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. 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

V. 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

VI. 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%)

VII. 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

VIII. 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)

IX. 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

X. Management

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Ontology: Hyperthyroidism (C0020550)

Definition (NCI_CTCAE) A disorder characterized by excessive levels of thyroid hormone in the body. Common causes include an overactive thyroid gland or thyroid hormone overdose.
Definition (NCI) Overactivity of the thyroid gland resulting in overproduction of thyroid hormone and increased metabolic rate. Causes include diffuse hyperplasia of the thyroid gland (Graves' disease), single nodule in the thyroid gland, and thyroiditis. The symptoms are related to the increased metabolic rate and include weight loss, fatigue, heat intolerance, excessive sweating, diarrhea, tachycardia, insomnia, muscle weakness, and tremor.
Definition (NCI_NCI-GLOSS) Too much thyroid hormone. Symptoms include weight loss, chest pain, cramps, diarrhea, and nervousness.
Definition (CSP) excessive functional activity of the thyroid gland.
Definition (MSH) Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.
Concepts Disease or Syndrome (T047)
MSH D006980
ICD10 E05.9
SnomedCT 190239004, 154655004, 267464006, 34486009
LNC MTHU020782
English Hyperthyroidism, HYPERTHYROIDISM, hyperthyroidism, hyperthyroidism (diagnosis), Hyperthyroidism NOS, Hyperthyroidism [Disease/Finding], hyperthyroidism nos, hyperthyroid, Primary Hyperthyroidism, Hyperthyroid, overactive thyroid, Hyperthyroidism (disorder), Hyperthyroidism, NOS, Overactive Thyroid
French HYPERTHYROIDIE, Hyperthyréose, Hyperthyroïdie, Hyperthyroïdisme
Spanish HIPERTIROIDISMO, hipertiroidismo (trastorno), hipertiroidismo, Hipertiroidismo
German HYPERTHYREOSE, Hyperthyroidismus, Hyperthyreoidismus, Hyperthyreose
Japanese 甲状腺機能亢進症, コウジョウセンキノウコウシンショウ
Swedish Hypertyreos
Finnish Kilpirauhasen liikatoiminta
Russian GIPERTIREOIDIZM, GIPERTIREOZ, ГИПЕРТИРЕОЗ, ГИПЕРТИРЕОИДИЗМ
Portuguese HIPERTIROIDISMO, Hipertiroidismo, Hipertireoidismo
Czech Hypertyreóza, primární hypertyreóza, hyperthyreoidismus, hypertyreóza, hypertyreoidismus, hyperthyreóza
Croatian HIPERTIREOZA
Polish Nadczynność tarczycy
Hungarian Hyperthyreosis
Norwegian Hypertyreose, Høyt stoffskifte
Dutch hyperthyroïdie, Basedow, ziekte van, Hyperthyreose, Hyperthyreoïdie, Hyperthyroïdie, Thyreoïdie, hyper-
Italian Ipertiroidismo

Ontology: Thyrotoxicosis (C0040156)

Definition (NCI) A hypermetabolic syndrome caused by the elevation of thyroid hormone levels in the serum. Signs and symptoms include tachycardia, palpitations, tremor, weight loss, warm weather intolerance, and moist skin. Causes include Graves disease, toxic nodular goiter, toxic thyroid nodule, and lymphocytic thyroiditis.
Definition (MSH) A hypermetabolic syndrome caused by excess THYROID HORMONES which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid HYPERPLASIA; THYROID NEOPLASMS; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by NERVOUSNESS; TACHYCARDIA; FATIGUE; WEIGHT LOSS; heat intolerance; and excessive SWEATING.
Concepts Disease or Syndrome (T047)
MSH D013971
ICD9 242
ICD10 E05.9
SnomedCT 154655004, 190267008, 190239004, 267464006, 154659005, 267373004, 90739004, 286909009
English Thyrotoxicoses, Thyrotoxicosis, unspecified, THYROTOXICOSIS, Thyrotoxicosis, Thyrotoxicosis +/- goiter, Thyrotoxicosis +/- goitre, Thyrotoxicosis [Disease/Finding], thyrotoxicosis, thyrotoxicosis with or without goiter, thyrotoxicosis (diagnosis), Thyrotoxicosis NOS (disorder), Thyrotoxicosis with or without goiter, Thyrotoxicosis with or without goitre, Thyrotoxicosis (disorder), Thyrotoxicosis with or without goiter (disorder), thyroid; toxic, toxic; thyroid, Thyrotoxicosis, NOS, Thyrotoxicosis [Ambiguous], Thyrotoxicosis NOS
Portuguese TIROTOXICOSE, Tirotoxicose com ou sem bócio, Tirotoxicose, Tireotoxicose
Spanish TIROTOXICOSIS, Tirotoxicosis con o sin bocio, tirotoxicosis, SAI (trastorno), tirotoxicosis, SAI, Thyrotoxicosis NOS, hipertiroidismo con o sin bocio (trastorno), hipertiroidismo con o sin bocio, hipertiroidismo, SAI (trastorno), hipertiroidismo, SAI, tirotoxicosis (trastorno), tirotoxicosis con o sin bocio (trastorno), tirotoxicosis con o sin bocio, tirotoxicosis, Tirotoxicosis
German THYREOTOXIKOSE, Thyreotoxikose mit oder ohne Struma, Hyperthyreose, nicht naeher bezeichnet, Thyreotoxikose
Dutch thyreotoxicose met of zonder struma, thyreotoxicose, schildklier; toxisch, toxisch; schildklier, Thyrotoxicose, niet gespecificeerd, Hyperthyreoidie, Thyreotoxicose, Thyrotoxicose, Toxicose, thyreo-, Hyperthyroïdie
French Thyrotoxicose avec ou sans goitre, THYREOTOXICOSE, Thyréotoxicose, Thyrotoxicose
Italian Tireotossicosi con o senza gozzo, Tireotossicosi
Japanese 甲状腺中毒症, 甲状腺腫を伴うまたは伴わない甲状腺中毒症, コウジョウセンシュヲトモナウマタハトモナワナイコウジョウセンチュウドクショウ, コウジョウセンチュウドクショウ
Swedish Tyreotoxikos
Czech tyreotoxikóza, Tyreotoxikóza se strumou nebo bez strumy, Tyreotoxikóza, thyrotoxikóza, thyreotoxikóza
Finnish Tyreotoksikoosi
Russian TIREOTOKSIKOZ, ТИРЕОТОКСИКОЗ
Korean 상세불명의 갑상샘중독증
Polish Tyreotoksykoza
Hungarian Hyperthyreosis strumával vagy anélkül, Thyreotoxicosis
Norwegian Tyreotoksikose