Pathophysiology of Hyperthyroidism
Hyperthyroidism results from excessive thyroid hormone synthesis and secretion, leading to a hypermetabolic state that profoundly affects multiple organ systems, most critically the cardiovascular system through decreased systemic vascular resistance, increased cardiac output, and tachycardia. 1, 2
Fundamental Mechanisms
Thyroid Hormone Overproduction
- Graves' disease (70% of cases) is caused by circulating immunoglobulins that bind to and stimulate the TSH receptor, resulting in sustained autonomous thyroid overactivity 3, 4
- Toxic nodular goiter (16% of cases) results from autonomous hyperfunctioning of localized areas of the thyroid, independent of TSH stimulation 3, 4
- Other mechanisms include destructive thyroiditis (3%), drug-induced hyperthyroidism (9%), and exogenous thyroid hormone ingestion 2, 4
Metabolic Consequences
- Excess circulating thyroid hormones increase basal metabolic rate, leading to weight loss despite normal or increased appetite, heat intolerance, and excessive sweating 5, 6
- Enhanced catabolism affects protein, carbohydrate, and lipid metabolism systemically 7
Cardiovascular Pathophysiology
Hemodynamic Alterations
- Systemic vascular resistance decreases while cardiac output increases dramatically, creating a hyperdynamic circulatory state 1, 6
- Tachycardia develops from direct thyroid hormone effects on cardiac pacemaker cells and increased sensitivity to catecholamines 1, 7
- Cardiac contractility typically increases, but in severe, long-standing cases, persistent tachycardia can paradoxically lead to heart failure despite enhanced contractility 1, 6
Cardiac Complications
- Atrial fibrillation occurs with increased frequency, particularly in elderly patients and those with pre-existing cardiac disease 1, 6
- Pulmonary artery hypertension and right ventricular dilatation can develop in chronic hyperthyroidism 1, 6
- Hypertension, particularly systolic hypertension, results from increased cardiac output despite decreased peripheral resistance 6, 8
Systemic Manifestations
Neuropsychiatric Effects
- Tremors, nervousness, anxiety, hyperactivity, and insomnia result from increased adrenergic sensitivity and direct effects on the central nervous system 1, 6
- Muscle weakness and fatigue occur despite hyperactivity, reflecting increased protein catabolism 7
Integumentary Changes
- Excessive sweating and heat intolerance develop from increased metabolic heat production 6
- Hair loss and skin changes reflect accelerated cellular turnover 6
Clinical Severity Spectrum
Overt Hyperthyroidism
- Suppressed TSH (<0.1 mIU/L) with elevated free T4 and/or T3 confirms the diagnosis 6, 4
- Full constellation of symptoms including cardiovascular, neuropsychiatric, and metabolic manifestations 7, 4
Thyroid Storm
- A rare but life-threatening emergency representing extreme thyroid hormone excess with multisystem decompensation 6, 8
- Requires immediate recognition and aggressive multidisciplinary treatment 8
Age-Related Considerations
- Patients over 50 years face significantly increased risk of cardiovascular complications and mortality from hyperthyroidism 1, 6
- Cardiovascular complications represent the chief cause of death after treatment, particularly in older populations 6