Hypothyroidism

• Overview: hypothyroidism
  1. cause: inadequate thyroid hormone synthesis
  2. Cretinism -- when hypothyroidism is present from birth and accompanied by developmental abnormalities
  3. Myxedema: severe hypothyroidism associated with:
     • deposition of hydrophilic mucopolysaccharides in the dermis (ground substance) and other tissues-- causing:
       • facial feature thickening
       • doughy skin induration
       • pretibia myxedema

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Hypothyroidism: Causes/Classification

*- Thyroprivic: refering to lack of thyroidhormone (e.g. removal of the gland or suppression of glandular function)

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• Hypothyroidism: pathogenesis
  1. inadequate thyroid hormone synthesisTSH hypersecretiongoiter
  2. if this compensatory physiological response is insufficient, goitrous hypothyroidism occurs

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  • Causes of goitrous hypothyroidism (North America)
    • most common cause: Hashimoto's disease
      • Mechanism:
        1. defective binding of iodide
        2. abnormal secretion of iodoproteins
    • Iodide-induced goiter with or without hypothyroidism: intrinsic defect inorganic binding mechanism
      • Euthyroid patients with Graves' disease {particularly following surgery or radioiodine therapy}, patients with Hashimoto's disease, and normal fetuses are particularly susceptible to iodide-induced goiter.

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• Hypothyroidism: Clinical presentation
  • Neonates (note that cretinism may be present at birth, but usually is apparent within the first few months after birth as a function of the extent of thyroid failure)
    • manifestations:
      • physiologic jaundice
      • constipation
      • somnolence
      • feeding problems
    • Since early clinical diagnosis may be difficult and early treatment is necessary to ensure normal intellectual development,all neonates should be screened for hypothyroidism by measuring serum T₄ or TSH

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  • Young Children:
    • coarse features, protruding tongue, broad, flat nose, widely set eyes, dry skin, coarse hair. impaired mental development, retarded bone age, epiphyseal dysgenesis, delayed dentition.

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  • Older Child:
    • retardation of linear growth, delayed puberty
    • poor school performance

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  • Adult:
    • fatigue, lethargy, constipation, cold intolerance,
    • slowing of intellectual and motor activity
    • lessened appetite; increased weight
    • dry skin; dry hair (may fall out)
    • deeper, hoarser voice
    • With Advanced Disease: (florid myxedema)
      • dull, expressionless facies, sparse hair, periorbital puffiness , large tongue, rough and doughy skin (cool, pale)
      • enlarged heart (dilation, pericardial effusion)
      • adynamic ileus
      •  Without treatment: myxedema coma possible with respiratory depression and increased P_CO2

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  • Laboratory Tests:
    • single most useful: serum TSH
      • increasedin thyroprivic and goitrous
      • normal or undetectable in pituitary or hypothalamic hypothyroidism
        • in hypothalamic hypothyroidism: TSH hypersecretion is associated with hypersecretion of other pituitary hormones: occasionally in hypothalamic hypothyroidism the TSH that is hypersecreted is immunoreactive but not biologically functional.
    • All hypothyroidism:
      • decreasedserum T₄ and free T₄I
      • serum T₃ may be decreased less than serum T₄
    • Some other abnormal laboratory results:
      • increase serum cholesterol (hypothyroidism of thyroid origin)
      • increased creatinine phosphokinase
      • increased aspartate transaminase
      • indications of pernicious anemia

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• Pharmacological treatment:
  • Synthetic hormones:
    • levothyroxine, preferred
    • liothyronine
    • liotrix (combination of L-thyroxine and liothyronine)
  • Neonatal, infantile, and juvenile hypothyroidism: early full replacement therapy vital to improve likelihood of:
    • normal intellectual development
    • normal growth
  • If neonatal, infantile, and juvenile presentations result from pituitary and hypothalamic hypothyroidism, treatment with hydrocortisone should precede thyroid replacement therapy:
    • Rationale:acute adrenocortical insufficiency may be caused by the increase in metabolic rate with increased glucocorticoid clearance following thyroid hormonal treatment
  • Adults:
    • rapid treatment desirable especially in patients with:
      1.  myxedema coma
      2.  hypothyroid patients needing to undergo emergency surgery (these patients have extreme sensitivity to CNS depressants);
         • IV levothyroxine with hydrocortisone may be appropriate
    • to patients with myxedema coma and systemic illness may have reduced ability to convert T₄ to T₃. In these cases supplemental liothyronine may be added to levothyroxine.

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