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Patients who do not have a clinical or biochemical remission after surgery are treated with a dopamine agonist (eg, cabergoline), somatostatin analogs, pegvisomant, or a combination of these medications Cabergoline may be used first, since it is an oral medication Cabergoline therapy is most successful for tumors that secrete both PRL and GH but can also be effective for patients with normal serum PRL levels Therapy with cabergoline will shrink one-third of such tumors by more than 50% The initial dose is 025 mg orally twice weekly, which is gradually increased to a maximum dosage of 1 mg twice weekly, if tolerated by the patient based on serum GH and IGF-I levels Side effects of cabergoline include nausea, fatigue, constipation, abdominal pain, and dizziness Cabergoline is expensive Long-term therapy with high-dose dopamine agonists, such as cabergoline, (> 3 mg/ d), may sometimes cause cardiac valve regurgitation, but doses such as these are seldom used for patients with acromegaly In 2007, the manufacturer of the dopamine agonist pergolide withdrew the drug from the US market after two studies showed that serious cardiac valvular abnormalities developed in some patients taking the drug Octreotide and lanreotide are somatostatin analogs that are given by subcutaneous injection Short-acting octreotide acetate in doses of 50 mcg is injected three times daily Responders who tolerate the drug are switched to long-acting octreotide acetate injectable suspension in a dosage of 20 mg intragluteally per month The dosage may be adjusted up to a maximum of 40 mg monthly to maintain the serum GH between 1 and 25 ng/mL, keeping IGF-I levels normal Octreotide long-acting release (LAR) preparations (Sandostatin LAR depot) are superior to shorter-acting octreotide, ultimately achieving serum GH levels under 2 ng/mL in 79% of patients and normal serum IGF-I levels in 53% of patients Headaches often improve, and tumor shrinkage of about 30% may be expected Acromegalic patients with pretreatment serum GH levels exceeding 20 ng/mL are less likely to respond to octreotide therapy Side effects are experienced by about one-third of patients and include injection site pain, loose acholic stools, abdominal discomfort, or cholelithiasis Lanreotide SR (not available in the United States) is given by subcutaneous injection at a dosage of 30 mg every 7 14 days Lanreotide Autogel (not available in the United States) is a newer formulation that is administered by deep subcutaneous injection in doses of 60 120 mg every 28 days; this preparation is better tolerated than lanreotide SR All somatostatin analogs are expensive and must be continued indefinitely or until other treatment has been effective Pegvisomant is a GH receptor antagonist that blocks the effects of GH Pegvisomant therapy produces symptomatic relief and normalizes serum IGF-I levels in over 90% of patients The starting dosage is 10 mg subcutaneously daily The maintenance dosage can be increased by 5 10 mg every 4 6 weeks, based on serum IGF-I levels and liver transaminase levels; the maximum dosage is 40 mg subcutaneously daily Pegvisomant does not shrink GH-secreting tumors Patients need to be monitored carefully with visual field examinations, GH levels, and MRI scanning of the pituitary Side effects of pegvisomant can include injection site reactions, hepatitis, edema, flu-like syndrome, nausea, and hyper-.

8:

MRI shows a pituitary tumor in 90% of acromegalic patients MRI is generally superior to CT scanning, especially in the postoperative setting Radiographs of the skull may show an enlarged sella and thickened skull Radiographs may also show tufting of the terminal phalanges of the fingers and toes A lateral view of the foot shows increased thickness of the heel pad

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Active acromegaly must be distinguished from familial coarse features, large hands and feet, and isolated prognathism and from inactive ( burned-out ) acromegaly in which there has been a spontaneous remission due to infarction of the pituitary adenoma GH-induced gigantism must be differentiated from familial tall stature and from aromatase deficiency (See Osteoporosis) Misleadingly high serum GH levels can be caused by exercise or eating just prior to the test; acute illness or agitation; hepatic or renal failure; malnourishment; diabetes mellitus; or concurrent treatment with estrogens, -blockers, or clonidine During normal adolescence, serum IGF-I is usually elevated and GH may fail to be suppressed

Complications include hypopituitarism, hypertension, glucose intolerance or frank diabetes mellitus, cardiac enlargement, and cardiac failure Carpal tunnel syndrome may cause thumb weakness and thenar atrophy Arthritis of hips, knees, and spine can be troublesome Cord compression may be seen Visual field defects may be severe and progressive Acute loss of vision or cranial nerve palsy may occur if the tumor undergoes spontaneous hemorrhage and necrosis (pituitary apoplexy) Colon polyps are more likely to develop in patients with acromegaly

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