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Acromegaly Management Guidelines: Update 2009 JCEM (Melmed et al);
meeting in Nov'07
usu benign but cv/resp/endocr/metabol abnlties
acral overgrowth ... diabetes...HF
also possible sympt fr expandg tu: VF defects/HA
SMR 1.72, imprvd in more recent studies
recently still 32% icrd risk all-cause mort
post Tx random GH {<|>} 2.5ng/ml SMR {1.1|1.9}
post Tx {nml|icrd} IGF SMR {1.1|2.5}
dcrd mort with freq use of SMS receptor ligands (SLRs)
dcrd mort with biochem remission after tx
Tx: surgery|medical|radiother
radiother: poss icrd mort


TSS: tx of choice for
intrasellar microadenomas
noninvasive macroadenomas (ie w/o {cavernous sinus|bone} invasion)
tumours causing compression symptoms
nml post-surg IGF-I in {75-95%|40-68%} for {micro-|macro-}adenomas
usu: tu>2cm a/w greatly dcrd success rate
need pit neurosurgeon with 50+ pit op/yr
complications of TSS (<1%):
transient oculomotor palsies,
deterioration of vision,
carotid artery injury,
CI for surgery:
severe cariomyopathy
severe resp dis
lack of available skilled surgeon;
Presurg Tx: SRL: possible improved success (VLQ)
Tu unlikely controlled by surgery alone:
40-60% of macroadenomas (eg invasive)
options: prim medical tx or surgical debulking + {medical|radio}tx
possible better nmlzation rates with debulking (esp if >75% tu removed)
classification system for adenoma size and invasiveness,
cost-effectiveness studies of SRL pre-tx

Medical Tx

3 drug classes
- DA=dopamine agonists
- SRL=somastostatin receptor ligands
- GHRA=GH receptor antagonists
SRL: Indications
- 1st line if lo prob for surg cure (eg large w/o compressive symptoms)
- post-surg if no biochem control
- pre-surg (?unproven benefit of dcrg complications)
- for dis control betw radiother admin and max benefit (...yrs)
70% achieve GH<2.5ng/ml and nml IGF-I
max benefit may be after 10yr tx
but biased by preselection for GH responsivity
if unselected: GH<2.5ng/ml in 44%, IGF-I nmlzation in 34%;
tu shrinkage >20% in 75% (mean: 50% tu vol dcr);
proven safety
SE: abdo bloating and cramping, gallstones, rare: pancreatitis
similar efficacy of 2 LA preparations: octreotide LAR, lanreotide Autogel
dose adjustments no earlier than 3 mths

GHRA (Pegvisomant): Indications:
- persistently icrd IGF-I despite max other tx
- possibly as monother or in comb with SRL
highly effective, improves QoL (combined with SRL)
SE: LFT abnlties (25%, usu transient), tu growth (<2%)

Comb ther SRL+GHRA
may be useful, and possibly cost-saving over hi-dose GHRA tx

DA: only Cabergoline, but not Bromocriptine, effective, and in <10%
- if pt wants oral medication
- post-surg eg if v icrd PRL
- combd with max dose SRL
SE: concerns about cardiac valvular abnlties with hi dose cabergoline (eg PD): monitor by echo

Tx of comorbidities for QoL:
arthropathy, htn, OSA, DM, CMP, colon polyps, goitre, headache

comparisons of SRLs, SRLs vs GHRA vs comb

Radiation therapy:
specialized center, reserved for 3rd [/2nd [/ 1st]] line
Possible indications:
- if failed tu growth or hormone level control after surg/medical tx
- if risk of tu expansion with GHRA tx
- for termination of otherwise lifelong medical tx
conventional RT (conformal, fractionated):
dcrd GH and nmlzd IGF-I in >60%, max response after 10-15yr
single-dose, focused RT (Gamma Knife, Linear Accelerator):
5yr remission: 29-60% for smaller tumours (no long-term data)
Safety issues:
hypopit >50% (both conventional and stereotactic)
vision defects: 5.5%
poss risk of second tu
poss risk of cerebrovasc events due to radiation vasculopathy
causative link betw RT and cerebrovasc mort
causative link betw RT and second tu
eval of neurocogn defects

Tx goals:

nml mort, ie aim for:
-nml IGF-I;
main determinants of mort:
-basal GH>2.5ng/ml,
-icrd IGF-I,
-dis duration,
-cardiac dis;
Tu shrinkage
Mx of comorbidities: tx as appropriate
if worsening DM on SRL, consider GHRA
colonoscopy at diagnosis of acromegaly


GH (OGTT, random)
"biochem control"=GH<1.0ng/ml dur OGTT, or
random GH<0.4ng/ml
pit fx: full pit assessment (eg adrenal insuff or post pit dysfx) 3mths post surg
repeated necessary after radiother
echo at baseline
OSA (25-60%): assess sleep disturbance
Colonoscopy: at baseline, and FU as per gen guidelines


Increased GH secretion

  • Sleep
  • malnutrition / fasting (low IGF-1)
  • Stress
  • Exercise
  • Hypoglycaemia
  • uncontrolled T1DM
  • liver cirrhosis