Acromegaly

Acromegaly is a chronic and progressive endocrine disorder characterized by excessive growth hormone (GH) production and insulin-like growth factor 1 (IGF-1). This overproduction usually results from a benign pituitary adenoma, although there are rarer causes, such as ectopic GH-secreting tumors.

The epidemiology of acromegaly indicates it is a rare condition, with a prevalence of approximately 50-70 cases per million population and an annual incidence of 3-4 new cases per million. The diagnosis is often delayed due to the insidious onset and slow progression of symptoms, leading to a latency period of several years before recognition and treatment.

The primary cause of acromegaly is a GH-secreting pituitary adenoma, which accounts for around 95% of cases. These adenomas are typically benign but cause significant clinical symptoms due to hormone overproduction. In rare instances, acromegaly can arise from ectopic production of GH or GH-releasing hormone (GHRH) from tumors located in organs such as the lungs or pancreas.

Pathophysiologically, the excessive production of GH from the pituitary adenoma stimulates the liver and other tissues to produce IGF-1, a hormone that mediates many of the growth-promoting effects of GH. Elevated levels of IGF-1 lead to the abnormal growth of bones and soft tissues, characteristic of acromegaly. The condition often manifests in adults between the ages of 40 and 50 after the growth plates have closed, leading to changes in the size and shape of bones and tissues rather than a height increase.

Symptoms of acromegaly develop gradually and include the enlargement of hands and feet, facial feature changes such as protruding jaw and brow, enlarged nose, lips, and tongue, and thickened skin. Patients often experience joint pain, muscle weakness, excessive sweating, fatigue, and carpal tunnel syndrome. Additionally, acromegaly is associated with metabolic complications such as insulin resistance and diabetes mellitus, as well as cardiovascular issues, including hypertension, cardiomegaly, and increased risk of atherosclerosis.

The differential diagnosis of acromegaly involves distinguishing it from other conditions that can cause similar symptoms, such as gigantism (in children, where excessive GH occurs before the closure of growth plates), Cushing's syndrome, and other endocrine or neoplastic disorders. The differentiation is critical as the management and prognosis vary significantly between these conditions.

Complications of untreated or inadequately treated acromegaly are significant and include cardiovascular diseases (such as heart failure and arrhythmias), respiratory issues (including obstructive sleep apnea), metabolic disorders (like diabetes and hyperlipidemia), and increased risk of certain malignancies, particularly of the colon. Arthropathy and spinal deformities due to prolonged excessive growth are also common, impacting the quality of life.

Treatment of acromegaly aims to reduce GH and IGF-1 levels to normal ranges, alleviate symptoms, and address any complications. Surgical removal of the pituitary adenoma is often the first-line treatment and can be curative, mainly if the tumor is small and accessible. Transsphenoidal surgery is the preferred approach due to its minimally invasive nature and effectiveness. In cases where surgery is not possible or residual tumor tissue remains, medication can be used. Somatostatin analogs (such as octreotide and lanreotide) inhibit GH release, GH receptor antagonists (like pegvisomant) block GH action, and dopamine agonists (such as cabergoline) can also reduce GH levels. Radiation therapy is another option, typically reserved for patients who are not candidates for surgery or do not respond adequately to medication.

Laboratory tests play a crucial role in the diagnosis and monitoring of acromegaly. Initial screening involves measuring IGF-1 levels, which are typically elevated in acromegaly. If IGF-1 levels are high, a GH suppression test following oral glucose tolerance (OGTT) is performed. Normally, glucose intake suppresses GH levels, but this suppression fails in acromegaly.

Imaging studies, primarily magnetic resonance imaging (MRI) of the pituitary gland, detect and characterize adenomas.

Long-term monitoring of patients with acromegaly involves regular GH and IGF-1 level assessments to ensure adequate disease control. Additionally, patients require ongoing evaluation for potential complications, including regular cardiovascular examinations, glucose monitoring for diabetes, and colonoscopies due to the increased risk of colorectal cancer. Management of associated comorbidities, such as hypertension and sleep apnea, is essential to improve overall outcomes and quality of life.