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Several different treatment modalities are available to attain tight control of GH hypersecretion in order to improve morbidity and mortality in patients with acromegaly. Multiple treatment options may be required, and an individualized therapeutic approach is recommended for each patient (Fig. 10).

In assessing the role of surgery as primary therapy, the likelihood of cure must be seriously considered. Surgery is the primary treatment for pituitary microadenomas or macroadenomas that have not spread beyond the sella. However, 70% of acromegalic patients have macroadenomas at the time of presentation, which have spread beyond the sella turcica and are not amendable to curative resection. There are no conclusive trials confirming that preoperative treatment with somatostatin analog therapy improves the surgical outcome. Postopera-tively, patients who are not "cured" require medical therapy. Dopamine agonist therapy has a low efficacy but is inexpensive, with mild side effects, and can be used initially. Subsequently somatostatin analog therapy can be instituted, initially by a subcutaneous injection of 50-100 ^g with measurement of GH and IGF-1 after 2 h (118) to assess efficacy. Tolerability and efficacy are assessed by administering octreotide subcutaneously three to four times a day, for 3-4 d. If GH levels are suppressed by more than 50% (97) and patients do not experience intolerable gastrointestinal side effects, therapy with Sandostatin LAR is initiated.

Patients treated with somatostatin analogs require assessment of postprandial glucose levels every 3 mo. Gallbladder ultrasound is performed only if symp-

Fig. 9. Action of growth hormone (GH) receptor antagonist. (A) Normally a single molecule of GH binds two GH receptors through sites 1 and 2, and the GH signal transduction pathway is activated. (B) Pegvisomant increases binding of the GH receptor to site 1 and blocks binding at site 2 to prevent functional GH receptor dimerization, initiation of GH action, and induction of IGF-1 synthesis and secretion. The peripheral effects of excess GH are antagonized at the cellular level, independent of the presence of somatostatin or dopamine receptors on the pituitary tumor. (Adapted from ref. 124.)

Fig. 9. Action of growth hormone (GH) receptor antagonist. (A) Normally a single molecule of GH binds two GH receptors through sites 1 and 2, and the GH signal transduction pathway is activated. (B) Pegvisomant increases binding of the GH receptor to site 1 and blocks binding at site 2 to prevent functional GH receptor dimerization, initiation of GH action, and induction of IGF-1 synthesis and secretion. The peripheral effects of excess GH are antagonized at the cellular level, independent of the presence of somatostatin or dopamine receptors on the pituitary tumor. (Adapted from ref. 124.)

toms of cholelithiasis occur. The development of asymptomatic gallbladder sludge does not require monitoring by serial ultrasound.

Primary medical therapy is recommended in patients who are at high risk for surgery or anesthesia or those who refuse surgery. There is also a role for primary medical therapy in patients with invasive macroadenomas not amenable to curative surgical resection, with a high likelihood of persistently elevated postoperative GH levels, who will require somatostatin analog therapy postoperatively despite surgery (119).

In patients whose pituitary lesions abut the optic chiasm with visual field defects, surgical resection is indicated. A second surgical resection is recommended for patients with tumor recurrence.

Radiation therapy is indicated in patients who are intolerant to medical therapy or fail to respond. However, medication may still be required for several years after radiation, until GH levels are lowered.

The criteria for "cure" of acromegaly include a GH suppressed to less than 1 ng/mL after an OGTT and normal age- and-sex-matched IGF-1 levels. Patients should be followed quarterly with titration of the dose of medication until biochemical control is achieved. In patients with no residual tumor tissue

Images Algorithm Hypopituitarism
Fig. 10. Algorithm for decision making in the treatment of acromegaly. GH, growth hormone; IGF-1, insulin-like growth factor-1. (Adapted from ref. 125.)

remnant and biochemical cure, IGF-1 levels should be assayed annually with a pituitary MRI repeated every 1-2 yr (121).

In patients with residual tumor tissue or those with hypopituitarism requiring hormone replacement medical treatment, as well as patients who have received pituitary radiation, testing of adrenal, gonadal, and thyroid reserve should be performed semiannually and pituitary MRI annually. Mammogram and colonoscopy should be performed annually in patients over the age of 50 yr, especially if skin tags are present.

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