Correct Answer: C. Hashimoto thyroiditis
Hashimoto thyroiditis is an autoimmune destruction of the thyroid gland characterized by elevated TSH (due to primary hypothyroidism), presence of thyroid peroxidase (TPO) antibodies, and pathognomonic histological findings. The key discriminating feature here is the presence of Hurthle cells (also called Askanazy cells or oncocytes)—these are follicular epithelial cells with abundant mitochondria and eosinophilic cytoplasm, seen in chronic autoimmune thyroiditis. The clinical triad of elevated TSH, TPO antibodies, and Hurthle cells on histology is diagnostic of Hashimoto thyroiditis. This is the most common cause of hypothyroidism in iodine-sufficient regions like urban India. The disease results from T-cell and B-cell mediated autoimmune attack on thyroid peroxidase and thyroglobulin. Histologically, there is lymphocytic infiltration, fibrosis, and the characteristic Hurthle cell metaplasia. TPO antibodies are the most sensitive marker (present in >90% of cases), while thyroglobulin antibodies are less specific. The elevated TSH reflects the thyroid's inability to produce adequate thyroid hormones, triggering compensatory TSH rise from the pituitary.
Why the other options are wrong
A. Follicular carcinoma — While Hurthle cell variant of follicular carcinoma exists and contains oncocytes, it is a malignancy characterized by capsular/vascular invasion and increased mitotic activity—not autoimmune features. Follicular carcinoma presents with a solitary nodule, normal or low TSH, and absence of TPO antibodies. The clinical context (elevated TSH, TPO antibodies) rules out malignancy. This is an NBE trap pairing Hurthle cells with cancer. B. Medullary carcinoma of thyroid — Medullary carcinoma arises from parafollicular C cells and produces calcitonin, not TPO antibodies. It presents with elevated calcitonin levels, often familial (MEN 2A/2B), and lacks the autoimmune serological markers. Histologically, it shows amyloid deposits and neuroendocrine features, not Hurthle cells. The presence of TPO antibodies and elevated TSH (not calcitonin) excludes this diagnosis. D. Graves' disease — Graves' disease is autoimmune hyperthyroidism caused by TSH receptor antibodies (TRAb), presenting with low TSH and elevated free T4/T3. Patients are thyrotoxic, not hypothyroid. While TPO antibodies may coexist in some patients, the elevated TSH indicates primary hypothyroidism, not hyperthyroidism. Graves' disease does not typically show Hurthle cell infiltration on histology.
High-Yield Facts
- Hurthle cells (Askanazy cells) are eosinophilic oncocytes with abundant mitochondria—pathognomonic for chronic autoimmune thyroiditis (Hashimoto).
- TPO antibodies are present in >90% of Hashimoto thyroiditis and are the most sensitive autoimmune marker; thyroglobulin antibodies are less specific.
- Elevated TSH with low/normal free T4 indicates primary hypothyroidism; Hashimoto is the most common cause in iodine-sufficient India.
- Lymphocytic infiltration and fibrosis on histology reflect T-cell and B-cell mediated autoimmune destruction of thyroid follicles.
- Hurthle cell carcinoma (malignant variant) differs from benign Hurthle cell metaplasia in Hashimoto by presence of capsular invasion and increased mitotic activity.
Mnemonics
HASH for Hashimoto Hurthle cells, Antibodies (TPO/Tg), Striking lymphocytic infiltration, Hypothyroidism (elevated TSH). Use this to recall the four pillars of Hashimoto diagnosis. TPO = Thyroid Peroxidase = Most sensitive in Hashimoto When you see 'antibodies' in Hashimoto, think TPO first (>90% sensitivity). Thyroglobulin antibodies are less specific and can appear in other thyroid diseases.
NBE Trap
NBE pairs Hurthle cells with follicular carcinoma to trap students who memorize 'Hurthle cells = cancer' without considering the clinical context (elevated TSH, TPO antibodies, and autoimmune features all point to benign Hashimoto, not malignancy).
Clinical Pearl
In Indian clinical practice, Hashimoto thyroiditis is the leading cause of hypothyroidism in urban populations with adequate iodine intake. A middle-aged woman presenting with thyroid swelling and elevated TSH should prompt immediate TPO antibody testing; if positive with Hurthle cells on biopsy, lifelong levothyroxine replacement is indicated to prevent myxedema and cardiovascular complications.
_Reference: Robbins & Cotran Pathology Ch. 24 (Endocrine System); Harrison's Principles of Internal Medicine Ch. 405 (Thyroid Disorders)_