Acromegaly is a chronic debilitating disease with an insidious onset, resulting from the effects of either hypersecretion of growth hormone (GH) or increased amounts of an insulin-like growth factor I (IGF-I).

• Coarse features resulting from growth of soft tissue
• Coarse, oily skin
• Hands and feet that are spade-like, fleshy, and moist
• Prognathism, which can give an underbite
• Carpal tunnel syndrome
• Excessive sweating
• Arthralgias and severe osteoarthritis
• History of increased hat, glove, and/or shoe size
• Hypertension
• Skin tags
• Muscle weakness and decreased exercise capacity
• Headache, often severe
• Diabetes mellitus
• Visual field defects

Cause is usually a pituitary adenoma, affecting the anterior lobe.

DIFFERENTIAL DIAGNOSIS
Ectopic production of growth hormone–releasing hormone (GHRH) from a carcinoid or other neuroendocrine tumor
WORKUP

1.First screening test: measure serum IGF-I level.
a.Direct measurement of the GH level is not as useful, because it is secreted in a pulsatile fashion and a random level may be falsely normal.
b.Upper limits of a normal IGF-I level, depending on the assay: >380 ng/ml or 2.5 U/ml.
 

2.Failure to suppress serum GH to less than 2 ng/ml after 100 g oral glucose is considered conclusive.
a.Patients may show suppression of GH or a paradoxical response.
b.Patients will not suppress GH to 2 ng/ml or less (the normal response).
c.GHRH level >300 ng/ml is indicative of an ectopic source of GH.
LABORATORY TESTS
• Elevated serum phosphate
• Elevated urine calcium
IMAGING STUDIES
• Imaging studies of choice: MRI of the pituitary and hypothalamus
• CT of the pituitary and hypothalamus used initially

SURGERY
Treatment of choice: transsphenoidal microsurgical adenomectomy
• Surgical failure rate: about 13.3% for microadenomas (tumors <10 11.1="11.1" and="and" for="for" macroadenomas="macroadenomas" mm="mm" tumors="tumors">10 mm confined to the sella)
• Preoperative IGF-I level: indicator of surgical outcome with higher levels in the surgical failure group
RADIOTHERAPY
• Irradiation to reduce further growth of the tumor in most patients
• Major complication: hypopituitarism, which may occur in up to 50% of patients; this complication is more likely in patients who had surgery irradiation
MEDICAL Rx
• Indicated when patients have failed surgical therapy, when surgery is contraindicated, and in patients waiting for the effects of radiotherapy to begin
• Octreotide
1.A somatostatin analog given tid at a dose of 100 µg subcutaneously
2.Important side effects: biliary sludge and gallstones; nausea, cramps, and steatorrhea; suppression of GH levels to about 5 µg/L in 52% of patients; IGF-I levels normalized to about 53%
3.Important in the preoperative shrinkage of pituitary tumors and softening of adenomatous tissue
• Bromocriptine

1.A dopamine analog given at a dosage of 10 to 60 mg PO tid to qid
2.Less effective than octreotide
3.Important advantages: less expensive than octreotide and taken orally
4.Important side effects: orthostatic hypotension, lightheadedness, nausea, constipation, and nasal stuffiness
5.Suppresses GH levels to <5 10="10" 20="20" about="about" adenomas="adenomas" and="and" approximately="approximately" br="br" g="g" gh="gh" igf-i="igf-i" in="in" levels="levels" normalized="normalized" normalizes="normalizes" of="of" patients="patients" pituitary="pituitary" shrinks="shrinks" to="to">• Pegvisomant is a growth hormone receptor antagonist that has shown promising results in the treatment of acromegaly.
CHRONIC Rx
Combination of bromocriptine and octreotide may be synergistic, allowing a lower combination dosage than alone.
DISPOSITION
• 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.

Trainer et al: Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant, N Engl J Med 342:1172, 2000.