Regarding the etiology and pathophysiology of hypothyroidism, all of the following are true EXCEPT:

Explanation

## Etiology and Pathophysiology of Hypothyroidism ### Causes of Hypothyroidism **High-Yield:** Hypothyroidism is classified as primary (thyroid failure), secondary (pituitary/TSH deficiency), or tertiary (hypothalamic/TRH deficiency). Primary hypothyroidism accounts for >95% of cases. | Cause | Prevalence | Mechanism | Notes | | --- | --- | --- | --- | | **Hashimoto thyroiditis** | Most common (iodine-sufficient regions) | Autoimmune destruction | TPO and thyroglobulin antibodies | | **Iodine deficiency** | Most common worldwide | Insufficient substrate for T4/T3 synthesis | Leading preventable cause globally | | **Post-thyroidectomy/RAI** | Common iatrogenic | Tissue destruction/removal | Often permanent | | **Medications** | Lithium, amiodarone, interferon-α | Various mechanisms | Reversible in most cases | | **Central hypothyroidism** | Rare | Pituitary/hypothalamic failure | Low TSH + low T4 | **Key Point:** The three most common causes in iodine-sufficient regions are (1) Hashimoto thyroiditis, (2) post-thyroidectomy, and (3) radioactive iodine therapy. ### Autoimmune Hypothyroidism: The Critical Distinction **Warning:** Do NOT confuse the antibodies in Hashimoto thyroiditis with those in Graves disease. | Feature | Hashimoto (Hypothyroidism) | Graves (Hyperthyroidism) | | --- | --- | --- | | **Primary antibody** | Anti-TPO, anti-thyroglobulin | **TSH receptor-stimulating antibodies** (TSI) | | **Mechanism** | Cytotoxic T-cell destruction; antibody-mediated inflammation | TSH receptor activation → excess T4/T3 | | **TSH receptor antibodies** | **TSH receptor-blocking antibodies** (rare, cause hypothyroidism) | TSH receptor-stimulating antibodies (TSI) | | **Clinical result** | Thyroid failure → ↑ TSH, ↓ T4 | Thyroid hyperactivity → ↓ TSH, ↑ T4 | **Mnemonic:** **HASH** = **H**ashimoto = **A**nti-TPO/**A**nti-thyroglobulin, **S**timulating antibodies in **G**raves (not Hashimoto). ### The Incorrect Statement **High-Yield:** In Hashimoto thyroiditis (the most common autoimmune cause of hypothyroidism), the primary pathogenic antibodies are **anti-TPO (thyroid peroxidase) and anti-thyroglobulin**, which cause cytotoxic destruction. TSH receptor-blocking antibodies are rare and are NOT the primary mechanism in autoimmune hypothyroidism. TSH receptor-*stimulating* antibodies (TSI) are characteristic of Graves disease (hyperthyroidism), not Hashimoto hypothyroidism. **Clinical Pearl:** TSH receptor-blocking antibodies can cause transient hypothyroidism in neonates born to mothers with Graves disease (due to passive transfer of maternal TSI), but they are not the primary mechanism in adult autoimmune hypothyroidism. [cite:Harrison 21e Ch 376; Robbins 10e Ch 24]