Cardiovascular Outcome After Surgery or Somatostatin Analogues
Cardiovascular Outcome After Surgery or Somatostatin Analogues
A direct comparison between the results of surgery or somatostatin analogues (SSA) on
 cardiovascular complication in acromegaly has never been performed.

 Our objective is to investigate whether first-line surgery or SSA have a different outcome on
 cardiomyopathy after 12 months. The design of the study is retrospective, comparative, non
 randomized, because of ethical problems.

 Setting University Hospital. All patients treated with SSA [either octreotide-LAR (10-40
 mg/q28d), or lanreotide (30-120 mg/q28d); dosages up-titrated to control GH and IGF-I levels]
 or operated on by transsphenoidal approach. For the purposes of this study only controlled
 patients will be included.

 Measurements Primary outcome measures were changes in left ventricular mass index (LVMi),
 diastolic [early to atrial mitral flow velocity (E/A)] and systolic perform-ance [LV ejection
 fraction (LVEF)]. Secondary outcome measures were reduction of total/HDL-cholesterol ratio,
 as a cardiovascular (CV) risk parameter, improvement of glucose profile and pituitary
 function, as indirect causes of CV improvement.

 Expected results: SSA and surgery groups should have similar results in terms of improvement
 of cardiomyopathy. However, recent data suggest that SSA reduce directly heart rate and
 cardiomyocytes performance: clinical implications of these evidences suggest that SSA will
 improve cardiovascular outcome more than surgery. Moreover, after surgery, replacement
 therapy already stabilised or of new onset, has never been considered so far in this setting.
We will review all files from consecutive patients with active acromegaly coming to the Units
 of Endocrinology or Neurosurgery of the "Federico II" University of Naples from Jan 1st 1997
 to December 31st 2006, primarily treated with either surgery or depot SSA, i.e. lanreotide
 (LAN) or slow-release octreotide (LAR), and with an available follow-up of at least 12
 months. Due to the study design, this is a non randomized study. However, our routine
 procedure generally considers first-line treatment with SSA for 6-12 months, unless the
 tumors are clearly non invasive on Magnetic Resonance Imaging (MRI) and/or the patients who
 do not present any surgical or anesthesiological risk.

 Cure criteria are considered according with Giustina et al. Acromegaly is considered to be
 controlled if mean fasting GH levels were ≤2.5 μg/liter in presence of normal IGF-I levels
 for sex and age. Nadir GH after oral glucose load (oGTT) ≤1 μg/liter is also an option to
 evaluate disease control according with the 2000 Consensus Statement. However, oGTT is
 generally not routinely performed in patients receiving SSA, since GH-induced glucose
 suppression is likely to be mediated by the endogenous somatostatin tone. To avoid
 ascertainment bias, disease control after surgery and SSA will be only based on fasting GH
 and IGF-I levels. The diagnosis of acromegaly is defined as previously reported, by high
 serum GH levels during a 6 hr time course, not suppressible <1 µg/l after oGTT and high
 plasma IGF-I levels for age [expressed as value upper limit of normal range (ULN)].

 For the purpose of this study only the patients with controlled acromegaly will be included
 to provide a period of follow-up long enough to investigate changes in cardiomyopathy
 parameters.

 Study protocol: As for our routine procedure, at diagnosis all the patients undergo a
 complete metabolic and endocrine screening. After an overnight fasting, serum IGF-I levels
 are assayed twice in a single sample at the time 0 of the GH profile; GH levels are
 calculated as the mean value of at least 5 (up to 8) samples drawn every 30 min over a period
 of three-six hours and the average value will be considered for the statistical analysis;
 fasting total cholesterol, HDL cholesterol, glucose and insulin levels are also measured. The
 total/HDL-cholesterol ratio, index of cardiovascular risk, is calculated.
Inclusion Criteria:

 -  Patients treated with first-line surgery via trans-sphenoidal route by microscopic
 and/or endoscopic approach or with first-line depot SSA treatment

 -  Achieving control of the disease; AND

 -  With available follow-up after 12 months of treatment

 Exclusion Criteria:

 -  Patients receiving second surgery within 3 months from first surgery

 -  Requiring combined dopamine-agonists and SSA because of a mixed GH/PRL-secreting tumor

 -  Receiving the s.c. octreotide for longer than 15 days; OR

 -  Requiring surgery or SSA as second-line treatment before the completion of the 12
 months or with a follow-up shorter than 6 months after surgery or pharmacotherapy