Guidelines for Acromegaly Management

Abstract

In May 2000, an Acromegaly Treatment Workshop was held to develop a consensus statement reflecting the integrated opinions of 68 leading neuroendocrinologists and neurosurgeons worldwide. Acromegaly is an insidious disorder caused by a pituitary GH-secreting adenoma resulting in high circulating levels of GH and IGF-I (1). Unfortunately, no single therapy is comprehensively successful in controlling the disease and its protean clinical manifestations, and different treatment modes are associated with unique adverse effects and clinical disadvantages (2). Surgery, radiation, and medical treatments are available for lowering GH and IGF-I hypersecretion, controlling pituitary tumor mass effects, and improving morbidity (3). Recent studies provide a compelling rationale for controlling GH and IGF-I secretion as being the most significant determinant of restoring the observed adverse mortality to control rates (4–6). Regardless of the therapeutic mode, the goal of treatment is to control GH levels to less than 1 μg/liter after an oral glucose load (Fig. 1), normalize age- and gender-matched IGF-I levels, ablate or reduce tumor mass and prevent its recurrence, and alleviate significant comorbid features, especially cardiovascular, pulmonary, and metabolic derangements (7, 8). Control implies GH less than 1 ng/ml after an oral glucose load and normalized age- and gender-matched IGF-I levels. DXRT, Radiation therapy. Transsphenoidal surgery is the procedure of choice for the initial management of acromegaly, and craniotomy is very rarely indicated (4, 5, 9–12). Uniform biochemical and local anatomic outcome criteria should be applied in determining success for all acromegaly treatments. Complete microadenoma resection and maximal removal of locally impinging tumor and hyperfunctioning macroadenomas are desired anatomic outcomes. Reoperation for surgically accessible residual or recurrent tumor remnants visualized by magnetic resonance imaging (MRI) should be considered in patients who fail to achieve surgical remission as defined by rigorous biochemical criteria. Somatostatin receptor ligand (SRL) pretreatment of patients destined for surgery may be useful in patients with serious medical complications of acromegaly (13), but no data are available on influencing surgical outcomes. Technical surgical adjuncts such as endoscopy, neuronavigation, intraoperative hormone assays, and intraoperative MRI may improve operative outcome, patient satisfaction, and complication rates, but definitive data on the impact of these procedures on surgical outcomes are not yet available. Early GH assessment after surgery is useful, and oral glucose tolerance testing and IGF-I assessment should be performed within 2–4 months after surgery and interpreted according to established criteria for defining disease control (8, 14). The results of pituitary surgery are optimal when performed in specialized centers encompassing a team approach to therapy, including expertise in endocrinology, neurosurgery, and pathology. Individual surgical expertise is a major determinant of surgical outcomes and may be defined as a record of peer-reviewed publication of surgical results encompassing both endocrine and surgical evaluation and follow-up; training experience of more than 100 pituitary surgery cases, and annual surgical activity of more than 25 cases/surgeon. Specialized pituitary pathology is desirable, and immunostaining is mandatory for rigorous evaluation of surgical results. GH-secreting adenomas express somatostatin receptor forms; the SSTR2 receptor subtype appears to be a particularly important mediator for signals suppressing GH secretion (15). SRLs, administered by sc or im injection, effectively control GH axis biochemical parameters in 50–70% of patients (16–18) and provide sustained hormone suppression and alleviation of soft tissue manifestations of acromegaly as long as drug administration is continued (19). SRLs are recommended as the mainstay of medical therapy. Oral dopamine agonists are only effective in about 10% of patients, and in selected patients with coexistent hyperprolactinemia, dopamine agonists may be a preferable therapeutic choice, whereas combined use of SRL and dopamine agonist therapy may improve therapeutic efficacy (20). Long-acting depot SRL preparations and longer acting dopaminergic agents are preferred over the short-acting agents (21–24). The GH receptor antagonist (25) represents a novel approach for the treatment of acromegaly, particularly in somatostatin analog-resistant patients (26). Although the drug is investigational, and its long-term safety profile remains to be established, it will be especially useful for patients with persistently elevated IGF-I levels. Radiotherapy administered by conventional means (∼45–50 Gy total dose) is associated with relatively few adverse events other than hypopituitarism. Administered in fractionated doses not exceeding 1.75 Gy/session, radiotherapy can be considere