What are the primary causes of hypothyroidism (underactive thyroid gland)?

From the Guidelines

The primary cause of hypothyroidism is chronic autoimmune (Hashimoto) thyroiditis, which is the most common cause in the United States. This condition is characterized by the immune system's attack on the thyroid gland, leading to a gradual destruction of its ability to produce thyroid hormones [1].

Key Causes of Hypothyroidism

• Chronic autoimmune (Hashimoto) thyroiditis: the most common cause in the United States [1]
• Iatrogenic factors: such as thyroid surgery, radioactive iodine treatment for hyperthyroidism, and certain medications
• Iodine deficiency: the most common cause worldwide, particularly in developing regions with inadequate dietary iodine
• Congenital hypothyroidism: occurs when babies are born without a properly functioning thyroid gland
• Pituitary or hypothalamic disorders (central hypothyroidism): where the problem lies in the glands that signal the thyroid to produce hormones
• Transient hypothyroidism: can occur during pregnancy or with certain viral infections
• Radiation therapy to the neck area for cancer treatment: can damage the thyroid gland These causes lead to insufficient production of thyroid hormones, which are essential for regulating metabolism, energy production, and numerous bodily functions. Risk factors for hypothyroidism include female sex, advancing age, white race, type 1 diabetes, Down syndrome, family history of thyroid disease, goiter, previous hyperthyroidism, and external-beam radiation in the head and neck area [1].

From the FDA Drug Label

Thyroid hormone drugs are indicated: As replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis This category includes cretinism, myxedema and ordinary hypothyroidism in patients of any age (pediatric patients, adults, the elderly), or state (including pregnancy); primary hypothyroidism resulting from functional deficiency, primary atrophy, partial or total absence of thyroid gland, or the effects of surgery, radiation, or drugs, with or without the presence of goiter; and secondary (pituitary) or tertiary (hypothalamic) hypothyroidism The primary causes of hypothyroidism include:

• Primary atrophy
• Partial or total absence of thyroid gland
• Effects of surgery
• Effects of radiation
• Effects of drugs
• Functional deficiency
• Secondary (pituitary) hypothyroidism
• Tertiary (hypothalamic) hypothyroidism 2

From the Research

Primary Causes of Hypothyroidism

The primary causes of hypothyroidism include:

• Chronic autoimmune thyroiditis (Hashimoto's thyroiditis) 3, 4, 5
• Drugs such as amiodarone, lithium, and immune checkpoint inhibitors 3
• Radioactive-iodine treatment 3
• Thyroid surgery 3
• Severe iodine deficiency (historically) 3
• Hashimoto's disease (autoimmune thyroiditis) 6, 5

Autoimmune Thyroiditis

Autoimmune thyroiditis (AIT) is characterized by:

• Lymphocytic infiltration of the thyroid gland with subsequent gradual destruction and fibrous replacement of thyroid tissue 4
• Genetic predisposition, epigenetic modifications, and environmental factors as suspected disease triggers 4
• Presence of antibodies against thyroid-specific antigens, primarily anti-thyroid peroxidase antibodies 4

Hashimoto Thyroiditis

Hashimoto thyroiditis (HT) is a common autoimmune disorder that:

• Affects women 7-10 times more often than men 5
• Develops due to genetic susceptibility, X-chromosome inactivation patterns modulated by environmental factors, and microbiome composition 5
• Leads to an imbalance in self-tolerance mechanisms and consequential thyroid infiltration by lymphocytes 5