Acromegaly is an insidious disorder, due to chronic hypersecretion of growth hormone (GH) occurring in adulthood. GH hypersecretion prior to epiphyseal fusion results in gigantism. Elevated GH and/or insulin-like growth factor-1 (IGF-1) levels affect multiple organ systems resulting in acral and soft tissue growth, and metabolic dysfunction. Untreated acromegaly causes significant morbidity and mortality. Furthermore, mortality rates are twice the expected value, most commonly due to cardiovascular and respiratory complications. Control of GH hypersecretion lowers the morbidity and mortality associated with acromegaly. Ninety-fne percent of cases of acromegaly are caused by benign GH secreting pituitary adenomas; ectopic pituitary tumors and extrapituitary tumors (hypothalamus, pancreas, carcinoid, lung, ovary, breast) are found in a very small percentage of cases.

Treatment goals for patients harboring pituitary tumors include normalization of GH and IGF-1 levels, as well as removal of the adenoma with preservation of pituitary function and surrounding structures.

Therapeutic options include surgery, radiotherapy and drug therapy.

Approximately 30% of GH secreting pituitary adenomas are microadenomas (lOmm), resulting in persistence of GH hypersecretion postoperatively in half of the cases. Several patients, demonstrating postoperative “biochemical cure”, show recurrent tumor growth and increased GH levels when retested subsequently. Transsphenoidal pituitary tumor resection should be performed by surgeons experienced in this technique.

Radiotherapy is very effective in shrinking GH secreting pituitary tumors, but may take up to 20 years to lower GH levels and is associated with a high incidence of hypopituitarism. Data from longterm studies investigating the safety and efficacy of stereotactic radiosurgery (gamma knife) are not yet available.

Medical therapy includes dopamine agonists (DA), somatostatin analogs and GH antagonists. Only 15-20% of patients demonstrate GH suppression and 10% normalization of IGF-1 level on high doses of DA therapy. Somatostatin analogs normalize IGF-1 levels in 60% of patients. Somatostatin analogs are administered by subcutaneous injection in divided doses three to four tlmes daily. However, longacting somatostatin analog formulations administered intramuscularly once or twice a month will soon be available in the USA. Trovert, a pegylated analog of human growth hormone, functions as a growth hormone antagonist, displacing GH from hepatic receptors, thereby lowering circulating IGF- 1 levels. The safety and efficacy of a once daily subcutaneous injection of Trovert are currently being evaluated.

The addition of these long-acting and novel formulations to the treatment modalities for acromegaly greatly enhance therapeutic options.


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