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

作者：Annamalai Anand K; Webb Alison; Kandasamy Narayanan; Elkhawad Maysoon; Moir Samantha; Khan Fakhar; Maki Petaja Kaisa; Gayton Emma L; Strey Christopher H; O'Toole Samuel; Ariyaratnam Shaumya; Halsall David J; Chaudhry Afzal N; Berman Laurence; Scoffings Daniel J; Antoun Nagui M; Dutka David P; Wilkinson Ian B; Shneerson John M; Pickard John D; Simpson Helen L; Gurnell Mark^*

来源：Journal of Clinical Endocrinology & Metabolism, 2013, 98(3): 1040-1050.

DOI：10.1210/jc.2012-3072

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[triangle]: GH, -6.88 mu g/L [interquartilerange - 16.78 to - 3.32, P = .000001]; IGF-1, - 1.95 x upper limit of normal [- 3.06 to - 1.12, P = .000002]; and pituitary tumor volume, -256mm(3) [-558 to - 72.5, P = .0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of triangle GH or triangle IGF-1, but moderately correlated with triangle weight (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 flow mediated dilatation, + 1.73% [-0.32 to +6.19, P = .0013]) were observed. Left ventricular mass index regressed in men(- 11.8g/cm(2) [-26.6 to -1.75], P = .019) but not in women (P = .98). Vascular and cardiac changes were independent of triangle GH or triangle IGF-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. (J Clin Endocrinol Metab 98: 1040-1050, 2013)

• 出版日期2013-3