- Clinical science
Hyperthyroidism refers to the symptoms caused by excessive circulating thyroid hormones. It is typically caused by 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), excessive production of β-hCG (gestational trophoblastic disease), or oral intake of thyroid hormones (factitious hyperthyroidism). Regardless of the cause, the most common symptoms of hyperthyroidism include fatigue, anxiety, heat intolerance, increased perspiration, palpitations, and significant weight loss despite increased appetite. Serological thyroid hormone assay confirms hyperthyroidism, while measurement of antithyroid antibodies, thyroid ultrasonography, and radioactive iodine uptake tests help identify the etiology. Management of any form of hyperthyroidism involves the initial control of symptoms with beta blockers and antithyroid drugs, followed by definitive therapy either with radioactive iodine ablation of the thyroid gland or surgery.
- 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 ( )
- Radiation thyroiditis
- Palpation thyroiditis: due to thyroid gland manipulation during parathyroid surgery.
- Exogenous hyperthyroidism
- Ectopic (extrathyroidal) hormone production
- Physiological regulation: See “thyroid gland” in .
Effects of hyperthyroidism
- Generalized hypermetabolism (increased substrate consumption)
- Cardiac effects
- Palpitations, irregular pulse (due to atrial fibrillation/ectopic beats)
- Hypertension with widened pulse pressure
- 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
- Osteopathy: osteoporosis due to the direct effect of T3 on osteoclastic bone resorption , fractures (in the elderly)
- Neuropsychiatric system
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 (Tg)
- Serum thyroid antibodies: if Graves disease/Hashimoto thyroiditis is suspected (see “Overview” in )
- Other: decreased total cholesterol, LDL, and HDL levels
Can be used to diagnose the underlying cause of hyperthyroidism (e.g., diffuse enlargement, solitary/multiple nodules, increased vascularity of the gland)
- 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 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
|Differential diagnoses of hyperthyroidism|
|Graves disease||Toxic multinodular goiter||Subacute granulomatous thyroiditis (de Quervain thyroiditis)||Subacute lymphocytic thyroiditis (silent thyroiditis)||Iodine-induced hyperthyroidism|
|Thyroid status|| || || |
|Epidemiology|| || || || |
|Causes|| || |
|Goiter||Consistency|| || || || |
|Pain|| || || || || |
|Other findings|| || |
|Thyroid function tests|
|Antibodies|| || |
|Iodine uptake on scintigraphy|| || || || |
|Pathologic findings|| || |
- Definition: hyperthyroidism due to excessive intake of thyroid hormone
- Clinical features: symptoms of hyperthyroidism but no goiter
The differential diagnoses listed here are not exhaustive.
Symptomatic therapy of thyrotoxicosis
- Beta blockers provide 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, and surgery. Toxic MNG and (TA) are not generally treated with antithyroid drugs, 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
Technical background: Radioactive 131I emits both gamma rays and beta rays
- Gamma rays: diagnostic effect
- Beta rays: therapeutic effect
- 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 radioactive iodine uptake and patients with high nodular
- 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
- 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 hyperparathyroidism, insufficient RAIA, or retrosternal extension and patients with concomitant
- Postprocedural care
- Definition: an acute exacerbation of hyperthyroidism that results in a life-threatening hypermetabolic state
- Hyperpyrexia with profuse sweating
- Tachycardia (> 140 beats/minute) and (possibly severe) arrhythmia (e.g., atrial fibrillation), hypertension (with wide pulse pressure), 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
- Possible increase of liver function tests
- General measures
- Beta blockers (propranolol) should be promptly started.
- Antithyroid drugs 
- Potassium iodide/Lugol iodine: clinical effect is due to the decrease of T4 production in response to iodine load (Wolff-Chaikoff effect)
- Glucocorticoids: IV hydrocortisone/dexamethasone
- Plasmapheresis: as a life-saving treatment, rarely needed
Treat thyroid storm with PROverbial PROficiency and POetic GLUttony: PROpanolol, PROpylthiouracil, POtassium iodide, and GLUcocorticoids.
We list the most important complications. The selection is not exhaustive.
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 non-pregnant patients, but thyroid scintigraphy is contraindicated
- Complications: : If left untreated → miscarriage, stillbirth, pre-eclampsia, 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.