What are the possible causes of thyroid issues?

Causes of Thyroid Issues

Primary Causes of Hypothyroidism

Hashimoto thyroiditis (chronic autoimmune thyroiditis) is the most common cause of hypothyroidism in areas with adequate dietary iodine, accounting for up to 85% of cases. 1, 2, 3, 4

Autoimmune Causes

• Hashimoto's thyroiditis represents the leading etiology in iodine-sufficient populations, characterized by lymphocytic infiltration, follicular destruction, gradual thyroid atrophy, and fibrosis 1, 4
• Atrophic thyroiditis causes thyroid gland shrinkage with replacement by connective tissue on a background of chronic inflammation 5
• Autoimmune thyroid disease is present in up to one-third of patients with other autoimmune conditions 5

Iatrogenic Causes

• Thyroidectomy (surgical removal of thyroid tissue) 1
• Radioiodine therapy for hyperthyroidism or thyroid cancer 1
• External neck irradiation for head and neck cancers 1

Drug-Induced Causes

• Amiodarone causes thyroid dysfunction through multiple mechanisms: it inhibits peripheral conversion of T4 to T3, releases large amounts of inorganic iodine, and can cause either hypothyroidism (2-10% of patients) or hyperthyroidism (approximately 2% of patients) 6, 7, 3
• Immune checkpoint inhibitors (anti-PD-1/PD-L1 therapy) cause thyroid dysfunction in 5-10% of patients on monotherapy and 20% with combination immunotherapy 8
• Lithium can induce thyroid dysfunction 7, 3
• Interferon-alfa and interleukin-2 are associated with drug-induced thyroiditis 7

Nutritional Causes

• Iodine deficiency remains the most common cause of hypothyroidism worldwide in areas with inadequate dietary iodine 1, 2, 9
• Iodine excess can paradoxically cause hypothyroidism in susceptible individuals 1

Primary Causes of Hyperthyroidism (Thyrotoxicosis)

The most common causes of thyrotoxicosis are Graves disease, toxic adenoma, toxic multinodular goiter, and subacute thyroiditis. 1

Autoimmune and Nodular Causes

• Graves disease is diagnosed by TSH receptor antibodies and represents the most frequent cause of hyperthyroidism 1
• Toxic adenoma (single autonomously functioning thyroid nodule) 1
• Toxic multinodular goiter (multiple autonomously functioning nodules) 1

Inflammatory Causes

• Subacute granulomatous thyroiditis causes painful thyroid inflammation with transient hyperthyroidism 1, 7
• Subacute lymphocytic thyroiditis (painless thyroiditis) 1, 7
• Postpartum thyroiditis occurs in women after delivery 7

Drug-Induced Hyperthyroidism

• Amiodarone-induced thyrotoxicosis occurs in approximately 2% of patients (higher in areas with prior inadequate iodine intake), presenting as either Type I (iodine-induced hyperthyroidism with enlarged/nodular gland) or Type II (destructive thyroiditis with normal/small gland) 1, 6

Rare Causes

• Trophoblastic disease 1
• Thyroid hormone resistance 1
• Iatrogenic thyrotoxicosis (excessive thyroid hormone administration) 1
• Factitious ingestion of thyroid hormone 1
• Struma ovarii (ectopic thyroid tissue in ovarian teratoma) 1

Risk Factors for Developing Thyroid Dysfunction

Genetic Factors

• Having a first-degree relative with hypothyroidism increases risk 2
• Genetic susceptibility combined with environmental factors causes loss of immunological tolerance in Hashimoto's thyroiditis 4

Demographic Factors

• Female sex - thyroid disorders are more common in women 2, 9
• Older age - prevalence increases with advancing years 2, 9
• Pregnancy in the setting of underlying autoimmune thyroid disease increases risk 2

Medical History

• History of thyroid nodules or goiter 6
• Previous thyroid dysfunction 6
• Type 1 diabetes and other autoimmune conditions 5, 2
• Autoimmune gastritis - screening for thyroid disease is recommended 5

Environmental Factors

• Iodine deficiency in the diet 2, 9
• Radiation exposure to the neck 7, 9
• Trauma to the thyroid gland 7

Critical Clinical Considerations

Thyroid function should be monitored prior to treatment with amiodarone and periodically thereafter, particularly in elderly patients and those with a history of thyroid nodules, goiter, or other thyroid dysfunction. 6

Amiodarone-induced hyperthyroidism poses a greater hazard than hypothyroidism due to the possibility of thyrotoxicosis, arrhythmia breakthrough or aggravation, all of which may result in death. 6

Because of amiodarone's slow elimination, high plasma iodide levels, altered thyroid function, and abnormal thyroid function tests may persist for several weeks or even months following withdrawal. 6