Thyroid function

• Hypothalamus-Pituitary-Thyroid Axis


  Hormonal cascade involving the hypothalamus, anterior pituitary, and thyroid gland

  
• Hypothalamus


  • Releases TRH
• Anterior Pituitary (thyrotrophs)


  • Releases TSH
• Thyroid gland


  • Releases T4 and T3

  
• Transport proteins


  • Transport thyroid hormones in the circulation

  
• Thyroid gland cell types

  • Follicular cells
  • Parafollicular cells (C-cells)

  
• Follicular cells


  Produce and store T4 and T3 in the colloid
• Parafollicular cells (C-cells)


  Produce calcitonin
• Thyroid gland consists of 2 lobes located in the lower part of the neck, just below the larynx

  
• Follicles/acini


  Fundamental structural unit of the thyroid gland

  
• Thyroid hormone synthesis


  1. Active transport of iodine

  2. Incorporation of iodine into tyrosine by TPO to form MIT and DIT

  3. Iodothyronine molecule coupling within Tg to form T3 and T4

  4. Release of iodothyronines through the cleavage of follicular Tg by proteases

  
• Follicle


  Spheres of thyroid cells

  
• Colloid/lacuna


  Viscous substances, major component is thyroglobulin
• Thyroglobulin (Tg)


  Glycoprotein rich in tyrosine that can be iodinated

  
• Thyroid peroxidase (TPO)


  Incorporates iodine in tyrosine, aids coupling of 2 tyrosine residues

  
• Biologic functions of thyroid hormones

  • Increase oxygen consumption in tissues
  • Enhance mitochondrial metabolism
  • Regulate calorigenesis and metabolic rate
  • Increase sensitivity to catecholamines with increased heart rate and myocardial contractility
  • Stimulate synthesis and carbohydrate metabolism
  • Increase synthesis and degradation of cholesterol and triglycerides
  • Increase vitamin requirements
  • Regulate and promote normal growth and development
  • Regulate and promote neurologic function

  
• T4 (Tetraiodothyronine)


  Principal secretory product of the thyroid gland, precursor to T3 production, elevated T4 causes inhibition of TSH secretion

  
• T3 (Triiodothyronine)


  Most active thyroid hormone, less tightly bound to serum proteins than T4, better indicator of recovery from hyperthyroidism

  
• rT3 (Reverse T3)


  Inactive form of T3, formed from inner ring deiodination of T4, markedly elevated in euthyroid sick syndrome
• Thyroid hormone binding proteins

  • Thyroxine-Binding Globulin (TBG)
  • Thyroxine-Binding Prealbumin (Transthyretin)
  • Thyroxine-Binding Albumin

  
• Thyroxine-Binding Globulin (TBG)


  Transports majority of T3 and 70-75% of total T4

  
• Thyroxine-Binding Prealbumin (Transthyretin)


  Transports 15-20% of total T4, T3 has no affinity for prealbumin

  
• Thyroxine-Binding Albumin


  Transports T3 and 10% of T4

  
• Disorders of the thyroid gland

  • Hyperthyroidism
  • Hypothyroidism

  
• Hyperthyroidism


  • Over production of thyroid hormone, most common cause is Graves' disease, occurs more commonly in females, manifests with characteristic symptoms like goiter and exophthalmos

  
• Causes of hyperthyroidism


  • Graves' disease
  • Thyroidal nodules (Toxic nodular goiters)
  • Thyroidal TSH receptor sensitivity to HCG (seen in pregnancy)

  
• Graves' disease


  • Most common cause of thyrotoxicosis, lab findings include high free T4 and/or T3 with undetectable TSH, TSH receptor antibody positive, anti-thyroid peroxidase positive, strong familial disposition, features include goiter, ophthalmopathy, and dermopathy
• Hypothyroidism


  • Underproduction of thyroid hormones, may present as subclinical or overt, symptoms include cold intolerance, weight gain, cognitive dysfunction, constipation, dry skin, hoarseness, edema, myalgia, depression, menorrhagia

  
• Causes of hypothyroidism


  • Primary hypothyroidism due to insufficient iodine or Hashimoto's thyroiditis
  • Secondary and tertiary hypothyroidism due to pituitary and hypothalamus dysfunction
• Hashimoto's thyroiditis/Chronic autoimmune thyroiditis


  • Most common cause of primary hypothyroidism in the developed world, characterized by thyroid replaced by lymphoid tissue, autoantibodies cause cell lysis and inflammation, best test is thyroid peroxidase antibody, also have anti-thyroglobulin antibodies

  
• Myxedema


  Nonpitting cutaneous edema due to infiltration of the skin by mucopolysaccharides, features include facial puffiness, periorbital edema, enlargement of the tongue, coarse and brittle hair, thinning of eyebrows, pale yellow skin
• Myxedema coma


  Severe form of primary hypothyroidism
• Euthyroid sick syndrome


  Abnormal thyroid hormones in the absence of thyroid disease, common in hospitalized patients, characterized by decreased conversion of T4 to T3 with increase in rT3, TSH may be low

  
• Characterization of thyroid disorders

  • Primary (originate in thyroid gland)
  • Secondary (originate in pituitary gland)
  • Tertiary (originate in hypothalamus)

  
• Laboratory findings in thyroid disorders

  • Subclinical hypothyroidism (increased TSH, normal fT4, normal T3, +/- antibodies)
  • Overt hypothyroidism (increased TSH, decreased fT4, decreased T3, often have antibodies)
  • Subclinical hyperthyroidism (decreased TSH, normal fT4, normal T3, +/- antibodies)
  • Overt hyperthyroidism (decreased TSH, increased fT4, increased T3, often have antibodies)
  • Euthyroid sick syndrome (increased/decreased TSH, normal fT4, decreased T3, increased rT3, no antibodies)

  
• Subclinical: Thyroid hormone levels are within normal range but serum thyroid hormone (TSH) are mildly elevated/decreased

  
• Hyperthyroidism is more common in blacks, older adults, cigarette smokers, during the first trimester of pregnancy, in nonthyroidal illness, and in patients treated with certain drugs (glucocorticoids, dopamine)
• Recommendations for thyroid disease screening

  • Screen high risk persons (elderly, neonates, postpartum females, those with family history of autoimmune/thyroid disease)
  • Diagnosis should include TSH and free thyroxine (fT4)
  • Delay thyroid testing in those who are sick until illness subsides, if unavoidable fT4 is most reliable indicator
  • TSH is the most sensitive indicator of thyroid status due to log linear relationship with fT4

  
• Specimen for thyroid testing

  Serum/plasma, free from hemolysis and lipemia
• Newborn screening for congenital hypothyroidism


  Whole blood collected by heel puncture within 48-72 hours after birth, metabolite tested is ___________