A 52-year-old woman from rural Maharashtra presents with a 6-month history of progressive fatigue, weight gain, cold intolerance, and constipation. She also reports a family history of autoimmune thyroid disease. On examination, she has a firm, diffusely enlarged thyroid gland with a bumpy surface. Serum TSH is 18 mIU/L (normal 0.4–4.0), free T4 is 0.5 ng/dL (normal 0.8–1.8), and anti-TPO antibodies are 850 IU/mL (normal <35). Fine needle aspiration cytology shows dense lymphocytic infiltration with Hürthle cells and germinal centers. What is the most likely diagnosis?

Explanation

## Clinical Diagnosis: Hashimoto Thyroiditis (Chronic Lymphocytic Thyroiditis) ### Key Clinical Features **Key Point:** Hashimoto thyroiditis is the most common cause of hypothyroidism in iodine-sufficient regions and presents with: 1. **Insidious onset** of hypothyroid symptoms (fatigue, weight gain, cold intolerance, constipation) 2. **Firm, diffusely enlarged thyroid** with bumpy surface (due to lymphocytic infiltration) 3. **Positive anti-TPO and anti-thyroglobulin antibodies** 4. **Female predominance** (10:1 female-to-male ratio) 5. **Family history** of autoimmune thyroid disease ### Laboratory & Pathological Findings | Feature | Hashimoto | De Quervain | Riedel | IDD Goiter | |---------|-----------|-------------|--------|------------| | **Onset** | Insidious (months–years) | Acute (days–weeks) | Insidious | Insidious | | **Neck pain** | Absent | Severe, prominent | Mild/absent | Absent | | **Viral prodrome** | No | Yes (typical) | No | No | | **TSH** | Elevated | Suppressed (early) | Elevated | Normal/low | | **Free T4** | Low | High (early) | Low | Normal/low | | **Anti-TPO** | Positive (>95%) | Negative | Negative | Negative | | **ESR/CRP** | Normal/mild ↑ | Markedly elevated | Markedly elevated | Normal | | **FNAC** | Lymphocytes, Hürthle cells, germinal centers | Granulomas, giant cells | Fibrosis, few cells | Colloid, follicular cells | | **Ultrasound** | Hypoechoic, heterogeneous | Patchy hypoechoic areas | Hard, fibrotic | Nodular, colloid-rich | **High-Yield:** The combination of **positive anti-TPO antibodies** (850 IU/mL, markedly elevated) and **lymphocytic infiltration with Hürthle cells** on FNAC is diagnostic of Hashimoto thyroiditis. ### Pathophysiology ```mermaid flowchart TD A[Genetic predisposition<br/>HLA-DR3, HLA-DR5]:::outcome --> B[Environmental trigger<br/>infection, iodine, drugs] B --> C[Loss of immune tolerance] C --> D[CD8+ T-cell mediated destruction<br/>of thyroid follicles] D --> E[Production of anti-TPO<br/>and anti-thyroglobulin antibodies] E --> F[Lymphocytic infiltration<br/>Germinal centers form] F --> G[Follicular destruction<br/>Fibrosis] G --> H[Hypothyroidism<br/>TSH elevated, T4 low]:::outcome F --> I[FNAC: Lymphocytes,<br/>Hürthle cells]:::outcome ``` ### Histopathology: The Hürthle Cell **Clinical Pearl:** Hürthle cells (also called oncocytes or Askanazy cells) are thyroid follicular cells with abundant mitochondria, giving them a granular, eosinophilic cytoplasm on H&E staining. They are a hallmark of Hashimoto thyroiditis and indicate chronic autoimmune destruction. They are NOT malignant but indicate active autoimmune process. ### Stages of Hashimoto Thyroiditis **Mnemonic:** **LYCH** = **L**ymphocytic infiltration → **Y**ield (loss of) follicles → **C**ollapse of follicles → **H**ypofunction 1. **Stage 1 (Lymphocytic infiltration):** Dense infiltrate of lymphocytes and plasma cells; follicles still functional 2. **Stage 2 (Follicular atrophy):** Loss of follicles, germinal centers prominent, Hürthle cells increase 3. **Stage 3 (Fibrosis):** Replacement of thyroid parenchyma with fibrous tissue; minimal residual follicles ### Why This Case Fits Hashimoto - **Insidious 6-month onset** (not acute like De Quervain) - **Classic hypothyroid symptoms** (fatigue, weight gain, cold intolerance, constipation) - **Firm, diffusely enlarged thyroid** with bumpy surface (lymphocytic infiltration) - **Markedly elevated TSH (18)** and **low free T4 (0.5)** (hypothyroid phase) - **Positive anti-TPO (850)** and **anti-thyroglobulin antibodies** (autoimmune) - **Dense lymphocytic infiltration with Hürthle cells and germinal centers** on FNAC (pathognomonic) - **Female patient** with **family history** of autoimmune thyroid disease - **No viral prodrome** or **neck pain** ### Management **Key Point:** Levothyroxine replacement is the mainstay of treatment. Initial dose is 25–50 μg daily in elderly or cardiac patients, 50–100 μg daily in younger patients. Titrate by 25 μg every 6–8 weeks based on TSH levels. Target TSH is 0.5–2.5 mIU/L in most patients. Selenium and zinc supplementation may have a role in reducing antibody titers, but evidence is limited. **Warning:** Do NOT use antithyroid drugs (PTU, methimazole) in Hashimoto thyroiditis—the hypothyroidism is due to follicular destruction, not hormone overproduction. [cite:Robbins 10e Ch 24]