Section 9.2: Thyroid Disorders & Goiter
Key Takeaways
- Graves' disease hyperthyroidism is caused by thyroid-stimulating immunoglobulins (TSI) and is characterized by a diffuse, high uptake scan and Graves-specific eye and skin signs.
- Hashimoto's thyroiditis is the primary cause of hypothyroidism, presenting with anti-TPO antibodies and managed with Levothyroxine, starting at a lower dose in the elderly/CAD patients.
- Subacute (de Quervain's) thyroiditis is a painful post-viral condition showing high ESR and near-zero uptake on a thyroid scan, treated symptomatically with NSAIDs or steroids.
- In thyroid storm, thionamides must be administered at least one hour before iodine to prevent iodine from being used as a substrate for new thyroid hormone synthesis.
Thyroid Disorders & Goiter (Hyperthyroidism, Hypothyroidism, Thyroiditis)
PANCE High-Yield Focus: Thyroid pathology is a high-yield topic on the PANCE. Master the interpretation of thyroid function tests, the differentiation between Graves' disease (elevated TSI), Hashimoto's thyroiditis (elevated anti-TPO), and subacute thyroiditis (painful goiter, low RAIU). Understand the selection and contraindications of antithyroid medications and levothyroxine dosing rules.
Graves' Disease & Hyperthyroidism
Pathophysiology and Etiology
Hyperthyroidism is characterized by excessive synthesis and secretion of thyroid hormones (T4 and T3). Graves' disease is the most common cause of hyperthyroidism (accounting for 60–80% of cases) and is an autoimmune disorder. It is caused by thyroid-stimulating immunoglobulins (TSI), also called TSH receptor antibodies, which bind to and chronically activate the TSH receptors on thyroid follicular cells, leading to diffuse gland hypertrophy and unregulated hormone release.
Clinical Presentation
Symptoms of hyperthyroidism reflect a hypermetabolic state: weight loss despite increased appetite, heat intolerance, palpitations, tachycardia, anxiety, hyperreflexia, a fine hand tremor, and warm, moist skin.
- Graves'-Specific Signs: Exophthalmos (proptosis, lid lag, and diplopia caused by retroorbital accumulation of glycosaminoglycans and fibroblast activation) and pretibial myxedema (non-pitting, erythematous infiltrative dermopathy on the anterior lower legs). A diffuse, non-tender goiter with a thyroid bruit is also classic.
Diagnostics
- Primary Thyroid Function Tests: Low TSH (suppressed due to negative feedback) and high Free T4 and Free T3.
- Antibodies: Elevated thyroid-stimulating immunoglobulins (TSI) are pathognomonic.
- Radioactive Iodine Uptake (RAIU) Scan: Demonstrates diffuse, homogeneous high uptake throughout the gland.
Management
- Symptomatic Relief: Beta-blockers (e.g., Propranolol) are initiated immediately to control sympathetic hyperactivity (tachycardia, tremor). Propranolol also inhibits the peripheral conversion of T4 to active T3.
- Antithyroid Drugs (Thionamides):
- Methimazole: First-line agent for most patients because of its longer half-life and lower risk of hepatotoxicity.
- Propylthiouracil (PTU): Preferred in the first trimester of pregnancy (due to Methimazole's association with embryopathy) and in thyroid storm.
- Side Effects: Both drugs can cause hepatotoxicity and agranulocytosis. Patients must be warned to immediately seek care and obtain a CBC if they develop a fever or sore throat.
- Radioactive Iodine Ablation (RAI): The most common definitive treatment. It is contraindicated in pregnancy and may worsen active Graves' ophthalmopathy.
- Thyroidectomy: Indicated for large obstructive goiters, pregnancy where medical therapy fails, or suspected malignancy.
Hashimoto's Thyroiditis & Hypothyroidism
Pathophysiology and Etiology
Hypothyroidism represents a deficiency of thyroid hormones. Hashimoto's thyroiditis (chronic autoimmune thyroiditis) is the most common cause in iodine-sufficient areas. It is caused by autoimmune-mediated destruction of thyroid follicular cells. The key antibodies are anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg). Histology shows marked lymphocytic infiltration and Hürthle cells.
Clinical Presentation
Symptoms reflect a generalized slowing of metabolism: fatigue, weight gain despite poor appetite, cold intolerance, constipation, bradycardia, dry skin, thinning hair, menorrhagia, and non-pitting edema (myxedema). Reflexes show delayed relaxation (Woltman's sign). Goiter is often present early in the disease, which is firm, bosselated, and non-tender.
Diagnostics
- Primary Thyroid Function Tests: High TSH and low Free T4.
- Antibodies: High titers of anti-TPO antibodies.
Management
- First-line Treatment: Levothyroxine (synthetic T4).
- Clinical Prescribing Rules:
- In young, healthy adults: Start at a full replacement dose of ~1.6 mcg/kg/day.
- In elderly patients or those with coronary artery disease: Start at a very low dose (12.5 to 25 mcg/day) and titrate slowly. Sudden increases in thyroid hormone can precipitate angina, cardiac arrhythmias, or myocardial infarction.
- Monitor TSH levels every 6–8 weeks after initiation or dose adjustments.
Subacute Thyroiditis & Other Forms
Subacute Granulomatous (de Quervain's) Thyroiditis
- Pathophysiology: A transient, self-limiting inflammatory disorder of the thyroid gland, typically preceding a viral upper respiratory infection. Giant cells and granulomatous inflammation lead to the rapid destruction of follicles and leakage of preformed thyroid hormones.
- Presentation: Characterized by a highly painful, tender goiter radiating to the jaw or ears, accompanied by fever and transient hyperthyroid symptoms.
- Clinical Course: Triphasic: 1. Hyperthyroid phase (lasting 2–8 weeks), 2. Transient hypothyroid phase (lasting 2–8 weeks), 3. Euthyroid resolution.
- Diagnostics: Low TSH, elevated Free T4/T3. Erythrocyte Sedimentation Rate (ESR) is markedly elevated (often > 50 or 100 mm/hr). RAIU scan shows very low or absent uptake due to follicular cell damage.
- Management: Symptomatic. Mild cases are treated with high-dose Aspirin or NSAIDs. Severe pain is managed with a tapering course of Prednisone. Beta-blockers are used for hyperthyroid symptoms. Antithyroid drugs (Methimazole/PTU) are ineffective because there is no excess hormone synthesis, only leakage.
Diagnostic Comparison of Thyroiditis & Goiter
| Condition | Thyroid Pain | Serum TSH | RAIU Scan Pattern | Key Laboratory Findings | First-line Treatment |
|---|---|---|---|---|---|
| Graves' Disease | None | Suppressed (Low) | Diffuse, High Uptake | Positive TSI antibodies | Methimazole (PTU in 1st trimester) |
| Hashimoto's | None | Elevated (High) | Variable / Patchy | Positive anti-TPO antibodies | Levothyroxine |
| Subacute (de Quervain's) | Severe (Painful) | Suppressed (Low) | Very Low (< 1%) | Markedly elevated ESR/CRP | High-dose NSAIDs or Prednisone |
| Silent Thyroiditis | None | Suppressed (Low) | Very Low (< 1%) | Positive anti-TPO (autoimmune) | Beta-blocker (symptomatic only) |
Classic PANCE Traps & Clinical Pearls
- Painful Goiter: A painful, tender thyroid gland is the hallmark of subacute thyroiditis. Contrast this with Hashimoto's or Graves', which are painless.
- Agranulocytosis warning: Always monitor for fever and sore throat in patients starting Methimazole or PTU. Obtain a CBC immediately.
- Levothyroxine Dosing: Starting a high dose of Levothyroxine in an elderly patient is a major PANCE trap; it can precipitate acute coronary syndrome. Start low and go slow.
- Thyroid Storm Sequencing: In thyroid storm, remember that Iodine must be given at least one hour AFTER a thionamide (PTU). Giving iodine first allows the gland to use it to synthesize more thyroid hormone, worsening the crisis.
A 28-year-old female presents with a 2-month history of palpitations, weight loss, and heat intolerance. Physical examination reveals a diffuse, non-tender goiter and mild proptosis. Serum TSH is less than 0.01 uIU/mL and free T4 is 2.8 ng/dL. Which of the following laboratory findings is most specific for confirming the diagnosis of this patient's condition?
A 72-year-old female with a history of coronary artery disease and prior myocardial infarction is diagnosed with primary hypothyroidism. Her serum TSH is 18 uIU/mL. Which of the following is the most appropriate initial dosing strategy for Levothyroxine in this patient?
A 35-year-old male presents with severe anterior neck pain radiating to his left ear, accompanied by low-grade fever and palpitations for the past three days. He reports having a mild upper respiratory infection two weeks ago. Physical examination reveals an extremely tender, firm thyroid gland. Labs demonstrate low TSH, elevated free T4, and an erythrocyte sedimentation rate (ESR) of 82 mm/hr. A radioactive iodine uptake (RAIU) scan is performed. Which of the following RAIU scan findings is most likely?