What are the primary causes of hypothyroidism in adult women?

Causes of Hypothyroidism in Adult Women

Chronic autoimmune thyroiditis (Hashimoto's disease) is the most common cause of hypothyroidism in adult women in the United States and other iodine-sufficient areas, accounting for approximately 85-90% of cases. 1, 2, 3

Primary Causes in Iodine-Sufficient Regions

Autoimmune Thyroid Disease

• Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is responsible for the vast majority of hypothyroidism cases in industrialized nations where dietary iodine is adequate 1, 4, 2
• This condition predominantly affects women aged 20-60 years, with nearly 10% showing overt hypothyroidism at diagnosis 3
• The prevalence increases with age, as euthyroid patients with Hashimoto's progressively develop hypothyroidism over time 3
• Thyroid stimulation blocking antibodies (TSBAb) may induce primary atrophic hypothyroidism by blocking TSH-induced thyroid function 3

Iatrogenic Causes

• Radioactive iodine therapy for hyperthyroidism or thyroid cancer leads to permanent hypothyroidism 1, 5
• Thyroidectomy (surgical removal of thyroid tissue) results in hypothyroidism requiring lifelong replacement 1, 5
• External-beam radiation to the head and neck area damages thyroid tissue 1
• Ablation therapy for previous hyperthyroidism commonly causes iatrogenic thyroid dysfunction 1

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, 6
• Tyrosine kinase inhibitors used for neoplastic diseases may induce hypothyroidism 5

Postpartum and Transient Causes

Postpartum Thyroiditis

• Postpartum thyroid dysfunction occurs in 2-4% of women at 3-8 months after delivery, though more than 90% of these cases are transient 3
• Maternal TSBAb can cause transient neonatal hypothyroidism when antibody activity exceeds 1500 IU/L 3

Subacute Thyroiditis

• Subacute thyroiditis causes temporary hypothyroidism following an initial thyrotoxic phase 1, 3
• Silent thyroiditis (pregnancy-unrelated) frequently presents with transient hypothyroidism in the post-thyrotoxic phase 3

Worldwide Leading Cause

Iodine Deficiency

• Iodine deficiency remains the most common cause of hypothyroidism worldwide, particularly in developing nations 1, 4, 2
• Salt iodination programs in many countries may paradoxically increase the incidence of overt hypothyroidism in previously iodine-deficient populations 5
• Maternal hypothyroidism from iodine deficiency increases risk of congenital cretinism with growth failure, mental retardation, and neuropsychologic defects 1

Risk Factors Specific to Women

Demographic and Genetic Factors

• Female sex is the strongest risk factor, with hypothyroidism being significantly more common in women than men 1, 4
• Advancing age increases risk, with prevalence rising substantially in elderly populations 1
• Family history of thyroid disease confers increased risk 1

Associated Autoimmune Conditions

• Type 1 diabetes increases risk of autoimmune thyroid disease 1
• Women with one autoimmune condition have higher likelihood of developing Hashimoto's thyroiditis 3

Pregnancy-Related Factors

• Pregnancy in the setting of underlying autoimmune thyroid disease increases risk of developing overt hypothyroidism 2
• Pre-existing thyroid antibodies predict higher risk of postpartum thyroid dysfunction 3

Less Common Causes

Central (Secondary) Hypothyroidism

• Hypothalamic dysfunction causing inadequate TRH production accounts for a small fraction of cases 1, 5
• Pituitary disease resulting in insufficient TSH secretion is rare but important to identify 7, 5
• Central hypothyroidism requires evaluation of other pituitary hormones, especially the hypothalamic-pituitary-adrenal axis 7

Other Structural Causes

• Goiter may be associated with hypothyroidism development 1
• Down syndrome increases risk of thyroid dysfunction 1

Critical Clinical Considerations

• In areas with adequate iodine intake, Hashimoto's disease accounts for up to 85% of primary hypothyroidism in adult women, making it the overwhelming predominant cause 2
• The female-to-male ratio for hypothyroidism is substantial, with clinical hypothyroidism occurring in 0.5-1.9% of women versus <1% of men 5
• Subclinical hypothyroidism (elevated TSH with normal free T4) affects 3-13.6% of women compared to only 0.7-5.7% of men 5
• Approximately 2-5% of subclinical hypothyroidism cases progress to overt hypothyroidism annually, with higher progression rates in those with positive anti-TPO antibodies (4.3% per year) 7, 3