Acromegaly Treatment

• Recommended for patients where surgery is not suitable or in patients with persistent disease after surgical resection of adenoma

Somatostatin Analogs (SSA) or Somatostatin Receptor Ligands (SRL)

• First generation: Lanreotide, Octreotide; Second generation: Pasireotide
• Analogs of naturally occurring somatostatin with similar pharmacological actions but with prolonged duration of action 
• Bind to somatostatin receptor subtypes 2 and 5 on growth hormone-secreting adenomas to suppress growth hormone secretion 
• First-generation SRLs are 1st-line pharmacotherapy agents
• May be used after surgery has failed to achieve biochemical control
• May provide full or partial disease control, in the time between administration of radiation therapy and the onset of maximum benefit attained from radiation therapy
• Available in long-acting release (LAR) depot, short-acting SC, and oral preparations
• Pasireotide LAR, may be used in patients with clinically relevant residual tumor not suitable for resection and inadequately controlled by first-generation SRL
• May be combined with dopamine agonists to improve therapeutic efficacy
• Somatostatin analogs are effective in normalizing growth hormone and insulin-like growth factor-1 levels
• Advantages include rapid onset, continued efficacy, with proven safety record
• Common side effects include cramping and abdominal bloating, with a reduction over the first few months of treatment
• To properly assess adequacy of treatment and the need for dose titration, it is recommended to have patients remain on the same dose for 3 months (if tolerated by patient)

Dopamine Agonists

• Eg Bromocriptine, Cabergoline, Quinagolide
• May be considered particularly in patients with mild biochemical activity (eg modestly elevated serum insulin-like growth factor-1 in the absence or concomitant presence of somatostatin analogs therapy)
• Bind to D2 dopamine receptors expressed on growth hormone-secreting adenoma and reduce growth hormone production
• Advantages include their low cost and that they are the only orally administered medications available for acromegaly
• May very occasionally be a first-line therapy post-surgery in selected patients (eg those with markedly elevated prolactin levels and/or modestly elevated growth hormone and insulin-like growth factor-1 levels)
  • Cabergoline may be considered in patients with persistent disease after surgery or added to SRL if insulin-like growth factor-1 levels <2.5 times the upper limit of normal
• An additive therapy to somatostatin analogs in patients partially responsive to a maximum somatostatin analogs dose
  
  • With combination therapy, approximately 50% of such patients may achieve control of insulin-like growth factor-1 and growth hormone levels
• Bromocriptine was shown to provide benefit in a minority of patients with acromegaly in earlier studies but Cabergoline, a more selective dopamine-2 receptor agonist, may be effective in a larger percentage of patients
• Repeated prolactin, growth hormone and insulin-like growth factor-1 levels should be determined 4-6 weeks after each dosage change of dopamine agonist
• Potential side effects include gastrointestinal upset, orthostatic hypotension, headache and nasal congestion

Growth Hormone Receptor Antagonist (GHRA)

Pegvisomant

• A GHRA that competes with endogenous growth hormone for its receptor and prevents functional dimerization and signal transduction by the growth hormone receptor
• Indicated in patients with persistently elevated insulin-like growth factor-1 levels despite maximal therapy with other treatment modalities
  
  • Effective in normalizing insulin-like growth factor-1 levels in >90% of patients, including those who are partially or completely resistant to other medical therapies
• Often used as medical therapy in patients with inadequate response to or partial tolerability to somatostatin analogs
• Potential side effects include flu-like illness, allergic reactions and elevated liver enzymes
  
  • Serial liver function test monitoring is recommended: Monthly for the 1st 6 months; quarterly for the next 6 months; then biannually
  • Patients with elevated baseline liver function tests require more frequent monitoring
• Serum growth hormone levels are not specific and should not be monitored in patients receiving Pegvisomant
  
  • Endogenous growth hormone levels increase with Pegvisomant administration and Pegvisomant may be cross-measured in growth hormone assays

Combination Therapy

• In patients with partial or inadequate response to somatostatin analogs therapy, Cabergoline may be useful for further lowering of insulin-like growth factor-1 or growth hormone levels
• In patients with a partial response to somatostatin analogs therapy, addition of daily, weekly or twice weekly Pegvisomant may be beneficial