The pituitary gland plays an important role in regulating the endocrine system of the body and is often referred to as the "master gland". It secretes hormones that influence growth, reproduction, metabolism, and stress responses. It is located in the sella turcica of the sphenoid bone and is divided into two parts anatomically. The anterior lobe and the posterior lobe of the gland are regulated by the hypothalamus, both by vascular as well as neural pathways. Knowledge of normative size and morphology of the pituitary gland in a cohort is essential for identifying pathological deviations such as adenomas, hypoplasia, cysts, and empty sella syndrome [1].  Magnetic resonance imaging (MRI) has evolved as a gold standard for analysis of the anatomy of the pituitary gland because of its capabilities, such as superior soft tissue contrast, high spatial resolution, and multiplanar capability [2]. The most commonly adopted sequences for studying the pituitary gland are mid-sagittal T1-weighted images because they offer optimal visualization of the gland's morphology and dimensions. Precise measurement of the height and width of the pituitary gland on MRI is of clinical importance since numerous pathological conditions are detected by deviations in normative dimensions. Some of the examples include that microadenomas can result in an insidious increase in the size of a gland, whereas pituitary hypoplasia can lead to congenital or acquired hypopituitarism [3]. The size of the pituitary gland increases with puberty, pregnancy, and age, as well as sex and hormonal state. Several studies have indicated that the height of the pituitary is maximum in adolescence and early adulthood, particularly in females, and diminishes with the progression of age [4,5]. The gland may temporarily swell around the time of a menstrual period or during pregnancy due to hormonal changes [6]. Therefore, it will be necessary to develop normative data that are population-specific, because this is needed to interpret the MRI findings in an appropriate clinical context. Some studies done internationally have documented the normative pituitary dimensions in the Western and the East Asian population, but there is a paucity in data of the Indian subcontinent, which has a genetically diverse population. Considering the impact of ethnicity and genetic composition, as well as the environmental factors on anatomical and hormonal features, direct application of normative data developed in the West to Indian patients may be unacceptable [7]. Moreover, the differences in the gland size across ethnicities limit the generalization of knowledge with regard to the accurate diagnosis and treatment of pituitary diseases and demand locally focused research. The present study was done to develop normative measurements of the pituitary gland in the Indian population through the usage of mid-sagittal T1-weighted MRI in a tertiary care hospital. The present study will provide reference data for clinicians and radiologists for interpreting pituitary morphology in clinical practice. This will lead to diagnostic accuracy and help in the early detection of pituitary pathologies.

This retrospective observational study was conducted in the Department of Radiology, Rajarajeswari Medical College and Hospital, Bengaluru, Karnataka, at a tertiary care hospital. Institutional ethical approval was obtained for the study. The data of the cases was collected from the Medical Records Department (MRD) of the hospital.

Sample Size Calculation: The sample size was calculated based on the formula for estimating a mean in a population

Where:

• n = required sample size
• Z = Z-value (1.96 for 95% confidence level)
• σ\sigma = estimated standard deviation of pituitary gland height (from previous literature, 1.5 mm)
• d = allowable error or precision (0.2 mm)

n (1.96)2⋅ (1.5)2(0.2)2≈216

To account for variability, population diversity, and potential exclusions, the sample size was increased to 300 subjects, who were included for normative data.

Inclusion Criteria

1. Individuals aged 11–70 years undergoing brain MRI for non-endocrine, non-pituitary-related indications.
2. MRI images with clear and high-quality mid-sagittal T1-weighted sections.
3. Patients without neurological or systemic illness known to affect the pituitary gland.
4. Males and females.
5. Subjects who provided informed consent (or assent in the case of minors with parental consent).

Exclusion Criteria

1. Patients with known or suspected pituitary or hypothalamic pathology.
2. History of endocrine disorders
3. Previous neurosurgery, radiation therapy, or trauma involving the sella region.
4. MRI images of inferior quality, where accurate measurements were not clear.
5. Intracranial mass or lesions that can distort anatomical landmarks.

All the included patients were analyzed to establish normative measurements of the pituitary gland. The records of High-resolution, mid-sagittal T1-weighted images (T1WI), which were acquired using a standardized MRI protocol, were included in the study. We selected precise mid-sagittal T1WI slices for morphometric analysis of the pituitary gland. The measurements of height and width of the gland were done using electronic calipers by experienced radiologists to ensure accuracy and consistency. The measurement of pituitary height was done as the vertical distance from the superior to the inferior border at the mid-sagittal plane. Width was measured at its widest horizontal part. The participants were divided into decades according to their age, and the average value of height and width of the pituitary was obtained in every decade. The statistical analyses of the values of pituitary gland height and width in relation to age were done.

Statistical analysis: All the available data were refined, segregated, and uploaded to an MS Excel spreadsheet and analyzed by SPSS version 25 in Windows format. The continuous variables were represented as frequencies, means, standard deviation, and percentages. The categorical variables were calculated by chi-square analysis for p-values. The values of p <0.05 were considered statistically significant.

The demographic profile of the distribution of cases included in the study is given in Table 1. A critical analysis of the table showed that the majority of cases were aged 31–40 years (26.7%), followed by the 11–20 (23.3%) and 21–30 (20%) age groups. The number of cases in older ages, more than 50 years 8.3% and only 1% were aged between 71 – 80 years. The overall distribution of males was 175 (58.3%) and females was 125(41.7%). This age and gender stratification provided a well-balanced collection of normative data when it comes to the measurement of the pituitary gland, with the emphasis on the younger subjects, where the gland sizes and shapes will be optimal, and, in the case of older individuals, the expected physiological size and shape reductions should be obtained.

Table 2 shows the pituitary height measurements by age groups. Analysis of the table shows that the highest mean pituitary height was (6.6 ± 2.5 mm) in the age group 21 – 30 years. The second highest measurements were in 11–20 (6.4 mm), followed by the age group 41–50 years (6.4 mm). We found a decrease in height in cases of more than 50 years, with the mean value of 5.6mm showing an age-related decrease in the measurements (p=0.05). The range of minimum and maximum in each age group should define normative values in our cohort, particularly for the assessment of hypopituitarism or pituitary hyperplasia in clinical evaluations.

The measurements of pituitary gland width based on the age groups are presented in Table 3. A critical analysis of the table shows that the pituitary gland distribution was relatively stable among the different groups, with a range from 9.8 mm to 10.4 mm. The lower width was found in the age group of 11 – 20 years, and the age group of > 50 years had the highest width (10.4mm). Therefore, the differences were very minor, and statistically, no significant differences were evident with advancing age. Overall, the mean width was 10.3 ± 2.6 mm, with a maximum of 13.1 mm.

Table 4 presents the gender based pituitary measurements and comparison. The overall results show that females had a significantly higher mean pituitary height (6.6 ± 2.7 mm) as compared to males (6.1 ± 2.4 mm), with a difference of +0.5 mm, and the p values were (p=0.002) and statistically significant. The measurements of width also favored females (10.2 mm vs. 10.1 mm), but the values were statistically not significant. The gender-based difference in the size of the gland was stable, potentially due to hormonal factors, especially estrogen, and should be taken into account when considering imaging of the pituitary in women of reproductive age.

The shape of the pituitary gland was evaluated, and the results are given in Table 5. The overall shapes were divided into convex, flat, and concave types in all 300 subjects. Convex shapes were common in females (n=79; 44%), followed by flat (N=28; 30%) and concave (N=18; 26%) configurations.  The predominant shapes in males were flat or concave. The cause of the convexity pattern in females could be due to higher gland volumes as well as hormonal fluctuations. Understanding shape distribution is clinically relevant as a convex superior surface may mimic microadenomas or hyperplasia, necessitating awareness of normal anatomical variants during radiological evaluations.

The current study was done to establish the normative morphometric data for the pituitary gland in our population using MRI. Since the pituitary gland is known to have variations in size with age, sex, and ethnicity, region-specific studies are crucial to establish the physiological size parameters and prevent misdiagnosis. Our study had a good sample size of 300 cases with a wide range of age groups and gender, which helps to provide measurements of pituitary height, width, and shape using mid-sagittal T1-weighted MRI. The results of this study showed that the mean pituitary height was the highest in the age group between 21 and 30 (6.6 ± 2.5mm) years, followed by the 11–20 (6.4 ± 2.4mm) and 41–50-year group (6.3 ± 2.4mm), respectively. There was a significant reduction in height in the age group beyond 50 years (mean: 5.6 ± 2.7 mm and p = 0.05). This observation is affirmed by the previous studies, where it is noted that pituitary atrophy starts after 30 years of age and is linked to the decreased production of hormones [8, 9]. According to Elink et al., gland height also reduces considerably after the period of menopause, which is indicative of decreasing levels of the estrogen hormone [10]. The pituitary width did not change much among the individuals, depending on the age, and the mean width was (10.3 ± 2.6 mm). This is also in accordance with the study conducted by Camacho et al., who did not find significant differences in pituitary width between age groups of adults, and thus concluded that height is a more sensitive marker of pathological changes [11]. Gender-wise comparisons showed that females had higher mean pituitary height in comparison to males (6.6 ± 2.7 mm vs 6.1 ± 2.4 mm and p = 0.002). Although the width difference was not significant (10.2 mm in females and 10.1 mm in males). The gender-based difference is attributed to hormonal effects of estrogens, particularly during puberty and reproductive age groups [12]. Takano et al. [13] have shown that increased pituitary volume in women was associated with higher estrogen levels even in the absence of pathology. Therefore, clinicians must consider sex specific thresholds for analysis during pituitary imaging. The analysis of shape in our study revealed that convex gland morphology was highest in females (44%) as compared to 30% flat-shaped and 26% concave-shaped. Males, on the other hand, predominantly showed concave-shaped morphology. A convex superior margin of the gland may be considered normal in adolescents and young adults, which can easily mimic pituitary hyperplasia or microadenomas on imaging [14]. Dinc et al. [15] emphasized the importance of recognising normal pituitary variants in order to reduce the possibility of overdiagnosis, particularly in young females with non-specific symptoms. Pituitary morphometry is used to estimate hypopituitarism, pituitary adenoma, empty sella syndrome, and Sheehan syndrome. Inadequate reference standards could result in wrong interpretation, particularly within heterogeneous ethnic environments.

In our research, we found evidence proving the idea that the pituitary dimensions need to be interpreted in terms of age, sex, and ethnicity, which was highlighted in the study by Shin et al. [16] in the examination of Korean and Western populations. The usefulness of recording normative data is also paramount in pediatric and adolescent patients whose gland undergoes a high rate of volumetric change in response to puberty. Although our study included individuals aged above 11 years, dedicated pediatric data would be valuable for endocrinologists in managing growth and pubertal disorders [17]. Factors such as technological variations, such as MRI slice thickness and field strength, can influence measurements. Our study was done on high-resolution T1-weighted mid-sagittal sequences, which minimize inter-observer variability and establish accuracy. However, inclusion of 3D volumetric assessments and automated segmentation techniques has been reported to improve reproducibility [18]. Although our study included individuals aged 11 years and above, dedicated pediatric data would be valuable for endocrinologists managing growth and pubertal disorders [17]. Even though our study group consisted of 11-year-olds and older, specialized pediatric data would be highly useful to the endocrinologists dealing with growth and pubertal treatments [17]. It should also be mentioned that differences in the technological aspect of the devices used can affect the measurements, including MRI slice thickness and field strength, among others. The accuracy of all the measurements was achieved because high-resolution T1-weighted mid-sagittal images were used in our studies, which reduced inter-observer variability. Nevertheless, in further research, 3D volumetric measurements and automated delineation of regions could be useful, as they were promising in enhancing reproducibility [18].

In conclusion, the present study establishes age and gender-specific normative measurements of the pituitary gland in our cohort. The present study found that the height of the gland is a reliable marker and is significantly influenced by age and sex. Pituitary gland size increased to its maximum during puberty. Decline in gland size with age was found in our study, which reflects the endocrinology of aging and physiological atrophy. Width measurements remain constant across age and sex groups. Understanding these variations of the gland based on size and shape is crucial to avoid diagnostic errors and improve clinical decision-making.

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