FINALS

• Thyroid gland


  Butterfly shaped gland located in the lower part of neck and just below the voice box or larynx, connected by a narrow band called isthmus
• Eleven (11) weeks of gestation, thyroid hormones produce
• Follicle


  Fundamental unit of thyroid gland, follicular cells secrete T3 and T4, parafollicular or C cells secrete Calcitonin
• Thyroglobulin


  Preformed matrix containing tyrosyl group, glycoprotein, stored in the follicular colloid of the thyroid gland
• Building blocks for active thyroid hormones

  • Thyroxine (T4): Half-life of one week in circulation
  • Triiodothyronine (T3): Half-life of one day
• Normal values: T4 5.5-12.5 ug/dL, T3 100-200 ng/dL
• T3 exerts majority of thyroidal hormone effects
• Both T4 and T3 are bound in serum proteins mostly with thyroxine binding globulin (TBG), 99.97% of T4 and 99.7% of T3 circulate in bound form
• Thyroid hormone synthesis


  1. Iodine enters through alimentary tract as iodide, 1/3 enters thyroid gland, 2/3 leaves body in urine

  2. Enzymes oxidize iodide to organic iodine into monoiodotyrosine and diiodotyrosine
• TSH stimulates synthesis of thyroid hormone
• T4 is secreted 100% in the thyroid gland, conversion of T4 to T3 takes place in many tissues particularly liver and kidney
• Protein bound hormones


  Inactive, do not enter cells, function as storage sites of circulating thyroid hormones
• Free hormones (FT4 and FT3)


  Physiologically active
• Reverse T3 (rT3)


  Produced by removal of one iodine from the inner ring of T4, inactive, product of T4 metabolism
• Functions of thyroid hormone

  • Tissue growth
  • Development of central nervous system
  • Elevated heat production
  • Control of oxygen consumption
  • Influences carbohydrate and protein metabolism
  • Energy conservation
• Pituitary-hypothalamic relationship


  1. Thyroid gland responds with production of thyroxine on stimulation of anterior pituitary hormone TSH

  2. TSH follows stimulation of the gland by the hypothalamic peptide TRH, which responds to active levels of T3 and T4

  3. Low hormone levels TRH provokes TSH secretion thus, increased thyroidal iodine metabolism and hormone production
• Effects of thyroid hormone

  • Control of oxygen consumption
  • Influence CHO and protein metabolism, mobilization of electrolytes, conversion of carotene to vitamin A
  • Essential for development of CNS, deficient in infant causes irreversible mental damage (cretinism), in adults slows deep tendon reflexes, diffuse psychomotor retardation
  • Treatment HRT
• Factors that decrease thyroid activity

  • Enzyme deficiencies may interfere with iodine metabolism causing congenital goiter
  • Exogenous thyroid hormone suppresses hormone production by depressing TSH levels
  • Thiocyanate and perchlorate interfere with iodide concentration
  • Thiourea and thiouracil prevent incorporation of thyroidal iodine into organic compounds
  • Anti-thyroid effects of iodine includes inhibition of iodine binding and of hormonal release
  • Radioactive iodine has the additional effect of selectively irradiating hormonally active tissue, owing to its uptake by the actively functioning gland
• Basal metabolic rate (BMR)


  Earliest test for thyroid function, measures oxygen consumption
• Thyroid hormones


  Affects synthesis, degradation and intermediate metabolism of adipose tissue and circulating lipids
• Hyperthyroidism


  Degradation and excretion of lipids, resulting in low levels of cholesterol, phospholipids and triglycerides
• Hypothyroidism

  Slows catabolism more than affecting synthesis, resulting in hypercholesterolemia and hypertriglyceridemia
• Increased serum cholesterol levels may indicate impending hypothyroidism, cholesterol levels drop to normal within 2-3 weeks after successful therapy for hypothyroidism
• Severe hypothyroidism serum levels of muscle-associated enzymes CK and LDH tend to rise, isoenzyme partition reveals skeletal muscle as the source
• Effects of hypothyroidism


  • Increased serum cholesterol, triglycerides
  • Increased serum carotene (yellow skin discoloration)
  • Increased serum levels of muscle enzyme: CPK, AST, LDH
  • Increased serum prolactin
  • Increased capillary fragility
  • Increased spinal fluid protein
  • Normochromic anemia, hemoglobin around 10g/dL
  • Decreased urinary excretion of 17KS, 17-OHCS
• Effects of hyperthyroidism


  • Increased skin temperature, pulse rate, pulse pressure
  • Decreased serum cholesterol, triglycerides
  • Increased serum levels of aminotransferases and alkaline phosphatase
  • Increased retention of BSP
  • Altered glucose insulin relationship
  • Increased proportion of lymphocytes in differential white count
  • Increased urinary calcium excretion
• Iodine levels


  Iodine plays one physiologic role in serum as a vital constituent of thyroid hormones, thus iodine measurements were used as indicator of thyroid function
• Protein bound iodine (PBI)

  Earliest measurement of iodine, but severely affected by organic and inorganic iodine contaminants, useful to document nonhormonal iodine, physical damage to the thyroid gland liberating iodine to the blood stream, diagnosis of iodine overload or toxicity
• Butanol-extractable iodine (BEI)


  Technically more difficult, does not offer great accuracy, high levels of iodinated radiographic contrast dyes causes interference
• Thyroxine (T4)


  Measured by radioimmunoassays (RIA) or Enzyme-Linked immunoassay, uses TBG as the specific binder, measurement of T4 is the first round test in screening thyroid disease
• Triiodothyronine (T3)


  Most active thyroid hormonal activity, 75-80% produced from tissue deiodination of T4, useful in the confirmation of a suspected thyroid abnormality, indicator of recovery from hyperthyroidism, recognition of recurrence, necessary to monitor thyroid replacement therapy consist of T3
• Thyroxine-binding globulin and free hormone

  Evaluated when T3 and T4 values are abnormal, use RIA or T3 uptake test, for hyperthyroidism both T4 and T3 have high values, for hypothyroidism both T4 and T3 have low values, increase in the plasma level seen in cases of hyperthyroidism
• Tetraiodothyronine (Thyroxine)


  Principal secretory product, originates in the thyroid gland, major fraction of organic iodine in the circulation, a prohormone for T3 production, serum T4 is an indicator of thyroid secretory rate, elevated thyroxine causes inhibition of TSH secretion and vice versa
• Reference values


  • Adult T4: 5.5-12.5 ug/dL or 71-161nmol/L
  • Neonates T4: 11.8-22.6 ug/dL or 152-292 nmol /L
  • Adult T3: 80-200 ng/dl or 1.2-3.1nmol/L
  • Children (1-14 y/o) T3: 105-245 ng/dl or 1.8-3.8 nmol/l
• Factors affecting thyroxine-binding globulin

  • Estrogens increase the amount of TBG
  • Androgens and glucocorticoids depress TBG
  • Pregnant women and patients taking exogenous estrogens, or endocrine secreting tumors, T3 uptakes are low due to increase TBG concentration
  • Low TBG concentration, high T3 uptake, protein levels are low e.g. liver disease, nephrotic syndrome
  • Drugs like salicylates and phenytoin, anticonvulsants binds TBG, competes with thyroxine, thus gives high residual T3 uptake occupied by the nonhormonal agents
  • Administration of heparin causes elevation of free fatty acids from breakdown of triglycerides by post-heparin lipoprotein lipase activation, false high T3 uptake
• Thyroid-stimulating hormone (TSH)


  Thyroid activity is regulated by the body's perceived need for hormone, if inadequate thyroid hormone circulates in free fraction, hypothalamus produces TRH that provokes rising TSH levels to stimulate thyroid output, measured by immunoassays, normal values 0-10 uIU/ml, increased in primary hypothyroidism, distinguishes true hypothyroidism from euthyroid condition with low thyroid hormone levels
• Hypothyroidism


  • Hypometabolism called myxedema, lethargy, constipation, dry skin, and hair, premenopausal women (excessive bleeding), slowed tendon reflexes, coarse skin texture, facial puffiness, cold intolerance, decreased sweating, impaired memory, slowing of speech and motor activity, systolic and diastolic is high but slow heart rate
• Congenital hypothyroidism causes irreversible, severe mental retardation, characteristic body changes, cretinism, all newborn are screened by heel-stick blood sample for low T4, confirmed by TSH assay, treatment is lifelong administration of thyroid hormone soon after birth
• Hyperthyroidism


  • Thyroid produces excessive hormone from nodular areas: hyperfunctioning (adenomas and toxic nodular goiter), overall hyperactivity (diffuse toxic goiter or Grave's disease), manifest nervousness, fatigue, weight loss, heat intolerance, increased sweating, toxic nodular goiter: excessive prominence of eyes (exopthalmos), widening of palpebral fissures, T3T4 are high T3 uptake and high free T4 index, subclass T3 thyrotoxicosis: normal T4 and FT4I but increased T3, stimulation of chorionic gonadotropin (same chemical structure with TSH) causes hyperthyroidism in patients with high hCG levels from hydatidiform mole, choriocarcinoma and embryonal carcinoma of the testis
• Thyroiditis


  • Lymphocytic infiltration and fibrosis occur, lymphocytic thyroiditis or Hashimoto's disease: often with glandular enlargement, high titer of thyroglobulin and microsomal antigen
  • Subacute thyroiditis: may indicate viral agent, disorder begins as sore throat with fever, progresses involving one or both lobes, large and tender on palpation or on swallowing, thyroid biopsy shows inflammatory cell infiltrates, atrophy leads to irreversible hypothyroidism, can recover with treatment of aspirin and steroids