Hyperthyroidism

Aka: Hyperthyroidism, Thyrotoxicosis

1. See Also
   1. Subclinical Hyperthyroidism
   2. Grave's Disease
   3. Thyroid Storm
   4. Hyperthyroidism in Pregnancy
2. 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]
3. Pathophysiology
   1. Excessive Thyroid hormone up-regulates beta-Adrenergic Receptors, increasing sensitivity to Catecholamines
4. Causes
   1. Stimulatory Causes (positive Radioactive Iodine scan)
      1. Grave's Disease (60-80% of Hyperthyroidism cases)
      2. Rare
         1. Trophoblastic Tumors activate TSH receptors via HCG (Choriocarcinoma)
         2. TSH-secreting Pituitary Adenoma
   2. Non-Stimulatory Causes
      1. Toxic Multinodular Goiter (5%, esp. elderly in Iodine deficient regions)
      2. Toxic Thyroid Adenoma (Plummer's Disease)
      3. Exogenous Thyroid hormone source
      4. Thyroiditis (common)
         1. Subacute Thyroiditis
         2. Acute Thyroiditis (Bacterial Infection)
         3. Postpartum Thyroiditis (lymphocytic Thyroiditis)
      5. Tumors (rare)
         1. Metastatic follicular Thyroid Cancer
         2. Ovarian Cancer producing Thyroxine (struma ovarii)
      6. Medication-Induced Hyperthyroidism
         1. See Medications Affecting Thyroid Function
   3. Combined Stimulatory and Non-Stimulatory Causes (positive Radioactive Iodine scan)
      1. Nodular Goiter with superimposed stimulation
5. 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
6. Signs
   1. Anxious, restless, fidgeting patient
   2. 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 (hand soft tissue swelling and Digital Clubbing)
         3. Skin Pigment Changes (patchy Hyperpigmentation or vitilgo)
   3. Neuromuscular
      1. Fine Tremor of fingers, Tongue
      2. Hyperkinesia
      3. Rapid speech
      4. Proximal Muscle Weakness (e.g. Quadriceps weakness)
   4. 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
   5. 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%)
7. 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
         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. Specific to Graves Disease
            2. Associated with ophthalmopathy
            3. Usually not needed for diagnosis unless imaging contraindicated
         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
8. Diagnostics
   1. Thyroid Uptake Scan
      1. Differentiate Hyperthyroidism causes
      2. Identify hot and cold Nodules
   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)
9. 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 serum Free T3
         1. Normal T3
            1. 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. Thyroid Uptake Scan with low uptake
         1. Single "Cold" Nodule
            1. Possible Thyroid Cancer
         2. Diffusely low uptake
            1. Go to Step 4
      2. Thyroid Uptake Scan with high uptake
         1. Diffusely high uptake
            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
10. Management
    1. See Hyperthyroidism Management
11. 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. Reid (2005) Am Fam Physician 72:623-36 [PubMed]
    6. Singer (1995) JAMA 273(10):808-12 [PubMed]
    7. Slatosky (2000) Am Fam Physician 61(4):1047-52 [PubMed]