Hyperthyroidism and Thyrotoxicosis
NICE CKS Hyperthyroidism. Last revised: Jan 2025.
NICE guideline [NG145] Thyroid disease: assessment and management. Last updated: Oct 2023.
Background Information
Definition
2 commonly confusing terms:
- Thyrotoxicosis: clinical manifestation of excess circulating thyroid hormones, irrespective of the cause (i.e. hyperthyroidism can cause thyrotoxicosis)
- Hyperthyroidism: overproduction of thyroid hormone by the thyroid gland
There are 3 main types of hyperthyroidism:
| Type | Free T4 | TSH |
|---|---|---|
| Primary overt hyperthyroidism | ↑ | ↓ |
| Secondary overt hyperthyroidism | ↑ | ↑ |
| Subclinical hyperthyroidism | Normal | ↓ |
Causes
Thyrotoxicosis with Hyperthyroidism
Primary causes:
- Graves’ disease – most common
- Toxic multinodular goitre – 2nd most common
- Toxic adenoma
- Excess iodine
- Amiodarone-induced thyrotoxicosis
- Struma ovarii (ectopic thyroid hormone secretion in an ovarian teratoma)
- Causes of high hCG levels (can stimulate TSH receptors on the thyroid gland)
- Gestational thyrotoxicosis
- Hyperemesis gravidarum
- hCG-secreting tumours (e.g. choriocarcinoma or hydatidiform mole)
Secondary causes:
- TSH-secreting pituitary adenoma
- Pituitary thyroid hormone resistance syndrome (rare)
- Hypothalamic disease (excess TRH production) (extremely rare)
Thyrotoxicosis without Hyperthyroidism
- Excess levothyroxine intake
- Acute phase of transient thyroiditis
- De Quervain’s (subacute) thyroiditis
- Postpartum thyroiditis
Diagnosis Guidelines
Clinical Features
Shared / Non-Specific Features
The clinical features of thyrotoxicosis, demonstrated in the order of a thyroid examination (starting from the periphery, then top to bottom):
| Body system | Clinical features |
|---|---|
| General (screening questions) |
|
| Hands |
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| Pulse and BP |
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| Skin changes |
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| Neck |
*NB a goitre can be seen in both hyperthyroidism and hypothyroidism (mainly Hashimoto’s thyroiditis and iodine deficiency) |
| Abdomen |
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| Lower limb |
|
Cause-Specific Features
Graves’ Disease
Graves’ disease presents with a diffuse goitre (diffusely enlarged thyroid gland with no nodules) +/- bruit (on palpation / auscultation)
Classic Graves’ triad (extra-thyroidal manifestations): [Ref1][Ref2]
Graves’ orbitopathy (Graves’ eye disease):
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Pretibial myxoedema
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Bilateral and asymmetrical lesions on the anterior shin (pretibial area)
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Thyroid acropachy
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Triad of:
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The extra-thyroidal features above (orbitopathy, pretibial myxoedema and thyroid acropachy) are highly specific for Grave’s disease.
Hence, the presence of any one of them in the context of hyperthyroidism strongly points towards graves disease, however, their absence does NOT exclude it.
Toxic Multinodular Goitre
Toxic multinodular goitre presents with an irregular nodular thyroid enlargement
- Not a diffusely enlarged goitre that is seen in Graves’
- Typically, an asymmetrically enlarged goitre with multiple palpable nodules
Toxic Adenoma
Toxic adenoma presents as a single, palpable thyroid nodule
Investigation and Diagnosis
NICE recommends testing for thyroid dysfunction in:
- Clinically suspected cases
- Type 1 diabetes or other autoimmune disease
- New-onset atrial fibrillation
Thyroid Function Test Interpretation
| Type | Free T4 | TSH |
|---|---|---|
| Primary overt hyperthyroidism | ↑ | ↓ |
| Secondary overt hyperthyroidism | ↑ | ↑ |
| Subclinical hyperthyroidism | Normal | ↓ |
Further Testing
- Anti-TSH receptor antibodies
- +ve Anti-TSH confirms Grave’s disease in the context of thyrotoxicosis
- Anti-TPO antibodies (marker of thyroid autoimmunity)
- FBC and LFT
- ESR and CRP (if thyroiditis is suspected)
Imaging:
- Consider technetium scanning of the thyroid gland if antibodies are -ve
- If there is palpable thyroid enlargement or focal nodularity → ultrasound neck
Summary Table
Comparison of Common Thyroid Disorders (Test Interpretation)
| Condition | Antibody serology | Ultrasound findings | Technetium / radioiodine uptake scan |
|---|---|---|---|
| Graves’ disease |
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| Toxic multinodular goitre |
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| Toxic adenoma |
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| Hashimoto’s thyroiditis |
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| Subacute (De Quervain’s) thyroiditis |
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| Thyroid cancer |
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Management Guidelines
Thyrotoxicosis without Hyperthyroidism
This section refers mainly to transient thyroiditis like De Quervain’s thyroiditis and postpartum thyroiditis
Mainstay of treatment → Supportive / Symptomatic
- Hyperadrenergic/thyrotoxicosis symptoms→ beta blockers (propranolol / metoprolol / nadolol) usually sufficient
Anti-thyroid drugs / radioactive iodine are NOT used, as the thyrotoxicosis occurs due to hormone release from damaged thyroid tissue rather than increased synthesis.
The typically self-limited hypothyroid phase in De Quervain’s thyroiditis / postpratum thyroiditis does NOT routinely require levothyroxine unless persistent / severely symptomatic.
Thyrotoxicosis with Hyperthyroidism
Primary Care Management
Offer a beta blocker (propranolol / metoprolol / nadolol) for symptomatic control +/- anti-thyroid drugs while awaiting specialist assessment and further treatment
Secondary Care Management
Offer a beta blocker (propranolol / metoprolol / nadolol) for symptomatic control
Definitive management depends on the underlying cause.
Graves’ Disease
Disclaimer: It is not feasible to structure NICE’s recommendations into a stepwise algorithm; therefore the author has chosen to organise them by indications and contraindications.
Key takeaways (does not replace the table below):
- In mild uncomplicated disease → 1st line is anti-thyroid drug (for 12-18 months) OR radioactive iodine
- Otherwise, radioactive iodine is recommended as the 1st line definitive management, unless contraindicated (see below)
| Treatment | Indication | Contraindication |
|---|---|---|
| Radioactive iodine | 1st line definitive management in most patients, unless
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Anti-thyroid drug for 12-18 months
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1st line option in:
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Carbimazole contraindications:
Propylthiouracil contraindications:
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| Total thyroidectomy | Typically as a last resort where anti-thyroid drugs and radioactive iodine are contraindicated or ineffective
However, surgery (thyroidectomy) is 1st line if:
This is because surgery provides rapid symptomatic relief and allows for definitive histopathological diagnosis via intraoperative biopsy |
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Important safety information regarding carbimazole:
- Risk of agranulocytosis (check baseline FBC, but no need for monitoring as the risk is sudden and unpredictable)
- Risk of congenital malformations (thus avoided in women trying to conceive and during the first 20 weeks of pregnancy)
- Risk of acute pancreatitis (rare but serious) (if acute pancreatitis develops, stop carbimazole immediately and permanently)
Toxic Nodular Goitre
Toxic multinodular goitre:
- 1st line: radioactive iodine
- 2nd line: surgery (total thyroidectomy) or anti-thyroid drug therapy (1st line: carbimazole, 2nd line: propylthiouracil)
Toxic adenoma:
- 1st line: radioactive iodine OR surgery (hemithyroidectomy)
- 2nd line: anti-thyroid drug therapy
Radioactive iodine contraindications:
- Pregnancy and breastfeeding
- Planning to conceive within the 4-6 months (both male and female)
- Active thyroid eye disease
- Children and young people (not a contraindication but typically avoided)
Follow-Up and Monitoring after Treatment
TSH +/- free T4 and free T3 should be monitored.
After total thyroidectomy:
- Offer levothyroxine replacement routinely (otherwise the patient goes into iatrogenic hypothyroidism)
After radioactive iodine:
- Offer levothyroxine replacement only if hypothyroidism develops
Subclinical Hyperthyroidism
Consider seeking specialist advice on treating subclinical hyperthyroidism if:
- TSH <0.1 on 2 separate occasions, 3 months apart, or
- Symptomatic, or
- Evidence of thyroid disease (e.g. goitre, +ve thyroid antibodies)
Untreated subclinical hyperthyroidism is associated with increased risks, including: atrial fibrillation, heart failure, bone loss, fractures, and possibly cognitive decline.
If indicated (under specialist guidance), treatment depends on underlying cause, and is similar to overt hyperthyroidism as above.
If treatment is not indicated:
- Monitor TSH +/- free T4 and T3 regularly
Hyperthyroidism in Pregnancy
See this article.
References