Acromegaly & Gigantism

Acromegaly refers to the clinical syndrome caused by excessive growth hormone (GH) in adulthood, after the closure of epiphyses (bone growth plates). GH produces many of its effects through the stimulation of insulin-like growth factor (IGF-I), produced in the liver and at epiphyses. Symptoms of acromegaly typically include the growth of hands and feet, the growth of jaw and brow, with coarsening of facial features. Bones grow thicker and the growth of spinal bone can cause spinal stenosis and serious neurologic problems. Affected individuals are usually very sweaty, and also have increased muscle mass and reduced subcutaneous fat. Carpal tunnel syndrome is common. Diabetes and hypertension commonly occur. Untreated patients have a reduced life expectancy due to cardiovascular complications.

Gigantism refers to excessive growth in stature during childhood and adolescence, caused by excessive growth hormone. Affected children are much taller than expected for their age. Without treatment, such children eventually develop acromegaly in addition to their gigantism.

In patients with acromegaly or gigantism, a pituitary adenoma (tumor) produces excessive amounts of GH. Such pituitary adenomas are generally benign, but they may grow such that they can impinge upon the optic chiasm (the crossing and recombination of the optic nerves) that is located just superior to the pituitary; such impingement can cause visual field defects. GH-secreting pituitary adenomas can also invade the cavernous sinuses that border the pituitary laterally; since the cavernous sinuses harbor veins, cranial nerves, and the carotid artery, pituitary tumors that have invaded a cavernous sinus are considered unresectable.

Diagnosis: When acromegaly or gigantism is suspected, it must be diagnosed with hormonal testing. Following an overnight fast, a serum specimen is obtained and assayed for prolactin, IGF-I, glucose, AST, BUN, phosphorus, TSH and free thyroxine. Glucose syrup 75 g is then given orally and serum GH is measured 60 minutes later. Acromegaly is excluded if the serum GH is less than 1 mcg/L (IRMA or chemiluminescent assays) or less that 2 mcg/dL (older radioimmunoassays) after glucose syrup, and if the IGF-I is normal. The IGF-I should be assayed at a reputable laboratory. Misleadingly high serum GH levels can be caused by exercise or eating just before the test, acute agitation or illness, renal or hepatic failure, malnourishment, diabetes mellitus, or concurrent treatment with clonidine, beta-blockers, or estrogens.

Magnetic resonance imaging (MRI) of the pituitary is obtained after the biochemical confirmation of acromegaly. The MRI is quite sensitive (about 90%) in identifying a GH-secreting pituitary adenoma.

Treatment: The best treatment for patients with a GH-secreting pituitary adenoma is transsphenoidal pituitary surgery by a skilled neurosurgeon. The surgical incision is ordinally in the inner nose or under the upper lip. A skilled surgeon can ordinarily identify and resect the pituitary tumor while leaving the normal pituitary gland in place. After the successful selective resection of a pituitary adenoma, pituitary funcion usually remains intact. After successful surgery, patients notice an immediate improvement in sweatiness and carpal tunnel syndrome. However, bone enlargement in permanent.

After pituitary surgery, patients must be followed regularly: clinically and with serial serum GH and IGF-I levels. Persistent or recurrent elevations in serum GH and IGF-I levels indicate the presence of residual tumor tissue in the pituitary, cavernous sinuses, or surrounding bone. Pituitary re-exploration may be warranted, if the recurrent tumor can be visualized on MRI and appears resectable. Otherwise, alternate treatment strategies are warranted: Oral cabergoline may be successful, particularly for patients whose pituitary tumor co-secretes prolactin along with GH. Another option is octreotide, which inhibits the secretion of GH from the tumor; it is ordinarily given by injection monthly. Pegvisomant is given by injection and inhibits the effect of GH at the GH receptors in tissues, thereby reducing GH effect. Some patients may require radiation therapy, but conventional radiation therapy typically causes hypopituitarism and long-term cognition changes. Therefore, better-focussed radiation is preferrable, when possible; gamma-knife and cybersknife are advanced radiation therapy techniques that can focus radiation therapy more accurately into recurrent tumor tissue.

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