Optimization of drug treatment of acromegaly (clinical and morphological comparison)

Background. Taking into account the morphological heterogeneity of somatotrophic tumors, the search for and stratification of possible predictors, which make it possible to predict the clinical course of the disease and the effectiveness of the treatment, is currently especially relevant. Objective. Clinical and morphological comparison between the effectiveness of long-term drug therapy with 1st generation somatostatin analogs (SA1) and immunophenotypic features of densely and sparsely granulated somatotrophic adenomas (DGSA and SGSA) identified using immunohistochemical assay (IHCA). Methods. 65 patients with acromegaly who underwent transsphenoidal adenomectomy were examined. DGSAs were detected in 28 (9 men), SGSAs - in 37 (14 men) patients. Patients with DGSA were characterized by a late age of diagnosis and smaller initial sizes of pituitary adenoma. Using IHCA, a greater percentage of cells with antibodies (AB) to growth hormone (GH), greater expression of the 2nd somatostatin receptor (SSR) subtype, as well as a large difference and ratio between the 2nd and 5th SSR subtypes were detected in DGSA. The vast majority of patients with DGSA showed good sensitivity to secondary drug therapy with SA1 with the achievement of early and stable biochemical remission. A correlation between the magnitude of the decrease in the insulin-like growth factor 1 (IGF-1) level after 3 months of treatment and the expression of the 2nd SSR subtype was found. On the contrary, patients with SGSA were characterized by an early age of diagnosis, large sizes of pituitary adenoma with extrasellar expansion and invasive growth. Using IHCA, low expression of the 2nd SSR subtype and increased expression of the 5th SSR subtype, a high percentage of cells with antibodies to cytokeratin, and high proliferative index Ki-67 were noted in SGSA. The use of SA1 in patients with SGSA was manifested by a low suppression of the IGF-1 level after 3, 6 and 12 months of treatment, as well as the absence of biochemical remission at the last visit. Conclusion. The results of the work confirm the existence of fundamental clinical and morphological differences between DGSA and SGSA, as well as the need for a differentiated approach to treatment. The magnitude of the decrease in the IGF-1 level after 3 months of treatment correlates with the 2nd SSR subtype expression level and can be used as a cut-off point for predicting the effectiveness of long-term primary or secondary therapy with SA1.

acromegaly, morphological subtypes of somatostatin receptors, predictive factors for the effectiveness of SA1 treatment