Thyroid disease frequently arises from autoimmune processes that stimulate overproduction of hormones or cause gland destruction which subsequently leads to underproduction of hormones.

Epidemiology

• Incidence
  • Hypothyroidism
    • 6-8/10,000
    • Increases with age (1 of 4 nursing home patients has hypothyroidism)
    • Primary congenital hypothyroidism - 1/3,000 infants
  • Hyperthyroidism
    • 1-2% of the population
    • In pregnant females - 2/1,000 pregnancies
• Age - Age of onset 40-60 years for both types
• Sex - 5-8 times more common in females for both hypo- and hyperthyroidism

Hypothyroidism

• Caused by underproduction of hormones
• Etiologies
  • Autoimmunity - Graves disease
  • Iatrogenic (treatment of hyperthyroidism)
  • Iodine deficiency most common cause worldwide
  • Drugs

Refer to Thyroid Disease topicat www.arupconsult.com for a chart of Drugs That May Alter Thyroid Function Tests

• Clinical Presentation
  • Insidious onset is common
  • Fatigue, hair loss, cold intolerance, weight gain, dry coarse skin, alopecia, bradycardia, carpal tunnel syndrome, skin thickening (myxedema), constipation, depression
  • Most serious manifestation is myxedema coma
  • Congenital disease
    • Growth retardation
    • Mental retardation
• Treatment
  • Hypothyroid pregnant patients may require increase of replacement
    • Monitor with TSH and Free T4 or T4

Hyperthyroidism (Thyrotoxicosis)

• Caused by overproduction of thyroid hormones
• Etiologies
  • Graves disease accounts for 60-80% of cases
    • Autoimmune - thyroid stimulating immune globulins (TSI IgG) bind to thyrotropin receptors on the thyroid gland
  • Toxic multinodular or uninodular goiter
    • Secrete hormone autonomously
  • Thyroiditis
    • Postpartum
    • Subacute
  • Other - TSH secreting tumors (rare), ingestion of T3, T4, drug-induced (amiodarone)
• Clinical Presentation
  • Hyperactivity, heat intolerance, fatigue, weakness, diarrhea, tachycardia, tremor, goiter, weight loss
  • Diffuse nontender enlargement of the gland
  • Ophthalmopathy - occurs in 30% of patients and consists of protrusion of the eyes & periorbital swelling
• Treatment usually required

Pregnancy-related thyroid disorders

• Pathophysiology
  • Thyroid binding globulin levels (TBG) are elevated as estrogen increases
  • Increased TBG causes a shift in T3 and T4 reference ranges 1.5 times the nonpregnant state; always use trimester specific reference values
  • Reference intervals for free T4 have not been well established in pregnant patients, and so some authors advocate use of total T4 in place of free T4 during pregnancy
  • TSH falls and may be below the lower adult reference limit in 20% of pregnancies
• Hypothyroidism
  • 0.3-0.7% of pregnancies
  • Associated with infertility, low birth weight, low fetal IQ, fetal demise, hypertension, placenta abruptio and post partum hemorrhage (fetus may be unaffected)
  • Symptoms - low energy, inappropriate weight gain, constipation, goiter, cold intolerance and bradycardia
  • Most common cause - chronic autoimmune thyroiditis
• Hyperthyroidism
  • 0.2% of pregnancies
  • Associated with spontaneous abortions, infertility, still births, low birth weight, pre-term delivery, fetal or neonatal hyperthyroidism, congestive heart failure in mother
  • In 2% of pregnancies, T4 is supranormal around 10-12 weeks because hCG is at its peak and TSH is at its nadir
  • Symptoms - weight loss, goiter, muscle weakness, palpitations, onycholysis, tachycardia and eye changes
  • Causes
    • Gestational transient thyrotoxicosis - frequently associated with hyperemesis gravidarum in first trimester
    • Hyperemesis gravidarum
    • Trophoblastic tumors such as choriocarcinoma
    • TSH receptor mutations
• Euthyroid sick syndrome
  • Low levels of thyroid hormone in clinically euthyroid patients who have systemic illnesses
  • Diagnosis - TSH normal; T3, T4 may be low

Diagnosis

• Hypothyroidism
  • Indications for testing - symptoms of hypothyroidism
  • Diagnosis
    • Laboratory testing
      • Initial evaluation should include thyroid stimulating hormone (TSH) (increased) followed with Free T4 (FT4)  (decreased), thyroid antibodies
      • Hypothyroidism during pregnancy may cause fetal demise and low IQ in liveborn (endemic cretinism) infants
        • Order TSH and TPO antibody testing for patients who have a prior diagnosis of or family history of hypothyroidism
        • Elevated TPO antibodies associated with post-partum thyroiditis
      • Subclinical disease
        • TSH minimally elevated with normal T4, T3
        • Presence of symptoms or experiencing infertility , consider testing for hypothyroidism
  • Monitoring - TSH and T4 are useful in monitoring thyroid replacement therapy
  • Screening
    • Neonatal in first 24 hours using TSH - abnormal tests must be followed up with T4
• Hyperthyroidism
  • Indications for testing - symptoms of hyperthyroidism, family history of autoimmune thyroiditis
  • Diagnosis
    • Laboratory testing
      • Initial evaluation involves TSH measurement (decreased), Free T4 (increased)
      • Further evaluation may include thyroid antibody evaluation, radioiodine uptake of the thyroid gland
  • Monitoring
    • Initial monitoring of TSH and T4 - 6 weeks after initiation of therapy until euthyroid
    • Patients eventually develop hypothyroidism in autoimmune disease as the gland burns out
    • Monitor TSH T4 every 1-2 years
• Differential Diagnosis
  • Drug-induced (amiodarone)
  • Thyrotoxicosis factitia
  • Trophoblastic tumors
  • Anxiety
  • Depression
  • Cushing disease
  • Obesity
  • PCOS