Dense sampling for mapping pituitary growth dynamics before, during, and after pregnancy

Pregnancy represents a period of profound endocrine activity and neural reorganization. While recent evidence highlights pituitary volume as a biomarker of endocrine dynamics during pregnancy, its precise trajectory (timing and relative magnitude of effect) across human pregnancy remains undescribed. Three healthy women (59 total observations) underwent T1-weighted MRI before conception (5 baseline observations), during pregnancy (38 total observations, spanning gestational weeks 1-36), and up to 1 year postpartum (16 total observations). Anterior and posterior pituitary lobes were manually delineated at every visit. A longitudinal pipeline co-registered each scan to all other intra-subject scans, propagated their labels, and generated majority-vote ensembles for objective and regularized volume estimates. Person-centered z-scores were computed, and generalized additive mixed models (GAMMs) with random intercepts estimated nonlinear volume trajectories. The anterior lobe followed a nonlinear trajectory, with gestational age explaining 73% of adjusted variance in anterior-pituitary volume (edf = 7.59, F = 20.2, p_bonf < 10^-10). Specifically, volume exhibited a modest first trimester decrease (local fit minima: -0.9 SD at 10.6 weeks), followed by a steep rise into the 3rd trimester (local fit maxima: +1.8 SD at 34.1 weeks, or ~ 17.5% increase from 1st trimester minima, by volume), before returning to baseline near 3 months postpartum. Sensitivity analyses restricted to linear regression during early (-5 to 12 weeks) and late (12 to 40 weeks) windows replicated the observed non-linear decreasing/increasing slopes (β_early = -0.09 SD/week, p_early = 0.036; β_late = 0.14 SD/week, p_late < 10^-10). In contrast, no significant volumetric changes in the posterior lobe were detected across the observation period (p_non-linear = 0.79). In one of the first studies of its kind to leverage a dense sampling approach in multiple pregnant women, non-linear analyses revealed rapid, reversible anterior pituitary hypertrophy across human pregnancy consistent with lactotrope expansion and heightened endocrine load.