Key Points
- Acromegaly is a chronic disorder caused by growth hormone (GH) hypersecretion.
- Over 95% of patients with acromegaly harbor a GH-secreting pituitary adenoma arising from somatotroph cells.
- In less than 5% of cases, excess growth hormone-releasing hormone (GHRH) secretion from a hypothalamic tumor or a neuroendocrine tumor (usually from lung or pancreas origin) may lead to somatotroph hyperplasia and acromegaly.
- More rarely, ectopic GH production by an abdominal or hematopoietic tumor may cause acromegaly.
- Hereditary conditions include multiple endocrine neoplasia-1 (MEN1), Carney complex, and McCune-Albright syndrome. Germline aryl hydrocarbon receptor interacting protein (AIP) mutations have been described in familial acromegaly with more aggressive tumors.
- Hypersecretion of GH leads to excess production of insulin-like growth factor-1 (IGF-1), leading to a multisystem disease characterized by somatic overgrowth, multiple comorbidities, premature mortality, and physical disfigurement.
- A multidisciplinary approach is critical for the management of acromegaly.
Diagnosis
- The Endocrine Society (ES) recommends measurement of IGF-1 levels in patients with typical clinical manifestations of acromegaly, especially those with acral and facial features. (1|⊕⊕⊕o)
- ES suggests the measurement of IGF-1 in patients without the typical manifestations of acromegaly, but who have several of these associated conditions: sleep apnea syndrome, type 2 diabetes mellitus, debilitating arthritis, carpal tunnel syndrome, hyperhidrosis, and hypertension. (2|⊕⊕oo)
- ES recommends measuring serum IGF-1 to rule out acromegaly in a patient with a pituitary mass. (1|⊕⊕⊕o)
- ES recommends against relying on the use of random GH levels to diagnose acromegaly. (1|⊕⊕⊕o)
- In patients with elevated or equivocal serum IGF-1 levels, ES recommends confirmation of the diagnosis by finding lack of suppression of GH to
<1 mcg/L following documented hyperglycemia during an oral glucose load. (1|⊕⊕⊕o) - Following biochemical diagnosis of acromegaly, ES recommends performing an imaging study to visualize tumor size and appearance, as well as parasellar extent. (1|⊕⊕⊕⊕) ES suggests magnetic resonance imaging (MRI) as the imaging modality of choice, followed by computed tomography (CT) scan when MRI is contraindicated or unavailable. (2|⊕⊕oo)
- ES suggests performing formal visual field testing when the tumor is found to abut the optic chiasm on an imaging study. (2|⊕⊕⊕o)
Presentation and Management of Comorbidities and Mortality Risk
- ES suggests evaluating all patients presenting with acromegaly for associated comorbidities, including hypertension, diabetes mellitus, cardiovascular disease, osteoarthritis, and sleep apnea. (2|⊕⊕oo)
- ES also recommends that such comorbidities be longitudinally monitored and rigorously managed. (Ungraded recommendation)
- ES suggests screening for colon neoplasia with colonoscopy at diagnosis. (2|⊕⊕oo)
- ES suggests a thyroid ultrasound if there is palpable thyroid nodularity. (2|⊕⊕oo)
- ES recommends assessing for hypopituitarism and replacing hormone deficits. (1|⊕⊕⊕o)
