How does acromegaly, caused by excess Growth Hormone (GH) or Insulin-like Growth Factor 1 (IGF-1), lead to Obstructive Sleep Apnea (OSA)?

Mechanism of Obstructive Sleep Apnea in Acromegaly

Acromegaly causes obstructive sleep apnea (OSA) primarily through craniofacial deformations and soft tissue hypertrophy of the upper airway structures, leading to narrowing and subsequent collapse during sleep. 1

Anatomical Changes in Acromegaly Leading to OSA

Soft Tissue Changes

• Macroglossia (enlarged tongue): Excess GH/IGF-1 causes tongue hypertrophy, which can obstruct the airway during sleep 2, 3
• Uvula hypertrophy: Significant correlation between uvula size and severity of upper airway collapse 3
• Soft palate thickening: Contributes to narrowing of the oropharyngeal space
• Laryngeal tissue hypertrophy: Causes narrowing at the level of the larynx 4

Skeletal Changes

• Mandibular prognathism: Forward growth of the jaw
• Maxillary widening: Expansion of the upper jaw
• Overall craniofacial deformations: Despite these bony changes that might seem to enlarge the airway, the disproportionate soft tissue growth overwhelms any potential benefit 1

Pathophysiological Mechanisms

Primary Mechanisms

1. Anatomical narrowing: The uvula and tongue base are the main sites of obstruction as confirmed by fiberoptic nasopharyngoscopy with Müller maneuver 3
2. Reduced total airway volume: 3D-MRI studies confirm smaller total volume of upper airways in acromegalic patients with severe OSA 3
3. Increased collapsibility: The hypertrophied tissues are more prone to collapse during the negative pressure of inspiration during sleep

Secondary Contributing Factors

• Cardiovascular complications: Left ventricular hypertrophy is more prevalent in acromegalic patients with OSA, potentially worsening the condition through fluid redistribution 3
• Metabolic effects: GH excess can lead to insulin resistance and metabolic syndrome, which independently contribute to OSA severity 5
• Central effects: Some studies suggest that elevated GH levels may cause defects in respiratory drive, potentially contributing to central sleep apnea components 4

Severity and Prevalence

• OSA prevalence in acromegaly ranges from 52-63.6% depending on disease activity 3
• Higher AHI (Apnea-Hypopnea Index) correlates with greater systemic inflammation 5
• The severity of OSA correlates with tongue measurements and uvula dimensions 3

Treatment Impact on OSA in Acromegaly

• Successful treatment of acromegaly improves OSA: 62.5% of patients with active acromegaly showed improvement in OSA after achieving hormonal control 3
• Persistent OSA despite disease control: OSA persisted or worsened in 66.6% of patients with controlled acromegaly, suggesting irreversible structural changes after prolonged exposure to elevated GH/IGF-1 3
• Transsphenoidal hypophysectomy: Can resolve OSA in acromegalic patients by addressing the root cause (excess GH production) 2
• CPAP therapy: Often required even after biochemical control of acromegaly is achieved 1

Clinical Implications

• Evaluation for OSA should be performed at diagnosis of acromegaly, during treatment, and even after biochemical control is achieved 1
• Early and intensive treatment of acromegaly is crucial to prevent irreversible upper airway changes 3
• Successful treatment of acromegaly can reduce cardiovascular morbidity and mortality, including OSA-related complications 6

Pitfalls and Caveats

• Don't assume OSA will resolve with acromegaly treatment alone: Long-standing disease may cause irreversible structural changes requiring ongoing OSA management 1
• Don't overlook central sleep apnea: While obstructive sleep apnea is more common, central sleep apnea can also occur in acromegaly 4
• Don't focus solely on surgical airway interventions: Treating the underlying acromegaly should be prioritized before considering surgeries like uvulopalatopharyngoplasty, which may be unsuccessful without addressing the hormonal excess 2