What are the common causes of hypothyroidism?

Common Causes of Hypothyroidism

In iodine-sufficient developed countries, Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common cause of hypothyroidism, accounting for 85-90% of cases, while iodine deficiency remains the leading cause worldwide. 1, 2

Primary Causes in Developed Nations

Autoimmune Disease

• Hashimoto thyroiditis (chronic lymphocytic thyroiditis) is the predominant etiology in areas with adequate dietary iodine supply, responsible for up to 85-90% of hypothyroidism cases 3, 1, 2
• This autoimmune condition predominantly affects women aged 20-60 years, with female sex being the strongest risk factor 1, 4
• The disease involves lymphocytic infiltration (especially T cells) and follicular destruction leading to gradual thyroid atrophy and fibrosis 4
• Approximately 90% of adult hypothyroidism has an autoimmune cause 5

Iatrogenic Causes

• Radioactive iodine (RAI) therapy for hyperthyroidism or thyroid cancer leads to permanent hypothyroidism 1
• Thyroidectomy (surgical removal of thyroid tissue) results in lifelong hypothyroidism requiring replacement therapy 1
• External-beam radiation to the head and neck area damages thyroid tissue and causes hypothyroidism 1
• These three iatrogenic causes, combined with autoimmune disease, account for approximately 90% of all hypothyroidism cases 6

Medication-Induced Hypothyroidism

• Amiodarone (iodine-containing cardiac medication) can induce thyroid dysfunction 1
• Immune checkpoint inhibitors (anti-PD-1/PD-L1 therapy) cause thyroid dysfunction in 5-10% of patients, with combination immunotherapy increasing risk to 20% 1
• Tyrosine kinase inhibitors used for neoplastic diseases may induce hypothyroidism 7

Worldwide Leading Cause

• Iodine deficiency remains the most common cause globally, particularly in developing nations where salt iodination is not routinely performed 1, 6, 2
• Maternal hypothyroidism from iodine deficiency increases risk of congenital cretinism with growth failure, mental retardation, and neuropsychologic defects 1
• Paradoxically, salt iodination programs may actually increase the incidence of overt hypothyroidism in previously iodine-deficient populations 7

Additional Risk Factors and Associations

• Advancing age substantially increases prevalence, with hypothyroidism being more common in elderly populations 1
• Family history of thyroid disease confers increased risk 1
• Type 1 diabetes increases risk of autoimmune thyroid disease 1
• Down syndrome increases risk of thyroid dysfunction 1
• Pregnancy and postpartum period: 2-4% prevalence at 3-8 months postpartum, though more than 90% of these cases are transient 5

Secondary (Central) Hypothyroidism

• Failure of adequate TSH secretion from the pituitary gland or TRH from the hypothalamus accounts for a minority of cases 7
• Post-surgical pituitary or hypothalamic tumor hypothyroidism represents a less common etiology 6

Clinical Pitfall

A critical caveat: Imaging has no role in determining the cause of hypothyroidism. All etiologies—whether Hashimoto thyroiditis, iodine deficiency, post-ablation status, or medication-induced—demonstrate decreased radioiodine uptake and cannot be differentiated by thyroid morphology on ultrasound, CT, MRI, or nuclear medicine studies 3, 8. The diagnosis relies on clinical history and laboratory testing (TSH and free T4), not imaging 8.