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Options Improving for Patients With Acromegaly and Gigantism

Scientific, technological and medical advances made in the past two decades are leading to more definitive diagnoses, earlier and more effective treatment options/// and better outcomes for patients suffering from a condition called acromegaly.

In the article, Shlomo Melmed, M.D., senior vice president for Academic Affairs and director of the Burns and Allen Research Institute at Cedars-Sinai, provides an update on medical progress related to the condition that stems from disorders – usually tumors – of the pituitary gland. He wrote a similar review article 16 years ago, published in the same journal in 1990.

“There have been remarkable advances in the therapy of this disease. Previously, all patients required surgery and/or radiotherapy for management, but now we have a whole new armamentarium of safe drugs that can effectively control the disorder. There also have been advances in diagnosis, such as the development of more sensitive blood assays for hormones,” said Melmed, who directs the medical center’s Pituitary Center and holds the Helene A. and Philip E. Hixon Endowed Chair in Investigative Medicine.

“Despite the improvements, acromegaly remains a very challenging and very complex disease,” he said. “If it occurs before the end of puberty, the patients become giants, suffering from a condition called gigantism. Unfortunately, several studies document a seven- to 12-year gap from symptom onset to time of diagnosis. During this time the children get bigger and their hormones get higher and the tissue damage gets worse. Therefore, the earlier we can diagnose and treat the disease, the more effectively we can control the negative implications.”

Acromegaly develops when somatotrophs, cells of the pituitary gland that are responsible for producing growth hormone, proliferate and oversecrete the hormone. The overabundance of growth hormone and the related insulin-like growth factor I (IGF-I), produce a range of effects including abnormal enlargement of the extremities, soft-tissue swelling, joint and spine conditions, protrusion of the jaws, and high blood sugar levels even when fasting. Patients often suffer from such complications as heart and valve disorders, high blood pressure and respiratory dysfunction.

“In addition to the variety of medical conditions, self-image is a major issue for these patients. At Cedars-Sinai, we have support groups in which patients can share their experiences with a professional counselor, and we offer the option of cosmetic surgery, especially for the jaw,” said Melmed. “We also have patient days that give patients the opportunity to meet with our physician experts and the coordinators of our support groups.”

Nearly all cases of acromegaly are caused by tumors of the pituitary gland. More than 90 percent of patients with acromegaly have a slow-growing type of tumor that is found in adults over 50 years of age. Younger patients usually have a more rapidly growing tumor, and a third type of tumor, commonly encountered by patients in their teens, often causes gigantism.

In general, ideal treatment includes surgery to remove the tumor, followed by medical therapy to manage or reverse any coexisting conditions. In many cases, however, the tumor may have grown too large or is positioned too close to vital structures for complete surgical removal to be possible or practical. Also, not all patients are good candidates for surgery.

Improvements in radiation therapy and radiosurgery, along with advances in computerized imaging systems, have improved targeting of a tumor mass, minimized radiation damage to normal surrounding tissues, and reduced treatment times. Also in the past two decades, new medications have been introduced, working at the cellular and molecular levels to suppress the secretion of growth hormone, interrupt the proliferation of somatotroph cells, and block the synthesis of IGF-I. High cost and temporary, unpleasant side effects continue to be factors, and the medications are not effective in or tolerated by all patients, but new alternatives are currently undergoing clinical trials.

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