thyroid physiology and hormones

• Thyroid hormones


  • Tetra-iodothyronine (T4, aka thyroxine)
  • Tri-iodothyronine (T3)

  
• Thyroid gland


  • Located immediately below the larynx on each side of and anterior to the trachea
  • Normally weighs 15-20g in adults
  • Two lobes of endocrine tissue joined by isthmus

  
• Thyroid follicle


  • Functional unit of the thyroid gland
  • Follicular cells arranged into hollow spheres
  • Colloid filled lumen is an extracellular storage site for thyroid hormone
  • Follicular cells secrete thyroid hormones (T3 & T4)
  • C cells secrete calcitonin

  
• Thyroid hormone synthesis


  1. Thyroglobulin synthesis

  2. Iodine transport into follicular cells

  3. Organification of iodine

  4. Coupling of iodinated tyrosine residues

  5. Secretion of T3 and T4

  6. Peripheral conversion of T4 to T3

  
• Organification


  The binding of iodide to tyrosine residues (within the thyroglobulin molecule) to form the iodotyrosines monoiodotyrosine (MIT) and diiodotyrosine (DIT)

  
• Secondary active transport


  The transport of iodide into thyroid cells via a Na+/I- (NIS) symporter, moving up a large concentration gradient
• Thyroperoxidase (TPO)


  A membrane bound enzyme that oxidises iodide (I-) to iodine (I) and catalyses the binding of iodide to tyrosine residues (within the thyroglobulin molecule)

  
• Propylthiouracil (PTU) and methimazole


  Reduce the synthesis of T3 and T4 by inactivating the TPO enzyme

  
• Propylthiouracil (PTU)


  Also reduces the peripheral conversion of T4 to T3
• T3


  More active than T4, shorter duration than T4
• T4


  Longer duration than T3
• Regulation of thyroid hormone secretion


  1. Thyrotropin-releasing hormone (TRH) stimulates release of thyroid-stimulating hormone (TSH)

  2. Negative feedback maintains relatively constant supply of thyroid hormones

  
• Effects of TSH


  • Promotes gene transcription for iodide pump, thyroglobulin, enzymes involved in T3 & T4 synthesis
  • Enhances iodide pump activity, increases iodination of tyrosine, increases proteolysis of thyroglobulin
  • Promotes local growth factors leading to hyperplasia and hypertrophy of the gland
  • Enhances nitric oxide synthase leading to vasodilation and increased blood flow

  
• Effects of thyroid hormones

  • Intracellular effects: Increase mitochondrial size, number and enzymes, increase Na-K ATPase activity
  • Whole body effects: Increase basal metabolic rate, increase heat production, increase heart rate and force of contractions, increase respiratory rate, increase blood flow and glomerular filtration rate, increase glucose absorption and GI motility, increase lipolysis and glycogenolysis, enhance effects of growth hormone, required for reproductive capabilities

  
• Thyroid hormones are not all-or-none signals – they act as modulators for the actions of many other hormones

  
• Hypothyroidism


  Failure of the thyroid gland, resulting in decreased T3 & T4, and increased TSH
• Hypothalamic or anterior pituitary failure


  Decreased T3 & T4, and decreased TRH/TSH
• Lack of dietary iodine


  Decreased T3 & T4, and increased TSH
• Hyperthyroidism


  Long-acting thyroid stimulation (Graves' disease), resulting in increased T3 & T4, and decreased TSH
• Excess hypothalamic or anterior pituitary secretion


  Increased T3 & T4, and increased TRH/TSH
• Hypersecreting thyroid tumour


  Increased T3 & T4, and decreased TSH
• Thyroid Dysfunction


  1. Hypothalamus decreases TRH

  2. Anterior Pituitary decreases TSH

  3. Thyroid Gland decreases T3 & T4 (negative feedback)

  4. Stimulus has been removed by very strong negative feedback
• Hypothyroidism due to Iodine deficiency


  1. Hypothalamus increases TRH

  2. Anterior Pituitary increases TSH

  3. Thyroid Gland T3 & T4 remain low (no iodine, no thyroid hormone to create negative feedback)
• Hyperthyroidism due to Graves' disease


  1. Thyroid stimulating immunoglobulins

  2. Hypothalamus increases TRH

  3. Anterior Pituitary increases TSH

  4. Thyroid Gland T3 & T4 remain high
• Assessing thyroid function


  • Accumulation of radioactive iodide (123I-) in follicular lumen
  • Uptake of radioactive iodide (123I-) by normal thyroid gland
  • "Cold nodule" that does not take up tracer is indicative of compromised thyroid function
  • Urinary excretion of radioiodide can also be used as a test of thyroid function
• Causes of Hypothyroidism


  • Autoimmune disease (Hashimoto's disease)
  • Pituitary deficit (adenomas or destruction)
  • Hypothalamic deficit (rare)
  • Peripheral resistance to thyroxine
  • Dietary iodine deficiency
  • Inherited defects of hormone synthesis
  • Defects in TSH and TSH receptor
  • Anti-thyroid substances (e.g. p-aminosalicylic acid, lithium)
  • Iatrogenic (treatments for hyperthyroidism)
• Signs & symptoms of Hypothyroidism


  • Fatigue, muscular sluggishness, slow heart rate, reduced cardiac output, weight gain, constipation, mental sluggishness, myxedema, cold intolerance, thick tongue, hoarseness
  • Goiter may or may not be present (often nodular due to TSH stimulation of healthy areas)
  • Hypercholesterolemia (decreased excretion by liver)
  • Untreated neonatal hypothyroidism can lead to severe mental retardation and stunted growth
• Immunogenic thyrotoxicosis


  Due to formation of thyroid stimulating immunoglobulin (TSI) - structurally similar to TSH, over-stimulates thyroid production (also known as Graves' disease, Basedow's disease, Parry's disease, diffuse toxic goiter)
• Signs & symptoms of Immunogenic thyrotoxicosis


  • Nervousness, tachycardia and tremor, fatigue associated with muscle atrophy, heat intolerance with sweating, weight loss without loss of appetite, +/- goiter, edematous swelling of retro-orbital tissues (exophthalmos), blurred or double vision, feeling of pressure behind eyes, irritation/ulceration of the cornea, degeneration of extraocular muscles (ophthalmoplegia)
• Toxic multinodular 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 Factitia


  Psychoneurotic disorder in which the patient ingests excessive amounts of thyroxine or thyroid hormone for the purpose of weight control
• Goitre can occur in both hypothyroidism and hyperthyroidism. Goitres can be diffuse or nodular depending on their etiology
• Oral manifestations of hyperthyroidism


  • 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
• Oral manifestations of hypothyroidism

  • 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)
• Considerations for patients with thyroid disease - Prior to treatment


  • Undiagnosed thyroid condition: assess for symptoms of thyroid disease
  • Diagnosed thyroid condition: establish type and current stage of treatment
  • Assess cardiovascular status - take blood pressure and heart rate
  • If blood pressure is elevated or there are signs of tachycardia/bradycardia, defer elective treatment and consult physician
  • Be aware that propylthiouracil (PTU) can cause leukopenia and L-thyroxine and PTU can both increase the anticoagulant effects of warfarin - appropriate coagulation tests may be required
  • Diabetic patients may become hyperglycaemic with L-thyroxine
• Considerations for patients with thyroid disease - During treatment


  • Oral examination should include salivary glands
  • Give attention to oral manifestations - Graves' disease, Sjogrens syndrome, systemic lupus erythematosus
  • If euthyroid, no contraindication to local anesthetic with adrenaline
  • If patient taking β-blockers, use adrenaline with caution (can increase blood pressure)
  • If uncontrolled hyperthyroidism, avoid adrenaline
  • Minimize stress - appointments should be brief
  • Recognize signs of thyroid storm - this is an emergency situation and client should be transferred to hospital immediately
• Considerations for patients with thyroid disease - After treatment


  • Patients who have hypothyroidism are more sensitive to central nervous system depressants and barbiturates
  • Use caution with non-steroidal anti-inflammatory drugs for hyperthyroid patients taking b-blockers (NSAIDs can decrease efficacy of b-blockers)
  • Continue hormone replacement therapy or anti-thyroid drugs as prescribed