Hyperthyroidism

Key Features

Essentials of Diagnosis

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

• Tachycardia; warm, moist skin; stare; tremor

• Graves disease

  • Most common cause of hyperthyroidism

  • Most patients 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) and alemtuzumab (for multiple sclerosis)

    • 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

    • Diagnosed when serum TSH levels are suppressed and serum T₃ or FT₃ levels are high or high-normal

    • Categorized as type 1, type 2, or mixed (27%)

    • Type 1 is caused by the active production of excessive thyroid hormone

    • Type 2 is caused by thyroiditis with the passive release of stored thyroid hormone

  • 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, ...