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SOURCE

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Source: Jonklaas J, Kane MP. Thyroid disorders. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146066204. Accessed April 14, 2017.

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DEFINITION

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  • Clinical and biochemical syndrome resulting from decreased thyroid hormone production.

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ETIOLOGY

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  • Primary.

    • Hashimoto’s disease.

    • Iatrogenic hypothyroidism.

    • Less common.

      • Iodine deficiency.

      • Enzyme defects.

      • Thyroid hypoplasia.

      • Goitrogens.

  • Secondary.

    • Pituitary disease.

    • Hypothalamic disease.

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PATHOPHYSIOLOGY

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  • Most patients have primary hypothyroidism due to thyroid gland failure from chronic autoimmune thyroiditis (Hashimoto’s disease).

  • Defects in suppressor T-lymphocyte function lead to survival of mutating clone of helper T lymphocytes that produce thyroid antibodies.

  • Iatrogenic hypothyroidism follows exposure to excessive amounts of radiation (radioiodine or external radiation) or after total thyroidectomy.

  • Other causes of primary hypothyroidism include:

    • Iodine deficiency.

    • Enzymatic defects within thyroid gland.

    • Thyroid hypoplasia.

    • Maternal ingestion of goitrogens during fetal development.

  • Secondary hypothyroidism may be due to:

    • Pituitary insufficiency because of pituitary tumors.

    • Surgical therapy.

    • External pituitary radiation.

    • Postpartum pituitary necrosis.

    • Trauma.

    • Infiltrative processes (eg, metastatic tumors, tuberculosis)

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EPIDEMIOLOGY

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  • Occurs in 1.5–2% of women and 0.2% of men.

  • Incidence increases with age.

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RISK FACTORS

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  • Postpartum status.

  • Family history of autoimmune thyroid disorders.

  • Previous head, neck, or thyroid irradiation or surgery.

  • Autoimmune endocrine conditions, including:

    • Type 1 diabetes mellitus.

    • Adrenal insufficiency.

    • Ovarian failure.

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CLINICAL PRESENTATION

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SIGNS AND SYMPTOMS
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  • Symptoms:

    • Dry skin.

    • Cold intolerance.

    • Weight gain.

    • Constipation.

    • Weakness.

    • Depression.

    • Lethargy.

    • Fatigue.

    • Exercise intolerance.

    • Muscle cramps.

    • Myalgia.

    • Stiffness.

    • Loss of ambition or energy.

    • Women: menorrhagia and infertility.

  • Signs:

    • Coarse skin and hair.

    • Cold or dry skin.

    • Periorbital puffiness.

    • Bradycardia.

    • Slowed or hoarse speech.

    • Proximal muscle weakness.

    • Slow relaxation of deep tendon reflexes.

    • Reversible neurologic syndromes: carpal tunnel syndrome, polyneuropathy, cerebellar dysfunction.

    • Women: galactorrhea.

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DIAGNOSIS

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LABORATORY TESTS
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  • In primary hypothyroidism, thyroid-stimulating hormone (TSH) elevated.

  • In secondary hypothyroidism, TSH levels may be within or below reference range.

  • Free and/or total thyroxine (T4) and triiodothyronine (T3) serum concentrations low.

  • Antithyroid peroxidase antibodies and anti-TG antibodies often elevated in autoimmune thyroiditis.

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DIFFERENTIAL DIAGNOSIS
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  • Chronic fatigue syndrome.

  • Depression

  • Congestive heart failure.

  • Anemia due to other causes.

  • Amyloidosis.

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DESIRED OUTCOMES

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  • Restore normal thyroid hormone concentrations in tissue.

  • Provide symptomatic relief.

  • Prevent neurologic deficits in newborns and children.

  • Reverse biochemical abnormalities.

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TREATMENT: PHARMACOLOGIC THERAPY

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  • Table 1. Thyroid preparations used for treatment of hypothyroidism.

  • Levothyroxine (T4) drug of choice for thyroid hormone replacement therapy.

    • Once product selected, therapeutic interchange discouraged.

    • Starting dose for young patients with longstanding disease and older patients without known cardiac ...

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