Pituitary adenoma (PA) is a benign tumor with slow progression, and the majority of pituitary tumors are PA, accounting for 94.0% of cases. PA is classified into three categories based on tumor size: microadenomas (<10 mm), macroadenomas (10-40 mm), and giant adenomas (>40 mm). In the United States (US), macroadenomas are the most common type of PA, according to the National Cancer Database [1]. Surgery is generally indicated for pituitary adenomas measuring ＜10 mm in diameter, tumors with extrasellar extension or significant mass effect causing compression of surrounding structures, persistent tumor growth despite medical therapy, persistently elevated hormone levels despite pharmacological treatment, or symptomatic lesions, particularly when visual function is compromised or at risk [2].

The epidemiology and clinical characteristics of PA are well documented in the US. The incidence of PA was 2.8 per 100,000 population between 1998 and 2016, with an increasing trend over the study period. The incidence did not differ significantly between sexes but was higher among individuals aged 65-84 years. PA was more prevalent in urban areas than in rural or suburban areas and was also more common among Black and Asian populations [3]. However, comparable epidemiological data from Indonesia remain scarce. To the best of our knowledge, no published studies have described the epidemiology of PA in Indonesia, particularly in Surabaya.

Epidemiological data are essential for developing prevention strategies because they help identify disease risk factors and populations at increased risk based on ethnicity, age, and other demographic characteristics. Such data also contribute to understanding disease etiology by evaluating potential causal factors and support the design of effective preventive interventions. Furthermore, epidemiological studies describe disease distribution across populations, providing evidence for appropriate resource allocation and targeted public health measures. These findings also inform evidence-based health policies aimed at improving healthcare outcomes and optimizing resource utilization [4,5]. Such information is particularly important for PA because its epidemiology varies among different racial and ethnic groups, with Asians reported to have the second highest susceptibility. Despite this, epidemiological data on PA in Indonesia remain scarce. To the best of our knowledge, this is the first study to describe the clinical and demographic characteristics of patients with PA in Surabaya, Indonesia, thereby providing baseline data for future epidemiological and clinical research.

Our study presents epidemiological data on PA in Surabaya. This study included 36 patients diagnosed with PA, with a mean age of 48.28 ± 13.88 years and a slight predominance of female participants. Most patients were middle-aged, particularly those aged 50-59. The majority of participants were classified as obese according to Asia Pacific BMI criteria. Macroadenomas were the most common tumor type, and non-functional adenomas slightly outnumbered functional adenomas. Among functional adenomas, prolactin-secreting tumors were the most prevalent. Visual impairment was the most frequently reported clinical symptom, and most patients were managed surgically using the EETS approach. Lifestyle factors including smoking, obesity, hormonal contraceptive use, and menopausal status were evaluated. However, no significant associations were identified between demographic characteristics, tumor features, or obesity status.

Due to the uncontrolled, cross-sectional design of this study, the observed proportions of characteristics such as smoking status, contraceptive use, and menopausal status merely describe the distribution within the study cohort. These findings cannot be compared with those of the general population nor used to infer causal relationships with PA. This represents a major methodological limitation of the study.

The age distribution of PA may vary across different populations, potentially reflecting differences in racial or ethnic background. In the United States, the highest incidence of PA has been reported among individuals aged 65-84 years [3], whereas our study, which was conducted in an Asian population, found the highest proportion of patients in the 50-59-year age group. However, given the relatively small sample size of our study, this finding should be interpreted with caution. Larger multicenter studies involving diverse Asian populations are needed to determine whether this age distribution is representative of the broader population.

Regarding weight status, higher BMI in the U.S. is associated with increased PA incidence, with cumulative incidences ranging from 1.33 to 2.28 [6]. Our findings are consistent with this, showing a higher incidence of PA in obese individuals, although the difference was not statistically significant. This contrasts with the commonly held view that obesity in functional PA results from hormonal aberrations [7]. Furthermore, our analysis did not reveal a significant correlation between BMI and tumor size. Similarly, our study found no correlation between age and tumor size. However, a study conducted in Canada reported a positive correlation between these variables [8].

In functional PA, our data revealed a higher prevalence of prolactinomas (58.8%), comparable to findings in Iceland, where prolactinoma is the predominant type [9]. The high prevalence of obesity observed in our cohort may be partially explained by the predominance of prolactinomas, the most common functional pituitary adenomas characterized by elevated circulating prolactin levels [10]. Larger prolactinomas are generally associated with greater prolactin secretion, potentially exacerbating their metabolic effects. Mechanistically, hyperprolactinemia disrupts metabolic homeostasis by affecting both the liver and adipose tissue. In the liver, it upregulates prolactin receptor expression, promotes hepatic steatosis, enhances the activity of the lipogenic transcription factor carbohydrate-responsive element-binding protein (ChREBP), and alters the sterol regulatory element-binding protein-1c (SREBP-1c) response to refeeding. In adipose tissue, hyperprolactinemia promotes adiposity while reducing the expression of these lipogenic transcription factors. Collectively, these alterations impair glucose metabolism, leading to glucose intolerance, hyperinsulinemia, insulin resistance, and ultimately obesity [11]. These findings underscore the importance of routine metabolic assessment and comprehensive metabolic management in patients with pituitary adenomas, particularly those with prolactinomas.

In terms of tumor size, our results align with U.S. data, which indicate that macroadenomas are the most common type of PA [1]. Tumors larger than 2.2 cm are often associated with visual impairment [12]. Although headache was not previously correlated with tumor size two decades ago [13], two studies have since reported a link between headaches and macroadenomas [12,14]. Concerning clinical symptoms, our study found that visual impairment was the most frequently reported complaint, followed by headaches. This aligns with previous data showing that headaches were reported in 48.5%-87.2% of cases [15,16] and that visual impairment was observed in 52.9%-74.0% of cases [17,18].

Smoking is generally recognized as a lifestyle factor associated with malignancy. However, in our study, only a small proportion of participants reported a history of smoking. This finding is consistent with previous studies that have shown no significant association between smoking and PA. Interestingly, smoking has even been reported as a potential protective factor in some studies [19]. Regarding contraceptive use, our data show a higher prevalence of contraceptive use among women with PA. This finding contrasts with previous reports from the United States, which found no association between contraceptive use and PA and reported that non-use of contraceptives was linked to an increased risk of PA [20]. This discrepancy may be due to the small sample size in our study.

In terms of menopausal status, previous studies have reported an increased risk of PA among menopausal women [21]. However, in our study, a higher proportion of participants with PA were non menopausal. This discrepancy may be attributed to ethnic differences, although further investigation is required. These studies would provide a more comprehensive understanding of the epidemiology of PA, which is essential for improving prevention, diagnosis, and management of PA-associated health conditions.

Our study has several limitations. First, selection bias may be present due to the single-center retrospective design, which may primarily represent patients with more severe disease who attend this hospital. Second, the small sample size and the absence of a control group limit the generalizability of the findings. Third, note that recall bias (e.g., for hormonal contraceptive use) and incomplete data may affect results. A prospective design would strengthen findings. Finally, the lack of molecular or genetic data prevented further exploration of underlying mechanisms.

Our study provides an overview of the epidemiology of PA in Indonesia, particularly in Surabaya. Although no statistically significant associations were identified, likely due to the relatively small sample size, our findings provide important baseline epidemiological data for this population. We hope these findings will encourage future multicenter prospective studies with larger sample sizes, standardized data collection, appropriate comparison groups, and molecular investigations to further characterize the epidemiology and risk factors of PA and to improve our understanding of its underlying biological mechanisms in the Indonesian population.