Hypothyroidism in Adults

Background

• Hypothyroidism is a deficiency of thyroid hormone usually caused by primary thyroid failure, and less often due to pituitary failure, hypothalamic failure, or congenital thyroid hormone resistance.
  • Overt primary hypothyroidism is defined as elevated thyroid stimulating hormone (TSH) with low free thyroxine (FT4), and can be autoimmune-related, congenital, or caused by thyroid surgery, previous radioablation or radiation therapy to the neck, or endemic iodine deficiency.
  • Subclinical hypothyroidism is defined as elevated TSH with normal free T4.
  • Central hypothyroidism usually presents with low to normal TSH with low FT4, and can be caused by hypopituitarism (secondary hypothyroidism), a hypothalamic process (tertiary hypothyroidism), or severe illness (nonthyroidal illness syndrome).
  • Drugs that may cause hypothyroidism include lithium and amiodarone.
• The most common cause of hypothyroidism is autoimmune disease (Hashimoto thyroiditis).
• There is a higher incidence of primary thyroid failure in older adults and among women.
• Complications of hypothyroidism include cardiovascular, neuropsychiatric, musculoskeletal, and other important sequelae.
• There is insufficient evidence to recommend routine screening for hypothyroidism in asymptomatic, nonpregnant adults with low risk for hypothyroidism, but screening may be considered for older adults (> 60 years old) and adults at increased risk for hypothyroidism (such as those with autoimmune disease or a first-degree relative with hypothyroidism).

Evaluation

• Hypothyroidism may present with:
  • no symptoms (condition detected on screening)
  • mild-to-moderate symptoms, such as slow mental and physical activity, cold intolerance, constipation, and weight gain
  • changes in mental status (myxedema coma) in advanced disease
• Examine symptomatic patients for bradycardia, hypothermia, dry skin, facial and periorbital edema, thyroid gland for size and irregularities, heart failure and other cardiopulmonary findings, and increased relaxation phase of deep tendon reflexes.
• In symptomatic patients or in those with signs of hypothyroidism, measure thyroid-stimulating hormone (TSH). Measure free thyroxine (FT4) if the TSH is elevated or if a disorder other than primary hypothyroidism is suspected.
• Serum TSH may be physiologically higher in older adults.
  • The most commonly used reference range in nonpregnant adults is 0.5-4 milliunits/L, but can be as high as 4.5 milliunits/L.
  • In older adults (> 70 years old), the reference range may extend to 4-6 milliunits/L.
• Diagnosing hypothyroidism in nonpregnant adults
  • The diagnosis of overt primary hypothyroidism may be suspected in patients with classic signs and symptoms of hypothyroidism, and is diagnosed when blood tests show:
    • elevated TSH, often > 10 milliunits/L
    • low serum FT4
  • The diagnosis of subclinical primary hypothyroidism (which is typically asymptomatic or mildly symptomatic) is confirmed by blood tests showing:
    • elevated TSH
    • normal serum FT4
  • The diagnosis of central (secondary and tertiary) hypothyroidism is usually made in patients with signs and symptoms consistent with primary hypothyroidism plus findings associated with hypothalamic or pituitary deficiency (such as menstrual disturbances, galactorrhea, diminished libido, and/or infertility) and confirmed by blood tests showing low to normal TSH and low serum FT4.
• In pregnancy, diagnose hypothyroidism if TSH is elevated above the normal limit of the trimester-specific reference range (Strong recommendation).
• The differential diagnosis includes nonthyroidal illness. Other conditions that cause similar symptoms are anemia, pregnancy, and liver failure, and falsely elevated TSH levels as a result of medications or other illnesses.

Management

• Thyroid hormone replacement therapy
  • Levothyroxine (LT4) monotherapy is the recommended treatment for patients with hypothyroidism (Strong recommendation).
  • Indications for levothyroxine
    • Treat all patients with overt hypothyroidism with levothyroxine (Strong recommendation).
    • The decision to treat subclinical hypothyroidism is controversial.
      • For nonpregnant patients with subclinical hypothyroidism, consider treatment with levothyroxine if serum TSH levels are > 10 milliunits/L due to increased risk for heart failure and cardiovascular mortality (Weak recommendation).
      • If the decision is made to treat subclinical hypothyroidism, consider a lower dose (25-75 mcg/day orally), depending on the degree of TSH elevation (Weak recommendation).
• Levothyroxine oral dosing
  • For young, healthy adults with overt hypothyroidism, consider starting with a full replacement dose (1.6 mcg/kg/day or 100-125 mcg/day in typical adults) (Weak recommendation).
  • For older patients with coronary artery disease, consider starting with 12.5-25 mcg/day.
• Monitor TSH levels 4-6 weeks after any dose change (Strong recommendation).
• After an adequate replacement dose has been determined, consider measuring TSH levels after 6 months and then at 12-month intervals, or more frequently based on clinical situation (Weak recommendation).
• Management in pregnant adults and postpartum
  • For pregnant adults with overt hypothyroidism, treat with levothyroxine (Strong recommendation).
  • A full starting dose of levothyroxine (2-2.4 mcg/kg/day orally) is suggested for overt hypothyroidism discovered during pregnancy.
  • For pregnant adults with subclinical hypothyroidism
    • Treat with levothyroxine if:
      • thyroid peroxidase antibody (TPOAb) titers are positive and TSH is greater than the trimester-specific reference range (Strong recommendation)
      • TPOAb titers are negative and TSH is > 10 milliunits/L (Strong recommendation)
    • Consider treating with levothyroxine if:
      • TPOAb titers are positive and TSH is > 2.5 milliunits/L and below the upper limit of the trimester-specific reference range (Weak recommendation)
      • TPOAb titers are negative and TSH is greater than the trimester-specific reference range but < 10 milliunits/L (Weak recommendation)
  • Monitoring during pregnancy and postpartum
    • In pregnant adults with overt and subclinical hypothyroidism (treated or untreated) or those at risk for hypothyroidism, monitor TSH level every 4 weeks until midgestation and at least once near 30 weeks (Strong recommendation).
    • For adults being treated for hypothyroidism during pregnancy, consider a target TSH goal in the lower half of a trimester-specific reference range (or < 2.5 milliunits/L if a specific range is not available) (Weak recommendation).
    • Follow-up after delivery
      • Readjust the levothyroxine dose to the preconception dose at delivery and monitor thyroid function at about 6 weeks postpartum (Strong recommendation).
      • Consider discontinuing levothyroxine in certain adults who initiated levothyroxine during pregnancy, especially those with a dose ≤ 50 mcg/day (Weak recommendation).
        • The patient should be involved in the decision.
        • Measure serum TSH at about 6 weeks postpartum if levothyroxine is discontinued.
• Management in patients with myxedema coma
  • Myxedema coma is a medical emergency and requires urgent recognition and treatment.
  • In patients with suspected myxedema coma, treatment should be initiated based on clinical suspicion alone and not delayed until results of blood tests are available.
  • Admit the patient to the intensive care unit for continuous pulmonary and cardiovascular monitoring and support.
  • Provide stress doses of IV glucocorticoid prior to levothyroxine administration (Strong recommendation) (for example, hydrocortisone 100 mg IV every 8 hours).
  • Administer a levothyroxine loading dose of 200-400 mcg IV (give lower doses for smaller or older patients and those with a history of coronary artery disease or arrhythmia) followed by a replacement oral dose of 1.6 mcg/kg/day (if given IV, use 75% of oral dose) (Strong recommendation).
  • In addition to levothyroxine, consider administering a liothyronine loading dose of 5-20 mcg IV followed by a maintenance dose of 2.5-10 mcg IV every 8 hours until the patient is clearly improving (Weak recommendation).
    • Use lower doses for smaller or older patients and those with coronary artery disease or arrhythmia.
    • High doses should be avoided because of the reported association of high serum triiodothyronine with mortality.
• Most patients with uncomplicated hypothyroidism will not require perioperative dose adjustments.