A comprehensive study of clinical, biochemical, radiological, vascular, cardiac, and sleep parameters in an unselected cohort of patients with acromegaly undergoing presurgical somatostatin receptor ligand therapy

J Clin Endocrinol Metab. 2013 Mar;98(3):1040-50. doi: 10.1210/jc.2012-3072. Epub 2013 Feb 7.

Abstract

Context: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management.

Objective: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort.

Study design: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy.

Results: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes [Δ]: GH, -6.88 μg/L [interquartile range -16.78 to -3.32, P = .000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P = .000002]; and pituitary tumor volume, -256 mm(3) [-558 to -72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of ΔGH or ΔIGF-1, but moderately correlated with Δweight (R(2) = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to +0.2, P = .046]) and endothelial function (flow mediated dilatation, +1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men (-11.8 g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of ΔGH or ΔIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged.

Conclusions: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / complications
  • Acromegaly / drug therapy*
  • Acromegaly / surgery
  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Female
  • Human Growth Hormone / blood
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / etiology
  • Hypertrophy, Left Ventricular / drug therapy*
  • Hypertrophy, Left Ventricular / etiology
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Middle Aged
  • Peptides, Cyclic / administration & dosage*
  • Preoperative Care / methods
  • Prospective Studies
  • Receptors, Somatostatin / antagonists & inhibitors
  • Sleep Apnea Syndromes / drug therapy*
  • Sleep Apnea Syndromes / etiology
  • Somatostatin / administration & dosage
  • Somatostatin / analogs & derivatives*
  • Treatment Outcome
  • Vascular Stiffness / drug effects
  • Young Adult

Substances

  • Antineoplastic Agents
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • lanreotide
  • Human Growth Hormone
  • Somatostatin
  • Insulin-Like Growth Factor I