Acromegaly is a chronic disease that develops due to hypersecretion of growth hormone (GH), which stimulates secretion of insulin-like growth factor (IGF-1). It is a progressive, debilitating disease with an insidious onset and potentially lethal outcome.

• Coarse features resulting from growth of soft tissue
• Coarse, oily skin
• Macrocephaly
• Hands and feet that are spadelike (Fig. E1), fleshy, and moist
• Prognathism, which can give an underbite
• Excessive sweating
• Menstrual dysfunction
• History of increasing hat, glove, and/or shoe size
• Enlargement of nose, brow, and jaw (Fig. E2)
• Muscle weakness and decreased exercise capacity
• Headache, often severe
• Visual field defects
• Arthralgias and severe osteoarthritis
• Carpal tunnel syndrome
• Diabetes mellitus
• Hypertension
• Severe obstructive sleep apnea due to soft tissue swelling and macroglossia
• Cardiac abnormalities (cardiomyopathy, left ventricular hypertrophy, valvular heart disease, diastolic failure, arrhythmias)
• Mild to moderate obesity
• Vertebral fractures
• Benign tumors (uterine myoma, skin tags, prostatic hypertrophy, colon polyps)

Acromegaly usually arises from a pituitary adenoma affecting the anterior lobe. In rare cases, extrapituitary production of either GH or GH-releasing hormone (GHRH) can also lead to clinical manifestations.

Ectopic production of GHRH from a carcinoid or other neuroendocrine tumor:

• McCune-Albright syndrome
• Pachydermoperiostosis

Workup involves biochemical diagnosis via laboratory testing in patients with clinical manifestations of acromegaly followed by imaging to visualize source of GH hypersecretion.

• First screening test: Measure serum IGF-I level
  1. Normal IGF-1 signifies acromegaly is unlikely
• Follow-up test for elevated or equivocal IGF-1: Oral glucose tolerance test
  1. Failure to suppress serum GH to <1 ng/ml after oral glucose load confirms acromegaly
• Measurement of random GH level not recommended due to pulsatile nature of GH secretion

• MRI of the pituitary and hypothalamus (preferred)
• CT of the pituitary and hypothalamus (if MRI is contraindicated or unavailable)

• Treatment of choice: Transsphenoidal microsurgical adenomectomy
• Surgical failure rate: Approximately 10% to 20% for microadenomas (tumors <10 mm) and 25% to 50% for macroadenomas (tumors ≥10 mm confined to the sella)

• Medical therapy is indicated when patients have not responded to surgical therapy (persistent elevation of IGF-1, abnormal glucose tolerance test), when surgery is contraindicated, and in patients with severe sleep apnea or high-output heart failure before surgery
• Somatostatin receptor ligands (SRLs): Octreotide, lanreotide, pasireotide
  1. Inhibit GH secretion
  2. Used for preoperative treatment in patients with comorbidities (sleep apnea and heart failure) or in patients with residual moderate to severe disease following surgery
• GH receptor antagonist: Pegvisomant
  1. Used for moderate to severe residual disease, especially in patients with intolerance to SRLs
• Combination therapy of SRL and pegvisomant
  1. Biochemical control rate of 96% at lower doses of each of the medications
• Dopamine agonists: Cabergoline
  1. Used for mild residual disease or in combination with SRLs in moderate to severe disease

• Stereotactic radiosurgery (gamma knife) can be used to increase the chance of remission or cure.
• Radiotherapy is usually reserved for tumor recurrence or persistence after surgery in patients with resistance to or intolerance of medical treatment.
• Major complication: Hypopituitarism, which may occur in up to 50% of patients; this complication is more likely in patients who had postoperative radiotherapy.

• Increased mortality rate in untreated patients primarily from cardiovascular and respiratory causes.
• Biochemical control is associated with lower hazard ratio of developing diabetes or cardiovascular system disorders.
• Treatment reduces or reverses soft tissue and metabolic symptoms, but bone and joint abnormalities are irreversible.
• Patients receiving radiotherapy need long-term follow-up to monitor the potential development of hypopituitarism.
• Continuation of medical therapy should be based on the normalization of IGF-I levels.

Pituitary Adenoma (Related Key Topic)

Acromegaly (Patient Information)