Acromegaly

Causes of acromegaly


Treatment of acromegaly

Surgery Somatostatin receptor ligands Pegvisomant Dopamine agonists
  • overall surgical cure rate about 50%
  • low cure rates for large tumours (>2cm), cavernous sinus invasion etc
  • 75-95% cure for intrasellar microadenomas
  • 40-70% cure in non-invasive macroadenomas
  • Bates et al show lower cure rates in the UK (see Figure)
  • first-line therapy when no hope of surgical cure, or surgery refused
    • rarely used pre-surgery
    • with octreotide, Colao (2009) reports 28% complete success and 40% partial success at 38 weeks
    • with lanreotide, Colao (2009) reports normalization of GH and IGF-1 in 54%, with 25% tumour shrinkage in 77%
  • second-line after surgery has failed
  • also used pending full effect of radiotherapy
  • about 40-70% of patients achieve long-term control
  • maximum benefit may be 10 years after initiation
  • about 75% show tumour shrinkage (mean reduction 50%)
  • side effects: bloating, cramps, gallstones, bile sludge, rare cholecystitis
  • pasireotide (high SST5 affinity) has shown success in patients not controlled on conventional SSTR ligands
  • growth hormone receptor antagonist
  • once-daily injection
  • Higham et al (2009) reported experience in 57 patients:
    • very effective: 95% achieved normal IGF-1
    • 56 out of 57 showed no tumour growth
  • transient LFT abnormalities occur occasionally
  • not generally recommended - efficacy was said to be about 10%, mainly those with raised prolactin
  • Sherlock et al show similar efficacy in normal and raised prolactin
  • Sherlock et al report reductions of 42% in GH and 8% in IGF-1, though neither statistically significant
Surgical cure rates for acromegaly in UK, from Bates et al (2008)

Acromegaly tumours express predominantly: somatostatin receptors SST2 and SST5, and dopamine receptors DR2 and DR4.



Monitoring treatment of acromegaly

Association between basal GH and nadir GH in OGTT in treated acromegaly, from Sherlock et al

Recent guidelines define cure as a nadir on OGTT of <1 µg/L, and a normal age- and sex-adjusted IGF-1 level. However, long-term mortality data have been based on random GH:

Sherlock et al (2009) show that basal GH is highly predictive of nadir GH in an oral glucose tolerance test - see Figure and Table. A basal GH <2.5 µg;/L strongly indicates that a formal OGTT is unnecessary.

Divide results in mIU/L by 2 to obtain results in µg/L.

GH µg/L GH nadir
OGTT <2.5
GH nadir
OGTT >2.5
Basal GH <2.5 98.6% 1.4%
Basal GH 2.5-5 50.9% 49.1%
Basal GH >5 11.2% 88.8%

Bowel surveillance