acromegaly
ACROMEGALY
Acromegaly is a chronic, slowly developing disease with progressive disfigurement and disability. An early diagnosis is difficult as most signs and symptoms are due to long-standing overproduction of growth hormone &/or insulin-like growth factor (IGF-I) causing metabolic, endocrine and morphological changes.
Surgical intervention is the first-line of treatment for almost all patients with acromegaly unless there are contraindications or the patient refuses to undergo the procedure.

Pharmacotherapy

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

Somatostatin Analogues (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
  • First-generation SRLs are 1st-line pharmacotherapy agents
  • May also be used after surgery has failed to achieve biochemical control
  • May provide disease control, or partial 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 and short-acting SC 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
  • Actions: Bind to somatostatin receptor subtypes 2 and 5 on growth hormone-secreting adenomas to suppress growth hormone secretion
  • Somatostatin analogues are effective in normalizing growth hormone and insulin-like growth factor-I levels in approximately 55% of patients
    • Decrease growth hormone secretion to <2.5 ng/mL in 44% of patients in unselected populations
    • Normalize insulin-like growth factor-I levels in 34% of patients in unselected populations
    • Tumor shrinkage of >20% in approximately 75% of acromegaly patients
  • Advantages: 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-I in the absence or concomitant presence of somatostatin analogues therapy)
  • Bind to D2 dopamine receptors expressed on growth hormone-secreting adenoma and reduces growth hormone production
  • Advantages include their low cost and that they are the only orally administered medication 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-I levels)
    • Cabergoline may be considered in patients with persistent disease after surgery or added to SRL if IGF-1 levels <2.5 times the upper limit of normal
  • An additive therapy to somatostatin analogues in patients partially responsive to a maximum somatostatin analogues dose
    • With combination therapy, approximately 50% of such patients may achieve control of insulin-like growth factor-I 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-I 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 growth hormone receptor antagonist 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-I levels despite maximal therapy with other treatment modalities
    • Effective in normalizing insulin-like growth factor-I 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 analogues
  • 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 LFTs 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 analogues therapy, Cabergoline may be useful for further lowering of insulin-like growth factor-I or growth hormone levels
  • In patients with a partial response to somatostatin analogues therapy, addition of daily, weekly or twice weekly Pegvisomant may be beneficial
Digital Edition
Asia's trusted medical magazine for healthcare professionals. Get your MIMS Endocrinology - Malaysia digital copy today!
Sign In To Download
Editor's Recommendations
Most Read Articles
2 days ago
Podcast: Dr Shamir Mehta briefly discusses the clinical impact of findings from the COMPLETE trial
2 days ago
Podcast: Prof Derek Chew explains the importance of a 1-hour troponin T protocol in suspected ACS as discussed in the RAPID-TnT trial
2 days ago
Sodium-glucose transport protein 2 (SGLT2) inhibitors exert a putative epigenetic regulation of the protecting cardiovascular effect, reports a study, adding that dapagliflozin may protect the kidneys by preserving renal vasodilating capacity.
Pank Jit Sin, 6 days ago

The Malaysian Endocrine and Metabolic Society (MEMS) and Malaysian Diabetes Educators Society (MDES) jointly launched the For Your Sweetheart campaign—a nationwide endeavour to increase public awareness and to educate Malaysians about diabetes-related heart disease.