Overview of thyrotoxicosis and hyperthyroidism

Thyrotoxicosis refers to the clinical condition that results from excess thyroid hormones (thyroxine [T₄] and triiodothyronine [T₃]) in body tissue, regardless of the cause. Most cases of thyrotoxicosis are due to hyperthyroid disorders (disorders in which the thyroid produces excess thyroid hormones). The most common causes of hyperthyroidism are Graves disease, multinodular goitre and an autonomously functioning thyroid nodule (toxic adenoma). Hyperthyroidism secondary to a pituitary disorder (eg a thyroid stimulating hormone [TSH]-secreting pituitary adenoma) is rare. Causes of thyrotoxicosis not associated with hyperthyroidism include excess exogenous thyroid hormone intake, thyroiditis with leakage of preformed thyroid hormone, and amiodarone.

Common symptoms of thyrotoxicosis include weight loss, heat intolerance, tremor, muscle weakness and palpitations. Thyroid hormones affect almost every tissue and organ system in the body, so atypical presentations are common (particularly in older people).

Long-term untreated thyrotoxicosis is associated with cardiovascular disease (particularly atrial fibrillation) and accelerated bone mass loss.

Overview of thyrotoxicosis gives an overview of the clinical and biochemical presentations, and usual treatment, for different causes of thyrotoxicosis.

Table 1. Overview of thyrotoxicosis
Graves disease toxic multinodular goitre toxic adenoma painless postpartum thyroiditis painful subacute thyroiditis painless sporadic thyroiditis amiodarone-induced thyrotoxicosis exogenous thyroid hormone
Graves disease
clinical presentation and course of disease	five to ten times more common in females than males onset usually between age 20 and 60 years diffuse, usually symmetrical goitre Graves ophthalmopathy (see Graves-related eye disease) often associated with other autoimmune diseases
expected investigation findings	laboratory results—TSH-receptor antibody elevated in 95% of cases (thyroid peroxidase antibody also often positive, but is not a required investigation) radionuclide thyroid scan—normal or elevated diffuse uptake pattern [NB1]
pathophysiology	TSH-receptor antibody increases thyroid hormone production and causes thyroid hyperplasia
treatment	see Overview of management of primary hyperthyroidism for details initial treatment with an antithyroid drug subsequent treatment determined by severity, patient factors and patient preference (see Subsequent management of primary hyperthyroidism) beta blocker for hyperthyroid symptoms
toxic multinodular goitre
clinical presentation and course of disease	more common in females than males onset usually occurs above age 50 years nodular goitre often present for years
expected investigation findings	laboratory results—TSH-receptor antibody absent; thyroid peroxidase antibody absent or incidentally positive in low titre radionuclide thyroid scan—normal or elevated multifocal pattern [NB1]
pathophysiology	nodule autonomy hyperthyroidism can be precipitated by iodine exposure (eg radiological contrast medium)
treatment	see Overview of management of primary hyperthyroidism for details usually treated initially with an antithyroid drug subsequent treatment determined by severity, patient factors and patient preference (see Subsequent management of primary hyperthyroidism)—remission is rare without definitive treatment (ie radioiodine or thyroidectomy) beta blocker for hyperthyroid symptoms
toxic adenoma
clinical presentation and course of disease	more common in females than males onset usually between age 30 and 50 years slowly growing solitary thyroid nodule, usually larger than 3 cm
expected investigation findings	laboratory results—TSH-receptor antibody absent; thyroid peroxidase antibody absent or incidentally positive in low titre radionuclide thyroid scan—focal uptake with suppression of uptake into surrounding thyroid tissue [NB1]
pathophysiology	mutation of TSH-receptor gene or of signal transduction gene (G protein gene)
treatment	see Overview of management of primary hyperthyroidism for details usually treated initially with an antithyroid drug subsequent treatment determined by severity, patient factors and patient preference (see Subsequent management of primary hyperthyroidism)—remission is rare without definitive treatment (ie radioiodine or thyroidectomy) beta blocker for hyperthyroid symptoms
painless postpartum thyroiditis
clinical presentation and course of disease	typically 1 to 6 months after delivery diffuse, small goitre thyrotoxicosis for 1 to 2 months often followed by hypothyroidism for 4 to 6 months; hypothyroidism can be permanent (in around 20% of cases) more common in women with type 1 diabetes
expected investigation findings	laboratory results—TSH-receptor antibody occasionally shows transient minor elevation; thyroid peroxidase antibody high titre in most; normal erythrocyte sedimentation rate radionuclide thyroid scan—near absent uptake
pathophysiology	autoimmune—destruction of thyroid follicles with release of stored thyroid hormone
treatment	beta blocker for hyperthyroid symptoms levothyroxine if the hypothyroid phase is prolonged or symptomatic, or if breastfeeding or attempting to conceive during the hypothyroid phase
painful subacute thyroiditis
clinical presentation and course of disease	five times more common in females than males onset usually between age 20 and 60 years often follows an upper respiratory tract infection tender goitre hyperthyroidism for 1 to 2 months often followed by hypothyroidism for 4 to 6 months; hypothyroidism can be permanent (in fewer than 10% of cases)
expected investigation findings	laboratory results—TSH-receptor antibody occasionally shows transient minor elevation; thyroid peroxidase antibody low titre or absent; erythrocyte sedimentation rate almost always greater than 50 mm/hr; normal or increased white blood cell count radionuclide thyroid scan—near absent uptake
pathophysiology	probably a postviral syndrome; destruction of thyroid follicles with release of stored thyroid hormone
treatment	beta blocker for hyperthyroid symptoms nonsteroidal anti-inflammatory drugs for thyroid pain; glucocorticoids may be required for more severe pain levothyroxine if the hypothyroid phase is prolonged or symptomatic
painless sporadic thyroiditis
clinical presentation and course of disease	more common in females than males cases peak between age 20 and 50 years diffuse, small goitre thyrotoxicosis for 1 to 2 months often followed by hypothyroidism for 4 to 6 months; hypothyroidism can be permanent (in around 20% of cases) can present postpartum and should be differentiated from postpartum Graves disease
expected investigation findings	laboratory results—TSH-receptor antibody occasionally shows transient minor elevation; thyroid peroxidase antibody high titre in most; normal erythrocyte sedimentation rate radionuclide thyroid scan—near absent uptake
pathophysiology	autoimmune: destruction of thyroid follicles with release of stored thyroid hormone
treatment	beta blocker for hyperthyroid symptoms levothyroxine if the hypothyroid phase is prolonged or symptomatic
amiodarone-induced thyrotoxicosis
clinical presentation and course of disease	can present up to 12 to 18 months after ceasing amiodarone two clinical types exist: type 1—underlying thyroid disease present; more common in iodine-deficient populations; diffuse or nodular goitre type 2—no underlying thyroid disease; normal gland or small goitre
expected investigation findings	radionuclide thyroid scan—usually low uptake and not discriminatory; uptake occasionally seen in type 1 disease ultrasound—colour-flow Doppler vascularity normal or increased in type 1 disease and diminished or absent in type 2 disease
pathophysiology	type 1—excess iodine type 2—destructive thyroiditis
treatment	type 1—antithyroid drugs type 2—glucocorticoids can be difficult to distinguish between type 1 and type 2 disease, so empirical dual therapy sometimes required thyroidectomy may be required
exogenous thyroid hormone
clinical presentation and course of disease	usually no goitre (incidental if present)
expected investigation findings	laboratory results—TSH-receptor antibody absent; thyroid peroxidase antibody low titre or absent; low thyroglobulin levels radionuclide thyroid scan—near absent uptake
pathophysiology	excess ingestion of thyroid hormone
treatment	stop or reduce thyroid hormone intake as appropriate
Note: TSH = thyroid stimulating hormone NB1: Uptake may be low in iodine-induced hyperthyroidism .