Statement C is true: Hashimoto's thyroiditis is histologically characterized by marked infiltration of the thyroid with activated T cells and B cells.
Analysis of Each Statement
Statement A: Hashimoto's thyroiditis is the most common cause of hypothyroidism worldwide
This is FALSE. Worldwide, environmental iodine deficiency remains the most common cause of all thyroid disorders, including hypothyroidism 1. However, in areas with adequate iodine intake (iodine-sufficient regions), Hashimoto thyroiditis is indeed the most common cause, accounting for up to 85% of primary hypothyroidism cases 2, 1. The statement fails because it claims "worldwide" prevalence without acknowledging the critical distinction between iodine-deficient and iodine-sufficient populations.
Statement B: The annual risk of developing overt clinical hypothyroidism from subclinical hypothyroidism in patients with positive TPO antibodies is 20%
This is FALSE. The actual annual progression risk is 4.3% per year in patients with positive anti-TPO antibodies, compared to 2.6% per year in antibody-negative individuals 3, 4, 5. The overall progression rate from subclinical to overt hypothyroidism is approximately 2-5% annually 5, with the presence of TPO antibodies increasing this risk but nowhere near the 20% claimed in the statement 3.
Statement C: Histologically, Hashimoto's thyroiditis is characterized by marked infiltration of the thyroid with activated T cells and B cells
This is TRUE. While the provided evidence does not explicitly detail the histological features, this statement accurately describes the pathological hallmark of Hashimoto's thyroiditis as an autoimmune disease 2, 1. The autoimmune nature of the condition inherently involves lymphocytic infiltration with both T and B cells, which is the defining histological characteristic that distinguishes it from other causes of hypothyroidism.
Statement D: A low TSH level excludes the diagnosis of hypothyroidism
This is FALSE. A low TSH level does not exclude hypothyroidism in cases of central (secondary) hypothyroidism, where pituitary or hypothalamic dysfunction results in inadequate TSH production despite low thyroid hormone levels 5, 6. In central hypothyroidism, free T4 is decreased while TSH is normal or even decreased 6. TSH cannot be used as a reliable screening test in patients with suspected pituitary or hypothalamic disease 4. The statement only holds true for primary hypothyroidism, where elevated TSH is the hallmark finding.
Statement E: Thyroid peroxidase antibodies are present in less than 50% of patients with autoimmune hypothyroidism
This is FALSE. The evidence indicates that anti-TPO antibodies are used to confirm autoimmune etiology in hypothyroidism 3, 4, 7, and their presence predicts higher progression risk to overt hypothyroidism 3, 7. While the exact percentage is not explicitly stated in the provided evidence, the widespread use of TPO antibody testing to identify autoimmune thyroiditis and the fact that Hashimoto's accounts for up to 85% of hypothyroidism in iodine-sufficient areas 2 suggests that TPO antibodies are present in the majority of autoimmune hypothyroidism cases, not less than 50%.
Critical Clinical Implications
For screening and diagnosis: TSH remains the primary screening test with 98% sensitivity and 92% specificity 3, 7, but clinicians must remember that low or normal TSH does not exclude central hypothyroidism 4, 6. In patients with pituitary disease or symptoms despite normal TSH, free T4 must be checked alongside TSH 4.
For risk stratification: Patients with positive TPO antibodies have a 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative patients 3, 4, warranting annual monitoring rather than the commonly cited but incorrect 20% risk 7.
For global context: The etiology of hypothyroidism varies dramatically by geographic region—iodine deficiency dominates worldwide, while Hashimoto's predominates only in iodine-sufficient populations 2, 1.