Thyroid Disease

Diagnosis

Indications for Testing

• Symptoms of hyper- or hypothyroidism
• Family history of autoimmune thyroiditis
• Goiter on physical exam

Laboratory Testing

• Initial evaluation for thyroid disease – thyroid stimulating hormone (TSH)
  • TSH and T4 normal – thyroid disease unlikely
  • TSH elevated – suggests hypothyroidism
    • Order free T4 (thyroxine)
      • Low – hypothyroidism confirmed
        • Consider thyroid antibody testing
      • Normal – consider T3 (triiodothyronine) testing
        • Low T3 – hypothyroidism confirmed
        • Normal T3 – hypothyroidism unlikely, but if indicated by clinical presentation, could be subclinical hypothyroidism
  • TSH low – suggests hyperthyroidism
    • Order free T4
      • High – hyperthyroidism confirmed
      • Normal – consider T3 testing
        • Normal T3 – if TSH levels 0.1-0.4, subclinical hyperthyroidism
        • High T3 – hyperthyroidism
      • Low – central hypothyroidism or severe illness
• Hypothyroidism during pregnancy may cause fetal demise and low IQ in liveborn infants (endemic cretinism)
  • Order TSH and thyroid peroxidase (TPO) antibody testing for patients who have a prior diagnosis or family history of hypothyroidism
  • Elevated TPO antibodies associated with postpartum thyroiditis
• Euthyroid sick syndrome
  • Low levels of thyroid hormone in clinically euthyroid patients who have systemic illnesses
  • Diagnosis – TSH variable; free T3, T4 may be low

Differential Diagnosis

• Hyperthyroidism
  • Drug-induced (amiodarone)
  • Thyrotoxicosis factitia
  • Trophoblastic tumors
  • Anxiety
  • Sepsis
• Hypothyroidism
  • Depression
  • Cushing disease
  • Obesity
  • Polycystic ovarian syndrome
  • Metabolic syndrome

Screening

Monitoring

Clinical Background

Thyroid disease frequently arises from autoimmune processes that stimulate overproduction of hormones (hyperthyroidism) or causes gland destruction that subsequently leads to underproduction of hormones (hypothyroidism).

Epidemiology

• Incidence
  • Hypothyroidism
    • 4-6% of the population
    • Increases with age – 1 of 4 nursing home patients has hypothyroidism
    • Primary congenital hypothyroidism – 1/3,000 infants
  • Hyperthyroidism
    • 2-3% of the population
    • 2/1,000 pregnancies
• Age – onset is 40s-50s for both hypo- and hyperthyroidism
• Sex – M<F, 1:5-8 for both types

Disorders

• Hypothyroidism

  Etiologies Autoimmunity – Graves disease, Hashimoto disease Iatrogenic – treatment hyperthyroidism Iodine deficiency most common cause worldwide – predominantly in underdeveloped countries Drugs – amiodarone, androgens, aspirin, cholestyramine, estrogens, furosemide, glucocorticoids, levodopa, lithium, neuroleptics, phenytoin, propranolol Clinical Presentation Insidious onset common Fatigue, depression, cold intolerance, weight gain, bradycardia, constipation, hair loss, alopecia, carpal tunnel syndrome, dry/coarse skin, skin thickening (myxedema) Myxedema coma – most serious manifestation Congenital disease Growth retardation Developmental delay/mental retardation

• Hyperthyroidism (thyrotoxicosis)

  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 (Plummer disease) 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 – subacute thyroiditis Ophthalmopathy – occurs in 30% of patients and consists of protrusion of the eyes and periorbital swelling (Graves disease)

• Pregnancy-related

  Thyroid binding globulin (TBG) levels 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 not well established in pregnant patients – some research recommends use of total T4 in place of free T4 during pregnancy TSH falls – 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 postpartum hemorrhage – fetus may be unaffected Symptoms – low energy, inappropriate weight gain, constipation, goiter, cold intolerance, bradycardia Most common cause – chronic autoimmune thyroiditis Hyperthyroidism 0.2% of pregnancies Associated with spontaneous abortions, infertility, still births, low birth weight, preterm 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, eye changes Causes Gestational transient thyrotoxicosis Hyperemesis gravidarum – frequently associated with gestational transient thyrotoxicosis Trophoblastic tumors such as choriocarcinoma TSH receptor mutations

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Triiodothyronine, Total (Total T3) 0070474 Method: Quantitative Electrochemiluminescent Immunoassay	Not recommended for routine thyroid screening Indications for ordering are rare cases of suppressed serum thyroid stimulating hormone (TSH) with normal free thyroxine (FT4) (eg, suspected T3 toxicosis, subclinical T3 hyperthyroidism, rare pituitary conditions)
Thyroid Stimulating Hormone 0070145 Method: Quantitative Chemiluminescent Immunoassay	Preferred test for screening and monitoring thyroid function, but does not include T4 reflex testing. Aid in the diagnosis of primary hyperthyroidism and differential diagnosis of hypothyroidism Monitor individuals on thyroid hormone replacement therapy Confirm suppression during thyroxine therapy for thyroid carcinoma
Thyroxine, Free (Free T4) 0070138 Method: Quantitative Electrochemiluminescent Immunoassay	Order following abnormal thyroid stimulating hormone (TSH) result  Order in conjunction with TSH if pituitary (secondary) hypothyroidism is suspected Assess thyroid status in pregnant women or those on estrogen supplementation, phenytoin, or salicylates Monitor thyroid hormone replacement therapy during pregnancy and treatment of secondary hypothyroidism
Thyroxine, Free by Equilibrium Dialysis/HPLC-Tandem Mass Spectrometry 0093244 Method: Quantitative Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry	Not recommended for routine evaluation of thyroid disorders; order free T4 instead
Triiodothyronine, Reverse by Tandem Mass Spectrometry 2007918 Method: Quantitative Liquid Chromatography-Tandem Mass Spectrometry	Generally not recommended for routine evaluation of thyroid disorders, although may be considered in pregnant women
Triiodothyronine, Free by Equilibrium Dialysis/HPLC-Tandem Mass Spectrometry 0093243 Method: Quantitative Equilibrium Dialysis/High Performance Liquid Chromatography-Tandem Mass Spectrometry
Thyroxine Binding Globulin 0070410 Method: Quantitative Chemiluminescent Immunoassay	Not recommended for routine thyroid screening Aid in interpreting T3 and T4 levels that do not correlate with clinical findings
Triiodothyronine, Free (Free T3) 0070133 Method: Quantitative Electrochemiluminescent Immunoassay	Not recommended for routine thyroid screening Indications for ordering are rare cases of suppressed serum thyroid stimulating hormone (TSH) with normal free thyroxine (FT4) (eg, suspected T3 toxicosis, subclinical T3 hyperthyroidism, rare pituitary conditions) Second-line test in evaluating individuals during pregnancy, those receiving steroids, or individuals with dysalbuminemia Do not order for individuals with abnormal total T3 values False positives may result from thyrotoxicosis or excess replacement therapy
Thyroid Panel 0070141 Method: Quantitative Electrochemiluminescent Immunoassay	Not recommended for routine thyroid screening Total T4, T3 uptake, and estimation of free thyroxine (FT4) index have limited clinical utility Replaced by the combination of more sensitive TSH and FT4 tests that provide direct measurements
T3 Uptake 0070135 Method: Quantitative Electrochemiluminescent Immunoassay	Not recommended for routine thyroid screening Replaced by the combination of more sensitive TSH and FT4 tests that provide direct measurements Little clinical value as stand-alone test

Diagnostic Algorithm

  Thyroid Disorders Testing Algorithm

  Thyroid Nodules Testing Algorithm