Investigation of metabolic parameters and the effects of cabergoline treatment on these parameters in prolactinoma patients

ABSTRACT Investigation of Metabolic Parameters and the Effects of Cabergoline Treatment on These Parameters in Prolactinoma Patients Objective: This study was conducted to examine the treatment outcomes and effects of cabergoline therapy on metabolic parameters in patients who presented with prolactinoma diagnosis and initiated cabergoline therapy within the last 5 years. Materials and Methods: Our study is a single-centre retrospective study of patients diagnosed with prolactinoma who were followed up at the Endocrinology Clinic of Çukurova University Faculty of Medicine Hospital over the last 5 years. All patients' age, gender, comorbidities, regularly used medications, smoking and alcohol consumption, initial symptoms and findings, initial physical examinations related to prolactinoma, waist circumference, body mass index (BMI), blood pressure, and other examination findings. The study also examined the cabergoline doses, duration of cabergoline use, prolactin (PRL) normalisation time, echocardiography (ECHO) findings, drug side effects, fasting plasma glucose (FPG) at 6-month intervals, liver and kidney function tests, haemogram, anterior pituitary hormones, lipid parameters, and pituitary MRI findings were retrospectively examined and recorded. Patient data were identified using the automation system (Mergen Tech EBYS) in use at Çukurova University Medical Faculty Balcalı Hospital and by reviewing patient files and e-pulse data. IBM SPSS Statistics (version 27.0) was used for data analysis. Results: The mean age of patients was 45.4±12.4 years; the median body weight was 75,0 kg (68.0–89.0) and the mean BMI was 28.1±4,4 kg/m². The most common symptoms and signs were galactorrhea (56.0%), amenorrhea (26.7%), neurological findings (36.0%) and suprasellar extension (45.3%), while infertility (6.7%), osteoporosis (1.3%), and gynaecomastia (1.3%) were observed at lower rates. Microadenoma was present in 49.3% of participants, macroadenoma in 50.7%, and the disease was ongoing in 26.7%. The starting dose of cabergoline treatment was usually 0,5 mg per week, the mean weekly dose throughout follow-up was 0,5 mg (range, 0.5–1.0), the highest weekly dose was 1,0 mg (range, 0.5–1.5), and the median duration of treatment was 48 months (range, 24–84). Sixty-nine point three per cent of participants were female and 30.7 per cent were male. Elevated baseline prolactin levels showed positive correlations with male gender, body weight, BMI, and alcohol consumption. In males, longer cabergoline treatment duration was found in those with advanced age and high body weight/BMI values. A significant negative correlation was found between baseline prolactin levels and the presence of microadenoma, while a significant positive correlation was found with the presence of macroadenoma. The duration of cabergoline use and the average weekly cabergoline dose showed a significant negative relationship with the presence of microadenoma and a significant positive relationship with the presence of macroadenoma. No significant relationship was found between the macroadenoma and microadenoma area and prolactin level and cabergoline duration of use. Positive significant correlations were found between PRL level and galactorrhea, compression findings, hypogonadism, neurological findings, and suprasellar spread. No statistically significant relationships were found between prolactin levels and infertility, amenorrhoea, impotence, osteoporosis, osteopenia, gynaecomastia, and hirsutism. A positive, statistically significant correlation was found between PRL levels and systolic and diastolic blood pressure, creatinine levels, and triglyceride (TG) levels. However, no significant correlations were found between white blood cell (WBC), neutrophil, lymphocyte, haemoglobin, platelet, fasting plasma glucose (FPG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), glycated haemoglobin (HbA1c), total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) levels. While no significant relationship was found between prolactin levels at six months and metabolic parameters, statistically significant negative correlations were found between PRL levels at twelve months and WBC, lymphocyte, platelet, and APG levels. Statistically significant negative correlations were found between prolactin levels at 18 months and platelet, APG, and HbA1c levels, while no significant correlation was observed between prolactin levels and other haemogram parameters or metabolic parameters. In the twenty-fourth month, statistically significant negative correlations were found between prolactin levels and WBC and LDL levels, while no correlation was detected with other parameters. The weekly average cabergoline dose showed a positive, significant correlation with prolactin levels, while it showed a negative, significant correlation with follicle-stimulating hormone (FSH) and a correlation with luteinising hormone (LH) that was borderline significant. No significant relationship was observed between the weekly cabergoline dose and other hormone parameters. A significant positive correlation was found between the duration of cabergoline use and the likelihood of abnormal ECHO findings, while a strong and statistically significant negative relationship was found between the duration of ECHO findings and the average weekly dose of cabergoline. A significant positive correlation was found between hypopituitarism and the presence of surgery. Furthermore, a significant negative relationship was found between the presence of microadenoma and hypopituitarism, while a positive relationship was found with microadenoma size. The presence of macroadenoma and macroadenoma size also showed a significant positive correlation with hypopituitarism. Conclusion: This study demonstrated that cabergoline treatment in patients diagnosed with prolactinoma has significant effects not only on tumour control but also on metabolic, hormonal, and cardiac parameters. These findings suggest that dopamine agonists may contribute positively to glycaemic control and lipid metabolism by increasing insulin sensitivity. However, a significant increase in the likelihood of abnormal echocardiographic findings was observed with increasing duration of cabergoline treatment and average weekly dose. This highlights the need for cardiac monitoring during long-term dopamine agonist use. Furthermore, the positive correlation between the presence of macroadenoma and tumour size with the development of hypopituitarism highlights the need for regular endocrine follow-up and imaging in these patients. Keywords: Dopamine agonist, pituitary gland, cabergoline, prolactinoma