title: The role of combination medical therapy in the treatment of acromegaly.
abstract: OBJECTIVE
  Uncontrolled acromegaly results in approximately 2-fold excess mortality. Pituitary surgery is first-line therapy, and medical treatment is indicated for persistent disease. While cabergoline and pegvisomant are used in select patients, somatostatin receptor ligands (SRLs) remain the cornerstone of medical treatment. Management of patients poorly responsive to SRLs is therefore, challenging. The purpose of this review is to highlight the options for combination medical therapy in the treatment of acromegaly, with an emphasis on efficacy and safety.
  
  
  METHODS
  All original articles/abstracts detailing combination medical therapy in acromegaly were identified from a PubMed search.
  
  
  RESULTS
  Studies reviewed included retrospective and open-label prospective studies. While the combination of SRL and cabergoline was generally well tolerated, a lower baseline insulin-like growth factor-1 (IGF-1) level was the best predictor of efficacy; this combination may be most effective in patients with mildly elevated IGF-1. SRL-pegvisomant combination normalized IGF-1 in the majority of patients; continued efficacy despite individual drug dosing reduction was also reported. The risk of significant liver enzyme elevation was, however, higher than that reported with SRL monotherapy; close monitoring is recommended. Data on pegvisomant-cabergoline combination is limited, but this may be an option in the setting of SRL intolerance. Reports on temozolomide used in combination with other medical therapies in patients with aggressive GH-secreting tumors are also summarized.
  
  
  CONCLUSIONS
  While more prospective, randomized controlled trials on long-term efficacy and safety are needed, combination medical therapy remains a treatment strategy that should be considered for acromegaly patients poorly responsive to SRLs.
authors: Departments of Medicine (Endocrinology) and Neurological Surgery, and Northwest Pituitary Center, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, 97239, USA.
authors: Dawn Shao Ting
authors: DS
authors: Lim
authors: Departments of Medicine (Endocrinology) and Neurological Surgery, and Northwest Pituitary Center, Oregon Health & Science University, 3303 SW Bond Ave, Mail Code CH8N, Portland, OR, 97239, USA. fleseriu@ohsu.edu.
authors: Maria
authors: M
authors: Fleseriu
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000077465:Cabergoline; D003131:Combined Modality Therapy; D004873:Ergolines / Q000627:therapeutic use; D006801:Humans; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism; D011986:Receptors, Somatotropin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004873:Ergolines; D017481:Receptors, Somatostatin; D011986:Receptors, Somatotropin; D000077465:Cabergoline
keywords: Acromegaly; Combination medical therapy; Dopamine agonist; Growth hormone receptor antagonist; Somatostatin receptor ligand