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Key Features

Essentials of Diagnosis

  • Sweating, weight loss or gain, anxiety, palpitations, loose stools, heat intolerance, fatigue, menstrual irregularity

  • Tachycardia; warm, moist skin; stare; tremor

  • In Graves disease: majority have a palpable goiter (sometimes with bruit); ophthalmopathy

  • Suppressed TSH in primary hyperthyroidism; usually increased T4, FT4, T3, FT3

General Considerations

  • Causes

    • Graves disease (most common)

      • Can be precipitated by chemotherapy with immune checkpoint inhibitors (such as ipilimumab, pembrolizumab, tremelimumab, and atezolizumab)

      • Must be distinguished from hyperthyroidism due to destructive autoimmune thyroiditis (silent thyroiditis) that can be caused by these same medications

    • Autonomous toxic adenomas, single or multiple

    • Jod-Basedow disease, or iodine-induced hyperthyroidism, may occur with multinodular goiters after significant iodine intake, radiographic contrast, or drugs, eg, amiodarone

    • Subacute de Quervain thyroiditis: hyperthyroidism followed by hypothyroidism

    • Autoimmune (Hashimoto) thyroiditis may cause transient hyperthyroidism during initial phase and may occur postpartum

    • Silent thyroiditis

      • Also known as subacute lymphocytic thyroiditis or "hashitoxicosis"

      • Can be caused by chemotherapeutic agents (such as tyrosine kinase inhibitors, denileukin diftitox, alemtuzumab, interferon-alpha, interleukin-2), immune checkpoint inhibitors as well as lithium and amiodarone

    • Amiodarone-induced thyrotoxicosis: can occur quite suddenly at any time during treatment and may even develop several months after it has been discontinued

    • Thyrotoxicosis factitia: excessive exogenous thyroid hormone

    • High serum human chorionic gonadotropin levels in first 4 months of pregnancy, molar pregnancy, choriocarcinoma, and testicular malignancies may cause hyperthyroidism

Clinical Findings

Symptoms and Signs

  • Heat intolerance, sweating

  • Palpitations

  • Pruritus

  • Frequent bowel movements

  • Weight loss (or gain)

  • Menstrual irregularities

  • Nervousness, fine resting tremor

  • Fatigue

  • Muscle weakness, muscle cramps, hyperreflexia

  • Tetany (rare)

  • Thyroid

    • Goiter (often with a bruit) in Graves disease

    • Moderately enlarged, tender thyroid in subacute thyroiditis

  • Eye

    • Upper eyelid retraction

    • Stare and lid lag with downward gaze

    • Thyroid associated ophthalmopathy (exophthalmos) in 20–40% of patients with Graves disease

    • Diplopia may be due to coexistent myasthenia gravis

  • Skin

    • Moist warm skin

    • Fine hair

    • Onycholysis

    • Dermopathy (myxedema) in 3% of patients with Graves disease

  • Heart

    • Palpitations or angina pectoris

    • Arrhythmias

      • Sinus tachycardia

      • Premature atrial contractions

      • Atrial fibrillation or atrial tachycardia (can precipitate heart failure)

    • Thyrotoxic cardiomyopathy due to thyrotoxicosis

  • Thyrotoxic crisis or "storm"

  • Hypokalemic paralysis (Asian or Native-American men)

  • Subclinical hyperthyroidism (suppressed serum TSH with normal FT4) may increase the risk of nonvertebral fractures

  • Clubbing and swelling of the fingers (acropachy) develop rarely

Differential Diagnosis

  • General anxiety, panic disorder, mania

  • Other hypermetabolic state, eg, cancer, pheochromocytoma

  • Exophthalmos due to other cause, eg, orbital tumor

  • Atrial fibrillation due to other cause

  • Acute psychiatric disorders (may falsely increase serum thyroxine)

  • High estrogen states, eg, pregnancy

  • Hypopituitarism

  • Subclinical hyperthyroidism

  • Diabetes mellitus and Addison disease may coexist with thyrotoxicosis and can aggravate the weight loss, fatigue, and muscle weakness seen with hyperthyroidism


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