Predictors of acromegaly clinical history and treatment effectiveness (based on Moscow Register Data)

• Mikhail B. Antsiferov
• Tatyana M. Alekseeva
• Evgeniy V. Pronin
• Vaytcheslav S. Pronin

Abstract

Acromegaly is a severe multi-organ disease that negatively affects the quality and life expectancy of patients. The continuing complexity of curation of acromegaly is due to the multiplicity of pathomorphological variants of growth hormone-secreting adenomas, which differ in the degree of cellular specialization, aggressiveness of intracranial growth and sensitivity to prescribed treatment. Absence of a differentiated approach when choosing a treatment strategy significantly reduces the effectiveness of expensive treatment measures. In this regard, it is important to search for clinical and laboratory predictors that allow predicting the clinical course and effectiveness of treatment of acromegaly.

The aim of this work is to analyze the long-term results of primary and secondary medicamentous therapy (PMT and SMT) with the allocation of clinical and laboratory markers that determine the characteristics of the course of the disease and affect the effectiveness of treatment measures, including the long-term use of somatostatin analogs of the 1^st generation (SA1).

Material and methods. 484 patients (138 men and 346 women) included in the Moscow register of acromegaly patients were examined. PMT was used in 217 (42 men and 175 women) and SMT - in 267 (96 men and 171 women) patients on average 4 (6) years after non-radical transnasal adenomectomy. As pharmacotherapy, SA1 [long-acting forms of lanreotide and octreotide (252 and 191 patients, respectively)], as well as a selective dopamine agonist cabergoline in the form of primary or combined MT were used. The average duration of MT was 68 (48) months [M(s)] with a maximum of 187 months (16 years). Adequacy of pharmacotherapy was assessed by the decrease in the level of IGF-1 therapy, duration of occurrence of biochemical remission [reduction of IGF-1 level to or below the upper age of normal (UAN), as well as duration of effective and ineffective treatment. The control points of sensitivity to SA1 were the value and percentage of decrease in IGF-1 from the baseline level after 3 and 12 months of SA1 treatment. Based on the obtained data, a retrospective analysis of the initial clinical, laboratory and functional features was performed in order to identify valid markers that allow predicting the effectiveness of MT.

Results. As a result of the treatment, the total IGF-1 index (IGF-1|UAN) decreased towards safe values (from 2.6 (1.2) to 1.1 (0.7) [M(s)] (p=0.001)), but persistent biochemical remission (IGF-1 index ≤1) was achieved only in 242 patients (49.3%) (with PMT and SMT in 46 and 54% of cases, respectively). It was found that the age of diagnosis, male gender, baseline levels of GH and IGF-1, size of pituitary adenoma, sensitivity to short-term treatment of SA1 are predictive factors of the effectiveness of long-term pharmacotherapy. It was found that the decrease in the level of IGF-1 after 3 months of treatment correlates with the level of IGF-1 after 12 months, the final IGF-1 index, as well as the duration of effective and ineffective treatment of SA1. Based on the results of the analysis, a point scale of clinical and laboratory predictors was proposed, which allows assessing the nature of the disease course and the prospects for long-term drug therapy.

Conclusions. The use of cut-off points (IGF-1 content after 3 and 12 months of SA1 treatment), as well as a predictor scale, allows predicting long-term MT results and performing timely correction of the treatment manual.

Keywords:acromegaly, somatotropinomas, drug treatment, somatostatin analogues, prognostic markers

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