Definition

Growth hormone (GH) hypersecretion, usually caused by a GH-secreting pituitary adenoma (99% of cases), can produce a highly distinctive syndrome in adults called acromegaly. Acromegaly occurs because of sustained hypersecretion of GH after adolescence. The condition occurs with equal frequency in both sexes. If hypersecretion of GH occurs before puberty—that is, before closure of the growth plates—the individual grows very tall (8–9 feet), a rare condition known as gigantism.

Pathophysiology

The excessive production of GH associated with acromegaly does not induce bone lengthening but rather enhances the growth of periosteal bone. The unrestrained bone growth in patients with acromegaly produces bones that are massive in size and thickness. Bones of the hands and feet (acral) become particularly large. Overgrowth of vertebrae may cause kyphoscoliosis and arthritis.

Soft tissue changes are also prominent with GH hypersecretion. The patient develops coarsened facial features (acromegalic facies), including a large, bulbous nose; a supraorbital ridge overgrowth; dental malocclusion; and a prominent prognathic mandible. The changes in appearance are insidious, and many patients do not seek treatment until the diagnosis is obvious and the disease course is advanced. Overgrowth of the internal organs is less apparent clinically but no less serious. The liver, heart, spleen, and kidneys become enlarged. Lung volumes increase, which may lead to ventilation–perfusion mismatch. Exercise tolerance may be limited because of increased body mass and skeletal muscle weakness.

Cardiomyopathy, hypertension (28% of cases), and accelerated atherosclerosis in patients with acromegaly can lead to symptomatic cardiac disease (congestive heart failure, arrhythmias). Echocardiography often shows left ventricular hypertrophy. Resting electrocardiograms (ECGs) are abnormal in 50% of patients with acromegaly. ST-segment and T-wave depression, conduction defects, and evidence of prior myocardial infarction may be present. The insulin antagonistic effect of GH produces glucose intolerance in up to 50% of patients with acromegaly and frank diabetes mellitus (DM) in 10% to 25% of patients. The insulin antagonistic effect of GH produces glucose intolerance in up to 50% of patients with acromegaly and frank DM in 10% to 25% of patients.