What is Acromegaly
Acromegaly is a rare acquired disorder caused by excessive and autonomous secretion of growth hormone (GH), most commonly from a pituitary adenoma, resulting in elevated insulin-like growth factor 1 (IGF-I) levels and leading to progressive somatic disfigurement, systemic manifestations, and increased mortality if untreated. 1, 2
Pathophysiology and Etiology
The disease is characterized by excessive circulating GH and its tissue mediator IGF-I, with approximately 60% of cases caused by purely GH-secreting pituitary adenomas and the remainder by mixed adenomas. 1, 3
In rare cases, acromegaly results from ectopic secretion of growth-hormone-releasing hormone (GHRH) causing pituitary hyperplasia, or from genetic syndromes including McCune-Albright syndrome, Carney complex, MEN1, and X-linked acrogigantism. 1
When GH excess occurs before epiphyseal fusion in children and young people, the condition manifests as gigantism with tall stature, whereas post-epiphyseal fusion it presents as acromegaly with characteristic acral enlargement. 1
Epidemiology
The annual incidence is approximately 4-6 cases per million population, with an estimated prevalence of 1:140,000-250,000. 1, 3
The disease affects men and women equally and is most often diagnosed in middle-aged adults with an average age of 40 years. 3
Due to insidious onset and slow progression, diagnosis is typically delayed by 4 to more than 10 years after disease onset. 3
Clinical Manifestations
Somatic Features
Characteristic physical changes include broadened extremities (hands and feet), widened and thickened fingers, coarsened facial features with prominent cheekbones, forehead bulges, widened nose, thick lips, and marked facial lines. 1, 3
Mandibular overgrowth with prognathism, maxillary widening, tooth separation, and jaw malocclusion are typical findings. 1, 3
Frontal bossing may develop from thickened forehead and overlying skin. 1
Systemic Manifestations
Cardiovascular complications are the most common cause of death in untreated acromegaly, including left ventricular hypertrophy, heart failure, and valvular heart disease. 4, 5
Metabolic complications include diabetes mellitus and glucose intolerance due to GH's effects on insulin resistance. 1, 4
Respiratory manifestations include obstructive sleep apnea, which is common in acromegaly patients. 1, 4
Musculoskeletal complications, particularly arthropathy and joint pain, are frequent and may persist even after biochemical control. 1, 4
Other manifestations include headache, visual field defects from tumor mass effect, hyperhidrosis, fatigue, carpal tunnel syndrome, and hypertension. 1, 3
Colorectal Neoplasia Risk
Patients with acromegaly have an increased prevalence of colorectal adenomas and cancer, requiring colonoscopic screening starting at age 40 years. 1, 4
The screening frequency should be every 3 years for patients with an adenoma at first screening or elevated IGF-I levels, and every 5 years for those with negative colonoscopy or hyperplastic polyps only. 1
Biochemical Diagnosis
Diagnosis is confirmed by elevated serum IGF-I levels (age and sex-adjusted) and failure to suppress GH to <1 μg/L during an oral glucose tolerance test (OGTT) using modern sensitive assays. 4, 6
IGF-I measurement serves as the initial screening test, with OGTT and GH measurement as the gold standard confirmatory test. 4
Both GH and IGF-I levels must be monitored at baseline and during follow-up, as elevated levels are predictors of mortality. 4, 5
Important Diagnostic Caveats
IGF-I levels may be falsely normal or low in severe hypothyroidism, malnutrition, or severe infection. 4
IGF-I levels may be falsely elevated in hepatic and/or renal insufficiency. 4
GH suppression during OGTT is not useful for monitoring medically treated patients due to inconsistent results. 4
Prognosis and Mortality
Before effective treatment, the majority of patients died by age 60 years, largely from diabetes mellitus, cardiovascular and cerebrovascular diseases. 1
Normalizing GH and IGF-I levels through treatment reduces mortality to rates similar to the general population. 1, 4, 5
With adequate hormonal disease control achieved in most cases, life expectancy can be normalized, though sequelae including joint pain, deformities, and altered quality of life often persist. 3