signs and symptoms of hyperthyroidism

A
  • 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
20
Q

Explain goitre including its causes

A
  • 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