Hyperthyroidism and thyrotoxicosis

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.

While thyrotoxicosis and hyperthyroidism are often used interchangeably, the two terms are not synonymous. ^[1]

• 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
    • ↓ Serum TSH levels with ↑ serum free T₄ and/or T₃ levels
    • Patients typically experience symptoms of thyrotoxicosis.
  • Subclinical hyperthyroidism
    • ↓ Serum TSH levels with normal serum free T₄ and T₃ levels
    • Patients are normally asymptomatic or mildly symptomatic.
    • May progress to overt hyperthyroidism

• Prevalence ^[9]
  • Overt hyperthyroidism: ∼ 1%
  • Subclinical hyperthyroidism: 2–3%
• Sex: ♀ > ♂ (5:1)
• Age range at presentation ^[10]
  • Graves disease: 20–30 years of age
  • Toxic adenoma: 30–50 years of age
  • Toxic MNG: peak incidence > 50 years of age

References:^[11][12]

Epidemiological data refers to the US, unless otherwise specified.

• Hyperfunctioning thyroid gland
  • Graves disease (∼ 60–80% of cases)
  • Toxic MNG (∼ 15–20% of cases)
  • Toxic adenoma (3–5% of cases)
  • TSH-producing pituitary adenoma (thyrotropic adenoma)
  • β-hCG-mediated hyperthyroidism (hydatidiform mole, choriocarcinoma)
• Destruction of the thyroid gland
  • Thyroiditis (see “Subacute thyroiditis”)
    • Subacute granulomatous thyroiditis (de Quervain thyroiditis)
    • Subacute lymphocytic thyroiditis (e.g., postpartum thyroiditis)
  • Drug-induced thyroiditis (e.g., amiodarone, lithium)
  • Contrast-induced thyroiditis (Jod-Basedow phenomenon)
  • Hashitoxicosis (see “Hashimoto thyroiditis”)
  • Radiation thyroiditis
  • Palpation thyroiditis: due to thyroid gland manipulation during parathyroid surgery.
• Exogenous thyrotoxicosis
• Ectopic (extrathyroidal) hormone production
  • Struma ovarii
  • Metastatic follicular thyroid carcinoma

References:^[2][13][14]

Hypothalamic-pituitary-thyroid axis

The hypothalamus, anterior pituitary gland, and thyroid gland, together with their respective hormones, make up a self-regulating circuit known as the hypothalamic-pituitary-thyroid axis.

• Physiological regulation: See “Thyroid gland” in “General endocrinology.”
• Hyperthyroidism
  • Disorders of the thyroid gland → excess production of T₃/T₄ → compensatory decrease of TSH
  • Thyrotropic adenoma → ↑ TSH levels → ↑ T₃/T₄ levels
• Other causes of thyrotoxicosis
  • Excess intake/ectopic production of thyroid hormone → ↑ levels of circulating T₃/T₄ → compensatory decrease of TSH
  • Trigger → inflammation of the thyroid gland → cellular damage and destruction → inappropriate release of T₃/T₄

Effects of thyrotoxicosis

• Generalized hypermetabolism (increased substrate consumption)
  • ↑ Number of Na⁺/K⁺-ATPase → elevation of basal metabolism → promoted thermogenesis
  • Upregulation of β-adrenergic receptors → hyperstimulation of the sympathetic nervous system
• Cardiac effects → ↑ cardiac output ^[15]
  • ↑ Numbers of ATPase on cardiac myocytes; ↓ amount of phospholamban (PLB) → ↑ transsarcolemmal Ca²⁺ movement → enhanced myocardial contractility
  • ↓ Peripheral vascular resistance

• General
  • Heat intolerance
  • Excessive sweating because of increased cutaneous blood flow
  • Weight loss despite increased appetite
  • Frequent bowel movements (because of intestinal hypermotility)
  • Weakness, fatigue
• Skin
  • Infiltrative dermopathy, especially in the pretibial area (pretibial myxedema)
  • Onycholysis
    • An early cutaneous manifestation of hyperthyroidism
    • Thickened nails with distal white discoloration and separation of the nail plate
    • Initially develops in the fourth fingers, but can involve all nails, including the toenails
  • Thyroid acropachy: nail clubbing seen in late stages of Graves disease
• Eyes
  • Lid lag; : caused by adrenergic overactivity, which results in spasming of the smooth muscle of the levator palpebrae superioris
  • Lid retraction; : “staring look”
  • Graves ophthalmopathy (exophthalmos, edema of the periorbital tissue)
• Goiter
  • Diffuse, smooth, nontender goiter
  • Often with an audible bruit at the superior poles
  • Also seen in subacute thyroiditis, toxic adenoma, and toxic MNG
• Cardiovascular
  • Tachycardia
  • Palpitations, irregular pulse (due to atrial fibrillation/ectopic beats)
  • Hypertension with widened pulse pressure
    • Systolic pressure is increased due to increased heart rate and cardiac output.
    • Diastolic pressure is decreased due to decreased peripheral vascular resistance.
  • 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
• Musculoskeletal
  • 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)
• Endocrinological
  • Female: oligo/amenorrhoea, anovulatory infertility, dysfunctional uterine bleeding
  • Male: gynecomastia, decreased libido, infertility, erectile dysfunction
  • Glucose intolerance ^[16]
    • ↓ Insulin sensitivity of peripheral tissue
    • Impaired insulin secretion
• Neuropsychiatric system
  • Anxiety
  • Emotional instability
  • Depression
  • Restlessness
  • Insomnia
  • Tremoulousness (results from the hyperadrenergic state)
  • Hyperreflexia

Approach

• Initial evaluation: perform clinical assessment and screen thyroid function tests (TFTs) alongside routine laboratory studies.
  • Consider alternate diagnoses if TFTs are normal.
  • If characteristic features of Graves disease are present (see “Overview”): can stop investigations and begin empiric treatment
  • Identify any tachyarrhythmia requiring treatment (see also “Atrial fibrillation” and “Acute management of tachycardia”).
• 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
  • Normal imaging and negative TRAb: consider serum thyroglobulin to identify exogenous thyrotoxicosis
  • Inconclusive imaging and negative TRAb: consider thyroid peroxidase antibodies to identify thyroiditis
  • Suspicious nodules visible on imaging: refer for FNAC (see also “Thyroid nodules”)

Initial evaluation ^[17][18]

• Thyroid function tests
  • Thyroid-stimulating hormone (TSH) level (initial screening test): Typically low/undetectable; a normal TSH level usually rules out hyperthyroidism.
  • Free T₄ (FT₄) and total T₃ levels: Typically both elevated; indicated when thyrotoxicosis is strongly suspected or TSH is abnormal

• Routine laboratory studies
  • CBC: leukocytosis and/or mild anemia
  • BMP
    • Hyperglycemia
    • Mild hypercalcemia
  • Liver chemistries: mildly elevated AST, ALT, ALP, and bilirubin
  • Serum cholesterol: decreased total cholesterol, LDL, and HDL
  • ESR: typically elevated (> 100 mm/hour) in subacute thyroiditis
• ECG findings
  • Tachycardia
  • Atrial fibrillation
  • LBBB and ECG signs of LVH in patients with dilated cardiomyopathy

Subsequent evaluation

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.

TSH receptor antibody (TRAb)

• Indication: if Graves disease is suspected but classic clinical features are absent ^[17]
• Interpretation
  • Positive: Diagnosis of Graves disease is established.
  • Negative: Further investigation is necessary.

Nuclear medicine thyroid scan and radioactive iodine uptake measurement ^[19]

• Definitions
  • 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 ^[20]
• Indications ^[17]
  • First-line test for most patients with uncertain etiology of thyrotoxicosis after initial evaluation
  • Assessment of functional status of thyroid nodules ^[20]
  • 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 ^[17]
• Findings
  • 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 “Diagnostic steps for thyroid nodules”

Thyroid ultrasound with Doppler

• Indications ^[21]
  • Palpable abnormality, e.g., goiter or nodules
  • Additional study following nuclear medicine thyroid scan or second-line initial imaging study
  • Preferred imaging technique in pregnant or breastfeeding women
• Typical findings ^[21]
  • 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

Further evaluation

These additional tests are not routinely required but may be performed depending on the suspected underlying etiology.

• Ultrasound-guided FNAC
  • Consider for suspicious nodules (see “Diagnostic steps for thyroid nodules” and “Indications for FNAC in thyroid nodules”).
  • Can help confirm etiology if diagnosis remains uncertain (see “Pathological findings” in “Common causes of thyrotoxicosis”)
• Other thyroid antibodies ^[17]
  • Thyroid peroxidase antibodies (TPOAb)
    • Indication: suspected subacute lymphocytic thyroiditis, including postpartum thyroiditis
    • Elevated levels may also be seen in Graves disease.
  • 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
  • Serum Tg should be assessed alongside TgAb because a TgAb-positive result indicates an unreliable serum Tg finding. ^[17]
  • Findings
    • Exogenous hyperthyroidism: ↓ Tg due to production that is suppressed by the administered thyroid hormones
    • Endogenous hyperthyroidism: normal or ↑ Tg

The symptoms of thyrotoxicosis are nonspecific and overlap significantly with other common conditions. If there is any clinical uncertainty, TSH should be assessed.

• 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

References:^{[2][4][5][6][7][8][14]}

The differential diagnoses listed here are not exhaustive.

Approach ^[17][18]

• Screen for thyroid storm in severely symptomatic patients (consider using BWPS) and start immediate therapy if needed (See “Treatment” in “Thyroid storm”)
• Initiate symptomatic therapy for thyrotoxicosis (e.g., beta blockers).
• Ensure definitive therapy for hyperthyroidism and thyrotoxicosis (i.e., 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. ^[17]
• Avoid triggers, e.g., contrast medium, amiodarone, and aspirin.

Symptomatic therapy for thyrotoxicosis ^[17]

The treatment of hyperadrenergic symptoms is important for decreasing the risk of cardiac complications in thyrotoxicosis, such as atrial fibrillation and heart failure.

• Indication: all symptomatic patients
• Treatment of hyperadrenergic symptoms: beta blockers (first line) ^[17];
  • Provide immediate control of symptoms, e.g., neuropsychiatric and/or hyperadrenergic symptoms
  • Treatment options
    • First line: propranolol
    • Alternatives: atenolol OR metoprolol
    • Severe thyrotoxicosis or thyroid storm treated in ICU: esmolol
  • If there are contraindications to beta blockers, e.g., severe asthma, Raynaud phenomenon , consider CCBs: verapamil OR diltiazem . ^[22]
• Treatment of cardiac complications ^[18]
  • Heart failure: patients should receive the same treatment as euthyroid patients with heart failure (see “Treatment” in “Acute heart failure”).
  • Atrial fibrillation
    • May be refractory to treatment until antithyroid therapy has been initiated
    • Amiodarone should be avoided.
    • See “Treatment” in “Atrial fibrillation” for details on further management.

Definitive therapy for hyperthyroidism and thyrotoxicosis ^[17][23]

• 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 toxic adenoma.

Antithyroid drugs for thyrotoxicosis

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.

• Indications
  • 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 ^[24]
  • Contraindications to both RAIA and surgery
  • Other: hyperthyroidism in pregnancy, limited life expectancy, patient preference
• Medication
  • The choice of medication depends on the severity of symptoms and patient factors.
    • Most patients: methimazole
    • Thyroid storm or first trimester of pregnancy: propylthiouracil
• Monitoring
  • CBC, liver chemistries, and bilirubin
    • Obtain baseline prior to therapy.
    • Repeat if febrile illness or symptoms of liver injury, e.g., jaundice.
  • TFTs: measure free T₄ and T₃ 2–6 weeks after initiation of therapy and adjust dosage accordingly.
  • See also “Adverse effects” in “Antithyroid drugs”.
• Duration of therapy
  • Primary therapy for Graves disease: typically 12–18 months
  • Preparation for surgery: given until TFTs normalize, after which surgery may be performed ^[25]
  • Preparation for RAIA: given until TFTs normalize and stopped 2–3 days before ablation

Radioactive iodine ablation (RAIA) ^[26]

• 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
• Indications
  • Toxic MNG and toxic adenoma with high nodular radioactive iodine uptake
  • Failure to achieve euthyroidism with antithyroid drugs (ATDs) in Graves disease, due to:
    • Refractory disease
    • Contraindications to ATDs, e.g., liver disease
    • Major adverse reactions to ATDs
  • 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 thyroid cancers, large/compressive nontoxic goiters ^[27]
• Contraindications
  • Pregnant/breastfeeding women
  • Children < 5 years of age
  • Initial treatment for confirmed or suspected thyroid malignancy
  • Moderate to severe Graves ophthalmopathy
  • Inability to follow radiation safety regulations
• 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.
    • Consider beta blockers even in asymptomatic patients (see “Symptomatic therapy for thyrotoxicosis” for dosages).
    • Administer methimazole to rapidly achieve a euthyroid state; must be discontinued 2–3 days before RAIA is started.
  • 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
• Complications ^[28][29]
  • Early
    • Most patients with Graves disease become hypothyroid after RAIA and require life-long thyroid hormone replacement with L-thyroxine
    • Gastritis: nausea and vomiting
    • Sialadenitis
    • Other: transient loss of taste or smell, stomatitis, transient bone marrow suppression
  • Late
    • 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)

Thyroid surgery ^[30]

The efficacy of antithyroid drugs and RAIA has reduced the need for thyroid surgery.

• Indications
  • Large goiters (≥ 80 g) or obstructive symptoms
  • Confirmed or suspected thyroid malignancy
  • Graves disease with: ^[31]
    • Concomitant primary hyperparathyroidism or periodic paralysis
    • Moderate to severe active Graves ophthalmopathy ^[24]
  • Toxic MNG or toxic adenoma with: concomitant primary hyperparathyroidism, insufficient RAIA, or retrosternal extension
  • Other: large thyroid nodules , refractory amiodarone-induced thyrotoxicosis , planned pregnancy within next 6 months , or patient preference
• Contraindications
  • Severe comorbidities that influence surgical risk
  • Pregnancy
• 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. ^[22][32]
• Procedure
  • Graves disease; or toxic MNG: near-total or total thyroidectomy
  • Isolated toxic adenoma: lobectomy
  • See also “Procedure/application” in “Thyroid surgery.”
• Postprocedural care
  • Wean beta blockers
  • Measure serum calcium and PTH levels

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.
• Pathogenesis
  • β-hCG molecule has a similar structure to that of the TSH molecule.
  • β-hCG binds to TSH receptors of the thyroid gland → thyroid stimulation → hyperthyroidism
• Clinical features
  • Graves disease: signs of hyperthyroidism, ophthalmopathy
  • β-hCG-mediated hyperthyroidism can cause:
    • Subclinical hyperthyroidism
    • Overt (severe) hyperthyroidism in cases of hydatidiform moles/choriocarcinoma (see “Gestational trophoblastic disease”)
• Diagnosis: same as in nonpregnant patients, but nuclear medicine thyroid scan is contraindicated
• Treatment
  • Propylthiouracil , methimazole
  • Beta blockers
  • Surgery: if medication cannot be tolerated; safest in second trimester
• Complications: if left untreated → miscarriage, stillbirth, preeclampsia, premature labor, cardiac failure, low birth weight, neonatal hyperthyroidism (see below)

Suspect a molar pregnancy or choriocarcinoma if severe hyperthyroidism manifests during pregnancy!

Neonatal hyperthyroidism

• Occurs in ∼ 5% of babies born to mothers with Graves disease
• Etiology: transplacental passage of maternal TRAbs
• Clinical features
  • 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)
• Treatment
  • Neonatal Graves disease resolves within 1–3 months
  • Infants with symptomatic hyperthyroidism: methimazole and propranolol
• Complications: Untreated symptomatic hyperthyroidism in infants can cause cardiac failure and intellectual disability.

Exogenous thyrotoxicosis

• Definition: thyrotoxicosis due to excessive intake of thyroid hormone
• Etiology
  • Intentional
    • Therapeutic: suppressive doses of thyroid hormones for thyroid cancer treatment
    • Patients with psychiatric disorders, like Munchausen syndrome
    • People who are trying to lose weight
  • Unintentional
    • Iatrogenic
    • Accidental ingestion (primarily in children)
    • Dietary supplement overdose
• Clinical features: symptoms of thyrotoxicosis but no goiter
• Diagnostics
  • Low/undetectable TSH, high levels of T₄/T₃, low Tg levels
  • Low RAI uptake in scintigraphy
• Treatment
  • Taper and stop the exogenous thyroid hormone.
  • Beta blockers: if symptoms are severe
  • Cholestyramine: binds to T₃ and T₄ in the intestine and interrupts the enterohepatic circulation

References:^[33][34][35]

Definition ^[17]

• An acute exacerbation of hyperthyroidism that results in a life-threatening hypermetabolic state.
• Also known as thyrotoxic crisis

Etiology ^[17]

• Iatrogenic
  • Thyroid surgery
  • RAIA
  • Exogenous iodine from contrast media or amiodarone
  • Discontinuation of antithyroid medication
• Stress-related catecholamine surge
  • Nonthyroidal surgery
  • Anesthesia induction
  • Labor
  • Intercurrent illness, e.g., sepsis, myocardial infarction, diabetic ketoacidosis

Clinical features ^[17]

• 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

Diagnostics ^[17]

• 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.:
  • ECG to assess for atrial fibrillation
  • Liver chemistries to assess for evidence of jaundice
• The Burch-Wartofsky Point Scale (BWPS) can be considered to assess disease severity and guide treatment.

Treatment of thyroid storm ^[17][36]

Thyroid storm has a high mortality rate and patients should receive aggressive treatment to manage complications and restore normal thyroid function.

Approach

• 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 definitive therapy for hyperthyroidism and thyrotoxicosis.
• Consider plasmapheresis or emergency surgery as life-saving treatment for rare refractory cases

Symptomatic treatment

• Hyperadrenergic symptoms: beta blockers are first-line
  • Preferred: Propranolol, due to combined beta-blockade and antithyroid effects
  • Alternatives
    • Preexisting heart failure: esmolol ^[18][37]
    • Mild obstructive airway disease/stable asthma: atenolol or metoprolol
  • Beta blocker contraindications: consider CCBs, e.g., diltiazem
• Hyperthermia
  • External cooling techniques (e.g., ice packs, cooling blankets, alcohol washes)
  • Antipyretics, e.g., acetaminophen (Consider IV administration )
  • Avoid aspirin.
• Hypotension and hypovolemia: fluid resuscitation to treat insensible and GI losses ^[36]
  • 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”)

If thyroid storm has led to congestive heart failure, esmolol is the preferred beta blocker. All patients receiving beta blockers should be monitored carefully for signs of heart failure.

Antithyroid drugs in thyroid storm ^[17][18][22]

• Inhibition of thyroid hormone synthesis
  • First line: propylthiouracil
  • Alternative: methimazole
• Inhibition of thyroid hormone release (through the Wolff-Chaikoff effect)
  • First line: iodine solutions given at least 1 hour after antithyroid drugs
    • Potassium iodide solution
    • Lugol solution
  • In patients with iodine allergy or iodine-induced thyrotoxicosis, lithium can be used .
• Inhibition of peripheral conversion of T₄ to T₃
  • Propranolol
  • Glucocorticoids: can also treat concurrent adrenal insufficiency
    • First line: hydrocortisone
    • Alternative: dexamethasone

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)
  • Begin IV fluid resuscitation
  • Identify and treat tachyarrhythmias or acute heart failure
  • Treat hyperadrenergic symptoms with beta blockers (first-line: propranolol).
  • Treat hyperthermia: external cooling and acetaminophen.
• Consider BWPS if uncertain diagnosis or for assessing severity and need for aggressive therapy.
• Consult critical care for ICU admission.
• Initiate antithyroid drugs:
  • PTU
  • KI
  • IV glucocorticoids
• Identify and treat reversible triggers.
• Electrolyte repletion as needed
• Administer benzodiazepines as needed for agitation.
• Consider plasmapheresis for life-threatening refractory cases.
• Ensure definitive therapy for hyperthyroidism and thyrotoxicosis when stabilized.