Aetiology
Previously iodine deficiency was the most common cause globally of primary hypothyroidism; however, efforts to universally iodise salt have diminished the magnitude of this problem.[10][11] Iodine deficiency remains an important cause in the few countries where iodine intake is insufficient and in high-risk individuals, such as pregnant women.[12][13][14] IGN: global scorecard of iodine nutrition 2023 Opens in new window Autoimmune thyroiditis (Hashimoto's disease) is the most common cause of primary hypothyroidism in iodine-sufficient areas.[1]
Less commonly, primary hypothyroidism can be caused by damage or destruction of the thyroid gland from other conditions such as thyroidectomy, radioactive iodine therapy for Graves' disease or nodular goitre, or radiotherapy for head and neck cancer.[2][17] Patients may also be at increased risk of hypothyroidism after radiotherapy for breast cancer, if it is directed at lymph nodes in the neck.[18] Infiltrative diseases such as sarcoidosis can rarely cause primary hypothyroidism.[2] Sub-acute granulomatous (De Quervain's) thyroiditis usually causes transient primary hypothyroidism.
Drugs that can cause hypothyroidism include lithium, amiodarone, aminoglutethimide, interferon alpha, thalidomide, stavudine, tyrosine kinase inhibitors, alemtuzumab, and immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab, ipilimumab).[2][5][19][20][21]
Pathophysiology
Thyroxine (T4) is the main hormone produced by the thyroid gland. It is converted to triiodothyronine (T3) in target tissues. T3 mediates the main actions of thyroid hormone, which include stimulation of cellular oxygen consumption and energy generation, by binding to nuclear receptors and modulating gene expression.[22][23] Through a negative feedback mechanism, failure of the thyroid to produce its hormones stimulates the pituitary to increase production of thyroid-stimulating hormone.
Iodine is an essential component of thyroid hormone.[24] Severe iodine deficiency causes hypothyroidism, despite an increase in thyroid activity and size (goitre), as iodine concentrations are not high enough to maintain thyroid hormone production.[25][26]
In autoimmune thyroiditis, the thyroid is diffusely infiltrated with lymphocytes.[17] Most patients have antithyroid peroxidase or antithyroglobulin antibodies.[17] The prevalence is higher in populations with high dietary iodine, which is thought to make the thyroid more antigenic.[27][28] Affected individuals have an increased risk for other autoimmune disorders such as vitiligo and Sjogren's syndrome.[17]
Autoimmune thyroiditis may be part of a polyglandular autoimmune syndrome, which can include adrenal failure, hypoparathyroidism, type 1 diabetes mellitus, hypogonadism, and hypopituitarism.[17][29]
Drugs can cause hypothyroidism through a variety of mechanisms. Amiodarone contains a high iodine load, which can interfere with thyroid hormone synthesis.[2][30] Lithium interferes with thyroid hormone synthesis and release.[1] The hypothyroidism is usually reversible upon discontinuation of the offending drugs.[19]
Use of this content is subject to our disclaimer