Endocrine Abstracts

Somatostatin analogues (SSA) are the mainstay of pituitary-targeted pharmacological treatment in acromegaly, but are characterized by high incidence of resistance in half of cases. The successful management of acromegaly involves in addition to targeting biochemical control the treatment of the metabolic comorbidities and hypopituitarism. In this study we analysed the impact of the concomitant antidiabetic treatment and hormone replacement on the response to SSA. Data were collected from 49 acromegalic patients: 45 had transsphenoidal surgery (35 as primary therapy), 36 SSA (11 as primary treatment). All patients with diabetes mellitus (25%) received metformin. Hypopituitarism affected 18 patients.

Binary logistic regression analysis (SPSS software) showed no correlation between SSA (P=0.71) and transsphenoidal surgery (P=0.541) on pituitary insufficiency incidence. Regression analysis showed no correlation between IGF-I lowering response to SSA and substitution treatment with hydrocorticosterone, testosterone or L-thyroxin (variance inflation factor <3). Linear regression analysis showed no correlation between age, gender, disease duration, hormone substitution modalities and change of IGF-1 levels after SSA treatment. However, the same analysis showed correlation between metformin therapy and IGF-I levels after SSA treatment (P=0.031; R-square change: 0.135; R-square: 0.321). In vitro investigation on 7 human acromegalic tumours showed that metformin (500 μM) enhances the GH-suppressive effect of octreotide (1nM) (% of control 63±13 versus 81±12). Metformin alone significantly suppressed GH secretion at the 1mM concentration (64±13) and similar observations were obtained on the rat GH promoter activity and GH secretion from rat immortalized GH-secreting GH3 cells. These preliminary observations indicate that hormone replacement does not affect SSA response, but metformin treatment improves it in terms of IGF-I reduction.