Endocrinology: Thyroid Glands and Hormones

Question 1

Location of thyroid gland

Answer 1

Thyroid gland is located immediately below the larynx on each side of and anterior to the trachea – it is bow shaped

Question 2

What do thyroid hormones act on?

Answer 2

Thyroid hormones act on almost all cell types in the body

Question 3

Effects of thyroid hormones categories

Answer 3

Broadly classified into two categories:
- Effects on metabolic pathways: thyroid hormones boost energy metabolism in mitochondria increasing basal metabolic rate - therefore will also influence body temperature
- Effects on cellular differentiation and development - thyroid hormones promote the development and differentiation of many cells, including the neurons and supporting cells of the CNS

Effects of thyroid hormones: not all or none signals, they act as modulators for actions of many other hormones

Question 4

Effect of thyroid hormones

Answer 4

• Increased mitochondrial size, number and enzymes, increased Na-K-ATPase activity, increased basal metabolic rate (rate of O2 consumption and energy expenditure at rest. Increased heat production
• Up regulation of beta-adrenergic receptors  sympathomimetic effect, increase HR, force of contractions, stroke volume, increased Ca2+ ATPases, increased resting respiratory rate, increased blood flow, increased glomerular filtration rate
• Increased RBC mass, increased O2 dissociation, increased glucose absorption from GIT, increased GIT motility
• Increased lipolysis, increased glycogenolysis. Down regulates insulin receptors
• Increased alertness, memory, learning, emotional stability, nerve reflexes
• Required for reproductive capabilities (follicular development, pregnancy, spermatogenesis)
• Enhances effects of growth hormone

Question 5

Thyroid hormones

Answer 5

Thyroid hormones
- Thyroid gland produces two iodine-containing hormones derived from the amino acid tyrosine
- Tetra-iodothyronine (T4 aka thyroxine)
- Tri-iodothyronine (T3) ~7% of total secretion (10x more potent)

Question 6

What secretes and stores thyroid hormones?

Answer 6

Follicular cells: secrete thyroid hormones
Colloid: extracellular storage site for thyroid hormone

Question 7

What is thyroperoxidase?

Answer 7

Enzyme produced by thyroid gland
I- –> I by oxidation (loss of electrons)
Used in production of thyroid hormones

Question 8

Thyroid hormone synthesis

Answer 8

Thyroglobulin (1)
- TSH (secreted by anterior pituitary) initiates thyroglobulin synthesis (by the endoplasmic reticulum and Golgi apparatus) and secretion within the thyroid gland
- Each thyroglobulin molecule contains ~70 tyrosine amino acids available for iodination
- The tyrosine residues within the thyroglobulin become iodinated and couple together, forming T3 and T4
- Considerable storage of thyroid hormone within the colloid (attached to thyroglobulin molecules
Iodine (2)
- Unlike tyrosine (an amino acid synthesised in body), iodine must be obtained from dietary intake. Iodine (I) is reduced to iodide (I-) and absorbed by the small intestine
- Iodide is transported in the bloodstream and enters thyroid cells via a Na+/I- (NIS) symporter (secondary active transport), moves up a large concentration gradient
- ~95% of iodide in the body is found (stored) in the thyroid
Organification (3)
- Thyroid peroxidase, aka thyroperoxidase (TPO) is a membrane bound enzyme that oxidises iodide (I-) to iodine (I) on the luminal membrane
- Within the colloid, TPO also catalyses the binding of iodide to tyrosine residues (within the thyroglobulin molecule) to form the iodotyrosines; monoiodotyrosine (MIT) and diiodotyrosine (DIT)
Coupling of residues within the colloid to form T3 and T4 (4)
Endocytosis into follicular cells (5)
Peripheral conversion of T4 to T3 (6)
- T3 is mostly obtained by peripheral conversion of T4 to T3
- Thyroid hormones can then enter the bloodstream

Question 9

Secondary active transport

Answer 9

Molecules transported across a cell membrane, using energy stored in the electrochemical gradient of another molecule, e.g., ions, that was previously created by primary active transport

Question 10

Organification

Answer 10

• Incorporation of iodine atoms into tyrosine residues within thyroglobulin
• Catalysed by thyroperoxidase

Question 11

Regulation of secretion of thyroid hormones

Answer 11

• Thyrotropin-releasing hormone (TRH) stimulates release of thyroid-stimulating hormone (TSH – aka thyrotropin)
• Negative feedback maintains relatively constant supply of thyroid hormones
• 99.5% of T3 and T4 is transported in the blood by carrier proteins (70% thyroxine binding globulin – TBG, transthyretin and albumin)
• It is the free T3 and T4 that is biologically active
• TRH can be increased by emotional states and other stimuli

Question 12

Storage of thyroid hormone

Answer 12

• The thyroid gland can store enough thyroid hormone to supply the body with its normal requirements for 2-3 months
• Thyroid hormones remain part of the thyroglobulin molecule during storage in the follicular colloid
• Thyroid hormones are also ‘stored’ in blood and target tissues bound with plasma and intracellular proteins and are used slowly over days/ weeks

Question 13

Effects of TSH

Answer 13

• Non-genomic effects
  o Enhances iodide pump activity: increases iodide trapping
  o Increases iodination of tyrosine: increase synthesis of T3 and T4
  o Increases proteolysis of thyroglobulin: increases release of T3 and T4
• Genomic effects: promotes gene transcription for:
  o Iodide pump, thyroglobulin, enzymes involved in T3 and T4¬ synthesis
  o Nitric oxide synthase  vasodilation: increased blood flow
  o Local growth factors: hyperplasia and hypertrophy of gland

Question 14

Hypothyroidism

Answer 14

• Failure of thyroid gland: decreased T3 and T4, increased TSH
• Hypothalamic or anterior pituitary failure: decreased T3 and T4, decreased TRH/ TSH
• Lack of dietary iodine: decreased T3 and T4, increased TSH

Question 15

Hyperthyroidism

Answer 15

• Long-acting thyroid stimulation (Graves’ disease): increased T3 and T4, decreased TSH
• Excess hypothalamic or anterior pituitary secretion: increased T3 and T4, increased TRH/ TSH
• Hypersecreting thyroid tumour: increased T3 and T4, decreased TSH

Question 16

Assessing thyroid function

Answer 16

• Accumulation of radioactive iodide in follicular lumen
• Uptake of radioactive iodide by normal thyroid gland
• ‘Cold nodule’ that doesn’t take up tracer is indicative or compromised thyroid function
• Urinary excretion of radioiodide

Question 17

Causes of hypothyroidism

Answer 17

o Autoimmune disease (Hashimoto’s disease) – autoantibodies against thyroglobulin, thyroperoxidase, TSH receptor (blocking type) decreased T3 and T4, increased TSH primary
o Pituitary deficit (adenomas or destruction) secondary
o Hypothalamic deficit (rare) tertiary
o Peripheral resistance to thyroxine peripheral
o Dietary iodine deficiency
o Inherited defects of hormone synthesis
o Defects in TSH and TSH receptor
o Anti-thyroid substances (e.g., p-amino salicylic acid, lithium)
o Iatrogenic (treatments for hyperthyroidism)

Question 18

Signs and symptoms of hypothyroidism

Answer 18

o Fatigue
o Mental and muscular sluggishness
o Slow heart rate
o Reduced cardiac output
o Weight gain
o Constipation
o Myxedema
o Cold intolerance
o Thick tongue
o Hoarseness
o Goitre may or may not be present
o Hypercholesterolemia

Question 19

Causes of immunogenic thyrotoxicosis

Answer 19

due to formation of thyroid stimulating immunoglobulin; structurally similar to TSH  overstimulates thyroid production, e.g., Graves’ disease

Question 20

Signs and symptoms of immunogenic thyrotoxicosis

Answer 20

o Nervousness
o Tachycardia and tremor
o Fatigue associated with muscle atrophy
o Heat intolerance with sweating
o Weight loss without loss of appetite
o +/- goitre
o Edematous swelling of retro-orbital tissues: protrusion of eyeballs (blurred or double vision, feeling pressure behind eyes)

Question 21

Causes of hyperthyroidism

Answer 21

• Imunogenic thyrotoxicosis
• Toxic multinodular goitre: seen most commonly in elderly with outstanding goitre. Autonomous hypersecretion of T4 and T3 from one or more thyroid adenomas (low TSH; secretory activity of the remainder of the thyroid is almost totally inhibited)
• Thyrotoxicosis factitial: psychoneurotic disorder in which pt ingests excessive amounts of thyroxine or thyroid hormone for purpose of weight control

Question 22

Oral manifestations of hyperthyroidism

Answer 22

• Increased susceptibility to caries and periodontal disease
• Accelerated dental eruption
• Burning mouth syndrome
• Maxillary or mandibular osteoporosis
• Increased levels of anxiety – stress/ surgery can trigger thyrotoxic crisis
• Note: hyperthyroidism can also stem from enlargement of extra-glandular thyroid tissue on lateral posterior tongue

Question 23

Oral manifestations of hypothyroidism

Answer 23

• Salivary gland enlargement
• Macroglossia (enlargement of the tongue)
• Glossitis (inflammation of the tongue)
• Delayed dental eruption
• Compromised periodontal health: delayed bone resorption
• Dysgeusia (taste distortion)

Question 24

Considerations for patients with thyroid disease prior to treatment

Answer 24

• Undiagnosed thyroid condition: are there symptoms of thyroid disease? Fi yes, defer elective treatment and consult a physician
• Diagnosed thyroid condition: establish type and current stage of treatment
• Assess CV status: take BP and HR
• If BP is elevated in three different readings or there are signs of tachycardia/bradycardia, defer elective treatment and consult physician
• Be aware that propylthiouracil (PUT) can cause leukopenia and L-thyroxine and PTU can both increase the anticoagulant effects of warfarin: appropriate coagulation tests may be required
• Diabetic pts may become hyperglycaemic with L-thyroxine

Question 25

Considerations during and after treatment with patients with thyroid disease

Answer 25

During treatment
- Oral exam should include salivary glands
- Give attention to oral manifestations: Graves’ disease – increased incidence of CT problems; Sjogren’s syndrome; systemic lupus erythematosus
o Euthyroid? No contraindication to LA with adrenaline
o Beta blockers? Use adrenaline with caution (can increase BP)
o Uncontrolled hyperthyroidism: avoid adrenaline
- Minimise stress: appointments should be brief
- Recognise signs of thyroid storm (tachycardia, irregular pulse, sweating, tremor, hypertension, etc) – dental treatment not a priority at this time – emergency situation, client transferred to hospital immediately (treated with beta blockers and anti-thyroid meds e.g., PTU)
After treatment
- Pts who have hypothyroidism are more sensitive to CNS depressants and barbiturates
- Use caution with non-steroidal anti-inflammatory drugs for hyperthyroid pts taking beta-blockers (NSAIDs can decrease their efficacy)
- Continue hormone replacement therapy or anti-thyroid drugs as prescribed