Overactive thyroid (hyperthyroidism)

Introduction
Hyperthyroidism refers to the clinical state resulting from excessive circulating thyroid hormones, leading to an increased metabolic rate and hyperactivity of multiple organ systems. It is most commonly caused by Graves’ disease, but can also occur due to toxic multinodular goiter, toxic adenoma, thyroiditis, or excessive thyroid hormone intake.

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Epidemiology

• More common in women (female:male ratio ~5–10:1).

• Peak incidence: 20–50 years for Graves’ disease; older age groups for toxic multinodular goiter.

• Worldwide prevalence varies by iodine intake—Graves’ disease predominates in iodine-sufficient areas, while nodular disease is more common in iodine-deficient regions.

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Causes

1. Primary Hyperthyroidism (thyroid overproduction)

   • Graves’ disease (autoimmune; most common).

   • Toxic multinodular goiter.

   • Toxic adenoma (Plummer’s disease).

   • Functioning thyroid carcinoma metastases (rare).

   • Excessive iodine exposure (Jod-Basedow phenomenon).

2. Secondary Hyperthyroidism (TSH-mediated)

   • TSH-secreting pituitary adenoma (rare).

3. Thyroiditis (transient hyperthyroidism due to hormone leakage)

   • Subacute (de Quervain’s) thyroiditis.

   • Painless (silent) thyroiditis, postpartum thyroiditis.

4. Exogenous

   • Excess levothyroxine intake.

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Pathophysiology
Excess thyroid hormones (T3, T4) increase basal metabolic rate and potentiate catecholamine action via increased β-adrenergic receptor sensitivity. In Graves’ disease, thyroid-stimulating immunoglobulins (TSI) bind to and activate TSH receptors, causing diffuse thyroid hyperplasia and increased hormone synthesis.

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Clinical Features

General

• Weight loss despite normal/increased appetite.

• Heat intolerance, sweating.

• Fatigue, muscle weakness (proximal myopathy).

Cardiovascular

• Palpitations, tachycardia, atrial fibrillation.

• Widened pulse pressure.

Neuropsychiatric

• Anxiety, irritability, tremor (fine).

• Hyperreflexia.

Gastrointestinal

• Increased bowel frequency or diarrhea.

Reproductive

• Oligomenorrhea, amenorrhea.

• Reduced fertility.

Skin and Hair

• Warm, moist skin.

• Hair thinning.

Graves’-specific signs

• Diffuse goiter with bruit.

• Ophthalmopathy: Proptosis, periorbital edema, diplopia.

• Dermopathy: Pretibial myxedema (rare).

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Complications

• Thyroid storm: Life-threatening hyperthyroid crisis with fever, delirium, tachyarrhythmia, and multi-organ dysfunction.

• Osteoporosis, muscle wasting.

• Cardiovascular complications: Heart failure, arrhythmias.

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Diagnosis

Laboratory

• Suppressed TSH (primary hyperthyroidism).

• Elevated free T4 and/or total/free T3.

• TSH-receptor antibodies (TRAb) positive in Graves’ disease.

Imaging

• Radioactive iodine uptake (RAIU) scan:

  • Diffuse increased uptake → Graves’.

  • Focal increased uptake → toxic adenoma.

  • Patchy uptake → toxic multinodular goiter.

  • Low uptake → thyroiditis, exogenous hormone.

• Thyroid ultrasound: Useful for nodules; not primary in diagnosis of diffuse disease.

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Management
Choice of treatment depends on cause, age, severity, comorbidities, and patient preference.

1. Symptomatic Control

• Beta-blockers (reduce adrenergic symptoms):

  • Propranolol: 10–40 mg orally three to four times daily.

  • Atenolol: 25–50 mg orally once or twice daily.

  • Metoprolol: 25–50 mg orally twice daily.

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2. Antithyroid Drugs (reduce thyroid hormone synthesis)

• Methimazole (MMI):

  • Initial: 10–30 mg orally daily; maintenance 5–10 mg daily.

  • Preferred except in first trimester of pregnancy or thyroid storm.

• Propylthiouracil (PTU):

  • Initial: 100–150 mg orally three times daily; maintenance 50 mg two or three times daily.

  • Preferred in first trimester of pregnancy and in thyroid storm (also inhibits peripheral conversion of T4 to T3).

• Monitor: CBC (risk of agranulocytosis), LFTs.

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3. Radioactive Iodine (RAI) Ablation

• Oral iodine-131, taken up by thyroid, causes gradual gland destruction.

• Indicated in Graves’, toxic nodular disease (non-pregnant adults).

• Side effect: Permanent hypothyroidism requiring lifelong levothyroxine.

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4. Surgery (Thyroidectomy)

• Indications: Large goiter, suspicion of malignancy, compressive symptoms, recurrence, pregnancy intolerance to drugs, patient preference.

• Preoperative preparation: Antithyroid drugs to achieve euthyroid state; potassium iodide 5–7 drops orally twice daily for 10–14 days pre-op to reduce vascularity.

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5. Management of Specific Causes

• Graves’ ophthalmopathy:

  • Smoking cessation.

  • Mild: Artificial tears, selenium supplementation (100 mcg twice daily).

  • Severe: Glucocorticoids, orbital radiotherapy, or surgery.

• Thyroiditis: Supportive care ± beta-blockers; antithyroid drugs not effective (low uptake).

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6. Thyroid Storm (Emergency)

• High-dose propylthiouracil: 500–1,000 mg loading dose, then 250 mg every 4 hours.

• 1 hour later: Iodine solution (e.g., Lugol’s iodine 8 drops orally every 6–8 hours).

• Beta-blocker (e.g., propranolol 60–80 mg orally every 4 hours or IV equivalent).

• Glucocorticoids (e.g., hydrocortisone 100 mg IV every 8 hours).

• Supportive measures: Cooling, IV fluids, electrolyte correction, treat underlying cause.

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Prognosis

• With appropriate treatment, prognosis is excellent.

• Untreated hyperthyroidism can cause cardiovascular, bone, and muscular complications.

• Lifelong follow-up is needed, as treatment often results in hypothyroidism or recurrence.