MODERN APPROACH ТО DIAGNOSTCS AND TREATMENT OF PATHOLOGICAL HYPERPROLACTINEMIA

Hyperprolactinemia is one of the most frequent neuroendocrinal disorders and consequently questions of diagnostics and treatment of this syndrome continue to remain actual. Diagnostics of hyperprolactinemia is not the simple task demanding not only determination of the prolactin levels, but also measurement of its fractions with an assessment of the bioactive prolactin levels, careful studying of the anamnesis, an exception of various somatic, endocrine and neuroendocrinal disturbances. Treatment of a pathological hyperprolactinemia demands the differentiated approach taking into account clinical and biochemical data and radiological data. A leading method of treatment is medical therapy by agonists of dopamin receptors. Diagnostics and treatment of hyperprolactinemia must be based on modern evidence-based guidelines

TUMORAL AND NON TUMORAL PITUITARY LESIONS AND REPRODUCTIVE SYSTEM

Activity of reproductive system is under the hypothalamic and hypophysial control, defining role in development and normal functioning of gonads is played by impulsive secretion of GnRH and gonadotropins. The congenital genetic defects leading to the central hypogonadism can be found at any level of a hypotalamo-hypophysial axis: from disturbance of secretion of GnRH to structural defects of gonadotropins. The majority of cases are sporadic though various ways of inheritance have also been reported. The acquired hypotalamo-hypophysial disturbances can be organic and functional. Organic disorders of such lesion include different types of tumors localized at chiasmo-sellar region (first of all, pituitary tumors), consequences of surgical or radial intervention concerning these neoplasms, brain injuries and also autoimmune, infiltrative and other more rare species of diseases. Functional neuroendocrine disturbances arise against absence of visible changes of structure of a brain as the main reasons consider superfluous exercise stresses, stresses and critical depression of mass of a bod

Octreotide in the treatment of acromegaly – the possibilities of high-dose therapy

Octreotide is a first-generation somatostatin analog that has been used for 40 years for the medical treatment of acromegaly, both after neurosurgical intervention and as first-line treatment. The frequency of biochemical control against the background of extended-acting octreotide varies from 25 to 56% depending on growth hormone and IGF-1 levels at the disease debut, presence of previous surgery, patient gender and age, treatment compliance and the dose of octreotide used. Longterm clinical experience with prolonged-acting octreotide demonstrates that more than half of patients require an increase in dosage to 30 mg or higher. If during treatment with Octreotide in a dose of 30 mg for 3 months there is no normalization of IGF-1 level, but there was a decrease of 50% or more of the initial level, further dose increase to 40 mg is possible, because this increases the effectiveness of treatment without increasing the frequency of side effects. Foreign researchers have shown that high doses of Octreotide (60 mg every 28 days) can improve biochemical control in patients who have not fully responded to therapy with doses of 30–40 mg of extended-acting Octreotide. Further studies are needed to determine the optimal dose of prolonged octreotide in acromegaly therapy, both at the start of treatment and during treatment. Management of patients by a team of specialists involved in the treatment of pituitary tumors will allow faster achievement of biochemical control of acromegaly

Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement

Introduction With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country

Adherence to somatostatin analog therapy for acromegaly

The main goals of treatment for many diseases are to improve the prognosis of diseases and to enhance the quality of life. Among the barriers that restrict achieving these goals we have to mention adherence to treatment. Patients with chronic diseases, including acromegaly, are at increased risk of poor adherence to treatment. The duration of supervision of patients with acromegaly in most cases exceeds 25-30 years, which makes the issue of adherence to treatment extremely important.One of the main goals of the acromegaly treatment is to achieve the target values of STH and IGF-1, which ensures the regression of most clinical symptoms and restoration of life expectancy. For this purpose, a significant proportion of patients with acromegaly receive somatostatin analog treatment - as a second line of treatment after non-radical neurosurgical intervention, or as the first line of treatment if neurosurgical intervention could not be performed for any reason. Adherence to treatment is influenced by socio-economic factors, the characteristics of the drug, and the characteristics of the patient. Recent studies have shown that the easy administration of lanreotide provides better treatment adherence than octreotide. Factors that can reduce adherence to the treatment of acromegaly are old age, mental disorders, subjective opinion about the low quality of life, the need to visit medical institutions to administer the drug. On the contrary, the ability to perform subcutaneous injections (on their own or with the help of relatives) without visiting medical facilities, providing accessible information about the disease and the need for its treatment significantly increases adherence to treatment. It is necessary to continue research on the factors and methods of increasing adherence to drug treatment of acromegaly

PREMATURE AGING MARKERS IN WOMEN OF REPRODUCTIVE AGE WITH HYPOPITUITARISM

Background: Premature aging reduces quality of human life, leads to development of “old age diseases” in younger age, and also shortens life expectancy. Aim: Investigation of premature aging markers in women of reproductive age with central untreated hypogonadism in association with other compensated pituitary deficiencies. Materials and methods: Hormonal and biochemical parameters, body mass index (BMI) and body mineral density (BMD) were investigated in 87 women of reproductive age (median – 24 y.o.) with the central untreated hypogonadism in association with other compensated pituitary deficiencies (hypopituitarism) and in 52 healthy age-matched controls. Results: Low levels of estrogens as well as androgens (total and free testosterone, DHEA-S) were found in women with hypopituitarism as compared to the controls. Such markers of premature aging as increased BMI (р=0,025), high levels of cholesterol (р<0,001) and triglycerides (р><0,001), ionized calcium (р><0,001), alkaline phosphatase (p=0,006), and CTx (p=0,025) were revealed; low BMD was found in 87% of patients with hypopituitarism (mainly ><-2.5 SD in lumbar vertebra). Correlation analysis elucidated that hypoandrogenemia as well as hypoestrogenemia was pathogenetic basis of premature aging in women with hypopituitarism and untreated hypogonadism. Conclusion: Such markers of premature aging as BMI increase, dislipidemia, increased levels of bone metabolism markers, and low BMD were revealed in women of reproductive age with uncured hypogonadism and other compensated types of hypophysial insufficiency. Treatment of hypogonadism in this cohort of patients needs to be considered a prevention of the premature aging

Quality of life in patients with acromegaly based on the AcroQoL questionnaire

Rationale: International experts emphasize that treatment strategies for patients with acromegaly should be aimed not only at normalization of biochemical parameters, but also at the achievement of better health-related quality of life (HRQL). However, the published data on the quality of life in patients with acromegaly is scarce.Aim: To assess HRQL in patients with acromegaly with a disease-specific validated questionnaire (AcroQoL) and to identify potential factors that may influence it.Materials and methods: One hundred fourteen (114) patients aged from 18 to 83 years (median age, 56 years, interquartile range, 46 to 63). All patients were divided into the age groups, as well as into the groups depending on the treatment they had received and on the control of acromegaly.Results: In the whole group of the patients (n = 114), the levels of insulin-like growth factor I significantly (p = 0.026) correlated with the domain “personal relationships”. When the patients with newly diagnosed acromegaly (n = 34) were compared to those who had been previously treated (n = 80), there were significant differences for “HRQL global” (p = 0.015) and “physical dimension” (p = 0.009). HRQL of the patients with controlled (n = 37) acromegaly did not differ from HRQL of those with uncontrolled disease (n = 43) (p > 0.05). Surgery and radiation treatment had no impact on the patients' HRQL (p > 0.05), whereas the treatment with somatostatin analogues improved only its physical dimension (p = 0.034).Conclusion: Treatment interventions do not improve quality of life in patients with acromegaly. This can be explained as follows: modern treatment approaches (surgery, radiation) do not lead to immediate noticeable results, whereas treatment-related complications can manifest themselves clearly. As a result, the patient may get an impression that his/ hers quality of life has not improved, despite the fact that the expediency of the specific treatment administered has been absolutely proven

GROWTH PARTICULARS OF PITUITARY MACROADENOMAS WITH VARIOUS HORMONAL ACTIVITIES

Background: Pituitary adenoma is not as infrequent as thought previously. The prevalence of macroadenomas in general population is up to 0.16–0.2%. Magnetic resonance imaging (MRI) is a method of choice in diagnosis of pituitary adenomas. Until now, specifics of imaging of pituitary adenomas with various hormonal activities have not been discussed.Aim: To analyze comparatively the size, volumes and growth direction in pituitary macroadenomas with various hormonal activities.Materials and methods: We analyzed MRI images of 305 patients with hypophyseal adenomas of more than 10 mm diameter, among them with non-functioning adenomas (n=109), prolactinomas (n=58), and somatotropinomas (n=138).Results: Depending on their hormonal activity, hypophyseal adenomas had different volumes (р<0.001): non-functioning hypophyseal adenomas had the volume of 6620 [2637; 14492] mm3 , prolactinomas – 5365 [1495; 10316] mm3 , somatotropinomas – 3052 [1696; 5727] mm3 . In the majority of patients from all groups, extrasellar growth at several directions was observed. Onedirectional growth was seen in 29% of non-functioning hypophyseal adenomas, 41% of prolactinomas and 37% of somatotropinomas (р>0.05). Non-functioning hypophyseal adenomas and prolactinomas demonstrated mostly suprasellar growth (in 83.5 and 79.3% of cases, respectively), whereas somatotropinomas were growing mostly in infrasellar direction (66.1%).Conclusion: These characteristic features of hypophyseal macroadenomas with various hormonal activities could be used for differential diagnosis, which may help to optimize patient assessment during the diagnostic work-up

EFFICIENCY OF THE ACROMEGALIC PATIENTS’ TREATMENT WITH DIFFERENT DOSES OF SANDOSTATIN LAR IN MOSCOW REGION

Background: Somatostatin analogues therapy is an important part of the acromegalic patients’ treatment. Aim: Assessment of treatment efficiency for patients with acromegaly using different doses of somatostatin analogues. Materials and methods: The data of 128 acromegaly patients registered in Moscow Region were analyzed, 79 (61.7%) of them were treated with somatostatin analogues. The treatment was started with a dose of 20 mg. If the target levels of growth hormone (GH) and type 1 insulin-like growth factor (IGF-1) were not achieved within 6-12 months, the dose was increased to 30 mg, and then to 40 mg. If GH and IGF-1 levels fell under the target values, the dose was decreased to 10 mg. The rate of achievement of optimal GH and IGF-1 levels was analyzed depending on the somatostatin analogue doses used. Results: The percentage of the acromegalic patients who were under the first and the second lines of drug therapy, was almost similar:  55.7 and 44.3%, respectively. Sandostatin LAR in dose of 10 mg was given to 4 (5.1%) of 79 patients, 20 mg – to 33 (41.8%), 30 mg – to 11 (13.9%), and 40 mg – to 31 (39.2%) patients. The target levels of GH and IGF-1 were achieved in 57.6, 54.5, and 32.2% of patients, who received preparation in doses 20, 30, and 40 mg, respectively. Achievement of, at least, one planned criterium (GH or IGF-1) was additionally noted in 10 of 33 (30.3%), 4 of 11 (36.2%), and 9 of 31 (29%) patients within these study groups. The rate of side effects didn’t increase with the raising of оctreotide dose. Conclusion: Application of long-acting release octreotide (Sandostatin-LAR) in doses of 30 and 40 mg is safe and allows to increase percentage of acromegalic patients who achieve a biochemical control over acromegaly