Definition of Hyperthyroidism
Hyperthyroidism is overactivity of the thyroid gland resulting in overproduction of thyroid hormone and increased metabolic rate. 1
Biochemical Definition
Hyperthyroidism exists on a spectrum of thyroid dysfunction, defined by specific laboratory parameters:
Overt Hyperthyroidism
- Low or undetectable TSH level (typically <0.1 mIU/L) combined with elevated free T4 and/or T3 levels 1
- Affects approximately 0.2% to 1.4% of people worldwide 2
- May or may not be associated with clinical symptoms 1
Subclinical Hyperthyroidism
- TSH level below the lower threshold of the reference interval (usually <0.4 mIU/L) but normal T4 and T3 levels 1
- Further classified as:
- Affects approximately 0.7% to 1.4% of people worldwide 2
Pathophysiology
Hyperthyroidism represents increased synthesis of thyroid hormones, excessive release of preformed thyroid hormones, or an extrathyroidal source 3
The condition is characterized by:
- Increased thyroid hormone synthesis and secretion from the thyroid gland 4
- Excess circulating thyroid hormones leading to increased metabolic rate 1
Common Etiologies
The most frequent causes include:
- Graves' disease (most common, affecting 2% of women and 0.5% of men globally; accounts for 70% of hyperthyroidism cases) 2, 5, 4
- Toxic nodular goiter (toxic multinodular goiter or toxic adenoma; accounts for 16% of cases) 3, 5, 4
- Thyroiditis (painless/silent thyroiditis with excessive passive release of preformed hormones; accounts for 3% of cases) 3, 5
- Drug-induced (amiodarone, tyrosine kinase inhibitors, immune checkpoint inhibitors; accounts for 9% of cases) 5
Clinical Manifestations
Symptoms are related to the increased metabolic rate and include 1:
- Weight loss
- Fatigue
- Heat intolerance
- Excessive sweating
- Diarrhea
- Tachycardia
- Insomnia
- Muscle weakness
- Tremor
- Anxiety and palpitations 2
Physical examination findings in Graves' disease may reveal diffusely enlarged thyroid gland, stare, or exophthalmos 2
Important Clinical Distinction
The term "overt" hyperthyroidism is misleading because it is defined biochemically and does not require the presence of symptoms 1. The spectrum ranges from asymptomatic biochemical changes to clinically symptomatic disease, with rare life-threatening complications such as thyroid storm 1.