Pineal Gland Volume Assessed by MRI and Its Correlation with 6-Sulfatoxymelatonin Levels among Older Men

Abstract

The pineal gland produces the hormone melatonin, and its volume may influence melatonin levels. We describe an innovative method for estimating pineal volume in humans and present the association of pineal parenchyma volume with levels of the primary melatonin metabolite, 6-sulfatoxymelatonin. We selected a random sample of 122 older Icelandic men nested within the AGES-Reykjavik cohort and measured their total pineal volume, their parenchyma volume, and the extent of calcification and cysts. For volume estimations we used manual segmentation of magnetic resonance images in the axial plane with simultaneous side-by-side view of the sagittal and coronal plane. We used multivariable adjusted linear regression models to estimate the association of pineal parenchyma volume and baseline characteristics, including 6-sulfatoxymelatonin levels. We used logistic regression to test for differences in first morning urinary 6-sulfatoxymelatonin levels among men with or without cystic or calcified glands. The pineal glands varied in volume, shape, and composition. Cysts were present in 59% of the glands and calcifications in 21%. The mean total pineal volume measured 207 mm(3) (range 65-536 mm(3)) and parenchyma volume 178 mm(3) (range 65-503 mm(3)). In multivariable-adjusted models, pineal parenchyma volume was positively correlated with 6-sulfatoxymelatonin levels (β = 0.52, p < 0.001). Levels of 6-sulfatoxymelatonin did not differ significantly by presence of cysts or calcification. By using an innovative method for pineal assessment, we found pineal parenchyma volume to be positively correlated with 6-sulfatoxymelatonin levels, in line with other recent studies.

Keywords: MRI; circadian; melatonin; pineal; sleep.

Figure 1

Magnetic resonance image of the brain showing pineal gland of one study participant, without (top) and with (bottom) manual labeling. Pink is for parenchyma, blue for cyst and green for calcification: axial (left) and sagittal (right).

Figure 2

Agreement between manual labeling of the pineal gland volume. Bland-Altman plot demonstrating the agreement between the first and second labeling. Broken red and blue lines are the mean bias and limits of agreement (2.00 standard deviation), respectively. Y-axis displays mean difference between first and second labeling and x-axis the average volume of the first and second labeling.

Figure 3

Simple scatterplot showing correlation between concentration of first morning urinary void 6-sulfatoxymelatonin and pineal parenchyma volume among the 122 study participants. Pearsons’s r=0.33, p<0.001 (unadjusted).