Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly
Condition: Acromegaly
MeSH terms: Acromegaly
Study type: Observational

Summary: 
      To investigate the 60 month impact of surgery and somatostatin analogues (SSA) on glucose
      metabolism in acromegaly we will analyzed data from 100 patients with acromegaly according
      with different treatments (group A=with SSA only; group B= SSA followed by surgery; group C=
      surgery only; group D= surgery followed by SSA). At diagnosis and after 6-12 and 60 months
      were analyzed as primary outcome measure changes in fasting glucose and as secondary outcome
      measures changes of glycated hemoglobin (HbA1c) and insulin levels, HOMA-R and HOMA-β,
      representing insulin resistance and β-cell function, respectively.

      We will enrol 100 patients and expect half of them to have IGT or diabetes mellitus. We do
      not expect changes according with different treatment after 60 months while SSA-treated
      patients might experience deterioration of glucose tolerance after 6-12 months. We intend to
      look for predictors of deterioration of glucose tolerance.
    

Detailed description: 
      Impaired glucose tolerance (IGT) and overt diabetes mellitus are frequently associated with
      acromegaly. Patients with acromegaly are insulin resistant both in the liver and in the
      periphery, displaying hyperinsulinemia and increased glucose turn-over in the basal
      post-absorptive states. The prevalence of diabetes mellitus and that of IGT in acromegaly is
      unknown but is reported to range 19-56% and 16-46% in different series. The increased
      cardiovascular morbidity and mortality associated with acromegaly may party be a consequence
      of the increased insulin resistance that frequently accompanies GH excess. Glucose tolerance
      may worsen in patients treated with somatostatin analogues (SSA), because insulin secretion,
      i.e. β-cell function, is also suppressed. SSA induce control of GH and IGF-I excess in
      approximately 60% of patients after 12 months of treatment with no significant difference as
      applied after unsuccessful surgery or as first-line in newly diagnosed patients and control
      of GH and IGF-I levels occur with an even higher prevalence after a longer period of
      treatment. The inhibitory effect of SSA on pancreatic insulin secretion might, however,
      complicate the overall effect of this treatment on glucose tolerance. We recently
      demonstrated that 12 months after first-line treatment with SSA or surgery produced a similar
      improvement in LV hypertrophy and diastolic filling while systolic function increased more
      evidently in SSA-treated patients, total/HDL-cholesterol ratio significantly reduced only in
      SSA-treated patients while fasting glucose levels significantly reduced only in
      surgery-treated patients. A normal pituitary function was found in 46.4% of SSA-treated and
      in 36.4% of surgery-treated patients, resulting unchanged in the former and slightly reduced
      in the latter. Both a direct effect of SSA and a more preserved pituitary function might
      explain these results. Longitudinal data of glucose tolerance in patients with acromegaly and
      with or without diabetes treated long-term with SSA or surgery or both are still very
      limited.

      In order to investigate whether SSA negatively impact glucose tolerance in acromegaly, we
      will analyze data collected prospectively during a 10 year period. We will compare the
      results of glucose tolerance at diagnosis after 6-12 months and after 60 months of treatment
      with SSA or surgery. Patients will be grouped according with their treatment (SSA only,
      surgery only, SSA followed by surgery and SSA followed by surgery and SSA) in order to
      establish the effects on glucose tolerance mediated by disease control and type of treatment.
    

Intervention name(s): Octreotide-LAR or lanreotide; Transsphenoidal adenomectomy
Intervention type(s): Drug; Procedure
Intervention description(s): Treated with octreotide-LAR will be given at dosages of 10-40 mg/q28d and treatment with lanreotide-SR at dosages of 60-120 mg/q28d. The dosages are up-titrated to control GH and IGF-I levels; Removal of pituitary adenomas via one-nostril transsphenoidal approach and endoscopy-assisted.
Other intervention name(s): Sandostatin-LAR (Novartis), Ipstyl (Ipsen)
Intervention MeSH terms: Octreotide; Lanreotide
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        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 June 1st 2008, 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 60 months. Due to the study design, this is a non ran-domized 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.
      
Biospecimen description: 
      Sera from most patients on a yearly bases are stored in our freezed at minus 80° for eventual
      further studies. No experimental parameters are included in the current study.
    
Keywords: Acromegaly; GH; IGF-I; Octreotide-LAR; Lanreotide; Transsphenoidal surgery