CLINICAL AND HORMONAL FEATURES OF ACROMEGALY IN PATIENTS FROM A UKRAINIAN NEUROENDOCRINOLOGY CENTRE

Abstract

Acromegaly (ACRO) is a rare disease of an excessive somatic growth and distorted proportions arising from hypersecretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1). Insidious clinical mani­festation of the GH excess, resulting from a GH-secreting pituitary adenoma, renders ACRO as the disease with a typically delayed diagnosis, approximately 10 years from the symptoms onset. Despite the increasing availability of modern diagnostic methods, the timely diagnosis of ACRO at present is still a problem which is directly connected with the further prognosis. Owing to this reasons, it is important to establish national registers of patients with hormonally active pituitary adenomas, including registers of patients with ACRO. But not all countries have the possibility to create such registries at the state level. In the countries of Eastern Europe, the research of the kind is carried out in the specialized national medical centers.
 The aim of this study is to investigate basic demographic parameters such as the age and gender related features, age at diagnosis of the disease, its clinical manifestations, biochemical control and structure of compli­cations in Ukrainian patients with ACRO in a single neuroendocrinological centre.
 Material and methods. Patients with acromegaly, including somatotropinoma (ST) and somatomam­motropinoma (SMT): the data collected within the Neuroendocrinological Centre, based in V. Danilevsky’ Institute for Endocrine Pathology Problems (n = 133 [including 47 de novo]: female — 88, male — 45) and retrospective study 133 patients (female — 91, male — 42) who had neurosurgical treatment (according to da­tabase of Romonadov’ Neurosurgery Institute). Diagnosis of ACRO was based on the Consensus Statement on acromegaly (2014). The levels of PRL, GH and IGF-1 were measured. All patients underwent an enhanced and a plain MRI scan using a Siemens 1.5 T MRI.
 Statistical analysis: SPSS 19.0 statistical software (IBM Corp., Armonk, NY, US) was used for statistical analysis. Comparisons between plasma GH and IGF-1 levels of patients in two groups were done by ANOVA for age, gender, and other hormonal and clinical parameters.
 Results. Our study has established that 88.8% (n = 238) of the overall sample consist of patients aged 31 to 60 years: 26.5 % (n = 71) of men and 55.2 % (n = 148) of women belong to the aforesaid age range (χ2 = 15.47; P = 0.0001). Peak of the ACRO manifestation in the overall sample falls on the age of working efficiency (41.3 ± 12.0) years: (39.0 ± 13.2) years for men and (42.8 ± 11.0) for women. Analysis of the complaints structure in patients with acromegaly at the time of its manifestation has shown that the severity of the common com­plaints (fatigability (45.5 %), asthenia (43.9 %), headache (43.9 %), and excessive sweating (42.3 %)) contributes to the blurring of the disease clinical features, which is one of the purposes for its late diagnosis. Complaints about the changes in their appearance (increasing sizes of hands and feet (60.2 %) and in facial features (42.3 %)), which are specific morphological markers of ACRO, more than 50 % of patients consider as age-related, so they do not cause special uneasiness. The average duration of an active phase in the overall sample is 139.2 months. (Me = 93.6 month) and it varies from 6 to 38 years. The active phase duration is more than twice of pre-nosological period that can be explained by the use of no effective methods and outlines of the dis­ease treatment (medical therapy, radiotherapy). It has been established that pre-nosological period has a linear proportional increase, related with age in patients with ACRO: R2 = 3.4 %; P = 0.041) and is also associated with the age of manifestation (R = 0.24; R2 = 5.96 %; P = 0.007).
 Conclusion. Sexual dimorphism of the clinical course of acromegaly is manifested at a young age at the time of manifestation of the disease and is characterized by a higher secretory activity of GH-secreting adenoma and a it greater mass effect in men. Secretory and proliferative activity of the GH secretive pituitary adenoma is associated with the age of the patient at the time of the manifestation of ACRO. High total secretory activity of GH-secreting pituitary adenoma, tumor growth rate, resistance to treatment and predisposition to relapse, which are associated with the young patient at the time of the manifestation of the disease, determine the «fast-moving» flow of ACRO. In elderly patients, the domination of the secretory over the proliferative activity of the GH-secreting pituitary adenoma gland and the satisfactory sensitivity to the treatment determine the «slowly progressive» clinical course of disease.