Technische Universität München

The Entrepreneurial University

Exposure to elevated endogenous levels of hGH and IGF-1 in the pathophysiological model of acromegaly results in both direct structural and functional tissue damage and the development of secondary systemic disorders.
Patients with acromegaly develop several respiratory alterations as a consequence of the hypertrophic action of hGH and IGF-1 on craniofacial bones and soft tissue, respiratory mucosa/cartilages, lung volumes and activity of respiratory muscles. This range of abnormalities results in sleep apnea and impaired respiratory functions. In the upper airways, remodelling of bones and soft tissues results in the impairment of normal pharyngeal patency during sleep and is a key to the onset of obstructive sleep apnea, the prominent type of sleep breathing disorder in acromegaly. Chronic GH excess causes several alterations which may contribute to impairing the intrapharyngeal balance during inspiration and thus increase pharynx collapsibility during sleep.
Impaired respiratory function originates from the alterations involving the bone, muscle structure of the chest and in lung volume and elasticity. In the lungs proliferations of pneumocytes and smooth muscles cells is reflected in the overgrowth of pulmonary epithelium and thickening of interstitial tissue. This alteration decreases pulmonary elasticity, whereas lung volumes are increased due to alveoli overgrowth. This process leads to respiratory dysfunction; the ventilatory response on effort is frequently inadequate in the face of a greater effort as well as the sense of physical exhaustion. Respiratory mortality appears to be 3-fold higher in acromegalic patients than in normal subjects.