What causes hyperphagia?

Causes of Hyperphagia (High Appetite)

Hyperphagia is primarily caused by hypothalamic dysfunction, medication side effects, genetic disorders, or psychological factors that disrupt normal appetite regulation mechanisms.

Neurological and Hypothalamic Causes

• Brain injury and lesions: Damage to appetite-regulating centers in the hypothalamus can lead to persistent hyperphagia, particularly when affecting regions involved in satiety signaling 1
• Dementia: Alzheimer's disease and other dementias can cause hyperphagia through:
  • Atrophy of the mesial temporal cortex affecting appetite regulation
  • Inflammatory processes in the brain with elevated pro-inflammatory cytokines
  • Pathological changes in the olfactory system 2

Genetic Disorders

• Prader-Willi Syndrome (PWS): The most well-documented genetic cause of hyperphagia
  • Characterized by excessive eating with obsession with food
  • Typically develops between ages 6-12 years after initial feeding difficulties
  • Results from absence of paternally inherited genes on chromosome 15
  • Associated with significant morbidity and mortality if not controlled 2, 3
• WAGR syndrome: Associated with morbid obesity and hyperphagia, suggesting possible satiety gene at 11p13 4

Medication-Induced Hyperphagia

• Antipsychotic medications: Major cause of medication-induced hyperphagia
  • Second and third-generation (atypical) antipsychotics particularly problematic
  • Diverse receptor binding profiles affect different appetite pathways
  • Can lead to significant weight gain, type 2 diabetes, and cardiovascular disease 5
• Other medications associated with increased appetite:
  • Some antidepressants (tricyclic antidepressants, certain SSRIs, MAOIs)
  • Glucocorticoids
  • Injectable progestins
  • Certain anticonvulsants (gabapentin, pregabalin)
  • Some β-blockers (atenolol, metoprolol, propranolol)
  • Sedating antihistamines 2

Psychological and Stress-Related Factors

• Chronic stress: Can induce hyperphagia and disrupt normal eating patterns
  • Associated with binge-eating behaviors
  • Can lead to obesity and metabolic syndrome 6
• Binge Eating Disorder: Characterized by:
  • Consuming larger than normal amounts of food in discrete periods
  • Sense of lack of control over eating
  • Marked distress
  • Often triggered by stressful life events 6

Other Medical Conditions

• Infections and inflammatory conditions: Can affect the esophagus and potentially influence eating behaviors 2
• Substance withdrawal: Certain substances like alcohol and sedatives can cause hyperphagia during withdrawal 2
• Cancer: Some cancers can cause metabolic changes leading to increased appetite, though cachexia and anorexia are more common 2

Clinical Implications

• Hyperphagia significantly impacts morbidity and mortality, particularly when leading to obesity
• In conditions like PWS, the behavior of hyperphagia itself (independent of obesity) can be dangerous, associated with:
  • Choking
  • Gastric rupture
  • Respiratory illness 3
• Management should focus on:
  • Identifying and treating underlying causes
  • Environmental and cue exposure control for neurological causes
  • Medication adjustment when drug-induced
  • Behavioral interventions and dietary management

Diagnostic Approach

• Consider age-appropriate causes (genetic syndromes more common in younger patients)
• Review medication history thoroughly
• Evaluate for neurological conditions, particularly with sudden onset hyperphagia
• Screen for psychological factors and eating disorders
• Consider genetic testing when appropriate, especially with developmental delays or other syndromic features

Early identification and management of hyperphagia is essential to prevent complications related to obesity and associated metabolic disorders.