Hyperthyroidism is a clinical syndrome resulting from excessive production and release of thyroid hormones (thyroxine, T4, and triiodothyronine, T3) by the thyroid gland, leading to a hypermetabolic state known as thyrotoxicosis.
Pathophysiology
- Excess thyroid hormones increase basal metabolic rate, causing heightened oxygen consumption and heat production.
- When caloric intake does not match increased metabolic demand, catabolism of fat and protein leads to weight loss.
- Muscle protein breakdown causes muscle weakness despite hyperactivity and fine tremors due to increased beta-adrenergic receptor sensitivity.
- Peripheral vasodilation facilitates heat dissipation, resulting in heat intolerance and sweating.
- Cardiovascular effects include increased heart rate, stroke volume, and cardiac output, partly due to heightened sensitivity of cardiac tissue to catecholamines.
Causes of Hyperthyroidism
- Graves' Disease (Diffuse Toxic Goiter):
- Autoimmune disease with thyroid-stimulating immunoglobulins that activate TSH receptors, causing diffuse thyroid hyperplasia and hormone overproduction.
- Toxic Adenoma ("Hot Nodule"):
- Autonomous functioning thyroid nodule producing excess hormone independent of TSH regulation.
- Toxic Multinodular Goiter (Plummer’s Disease):
- Multiple autonomously functioning nodules cause sustained hormone overproduction.
- Subacute Thyroiditis:
- Viral or postpartum inflammation causes transient release of preformed thyroid hormone, usually self-limiting.
- Drug-Induced Hyperthyroidism:
- Amiodarone (iodine-rich antiarrhythmic) can cause thyrotoxicosis by excess iodine or destructive thyroiditis.
- Iodine contrast exposure can precipitate hyperthyroidism in patients with preexisting nodular thyroid disease.
Clinical Features
- Nervousness, irritability, anxiety
- Heat intolerance, increased sweating
- Weight loss despite increased appetite
- Palpitations, tachycardia, atrial fibrillation (especially in elderly)
- Tremors (fine, distal)
- Muscle weakness (proximal)
- Warm, moist skin
- Lid lag and stare (due to sympathetic overactivity)
- Systolic hypertension with widened pulse pressure
- Oligomenorrhea or amenorrhea
- Diarrhea, hyperdefecation
Diagnostic Workup
- Thyroid Function Tests:
- Suppressed TSH (most sensitive marker)
- Elevated free T4 and free T3 (may see T3 toxicosis if T3 elevated with normal T4)
- Autoantibodies:
- TSH receptor antibodies (TRAb) for Graves’ disease
- Anti-thyroid peroxidase (anti-TPO) antibodies (can be elevated)
- Imaging:
- Thyroid ultrasound to evaluate nodules or goiter
- Radioactive iodine uptake scan to differentiate causes (diffuse high uptake in Graves, focal in toxic adenoma, patchy in multinodular goiter)
Management
Supportive Therapy
- Beta-blockers (e.g., propranolol) for symptom control of tachycardia, tremors, anxiety.
- Adequate hydration and nutrition.
Antithyroid Medications
- Methimazole: Preferred due to potency and longer half-life.
- Propylthiouracil (PTU): Reserved for first trimester pregnancy, thyroid storm, or methimazole intolerance.
- Titrate doses every 4-6 weeks based on thyroid function tests.
- Treatment duration often 12-18 months; remission rates vary.
Definitive Therapy
- Radioactive Iodine (RAI) Therapy:
- Oral administration causes gradual thyroid tissue destruction.
- Contraindicated in pregnancy, lactation, young children, and severe ophthalmopathy.
- May result in hypothyroidism requiring lifelong levothyroxine replacement.
- Surgery (Thyroidectomy):
- Indicated in large goiters causing compressive symptoms, severe ophthalmopathy, pregnancy intolerance, or patient preference.
- Requires careful perioperative management.
Special Considerations
- Ophthalmopathy:
- Mild: Supportive care with lubricants, sunglasses.
- Severe (vision-threatening): High-dose corticosteroids, orbital decompression, radiotherapy
