Acromegaly Management Guidelines: Update 2009 JCEM (Melmed et al)

http://jcem.endojournals.org/cgi/reprint/94/5/1509.pdf;
meeting in Nov'07
GRADE system: VLQ|LQ|MQ|HQ
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

Neurosurg:

TSS: tx of choice for
intrasellar microadenomas
noninvasive macroadenomas (ie w/o {cavernous sinus|bone} invasion)
tumours causing compression symptoms
Efficacy:
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,
epistaxis;
CI for surgery:
refusal,
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)
Challenges:
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)
Efficacy:
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%
Indications:
- 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

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

Monitoring:

GH (OGTT, random)
IGF-I
"biochem control"=GH<1.0ng/ml dur OGTT, or
random GH<0.4ng/ml
MRI
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

JCEM'09;

Increased GH secretion

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