- Clinical science
The term hyperthyroidism refers to the symptoms caused by excessive amounts of circulating thyroid hormone. Hyperthyroidism typically results from thyroid gland hyperactivity, the most common causes of which are Graves' disease (most common), toxic multinodular goiter (MNG), and toxic adenoma. In rare cases, hyperthyroidism is caused by TSH-producing pituitary tumors (central hyperthyroidism), β-hCG mediated hyperthyroidism (gestational trophoblastic disease), or oral intake of thyroid hormones (factitious hyperthyroidism). Regardless of the cause, the characteristic symptoms of hyperthyroidism include fatigue, anxiety, heat intolerance, increased perspiration, palpitations, and significant weight loss despite an increased appetite. Serological thyroid hormone assay confirms hyperthyroidism, while measurement of antithyroid antibodies, thyroid ultrasonography, and radio-active iodine uptake tests help identify the etiology. Management, in general, includes the initial control of symptoms with beta-blockers and anti-thyroid drugs followed by definitive therapy either with radioactive iodine ablation of the thyroid gland or surgery.
- Prevalence: ∼ 1% of the general population have
- Sex: ♀ > ♂ (5:1)
- Age range at presentation
Epidemiological data refers to the US, unless otherwise specified.
- Hyperfunctioning thyroid gland
- Destruction of the thyroid gland
- Exogenous hyperthyroidism
- Ectopic (extrathyroidal) hormone production
- Physiological regulation: See “thyroid gland” in .
Effects of hyperthyroidism
- Generalized hypermetabolic state (increased substrate consumption)
- Hyperstimulation of the sympathetic nervous system
- Cardiac effects
- Heat intolerance, excessive sweating (moist, warm skin)
- Weight loss despite increased appetite
- Hyperdefecation (increased frequency of bowel movements)
- Weakness, fatigue
- Eyes: lid lag: , lid retraction; (“staring look”),
- Tachycardia: seen in almost all cases of hyperthyroidism.
Palpitations, irregular pulse (due to atrial fibrillation/ectopic beats)
- Atrial fibrillation occurs in about 20% of patients with hyperthyroidism, especially in the elderly.
- In most cases, the rhythm converts spontaneously to sinus rhythm once the hyperthyroidism is treated.
- Electrical cardioversion is required for those who do not convert spontaneously to sinus rhythm.
- Anticoagulation is often required for hyperthyroid patients with atrial fibrillation.
- Hypertension with a widened pulse pressure
- Cardiac failure: Elderly patients often present with features of cardiac failure (e.g., pedal edema, dyspnea on exertion).
- Neuropsychiatric system: anxiety; , agitation, depression, insomnia, emotional instability
Overview of changes in hormone levels
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Thyroid function tests
- Test of choice: thyroid stimulating hormone (TSH) levels
- Free T3 and free T4 levels: both are characteristically high
- Serum thyroglobulin levels (Tg): indicated if exogenous hyperthyroidism is suspected → characteristically low levels
- Serum thyroid antibodies: if Graves disease/Hashimoto thyroiditis is suspected (see “Overview” in t )
- Thyroid ultrasonography: Can diagnose the etiology of hyperthyroidism (e.g., diffuse enlargement, solitary/multiple nodules, increased vascularity of the gland)
Thyroid scintigraphy: A nuclear medicine imaging technique, which demonstrates the structure and function of thyroid tissue based on its selective uptake of radioactive iodine (RAI).
- Contraindications: pregnant or breast-feeding women
Interpretation of results
- Only the functional part of the gland takes up RAI.
- Normal thyroid tissue: normal sized gland with a diffuse uptake of RAI.
- Most common findings
Common differential diagnoses
- Neuropsychiatric symptoms: Anxiety/panic disorders
- Hyperadrenergic symptoms: Intoxication with anticholinergics; cocaine/amphetamine abuse; withdrawal syndromes
- Weight loss: Diabetes mellitus, malignancy
- Cardiac symptoms: Congestive cardiac failure
- Definition: hyperthyroidism due to excessive intake of thyroid hormone
- Clinical features: symptoms of hyperthyroidism, but no goiter
- Dermatological causes: primary, idiopathic hyperhidrosis
- Psychoautonomic causes: physical and emotional stress (e.g., hypoglycemia, agitation, anxiety)
- Endocrinological causes
- Neurological causes: Huntington's disease, Parkinson's disease
- Medication/recreational drug use or withdrawal symptoms (e.g., opioides, amphetamines)
- Malignoma: esp. lymphoma (night sweats!)
The differential diagnoses listed here are not exhaustive.
Symptomatic therapy of thyrotoxicosis
- Beta-blockers offer immediate control of symptoms
- Indication: all symptomatic patients
- Contraindications: e.g., asthma, Raynaud phenomenon; for more information see section “Contraindications” in .
- Drugs used:
There are currently three effective initial treatment options for Graves disease: antithyroid drugs, radioactive iodine ablation, or surgery. Toxic multinodular goiter (TMNG) and toxic adenoma (TA) are not generally treated with ATDs, but rather with ablation or surgery.Which form of therapy is chosen depends on the individual clinical situation and the patient preference.
- Antithyroid drugs can effectively render a patient euthyroid; 20–75% of patients achieve permanent remission after 1–2 years of treatment. Some patient groups have a higher likelihood of remission than others.
- Patients with high likelihood of remission (e.g., small goiter, negative or low TRab titer, women)
- Active Graves ophthalmopathy
- Children age ≤ 5 years
- Thyroid storm
- Patient preference
- Patients who need rapid disease control before further treatment, e.g., achievement of euthyroid state prior to surgery.
- Patients with an inability to follow radiation safety regulations
- Contraindications: history of adverse reactions to ATD
- Adverse effects: see
- Drugs used
- Definition: destruction of thyroid tissue using radioactive iodine (iodine 131) through a sodium/iodine symporter
- High surgical risk; limited life-expectancy
- Liver disease
- Major adverse reaction to ATDs
- Previous operations or radiation of the neck
- No access to a high volume thyroid surgeon
- Failure to achieve euthyroidism with ATDs
- Patient preference
- Patients with congestive heart failure, right heart failure, pulmonary hypertension, or periodic hypokalemic paralysis
- Recommended especially for TMNG and TA patients with high nodular radioactive iodine uptake
- Pre-treatment methimazole: in patients who are at high risk for complications due to worsening of hyperthyroidism
- Avoidance of excess iodine for 7 days prior to RAIA
- Single oral dose of (131I) → isotope uptake by thyroid gland → emission of β-radiation that slowly destroys the thyroid tissue
- Patients treated with RAIA have the potential to expose others to radiation and are advised to avoid close contact (6 feet), especially to children/pregnant women.
- The period of restricted contact depends on the dose received.
- Women treated with RAI are advised to avoid becoming pregnant for a minimum of 4–6 months.
- Post-procedural care
- Surgery is rarely indicated
- Large goiters (≥ 80 g) or obstructive symptoms
- Confirmed or suspected thyroid malignancy
- Moderate to severe active Graves ophthalmopathy
- Women planning to become pregnant in the next < 6 months
- Large thyroid nodules
- Patient preference
- Access to a high-volume thyroid surgeon
- Recommended especially for TMNG and TA patients with concomitant hyperparathyroidism, insufficient RAIA or retrosternal extension
- Severe comorbidities that influence surgical risk
- First and third trimester of pregnancy
- See “procedure/application” in .
- For Graves disease: near-total thyroidectomy
- Postprocedural care
- Definition: An acute exacerbation of hyperthyroidism, resulting in a life-threatening hypermetabolic state.
- Etiology: Thyroid storm may occur spontaneously, but is often precipitated by one of the following conditions:
- Hyperpyrexia with profuse sweating
- Tachycardia (> 140 beats/minute), hypertension (with wide pulse pressure), atrial fibrillation, congestive cardiac failure
- Severe nausea, vomiting, diarrhea, possibly jaundice
- Severe agitation and anxiety, delirium and psychoses, seizures, coma
- Low/undetectable TSH, elevated free T3/T4
- General measures
- Intensive care monitoring with fluid and electrolyte substitution
- Treatment of hyperthermia: ice packs, cooling blankets, and antipyretics (e.g., acetaminophen)
- Treatment of underlying condition
- Beta blockers should be promptly started (propranolol)
- Antithyroid drugs 
- Potassium iodide/Lugol's iodine
- Glucocorticoids: IV hydrocortisone/dexamethasone
- Plasmapheresis: as a life-saving treatment, rarely needed
- General measures
We list the most important complications. The selection is not exhaustive.
Hyperthyroidism in pregnancy
- Hyperthyroidism is rare in pregnancy (< 0.5% of cases)
- Most common causes: Graves disease, β-hCG-mediated hyperthyroidism
- Clinical features
- Diagnosis: same as in non-pregnant patients, but thyroid scintigraphy is contraindicated.
- 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, intellectual disability