Thyrotoxicosis
Hyperthyroidism is caused by excess hormone production by the thyroid gland. Thyrotoxicosis is the clinical state arising from excess circulating thyroid hormones due to any cause, including hyperthyroidism. The overall population prevalence of hyperthyroidism is 0.3% to 2.0% and the annual incidence is 0.1 to 4.0 cases per 1000 people. Graves’ disease accounts for up to 80% of cases, with the peak incidence occurring between the ages of 30 to 50 years. The female to male ratio is 10 to 1. In older adults, toxic adenoma and multinodular goiter are responsible for a higher proportion of cases.
The complications of thyrotoxicosis include atrial fibrillation, cardiac failure, thyroid eye disease, osteoporosis, anxiety, and mood disorders. Thyrotoxic crisis (thyroid storm) is a medical emergency that is characterized by the presence of tachycardia, fever, atrial fibrillation, vomiting, dehydration, jaundice, agitation, delirium, and coma.
A personal or family history of autoimmune disease increases the likelihood of Graves’ disease. Smoking increases the risk of Graves’ and thyroid eye disease. Exogenous causes of thyrotoxicosis include recent administration of iodinated radiological contrast media, intentional or unintentional use of thyroid hormone and ingestion of iodine containing over-the-counter supplements such as kelp. Increasingly, new medications such as antiretrovirals (non-nucleoside reverse-transcriptase inhibitors and protease inhibitors) and cancer immunotherapy drugs are precipitating thyroiditis.
A list of the most common drugs causing hyperthyroidism includes:
- Amiodarone
- Lithium
- Iodinated radiological contrast
- Interferon alpha
- Tyrosine kinase inhibitors
- Immune checkpoint inhibitors
- Antiretroviral non-nucleoside reverse-transcriptase inhibitors, protease inhibitors
- Factitious levothyroxine use
- Iodine containing supplements such as kelp
- Thyroid hormone containing weight loss supplements
Pregnancy within the last six months suggests postpartum thyroiditis, a common and self-limiting condition for which anti-thyroid drugs are not indicated. Risk of relapse of Graves’ disease is also higher postpartum. Active thyrotoxicosis confers a higher risk of miscarriage, preeclampsia, intrauterine growth restriction, preterm labor, and stillbirth. Pregnancy also influences treatment choice.
Thyroid function tests include TSH and free T4. Free T3 should be considered if fT4 is within normal limits. Thyroid stimulating hormone receptor antibodies are 98% sensitive and 99% specific for Graves’ disease. Anti-thyroid peroxidase and anti-thyroglobulin antibodies are non-specific and less helpful. Thyroid function tests should be repeated in 2 to 4 weeks after anti-thyroid drugs have been started.
Inflammatory markers such as C reactive protein and erythrocyte sedimentation rate are useful if thyroiditis is suspected. Baseline complete blood count and liver function tests should be ordered prior to initiating anti-thyroid drugs.
Typically, patients are treated with high initial doses of carbimazole (30 to 40 mg daily) when thyroid hormone levels are markedly elevated (fT4 > 3.1 ng/dL) and then gradually decreased. Lower doses (10 to 25 mg daily) can be considered if the thyroid hormone levels are less markedly elevated (fT4 1.9-3.1 ng/dL). Propylthiouracil (PTU) is not typically used for first line therapy because of a small risk of severe liver injury. PTU can be considered for women with a history of an adverse reaction to carbimazole or those who are currently pregnant or planning to conceive in the near future.
If Graves’ disease is confirmed, anti-thyroid drugs are continued for 12 to 18 months until autoimmune activity is under control. Radioactive iodine or thyroidectomy constitutes definitive treatment in toxic adenoma and multinodular goiter or persistent thyrotoxicosis in Graves’ disease after withdrawal of anti-thyroid drugs.
Reference
Bathgate G, Karra E and Khoo B. New diagnosis of hyperthyroidism in primary care. BMJ 2018;362:2880.
