Thyroid Hormone Testing Waco

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THYROID HORMONE

• Gross and Microscopic Anatomy of the Thyroid
  Gland.
• Production of Thyroid Hormones.
• Transport of T3 and T4
• Actions of Thyroid Hormones.
• Regulation of Thyroid Hormones.
• Hyper- and Hypothyroidism

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Histology of the Thyroid Gland

• The thyroid gland contains numerous follicles,
  composed of epithelial follicle cells and
  colloid.
• Also, between follicles are Para-follicular
  cells, which produce Calcitonin.

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The Thyroid Gland Histology

• Squamous epithelial cells, cuboidal cells
  (follicle cells).Gland is composed of hollow
  spheres, called colloid follicles.Colloid fills
  the follicle cavities.
• Follicle cells produce thyroglobulin.

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Thyroid Hormones

• There are two biologically active thyroid
  hormones
• - Tetraiodothyronine(T4 usually called
  thyroxine)
• - Triiodothyronine (T3)
• Derived from modification of tyrosine(amino acid).

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Differences between T4 and T3

• The thyroid secretes about 80mg of T4, but only
  5mg of T3 per day.
• However, T3 has a much greater biological
  activity about 10 folds than T4.
• An additional 25mg/day of T3 is produced by
  peripheral monodeiodination of T4 by enzyme
  called 5 Monodeiodenase.

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Major sources of iodine

• Thyroid hormones are unique biological molecules
  in that they incorporate iodine in their
  structure.
• Thus, adequate iodine intake either through diet
  or water is required for normal thyroid hormone
  production.
• Major sources of iodine are
• - iodized salt
• - iodated bread
• - dairy products
• - shellfish
• Minimum requirement(RDA) 75 micrograms/day
• US intake 200 - 500 micrograms/day

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The Next Step Production of Thyroglobulin

• Pituitary produces TSH, which binds to follicle
  cell receptors.
• The follicle cells of the thyroid produce
  thyroglobulin.
• Thyroglobulin is a very large glycoprotein.
• Thyroglobulin is released into the colloid space,
  where its tyrosine residues are iodinated by I.
  
• This results in formation of monoiodotyrosine or
  diiodotyrosine.

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Transport of Thyroid Hormones

• Thyroid hormones are lipid-soluble.
• Thus, they are found in the circulation
  associated with binding proteins
• - Thyroid Hormone-Binding Globulin(TBG) (70 of
  hormone)
• - Pre-albumin(Transthyretin) (15)
• - Albumin (15)
• Less than 1 of thyroid hormone is found free in
  the circulation.
• Only free and albumin-bound thyroid hormone is
  biologically available to tissues.
• Among the amount of thyroid hormone production
  and release T4 is approximately 95 and T3 is
  5. But biological active is T3 so T4 is
  converted to T3 in peripheral tissues by the
  enzyme 5monodeiodinase and become active.

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Conversion of T4 to T3

• T3 has much greater biological activity than T4.
• A large amount of T4 (25) is converted to T3 in
  peripheral tissues.
• This conversion takes place mainly in the liver
  and kidneys. The T3 formed is then released to
  the blood stream.
• In addition to T3, an equal amount of Reverse
  T3 may also be formed. This has no biological
  activity.
• T3 MIT
  DIT
• Reverse T3 DIT MIT

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Regulation of Thyroid Hormone Levels

• Thyroid hormone synthesis and secretion is
  regulated by two main mechanisms
• - An auto regulation mechanism, which reflects
  the available levels of iodine.
• - Regulation by the hypothalamus and anterior
  pituitary.

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Auto regulation of Thyroid Hormone Production

• The rate of iodine uptake and incorporation into
  thyroglobulin is influenced by the amount of
  iodide available
• - Low iodide levels increase iodine transport
  into follicular cells
• - High iodide levels decrease iodine transport
  into follicular cells
• Thus, there is negative feedback regulation of
  iodide transport by iodide.

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Neuro endocrine Regulation of Thyroid Hormones
Role of TSH

• Thyroid-stimulating hormone (TSH) is produced by
  thyrotroph cells of the anterior pituitary.
• TSH is a glycoprotein hormone composed of two
  subunits
• - alpha subunit (common to LH, FSH, TSH, hCG)
• - TSH beta subunit, which gives specificity of
  receptor binding and biological activity.

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Other Factors Regulating Thyroid Hormone Levels

• Diet a high carbohydrate diet increases T3
  levels, resulting in increased metabolic rate
  (diet-induced thermo genesis).
• Low carbohydrate diets decrease T3 levels,
  resulting in decreased metabolic rate.
• Cold Stress increases T3 levels in other
  animals, but not in humans.
• Any condition that increases body energy
  requirements (e.g., pregnancy, prolonged cold)
  stimulates hypothalamus ? TRH ? TSH.

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Actions of Thyroid Hormones

• Thyroid hormones are essential for normal growth
  of tissues, including the nervous system.
• Lack of thyroid hormone during development
  results in short stature and mental deficits
  (cretinism).
• Thyroid hormone stimulates or increase Basal
  Metabolic Rate(BMR).

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• Required for GH and prolactin production and
  secretion
• Required for GH action
• Increases intestinal glucose reabsorption
  (glucose transporter)
• Increases mitochondrial oxidative phosphorylation
  (ATP production)
• Increases activity of adrenal medulla
  (sympathetic glucose production)
• Induces enzyme synthesis
• Result stimulation of growth of tissues and
  increased metabolic rate. Increased heat
  production (calorigenic effect)

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Effects of Thyroid Hormone on Nutrient Sources

• Effects on protein synthesis and degradation
• -increased protein synthesis at low thyroid
  hormone levels (low metabolic rate growth)
• -increased protein degradation at high thyroid
  hormone levels (high metabolic rate energy)
• Effects on carbohydrates
• -low doses of thyroid hormone increase glycogen
  synthesis (low metabolic rate storage of energy)
• - high doses increase glycogen breakdown (high
  metabolic rate glucose production)

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One Major Target Gene of T3 The Na/K ATPase
Pump

• Pumps sodium and potassium across cell membranes
  to maintain resting membrane potential
• Activity of the Na/K pump uses up energy, in
  the form of ATP
• About 1/3rd of all ATP in the body is used by the
  Na/K ATPase
• T3 increases the synthesis of Na/K pumps,
  markedly increasing ATP consumption(BMR
  increases).
• T3 also acts on mitochondria to increase ATP
  synthesis(size and number of mitochondria will
  increase).
• The resulting increased metabolic rate increases
  thermo genesis (heat production).

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Thyroid Hormone Actions which Increase Oxygen
Consumption

• Increase mitochondrial size, number and key
  enzymes.
• Increase plasma membrane Na-K ATPase activity.
• Increase futile(ineffective) thermogenic energy
  cycles.
• Decrease super oxide dismutase activity.

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Effects of Thyroid Hormones on the Cardiovascular
System

• Increase heart rate
• Increase force of cardiac contractions
• Increase stroke volume
• Increase Cardiac output
• Up-regulate catecholamine receptors

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Effects of Thyroid Hormones on the Respiratory
System

• Increase resting respiratory rate
• Increase minute ventilation
• Increase ventilatory response to hypercapnia and
  hypoxia

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Effects Thyroid Hormones in Growth and Tissue
Development

• Increase growth and maturation of bone.
• Increase tooth development and eruption.
• Increase growth and maturation of epidermis, hair
  follicles and nails.
• Increase rate and force of skeletal muscle
  contraction.

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Effects of Thyroid Hormones on the Nervous System

• Critical for normal CNS neuronal development
• Enhances wakefulness and alertness
• Enhances memory and learning capacity
• Required for normal emotional tone
• Increase speed and amplitude of peripheral nerve
  reflexes

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Effects of Thyroid Hormones on the Reproductive
System

• Required for normal follicular development and
  ovulation in the female
• Required for the normal maintenance of pregnancy
• Required for normal spermatogenesis in the male

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How is Hypothyroidism Related to Goiter?

• During iodine deficiency, thyroid hormone
  production decreases.
• This results in increased TSH release (less
  negative feedback).
• TSH acts on thyroid, increasing blood flow, and
  stimulating follicular cells and increasing
  colloid production.

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Midwest the Goiter Belt

• If goiter is due to decreased I, then thyroid
  gland enlarges called endemic or colloidal
  goiter.
• Pituitary gland ? TSH stimulate thyroid gland to
  produce TH, but the only result is that the
  follicles accumulate more and more unusable
  colloid.
• Cells eventually die from over activity and the
  gland atrophies.

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Thyroid Hormone Excess Hyperthyroidism

• Emotional symptoms (nervousness, irritability),
  fatigue, heat intolerance, elevated metabolic
  rate, weight loss, tachycardia, goiter, muscle
  wasting, apparent bulging of eyes, may develop
  congestive heart failure.
• Causes
• (a) Excessive TSH release.
• (b) Autoimmune disorders.

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76710 Phone [phone] Fax (254)
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