Hyperthyroidism

Aka: Hyperthyroidism, Thyrotoxicosis

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II. Epidemiology

  1. Prevalence Overt Hyperthyroidism (US): 0.5% (Subclinical Hyperthyroidism in another 0.7%)
    1. Women: 2%
    2. Men 0.2%
  2. References
    1. Turnbridge (1977) Clin Endocrinol 7:481-93 [PubMed]

III. Pathophysiology

  1. Excessive Thyroid Hormone up-regulates beta-Adrenergic Receptors, increasing sensitivity to Catecholamines

IV. Causes

  1. Stimulatory Causes (positive Radioactive Iodine scan)
    1. Grave's Disease (60-80% of Hyperthyroidism cases)
    2. Other Rare Causes
      1. Trophoblastic Tumors activate TSH receptors via HCG (Choriocarcinoma)
      2. TSH-Secreting Pituitary Adenoma
  2. Non-Stimulatory Causes (TSH independent)
    1. Thyroid follicular cell hyperplasia with increased Thyroid Hormone production
      1. Toxic Multinodular Goiter (5%, esp. elderly in Iodine deficient regions)
      2. Toxic Thyroid Adenoma (Plummer's Disease)
    2. Thyroiditis (common)
      1. Subacute Thyroiditis (Granulomatous Thyroiditis)
      2. Acute Suppurative Thyroiditis (Bacterial Infection)
      3. Postpartum Thyroiditis (lymphocytic Thyroiditis)
    3. Medication-Induced Hyperthyroidism
      1. See Medications Affecting Thyroid Function
      2. Exogenous Thyroid Hormone source
    4. Tumors (rare)
      1. Metastatic follicular Thyroid Cancer
      2. Ovarian Cancer producing Thyroxine (struma ovarii)
  3. Combined Stimulatory and Non-Stimulatory Causes (positive Radioactive Iodine scan)
    1. Nodular Goiter with superimposed stimulation

V. Findings: Common Presentations

  1. Unintentional Weight Loss, heat intolerance, Palpitations and generalized weakness
  2. Exam with palpable Goiter, Tachycardia, Tremor and proximal Muscle Weakness

VI. Symptoms

  1. Neurologic and psychiatric symptoms
    1. Nervousness or alertness
    2. Emotional lability (Anxiety, Irritability or even Psychosis)
    3. Proximal Muscle Weakness
    4. Insomnia
  2. Adrenergic symptoms
    1. Palpitations
    2. Tremor
    3. Frequent Bowel Movements, Diarrhea
    4. Excessive Sweating
    5. Heat intolerance
  3. Miscellaneous
    1. Weight loss despite increased appetite (hypermetabolism)
    2. Oligomenorrhea or Amenorrhea

VII. Signs

  1. Vital Signs
    1. Body weight
      1. Compare to prior recorded values
    2. Temperature
      1. Fever may be present (Acute Thyroiditis)
  2. Neck
    1. Palpable Thyroid Goiter
    2. Thyroid may be tender (Acute Thyroiditis)
  3. Dermatologic
    1. Warm, moist and velvety
    2. Palmar erythema
    3. Hair fine and silky
    4. Fingernails
      1. Onycholysis (Plummer's Nails)
      2. Brown Nail Discoloration
    5. Graves Dermopathy
      1. Pretibial Myxedema (Thyroid dermopathy) occurs in 1.5% of cases
      2. Thyroid Acropachy (finger soft tissue swelling and Digital Clubbing)
      3. Skin Pigment Changes (patchy Hyperpigmentation or vitilgo)
  4. Neuropsychiatric
    1. Anxious, restless, fidgeting patient
    2. Fine Tremor of fingers, Tongue
    3. Hyperkinesia
    4. Rapid speech
    5. Proximal Muscle Weakness (e.g. Quadriceps weakness)
  5. Eye changes
    1. See Thyroid Eye Disease
    2. Stare
    3. Widened palpebral fissures
    4. Infrequent blinking
    5. Chemosis
    6. Lid Lag
    7. Proptosis (Exophthalmos) - Graves Disease
    8. Periorbital edema
  6. Cardiovascular
    1. Increased Blood Pressure and Heart Rate
      1. Systolic Hypertension
      2. Wide Pulse Pressure
      3. Tachycardia
    2. Auscultation
      1. Loud S1 Heart Sound
      2. Loud S2 Heart Sound
      3. Systolic Murmur
    3. Chronic changes
      1. Atrial Fibrillation (10-15%)
      2. Cardiac hypertrophy or Cardiomyopathy (5%)

VIII. Labs

  1. Thyroid testing
    1. See Thyroid Function Testing
    2. Obtain Thyroid Stimulating Hormone (TSH) with reflex to Free T4
      1. Serum Thyroid Stimulating Hormone (TSH) suppressed
      2. Serum Free Thyroxine (Free T4) elevated
    3. Normal findings despite abnormal labs
      1. Pregnancy or Estrogen therapy
        1. Estrogen increases Thyroxine Binding Globulin and, in turn, Total T4 and Total T3
        2. TSH and Free T4 will be normal and requires no management
        3. In pregnancy, interpret based on trimester specific normal Thyroid Hormone level references
      2. Acute illness
        1. TSH mildly decreased (0.1 to 0.4 mIU/ml)
        2. Normal or mildly decreased Free T4
        3. Resolves as acute illness does and requires no management
        4. Exogenous Corticosteroids or Dopamine (e.g. ICU) may cause a similar finding
    4. Advanced labs: Thyroid Antibodies (indicated in some cases)
      1. Thyroid Stimulating Immunoglobulin (TSH receptor ab)
        1. Sensitive and Specific for Graves Disease
          1. Test Sensitivity: 97%
          2. Test Specificity: >=98%
        2. Associated with ophthalmopathy
        3. Usually not needed for diagnosis unless imaging contraindicated
          1. However, may also be used in lieu of Thyroid uptake scan in Grave's Disease diagnosis
      2. Antithyroid Peroxidase Antibody
        1. Negative in Graves Disease and positive in Hashimoto's Thyroiditis
  2. Non-specific lab changes (variably present)
    1. Complete Blood Count (CBC)
      1. Anemia
      2. Granulocytosis and Lymphocytosis
    2. Electrolytes
      1. Hypercalcemia
    3. Liver Function Tests
      1. Liver transaminases (AST,ALT) increased
      2. Alkaline Phosphatase increased
    4. Acute Phase Reactants (ESR, C-RP)
      1. Erythrocyte Sedimentation Rate >50 mm/h (Acute Thyroiditis)

IX. Diagnostics

  1. Electrocardiogram
    1. Sinus Tachycardia
    2. Atrial Fibrillation (esp. age >60 years, males, CAD, CHF, valvular disease)

X. Imaging

  1. Thyroid Uptake Scan
    1. Differentiate Hyperthyroidism causes
    2. Identify hot and cold Nodules
    3. Doppler may differentiate Hyperthyroidism types
      1. Normal Thyroid perfusion: Painless Thyroiditis
      2. Increased Thyroid perfusion: Graves Disease
  2. Thyroid Ultrasound
    1. Differentiate solid from cystic Nodules
    2. May be used when Thyroid uptake scan cannot be used (e.g. pregnancy and Lactation)
  3. If solid cold Nodule:
    1. Fine needle biopsy
    2. CT Head and Neck (evaluate for metastatic disease)

XI. Evaluation

  1. Step 1: Check TSH
    1. TSH Normal
      1. No Hyperthyroidism
    2. TSH Suppressed
      1. Go to Step 2 below
    3. TSH Increased: Check Free T4
      1. Normal or Low
        1. Consider Hypothyroidism
      2. Free T4 High
        1. Secondary Hyperthyroidism (rare)
        2. Obtain CT or MRI Brain with cone down of Pituitary Gland (sella turcica)
  2. Step 2: Check Free T4 (for suppressed TSH)
    1. Free T4 High: Go to Step 3
    2. Free T4 Normal: Measure Total Triiodothyronine (Total T3, preferred over Free T3)
      1. Normal T3
        1. See Subclinical Hyperthyroidism
        2. Follow for transient cause resolution
      2. Free T3 high
        1. Go to Step 3
        2. T3 toxicosis (seen in 10-15% cases)
  3. Step 3: Thyroid Uptake Scan (Primary Hyperthyroidism)
    1. Alternative Protocol: TSH Receptor Antibody
      1. In classic Grave's Disease, TSH Receptor Antibody may be obtained
      2. TSH Receptor Antibody is highly sensitive and specific for Grave's Disease
        1. Positive TSH Receptor Antibody may be used in lieu of Thyroid Uptake Scan
    2. Thyroid Uptake Scan with low uptake
      1. Single "Cold" Nodule
        1. Possible Thyroid Cancer
      2. Diffusely low uptake
        1. Go to Step 4
    3. Thyroid Uptake Scan with high uptake
      1. Diffusely high uptake (or TSH Receptor Antibody positive)
        1. Grave's Disease
      2. Single "Hot" Nodule
        1. Toxic Thyroid Adenoma
      3. Multiple "Hot" Nodules
        1. Toxic Multinodular Goiter
  4. Step 4: Check Thyroglobulin (scan with low uptake)
    1. Thyroglobulin Low
      1. Exogenous Hormone source
    2. Thyroglobulin High
      1. Thyroiditis
      2. Ectopic Thyroid Hormone production (e.g. ovary)
      3. Excess Iodide exposure

XII. Management

  1. See Hyperthyroidism Management

XIII. Complications

  1. Thyroid Storm

XIV. References

  1. Bahn (2011) Thyroid 21(6):593-646 [PubMed]
  2. Haddard (1998) Postgrad Med 104(1):42-59 [PubMed]
  3. Hennessey (1996) Am Fam Physician 54(4):1315-24 [PubMed]
  4. Kravets (2016) Am Fam Physician 93(5): 363-70 [PubMed]
  5. Mounsey (2025) Am Fam Physician 112(2): 146-52 [PubMed]
  6. Reid (2005) Am Fam Physician 72:623-36 [PubMed]
  7. Singer (1995) JAMA 273(10):808-12 [PubMed]
  8. Slatosky (2000) Am Fam Physician 61(4):1047-52 [PubMed]

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