endocrine and metabolic disorders
Gigantism and Acromegaly
Treatment of Gigantism and Acromegaly
Surgery or radiation therapy Sometimes pharmacologic suppression of GH secretion or activity Selective removal of the pituitary tumor with surgery is considered first-line therapy for most patients. Patients with comorbidities that prevent safe surgical resection and those with unresectable tumors may be treated with primary medical therapy. Rates of remission after surgical resection are dependent on the size and degree of invasion of the pituitary adenoma and the experience of the neurosurgeon. Surgical removal of the tumor is likely to have been curative if GH levels measured after a glucose load and IGF-1 levels reach normal values. If one or both values are abnormal, further therapy is usually needed. If GH excess is poorly controlled, hypertension, heart failure, and an increased mortality occur. Predictors of mortality in acromegaly include hypertension, age, use of radiation, and hypopituitarism, especially adrenocorticotropic hormone deficiency. Reduction of IGF-I and GH levels to the normal range seems to reduce mortality rates to normal. In general, medication therapy is indicated if surgery is contraindicated, if surgery or radiation therapy has not been curative, or if radiation therapy is being given time to work. Medications available for the treatment of acromegaly include those that target tumor secretion of GH and one that blocks GH at the level of the GH receptor. Somatostatin receptor ligands are a mainstay of therapy because they decrease GH secretion from the pituitary tumor mediated through interactions predominately with the somatostatin subtype receptor-2 (SSTR-2). Drugs in this class includeoctreotideandlanreotide, which have high affinity for the SSTR-2 and come in short-acting (octreotide) and long-acting (octreotideLAR andlanreotide) preparations.Pasireotide, a somatostatin receptor ligand with affinity for SSTR-1, 2, 3, and 5, is also available in short- and long-acting preparations. All somatostatin receptor ligands may also cause tumor shrinkage. Octreotideis started with a 20-mg intramuscular injection delivered monthly and titrated to an effective dose after the third injection. Effective doses range from 10 to 40 mg monthly.Lanreotideis given in doses of 60 to 120 mg monthly, with the possibility of extended dosing (120 mg every 6 to 8 weeks) in patients with well-controlled disease.Pasireotideis generally considered ifoctreotideorlanreotideis unsuccessful in returning IGF-I levels to normal.Octreotideis also available in an oral preparation given twice daily. Cabergoline, adopamineagonist, has been used alone or in combination with a somatostatin receptor ligand and works by suppressing GH secretion at the pituitary.Cabergolineis typically used in mild disease and has the advantage of being an oral drug. Pegvisomant, the GH receptor antagonist, is given as a daily subcutaneous injection and decreases IGF-I levels and symptoms but does not decrease GH levels or act on the pituitary tumor.Pegvisomantis given with a loading dose 40 mg subcutaneously under physician supervision followed by a maintenance dose of 10 mg subcutaneously once a day and titrated by 5-mg increments every 4 to 6 weeks, depending on IGF-I levels. Radiation therapy may be used at any step of treatment but is typically used as primary therapy only when surgery is not available. Timing of radiation in the treatment of patients with acromegaly varies among institutions. Stereotactic radiation, delivering about 5000 cGy to the pituitary, is used, but GH levels may not fall to normal for several years. Treatment with accelerated protons (heavy particle radiation) permits delivery of larger doses of radiation (equivalent to 10,000 cGy) to the pituitary; such therapy poses higher risk of cranial nerve and hypothalamic damage and is available only in a few centers. Generalized Hypopituitarism commonly develops several years after irradiation. Because radiation damage is cumulative, proton beam therapy should 