Thyrotoxicosis refers to the symptoms caused by the excessive circulation of thyroid hormones. It is typically caused by thyroid gland hyperactivity (i.e., hyperthyroidism), the most common causes of which are Graves disease (most common), toxic multinodular goiter (MNG), and toxic adenoma. It may also be caused by the inappropriate release of thyroid hormone from a damaged or inflamed thyroid gland (e.g., thyroiditis). In rare cases, thyrotoxicosis is caused by TSH-producing pituitary tumors (central hyperthyroidism), excessive production of β-hCG (gestational trophoblastic disease), or oral intake of thyroid hormones (exogenous hyperthyroidism). The most common symptoms of thyrotoxicosis include fatigue, anxiety, heat intolerance, increased perspiration, palpitations, and significant weight loss despite increased appetite. Serological thyroid hormone assay confirms thyrotoxicosis, while the measurement of antithyroid antibodies, thyroid ultrasonography, and radioactive iodine uptake tests help to identify the etiology. Management of any form of thyrotoxicosis involves the initial control of symptoms with beta blockers and antithyroid drugs, often followed by definitive therapy with either radioactive iodine ablation (RAIA) of the thyroid gland or surgery. An acute exacerbation of thyrotoxicosis can lead to a life-threatening hypermetabolic state known as thyroid storm, which is diagnosed clinically along with thyroid function tests. Patients with thyroid storm require urgent stabilization in critical care settings with fluids, beta blockers, antithyroid medications (propylthiouracil, potassium iodide, and parenteral glucocorticoids), active cooling, and management of tachyarrhythmias. Definitive therapy with RAIA or surgery is considered once they are stable.
- Thyrotoxicosis: a hypermetabolic condition caused by an inappropriately high level of circulating thyroid hormones irrespective of the source.
Hyperthyroidism: a condition characterized by the overproduction of thyroid hormones by the thyroid gland; can cause thyrotoxicosis
- Overt hyperthyroidism
- Subclinical hyperthyroidism
Overview of common etiologies in hyperthyroidism and thyrotoxicosis 
|Graves disease||Toxic MNG||Subacute granulomatous thyroiditis (de Quervain thyroiditis)||Subacute lymphocytic thyroiditis (silent thyroiditis)||Iodine-induced hyperthyroidism|
|Thyroid status|| || |
|Causes|| || |
|Goiter||Consistency|| || || || |
|Pain|| || || || || |
|Other findings|| || |
|Thyroid function tests|| || || |
|Iodine uptake on scintigraphy|| || || || |
|Pathologic findings|| || |
- Prevalence 
- Sex: ♀ > ♂ (5:1)
- Age range at presentation 
Epidemiological data refers to the US, unless otherwise specified.
- Hyperfunctioning thyroid gland
Destruction of the thyroid gland
- Thyroiditis (see “ )
- Drug-induced thyroiditis (e.g., amiodarone, lithium)
- Contrast-induced thyroiditis ( )
- Hashitoxicosis (see “ ”)
- Radiation thyroiditis
- Palpation thyroiditis: due to thyroid gland manipulation during parathyroid surgery.
- Exogenous thyrotoxicosis
- Ectopic (extrathyroidal) hormone production
- Physiological regulation: See “Thyroid gland” in “ .”
- Other causes of thyrotoxicosis
Effects of thyrotoxicosis
- Generalized hypermetabolism (increased substrate consumption)
- Cardiac effects → ↑ cardiac output 
- Palpitations, irregular pulse (due to atrial fibrillation/ectopic beats)
- Hypertension with widened pulse pressure
- Thyrotoxicosis-induced cardiac failure; : elderly patients often present with features of cardiac failure (e.g., pedal edema, exertional dyspnea).
- Abnormal heart rhythms, including atrial fibrillation
- Chest pain
- Fine tremor of the outstretched fingers
Hyperthyroid myopathy: a condition of muscle weakness, pain, and atrophy associated with hyperthyroidism (e.g., from Graves disease, thyroiditis)
- Predominantly affects individuals > 40 years of age
- Can develop acutely or several weeks to months after the onset of hyperthyroidism.
- Typically affects proximal muscles (e.g., hip flexors, quadriceps) more than distal muscles
- Serum creatine kinase levels are most often normal
- Treatment of hyperthyroidism often reverses myopathy
- Osteopathy: osteoporosis due to the direct effect of T3 on osteoclastic bone resorption , fractures (in the elderly)
- Neuropsychiatric system
- Initial evaluation: perform clinical assessment and screen thyroid function tests (TFTs) alongside routine laboratory studies.
Subsequent evaluation depends on the clinical picture . Options include:
- Thyroid scintigraphy: first-line for most patients with uncertain diagnoses, e.g., suspected thyroid adenoma or toxic MNG
- TSH receptor antibody (TRAb): for suspected Graves disease without characteristic features
- Thyroid ultrasound: first-line for pregnant/lactating patients, palpable nodules or suspected thyroiditis
- Further evaluation: based on initial results
Initial evaluation 
- Thyroid function tests
|Interpretation of elevated thyroid hormones |
|Condition||TSH level||Free T4||Total T3|
|Overt hyperthyroidism and thyrotoxic-phase thyroiditis||↓||↑ In 90% of cases||↑|
|Exogenous thyrotoxicosis or hyperthyroidism in older adults/comorbid illness||↓||↑||Normal or ↑|
|Thyrotropic adenoma||Normal or ↑||↑||↑|
- Routine laboratory studies
- ECG findings
Indicated if the diagnosis remains uncertain after clinical assessment and initial evaluation. The choice and priority of studies depends on the clinical picture, patient characteristics and test availability.
- Indication: if Graves disease is suspected but classic clinical features are absent 
- Positive: Diagnosis of Graves disease is established.
- Negative: Further investigation is necessary.
Nuclear medicine thyroid scan and radioactive iodine uptake measurement 
- Nuclear medicine thyroid scan: a nuclear medicine imaging technique that visualizes the distribution of thyroid function using an oral or IV radiotracer (most commonly Tc-99m pertechnetate or iodine-123)
- Radioactive iodine uptake measurement (RAIU test): a test that quantifies the percentage of the administered amount of radioactive iodine taken up by the thyroid gland 
- First-line test for most patients with uncertain etiology of thyrotoxicosis after initial evaluation
- Assessment of functional status of thyroid nodules 
- Thyroid malignancy
- Identification of ectopic thyroid tissue (e.g., lingual thyroid, struma ovarii)
- Evaluation of retrosternal goiters
- Evaluation of thyroglossal cysts
- Contraindications: pregnant or breastfeeding women 
- Hot nodule: Hyperfunctioning tissue takes up large amounts of radioactive iodine
- Cold nodule: Non-functioning nodules do not take up any radioactive iodine and appear "cold”, but the surrounding normal thyroid tissue takes up radioactive iodine and appears "warm"
- See also “Diagnostics” in “Thyroid cancer” and “ ”
|Characteristic findings of nuclear medicine thyroid scan and RAIU measurement |
|Appearance of thyroid||RAIU measurement|
|Normal thyroid tissue|| || |
|Graves disease|| || |
|Toxic MNG|| || |
|Toxic adenoma|| || |
|Subacute thyroiditis (de Quervain thyroiditis)|| || |
|Exogenous thyrotoxicosis|| || |
|Thyrotropic adenoma|| || |
Thyroid ultrasound with Doppler
- Indications 
Typical findings 
- Changes to morphology: diffuse enlargement or nodules
- Increased perfusion: either diffuse (Graves disease, toxic adenoma) or nodular (toxic MNG)
- Decreased perfusion: destructive causes of hyperthyroidism (e.g., subacute thyroiditis or postpartum destructive thyroiditis)
- Hypoechoic areas in acute thyroiditis and malignancy
These additional tests are not routinely required but may be performed depending on the suspected underlying etiology.
- Consider for suspicious nodules (see “ ” and “ ”).
- Can help confirm etiology if diagnosis remains uncertain (see “Pathological findings” in “ ”)
Other thyroid antibodies 
- Thyroid peroxidase antibodies (TPOAb)
- Thyroglobulin antibodies (TgAb): not routinely indicated but can be elevated in Graves disease, autoimmune conditions, and thyroid cancer
- See also “Thyroid antibodies.”
- Serum thyroglobulin (Tg): indicated for suspected exogenous hyperthyroidism with unclear history
- Neuropsychiatric symptoms: anxiety/panic disorders
- Hyperadrenergic symptoms: intoxication with anticholinergics; cocaine/amphetamine misuse; withdrawal syndromes
- Weight loss: diabetes mellitus, malignancy
- Cardiac symptoms: congestive cardiac failure
The differential diagnoses listed here are not exhaustive.
- Screen for thyroid storm in severely symptomatic patients (consider using ) and start immediate therapy if needed (See “Treatment” in “Thyroid storm”)
- Initiate beta blockers). (e.g.,
- Ensure antithyroid drugs, RAIA, and/or surgery) in the following groups:
- Symptomatic patients
- Asymptomatic patients > 65 years old or with risk factors
- Identify and treat reversible causes (e.g., discontinuing offending medications , starting NSAIDs or corticosteroids for thyroiditis).
- Consider definitive therapy vs. observation for asymptomatic patients < 65 years old or without risk factors. 
- Avoid triggers, e.g., contrast medium, amiodarone, and aspirin.
Symptomatic therapy for thyrotoxicosis 
- Indication: all symptomatic patients
Treatment of hyperadrenergic symptoms: beta blockers (first line) ;
- Provide immediate control of symptoms, e.g., neuropsychiatric and/or
- Treatment options
- If there are contraindications to beta blockers, e.g., severe asthma, Raynaud phenomenon , consider CCBs: verapamil OR diltiazem . 
Treatment of cardiac complications 
- Heart failure: patients should receive the same treatment as euthyroid patients with heart failure (see “Treatment” in “Acute heart failure”).
- Atrial fibrillation
Definitive therapy for hyperthyroidism and thyrotoxicosis 
- The choice of therapy depends on the individual clinical situation and patient preference.
- There are three effective initial treatment options for Graves disease: antithyroid drugs, RAIA, and surgery
- RAIA or surgery is preferable to antithyroid drugs for toxic MNG and .
Antithyroid drugs can effectively render a patient euthyroid. 20–75% of patients with Graves disease achieve permanent remission after 1–2 years of treatment; however, some patient groups have a higher likelihood of remission than others.
- Thyroid storm: initial management as well as prevention in at-risk patients prior to surgery or RAIA
- Graves disease: Patients with high remission likelihood , and/or moderate to severe active Graves ophthalmopathy 
- Contraindications to both RAIA and surgery
- Other: hyperthyroidism in pregnancy, limited life expectancy, patient preference
- Duration of therapy
Radioactive iodine ablation (RAIA) 
- Definition: destruction of thyroid tissue via radioactive iodine (iodine-131) through a sodium/iodine symporter
Technical background: Radioactive iodine-131 emits both gamma and beta rays.
- Gamma rays: diagnostic effect
- Beta rays: therapeutic effect
- with high nodular radioactive iodine uptake and
- Failure to achieve euthyroidism with antithyroid drugs (ATDs) in Graves disease, due to:
- High surgical risk ; due to comorbidities or previous surgery or radiation of the neck
- Limited life-expectancy
- Other: thyrotoxic periodic paralysis, post-surgical treatment of certain , large/compressive nontoxic goiters 
Preparation for RAIA
- RAIA can cause a transient worsening of hyperthyroidism.
- Prophylactic treatment can reduce the risk of complications in high-risk patient groups, e.g., severe hyperthyroidism, older patients, and those with comorbid conditions.
- Avoid excess iodine for 7 days prior to RAIA.
- In women of childbearing potential, a negative pregnancy test must be confirmed within 48 hours before RAIA.
- Procedure: Single oral dose of iodine-131 → isotope uptake by thyroid gland → emission of beta radiation that slowly destroys the thyroid tissue
Radiation-induced thyroiditis: a form of acute thyroiditis that occurs a few days after the thyroid gland is exposed to radiation
- It is most commonly seen following radioiodine therapy in patients with Graves disease, or following external beam radiotherapy for head and neck cancers.
- Patients present with pain in the thyroid region and thyrotoxicosis (due to the release of T3 and T4 following rapid destruction of thyroid tissue).
- Secondary malignancy or leukemia
- Dry mouth (xerostomia)
- Radiation-induced thyroiditis: a form of acute thyroiditis that occurs a few days after the thyroid gland is exposed to radiation
Thyroid surgery 
- Large goiters (≥ 80 g) or obstructive symptoms
- Confirmed or suspected thyroid malignancy
- Graves disease with: 
- toxic adenoma with: concomitant primary hyperparathyroidism, insufficient RAIA, or retrosternal extension or
- Other: large thyroid nodules , refractory amiodarone-induced thyrotoxicosis , planned pregnancy within next 6 months , or patient preference
- Severe comorbidities that influence surgical risk
Preparation for surgery
- Achieving euthyroidism prior to surgery: preoperative application of antithyroid drugs (and beta blockers if necessary) for at least 4–8 weeks if possible (see “Symptomatic therapy for thyrotoxicosis” and “Antithyroid drugs for thyrotoxicosis” for doses).
- Patients with Graves disease: potassium iodide solution; for 10 days preoperatively (harnesses the Wolff-Chaikoff effect)
- Hypocalcemia risk: Replete calcium and 25-hydroxy vitamin D as needed
- Urgent surgery or antithyroid drug allergy/intolerance: Consider adding corticosteroids and cholestyramine in consultation with a specialist. 
- Postprocedural care
Special patient groups
Hyperthyroidism in pregnancy
- Epidemiology: Hyperthyroidism is rare in pregnancy (< 0.5% of cases).
- Etiology: Graves disease and β-hCG-mediated hyperthyroidism are the most common causes.
- Clinical features
- Diagnosis: same as in nonpregnant patients, but nuclear medicine thyroid scan is contraindicated
- Complications: if left untreated → miscarriage, stillbirth, preeclampsia, premature labor, cardiac failure, low birth weight, neonatal hyperthyroidism (see below)
- Occurs in ∼ 5% of babies born to mothers with Graves disease
- Etiology: transplacental passage of maternal TRAbs
- Hyperthyroidism: irritability, restlessness, tachycardia, diaphoresis, hyperphagia, poor weight gain, diffuse goiter (can cause tracheal compression), microcephaly (due to craniosynostosis)
- May arise directly after birth or delayed up to 10 days later as a result of transplacental maternal antithyroid medication (including propylthiouracil or carbimazole)
- Complications: Untreated symptomatic hyperthyroidism in infants can cause cardiac failure and intellectual disability.
- Definition: thyrotoxicosis due to excessive intake of thyroid hormone
- Clinical features: symptoms of thyrotoxicosis but no goiter
- An acute exacerbation of hyperthyroidism that results in a life-threatening hypermetabolic state.
- Also known as thyrotoxic crisis
- Stress-related catecholamine surge
Clinical features 
- Hyperpyrexia with profuse sweating
- Tachycardia (> 140/minute) and (possibly severe) arrhythmia (e.g., atrial fibrillation), hypertension with wide pulse pressure, congestive cardiac failure
- Hypotension/shock secondary to high output heart failure or hypovolemia as a result of GI and insensible losses
- Symptoms of thyrotoxicosis
- Abdominal pain
- Severe nausea, vomiting, diarrhea, possibly jaundice
- Severe agitation and anxiety, delirium and psychoses, seizures, coma
- A thyroid storm is diagnosed on the basis of classic clinical features and supporting TFT abnormalities, e.g., low/undetectable TSH, elevated free T3/T4.
- Further tests should be performed to identify any underlying precipitants and to assess for complications, e.g.:
- The Burch-Wartofsky Point Scale (BWPS) can be considered to assess disease severity and guide treatment.
|Burch-Wartofsky Point Scale for the diagnosis of thyroid storm (BWPS) |
|≥ 40°C (≥ 104°F)||30|
|Congestive heart failure||Absent||0|
|Moderate (e.g., diarrhea, abdominal pain, nausea/vomiting)||10|
|Central nervous system disturbance||Absent||0|
|Moderate (e.g., delirium, psychosis, extreme lethargy)||20|
|Severe (e.g., seizure, coma)||30|
Treatment of thyroid storm 
- Consult critical care for ICU admission and monitoring.
- Start symptomatic treatment to manage hypotension, hyperpyrexia, and tachycardia.
- Administer medication to reduce thyroid hormone synthesis and release, and inhibit their peripheral action.
- Identify and treat any precipitating cause.
- Once the patient is stable, initiate .
- Consider plasmapheresis or emergency surgery as life-saving treatment for rare refractory cases
- Hyperadrenergic symptoms: beta blockers are first-line
Hypotension and hypovolemia: fluid resuscitation to treat insensible and GI losses 
- Fluids containing 5–10% dextrose are preferred to meet the high metabolic demand.
- Fluid requirement is often high (3–5 L/day).
- Electrolyte disturbances: (see “Electrolyte repletion” for specific repletion regimens)
- Agitation: benzodiazepines, e.g., lorazepam
- Concurrent conditions: e.g., CHF and/or Atrial fibrillation (See “Management” in “Acute heart failure” and “Management of Afib with RVR”)
Antithyroid drugs in thyroid storm 
- Inhibition of thyroid hormone synthesis
- Inhibition of thyroid hormone release (through the Wolff-Chaikoff effect)
- Inhibition of peripheral conversion of T4 to T3
Treat thyroid storm with PROverbial PROficiency and POetic GLUttony: PROpranolol, PROpylthiouracil, POtassium iodide, and GLUcocorticoids.
Acute management checklist for thyroid storm
- Conduct ABCDE survey and draw initial laboratory studies (e.g., TFTs, BMP, liver chemistries)
- Consider BWPS if uncertain diagnosis or for assessing severity and need for aggressive therapy.
- Consult critical care for ICU admission.
- Initiate antithyroid drugs:
- Identify and treat reversible triggers.
- Electrolyte repletion as needed
- Administer benzodiazepines as needed for agitation.
- Consider plasmapheresis for life-threatening refractory cases.
- Ensure when stabilized.