CC2

• Thyroid gland


  Also known as the butterfly-shaped gland
• Thyroid gland

  • Consists of two lobes (one on either side of the trachea located in the lower part of the neck, just below the voice box (larynx)
  • The lobes are connected by a narrow band called the isthmus
  • By 11 weeks of gestation, the gland begins to produce measurable amounts of hormone
• Follicle


  The fundamental structural unit of the thyroid gland
• Thyroglobulin


  A glycoprotein; it acts as a preformed matrix containing tyrosyl groups; it stores the follicular colloid of the thyroid gland
• Types of thyroid cells

  • Follicular cells (T3 and T4)
  • Parafollicular or C cells (Calcitonin)
• Biosynthesis of thyroid hormones

  1. Iodine is the most important element

  2. Iodination of tyrosine residues in thyroglobulin results in formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT)

  3. TSH stimulates synthesis of thyroid hormones

  4. Protein bound hormones are metabolically inactive - free hormones (FT3 and FT4) are the physiologically active portions

  5. Protein-bound thyroid hormones do not enter cells and are considered to be biologically inert and function as storage sites

  6. The minute levels of free hormone fractions readily enter cells by specific membrane transport mechanism to exert their biological effects

  7. When iodide sources are diminished, MIT is produced in greater quantities, leading to increased T3 formation and release

  8. Reverse T3 is produced by removal of one iodine from the inner ring of T4, metabolically inactive; product of T4 metabolism
• Hypothalamic-pituitary-thyroid axis (HPTA)


  The neuroendocrine system that regulates the production and secretion of thyroid hormones
• Iodine intake below 50g/day is an indication of the deficiency of hormone secretion
• Thyroid hormones affect synthesis, degradation, and intermediate metabolism of adipose tissue and circulating lipids
• Functions of thyroid hormones


  • For tissue growth
  • For mental development
  • For development of the central nervous system
  • Elevated heat production
  • Control of oxygen consumption
  • It influences carbohydrate and protein metabolism
  • For energy conservation
• Triiodothyronine (T3)

  • It has the most active thyroid hormonal activity
  • Almost 75-80% is produced from the tissue deiodination of T4 - conversion of T4 to T3 takes place in many tissues, particularly the liver and the kidneys
  • The principal application of this hormone is in diagnosing T3 thyrotoxicosis. It is a better indicator of recovery from hyperthyroidism as well as the recognition of recurrence of hyperthyroidism - it is helpful in confirming the diagnosis of hyperthyroidism, especially in patients with no or minimally elevated T4
  • An increase in the plasma level of T3 is the first abnormality seen in cases of hyperthyroidism
• Tetraiodothyronine (T4)


  • It is the principal secretory product
  • It has the major fraction of organic iodine in the circulation
  • It is a prohormone for T3 production
  • All circulating T4 originates in the thyroid gland - it is secreted 100% in the thyroid gland
  • The amount of serum T4 is a good indicator of the thyroid secretory rate
  • Elevated thyroxine causes inhibition of TSH secretion, and vice versa
• Thyroid binding proteins

  • Thyroxine-Binding Globulin (TBG) - it transports the majority of T3 (affinity for T3 is lower than T4), it transports 70-75% of total T4
  • Thyroxine-Binding Prealbumin (transthyretin) - it transports 15-20% of total T4, T3 has no affinity for prealbumin
  • Thyroxine-Binding Albumin - it transports T3 and 10% of T4
• Thyroid autoantibodies responsible for autoimmune thyroid disorders

  • Thyroperoxidase (TPO) - involved in the tissue destructive process (Hashimoto's disease)
  • Thyroglobulin (Tg)
  • TSH receptor (TR) - involved in Grave's disease
• Hyperthyroidism

  Refers to an excess of circulating thyroid hormone
• Signs and symptoms of hyperthyroidism


  • Tachycardia
  • Tremors
  • Weight loss
  • Heat intolerance
  • Emotional lability
  • Menstrual changes
• Types of hyperthyroidism

  • Primary hyperthyroidism - elevated T3 and T4, decreased TSH
  • Secondary hyperthyroidism - increased FT4 and TSH (due to primary lesion in the pituitary gland)
• Diseases associated with hyperthyroidism

  • Thyrotoxicosis - a group of syndromes caused by high levels of free thyroid hormones in the circulation
  • Graves disease (diffuse toxic goiter) - the most common cause of thyrotoxicosis, an autoimmune disease in which antibodies are produced that activate the TSH receptor
  • Riedel's thyroiditis - the thyroid turns into a woody or stony-hard mass
  • Subclinical hyperthyroidism - show no clinical symptoms but TSH level is low, and FT3 and FT4 normal
  • Subacute granulomatous/Subacute nonsuppurative thyroiditis/De Quervain's thyroiditis (painful thyroiditis) - associated with neck pain, low-grade fever and swings in thyroid function tests
• Hypothyroidism


  Refers to an insufficient circulating thyroid hormone
• Signs and symptoms of hypothyroidism

  • Bradycardia
  • Weight gain
  • Coarsened skin
  • Cold intolerance
  • Mental dullness
• Types of hypothyroidism

  • Primary hypothyroidism - primarily due to deficiency of elemental iodine, also caused by destruction or ablation of the thyroid gland
  • Hashimoto's disease (chronic autoimmune thyroiditis) - the most common cause of primary hypothyroidism, characterized by a thyroid replaced by a nest of lymphoid tissue
  • Myxedema - describes the peculiar non pitting swelling of the skin, the skin becomes infiltrated by mucopolysaccharides
  • Secondary hypothyroidism - due to pituitary destruction or pituitary adenoma
  • Tertiary hypothyroidism - due to hypothalamic disease
  • Congenital hypothyroidism/Cretinism - a defect in the development or function of the gland
  • Subclinical hypothyroidism - T3 and T4 normal but TSH is slightly increased
• Thyroid function tests

  • TRH stimulation test - measures the relationship between the TRH and TSH secretions
  • TSH - the most important thyroid function test, the best method for detecting clinically significant thyroid dysfunction
  • Radioactive iodine uptake (RAIU) - used to measure the ability of the thyroid gland to trap iodine
  • Thyroglobulin (Tg) assay - normally used as a postoperative marker of thyroid cancer, used in monitoring the course of thyroid cancer
• Screening of thyroid disorders is recommended when a person reaches 35 years old and every 5 years thereafter
• Subclinical disease

  Mild degree of thyroid dysfunction
• Reference values for TSH

  0.5-5 μU/mL
• Causes of increased TSH

  • Primary hypothyroidism
  • Hashimoto's thyroiditis
  • Thyrotoxicosis due to pituitary tumor
• Causes of decreased TSH

  • Primary hyperthyroidism
  • Secondary and Tertiary hypothyroidism
  • Treated Grave's disease
  • TSH antibodies
  • Thyroid hormone resistance
  • Euthyroid sick disease
  • Overreplacement of thyroid hormone in hypothyroidism
• RAIU (Radioactive Iodine Uptake)

  Measures the ability of the thyroid gland to trap iodine, helpful in establishing the cause of hyperthyroidism, high uptake indicates metabolically active gland (active hormone production), high uptake + TSH deficiency = autonomous thyroid activity
• Thyroglobulin (Tg) assay


  Normally used as a postoperative marker of thyroid cancer, used in monitoring the course of metastatic or recurrence of thyroid cancer, well-differentiated tumors typically display a 10-fold increase in Tg in response to a high TSH, differentiates subacute thyroiditis (↑Tg) from thyrotoxicosis factitia (↓Tg), reference value: adult = 3-42 ng/mL or μg/mL, infant = 38-48 ng/mL or μg/mL, methods for testing: double-antibody RIA, ELISA, IRMA, immunochemiluminescent assay (ICMA)
• Causes of increased thyroglobulin


  • Untreated and metastatic differentiated thyroid cancer
  • Nodular goiter
  • Hyperthyroidism
  • Infants with goitrous hypothyroidism
• Causes of decreased thyroglobulin


  • Thyrotoxicosis factitia
• Reverse T3 (rT3)

  Formed by the removal of one iodine from the inner ring of T4, an endproduct of T4 metabolism, the 3rd major circulating thyroid hormone, identifies patients with euthyroid sick syndrome (elevated rT3), used to assess borderline or conflicting laboratory results, reference value: 38-44 ng/dL
• Free Thyroxine Index (FTI or T7)


  Indirectly assesses the level of free T4 in blood, based on the equilibrium relationship of bound T4 and FT4, important in correcting euthyroid individuals, elevated in hyperthyroidism and decreased in hypothyroidism, reference value: 5.4-9.7, calculated as: FTI = (T4 x T3U(%)) / 100 or FTI = TTA x THBR
• Total T3 (TT3), Free T3 (FT3), Free T4 (FT4)


  FT4 test is used to differentiate drug-induced TSH elevation and hypothyroidism, the value of TT3 or FT4 is in confirming hyperthyroidism, direct/reference method for FT4 is equilibrium dialysis
• T3 Uptake


  Measures the number of available binding sites of the thyroxine-binding proteins, most notably TBG, a test for TBG, is inversely related to TBG - decreased T3 uptake results to elevated TBG result, and vice versa, reference value: 25-35%
• Causes of increased T3 uptake

  • Hyperthyroidism
  • Euthyroid patients
  • Chronic liver disease
• Causes of decreased T3 uptake

  • Hypothyroidism
  • Oral contraceptives
  • Pregnancy
  • Acute hepatitis
• Thyroxine Binding Globulin (TBG)

  Used to confirm results of FT3 and FT4 or abnormalities in the relationship of the total thyroxine (TT4) and THBR test, useful in distinguishing between hyperthyroidism (↑T4 + N TBG) and euthyroidism (↑T4 and TBG), helps in the diagnosis of patients having elevated T3 and T4 levels but no correlation with the other thyroid function tests, or not compatible with clinical findings, TBG excess leads to increased serum levels of T3 and T4, but the unbound or free form of these hormones in the blood remains unchanged, hormonal effect: estrogen increases TBG while androgens depress, reference value: 13-39 μg/dL (150-360 nmol/L)
• Causes of increased TBG

  • Euthyroidism
  • Pregnancy
  • Estrogen surge
• Causes of decreased TBG

  • Anabolic steroids
  • Nephrosis