What is acromegaly?

What is Acromegaly

Acromegaly is a rare chronic disease caused by excessive growth hormone (GH) secretion, almost always from a pituitary somatotroph adenoma, leading to elevated insulin-like growth factor-1 (IGF-1) levels and resulting in progressive somatic disfigurement, multi-system complications, and increased mortality if untreated. 1, 2, 3

Pathophysiology and Epidemiology

• The disease results from autonomous GH hypersecretion by a pituitary adenoma in nearly all cases, with rare causes including somatotroph hyperplasia from McCune-Albright syndrome, Carney complex, X-linked acrogigantism, or GH-releasing hormone-secreting tumors. 4, 3

• The prevalence is approximately 40-130 cases per million population, with an annual incidence of 4-6 per million, making it a rare endocrine disorder. 4, 3

• In children and adolescents before epiphyseal closure, GH excess causes gigantism (tall stature), while in adults after epiphyseal fusion, it causes acromegaly (acral enlargement without increased height). 4

Clinical Manifestations

Characteristic Physical Features

• Progressive acral enlargement including enlarged hands, feet, nose, and jaw (prognathism), along with coarsened facial features, frontal bossing, teeth separation, and dental malocclusion develop insidiously over years. 4, 2, 3

• Soft tissue swelling, excessive sweating (hyperhidrosis), skin thickening, and joint pain are prominent symptoms that significantly impact quality of life. 4, 3

Systemic Complications Determining Prognosis

• Cardiovascular disease is the leading cause of death in untreated acromegaly, including left ventricular hypertrophy, valvular heart disease, heart failure, hypertension, and arrhythmias. 1, 2, 3

• Metabolic complications include insulin resistance, diabetes mellitus (present in a substantial proportion of patients), and dyslipidemia. 1, 3

• Respiratory complications include sleep apnea (extremely common), upper airway obstruction, and restrictive lung disease. 1, 3

• Increased risk of colorectal adenomas and cancer necessitates colonoscopic screening starting at age 40 years. 4, 1

• Arthropathy affecting multiple joints, carpal tunnel syndrome, headaches, visual field defects from tumor mass effect, and hypopituitarism from compression of normal pituitary tissue. 4, 3

Pediatric Presentation

• In children, height >2 standard deviation scores (SDS) above age-adjusted and sex-adjusted norms or persistently elevated growth velocity (>2 SDS) with acromegalic features should prompt testing for GH excess. 4, 5

• Additional pediatric features include delayed or arrested puberty (from gonadotrophin suppression), delayed bone age, and in X-linked acrogigantism, onset before age 5 years with disproportionately enlarged extremities. 4

Diagnostic Approach

Initial Screening

• Measure serum IGF-1 as the first-line screening test when acromegaly is clinically suspected, using age-specific, sex-specific, and (in adolescents) Tanner stage-specific reference ranges. 1, 5

• IGF-1 levels can be falsely normal or low in severe hypothyroidism, malnutrition, or severe infection, and falsely elevated in hepatic or renal insufficiency. 1

Confirmatory Testing

• An oral glucose tolerance test (OGTT) with GH measurement is the gold standard diagnostic test, where failure to suppress GH to <1 μg/L (using modern sensitive assays) confirms acromegaly. 1, 5

• With ultrasensitive assays, the suppression cutoff may be as low as 0.4 μg/L, and both GH and IGF-1 must be evaluated together at baseline and during follow-up. 1, 5

• Critical pitfall: Do NOT use GH suppression during OGTT for monitoring patients on medical therapy, as results are inconsistent and unreliable in this setting. 1, 5

Imaging

• Contrast-enhanced pituitary MRI is essential after biochemical confirmation to identify and characterize the pituitary adenoma, assess tumor volume and extension, and evaluate relationship to surrounding structures including the optic chiasm. 5, 3

Treatment Goals and Prognosis

• The primary treatment goal is to normalize GH (<1 μg/L) and age/sex-normalized IGF-1 levels, which reduces mortality to rates similar to the general population. 1, 2

• Elevated GH and IGF-1 levels are independent predictors of mortality, and achieving biochemical control reverses this increased risk and may improve comorbidities. 1, 2

• Despite treatment, some permanent sequelae (particularly arthropathy and cardiovascular changes) may persist and impair quality of life, requiring lifelong monitoring and management of comorbidities. 3, 6