Optimization of medical therapy in patients with acromegaly
E. Pronin*a (Dr), T. Alekseevaa (Dr), A. Lapshinab (Dr), M. Antsiferova (Prof)
a Endocrinological dispensary, Moscow, RUSSIAN FEDERATION ; b National Medical Research Center for Endocrinology, Moscow, RUSSIAN FEDERATION
Introduction:Taking into account the morphological heterogeneity of somatotrophic tumors, the search for and stratification of potential predictors,which make it possible to forecast the clinical course of acromegaly and the effectiveness of the treatment,is especially relevant nowadays.
The aim:A clinical and morphological comparison between the effectiveness of long-term medical therapy (MT) with somatostatin analogs of the first-generation (SA1) and the immunophenotypic features of densely and rarely granulated somatotrophic adenomas (DHA and RHA) identified using immunohistochemical analysis (IHA).
Materials and Methods:The retrospective study included 65 patients with acromegaly (from the Moscow register),which underwent transsphenoidal adenomectomy (followed by a morphological diagnosis) supplemented in 47 patients with secondary MT SA1 (Lanreotide/Octreotide).The presence of biochemical remission was recorded with the value of IGF-1 index (II) [IGF-1/VVN] <1.The values of IGF-1 decrease from baseline after 3&6months of SA1 treatment were compared with IGF-1 and II values after 12months of treatment and at the last visit.
Results:Patients with DHA were distinguished by late age of diagnosis and smaller initial sizes of pituitary adenoma.With IHA in DHA,a greater percentage of cells with antibodies to growth hormone (GH),a greater expression of the 2nd subtype of somatostatin receptors (SSR),as well as a large difference and ratio between the 2nd&5th subtypes of SSR were detected.
On the contrary,patients with RHA were characterized by an early age of diagnosis,large sizes of pituitary adenoma with extrasellar distribution and invasive growth.
The most significant independent signs associated with % decrease in the level of IGF-1 after 3months of SA1 treatment are:
1.duration of effective SA1 MT (months) (beta=0.56;p=0.034);
2.severity of expression of the 2nd subtype of SSR (beta=0.42;p=0.011);
3.difference in expression scores of the 2nd&5th SSR subtypes (beta=0.39;p=0.015).
1.The presence of fundamental clinical and morphological differences between DHA and RHA was confirmed,as well as the need for a differentiated approach to secondary MT of patients with acromegaly.
2.The magnitude of the decrease in the level of IGF-1 after 3months of treatment correlates with the severity of expression of the 2nd subtype of SSR and can be used as a cut-off point for predicting the effectiveness of long-term primary or secondary therapy for SA1.
The author has declared no conflict of interest.