Differentials
Toxic nodular goitre
SIGNS / SYMPTOMS
Hyperthyroidism has gradual onset and is mild in nodular disease. Toxic multinodular goitre usually occurs in an older age group.
Nodular goitre is found on physical examination.
Extrathyroidal manifestations, such as orbitopathy, dermopathy, and acropachy, are absent.
INVESTIGATIONS
Peripheral thyroid hormone levels are not usually as high as in Graves' disease.
Thyroid isotope scan and thyroid ultrasound show nodular goitre.
Radioactive iodine (or technetium-99) uptake is usually normal.
Thyroid receptor antibodies are absent.
Painless and postnatal thyroiditis
SIGNS / SYMPTOMS
Transient hyperthyroid phase is mostly followed by transient hypothyroid phase. Fifty percent of patients will ultimately develop permanent hypothyroidism in the following years.[65]
INVESTIGATIONS
Radioactive iodine (or technetium-99) uptake is very low.
Thyroid receptor antibodies are absent.
A high T3/T4 ratio is suggestive of Graves’ disease rather than thyroiditis.
Gestational hyperthyroidism
SIGNS / SYMPTOMS
High levels of hCG during the first trimester stimulate the thyroid-stimulating hormone (TSH) receptor.[66] Hyperthyroidism is usually subclinical but may be overt, especially if hyperemesis is present.
INVESTIGATIONS
Hyperthyroidism is subclinical or mild and resolves in the second trimester.
Thyroid receptor antibodies are absent.
Subacute thyroiditis
SIGNS / SYMPTOMS
Subacute (granulomatous or de Quervain) thyroiditis starts with thyroid pain and systemic febrile symptoms. Transient hyperthyroid phase followed by transient hypothyroid phase and resolution in a few months is typical, with painful thyroid and systemic febrile symptoms.[67]
INVESTIGATIONS
Radioactive iodine uptake (or technetium-99) is very low and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are high.
Thyroid receptor antibodies are absent.
Iodine-induced hyperthyroidism
SIGNS / SYMPTOMS
History of iodine exposure is typical. Examples include radiographic contrast or amiodarone.
INVESTIGATIONS
Increased urinary iodine and low thyroidal uptake of radioactive iodine (or technetium-99) are typical.[2]
Thyroid receptor antibodies are absent.
TSH-producing pituitary adenoma
Thyroid hormone resistance
SIGNS / SYMPTOMS
The patient may be clinically hypothyroid, euthyroid, or hyperthyroid depending on the type of resistance. Family history is mostly positive for the syndrome, but isolated cases have been reported.
INVESTIGATIONS
Thyroid hormone levels are elevated with inappropriately normal or elevated TSH.[71]
Thyroid receptor antibodies are absent.
Molecular genetic testing is diagnostic.
Inflammatory eye conditions, myasthenia gravis
SIGNS / SYMPTOMS
Inflammatory eye conditions and non-autoimmune causes of orbitopathy or proptosis may indicate patient is clinically euthyroid. Ophthalmic findings are more typically unilateral, and presentation is atypical for Graves' orbitopathy (e.g., no previous or present evidence of thyroid dysfunction, absence of upper eyelid retraction, divergent strabismus, diplopia sole manifestation, or history of diplopia worsening towards the end of the day).[34]
INVESTIGATIONS
MRI or CT scan of orbit suggests a non-thyroidal diagnosis such as orbital myositis, neoplasm, or cavernous sinus thrombosis.[2] Thyroid function tests (TFTs) are normal. TSH receptor antibody activity is absent.
Factitious ingestion of thyroid hormone (thyrotoxicosis factitia)
SIGNS / SYMPTOMS
Rare presentation of thyrotoxicosis. Goitre not usually present. May not be distinguishable based on symptoms or examination alone.
Biotin, a common component of multivitamin preparations, has been reported to cause abnormal TFTs in a patient through assay interference.[72]
INVESTIGATIONS
4-, 6-, or 24-hour radioiodine uptake and serum thyroglobulin low.[73]
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