• Clinical science

Hyperthyroidism

Summary

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.

Epidemiology

References:[2][3][4][5]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[4][6][7]

Pathophysiology

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.

Effects of hyperthyroidism

  • Generalized hypermetabolism (increased substrate consumption)
  • Hyperstimulation of the sympathetic nervous system
  • Cardiac effects

References:[8][9]

Clinical features

References:[6][10]

Diagnostics

Overview of changes in hormone levels

Overt hyperthyroidism

Subclinical hyperthyroidism

Basal TSH

  • ↓ Or undetectable

FT3

  • Normal

FT4

  • ↑ in 90% of cases
  • Normal

Laboratory studies

Imaging

Thyroid ultrasound

Can be used to diagnose the underlying cause of hyperthyroidism (e.g., diffuse enlargement, solitary/multiple nodules, increased vascularity of the gland)

Thyroid scintigraphy

A nuclear medicine imaging technique that allows the structure and function of thyroid tissue to be visualized based on its selective uptake of radioactive iodine (RAI).

  • Indications
  • 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

References:[6][11][10]

Differential diagnoses

Common differential diagnoses

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
  • Acute to chronic hyperthyroidism
  • Chronic hyperthyroidism
  • Thyrotoxicosis in patients with a preexisting iodine-deficiency thyroid disorder
Epidemiology
  • Most common cause of hyperthyroidism in the US
  • Peak incidence: 20–30 years of age
  • > (8:1)
  • Peak incidence: > 50 years of age
  • >
  • Peak incidence: 30–50 years of age
  • > (3:1)
  • More common in iodine-deficient regions
Causes
  • Viral and mycobacterial infections causing damage to follicular cells
Goiter Consistency
  • Diffuse and smooth
  • Multinodular
  • Diffuse and firm
  • Depends on underlying thyroid disorder
Pain
  • Painless
  • Painless
  • Painful
  • Painless
  • Painless
Other findings
  • Nonspecific
  • ESR
  • Fever, malaise
  • Possible history of upper respiratory tract infections a few weeks prior to the onset of subacute thyroiditis
  • Nonspecific
Thyroid function tests
Antibodies
  • Absent
Iodine uptake on scintigraphy
  • Diffuse
  • Multiple focal areas of increased uptake
  • Reduced
  • Reduced
Pathologic findings
  • Patches of enlarged follicular cells distended with colloid and flattened epithelium
  • Granulomatous inflammation, multinucleated giant cells on histology
  • Absence of germinal follicles, lymphocytic infiltration on histology
  • Depends on underlying thyroid disorder

Exogenous hyperthyroidism or factitious hyperthyroidism

  • Definition: hyperthyroidism due to excessive intake of thyroid hormone
  • Etiology
    • Intentional
    • Unintentional
      • Iatrogenic
      • Accidental ingestion (primarily in children)
      • Dietary supplement overdose
  • Clinical features: symptoms of hyperthyroidism but no goiter
  • Diagnostics
    • Low/undetectable TSH, high levels of T4/T3, low Tg levels
    • Low RAI uptake in scintigraphy
  • Treatment

References:[12][13][14][15][16] [17][18][19]

The differential diagnoses listed here are not exhaustive.

Treatment

Symptomatic therapy of thyrotoxicosis

Definitive therapy

There are currently three effective initial treatment options for Graves disease: antithyroid drugs, radioactive iodine ablation, and surgery. Toxic MNG and toxic adenoma (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 (ATDs)

  • 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.
  • Indications
    • Patients with high likelihood of remission (e.g., small goiter, negative or low TRab titer, women)
    • Active Graves ophthalmopathy
    • Children age ≤ 5 years
    • Pregnancy
    • 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 antithyroid drugs.
  • Drugs used

Radioactive iodine ablation (RAIA)

Thyroid surgery

References:[6][13][20][21][22][23][24][25][26]

Complications

Thyroid storm (thyrotoxic crisis)

In the case of simultaneous heart failure, the administration of beta blockers may worsen hemodynamics and is therefore contraindicated!
References:[13][27]

We list the most important complications. The selection is not exhaustive.

Special patient groups

Hyperthyroidism in pregnancy

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
  • Treatment
  • Complications: Untreated symptomatic hyperthyroidism in infants can cause cardiac failure and intellectual disability.

References:[28][29]