Empty Sella Syndrome as a Window Into the Neuroprotective Effects of Prolactin

Abstract

Background: The goal of this study was to relate diffusion MR measures of white matter integrity of the retinofugal visual pathway with prolactin levels in a patient with downward herniation of the optic chiasm secondary to medical treatment of a prolactinoma.Methods: A 36-year-old woman with a prolactinoma presented with progressive bilateral visual field defects 9 years after initial diagnosis and medical treatment. She was diagnosed with empty-sella syndrome and instructed to stop cabergoline. Hormone testing was conducted in tandem with routine clinical evaluations over 1 year and the patient was followed with diffusion magnetic resonance imaging (dMRI), optical coherence tomography (OCT), and automated perimetry at three time points. Five healthy controls underwent a complementary battery of clinical and neuroimaging tests at a single time point.Results: Shortly after discontinuing cabergoline, diffusion metrics in the optic tracts were within the range of values observed in healthy controls. However, following a brief period where the patient resumed cabergoline (of her own volition), there was a decrease in serum prolactin with a corresponding decrease in visual ability and increase in radial diffusivity (p < 0.001). Those measures again returned to their baseline ranges after discontinuing cabergoline a second time.Conclusions: These results demonstrate the sensitivity of dMRI to detect rapid and functionally significant microstructural changes in white matter tracts secondary to alterations in serum prolactin levels. The inverse relations between prolactin and measures of white matter integrity and visual function are consistent with the hypothesis that prolactin can play a neuroprotective role in the injured nervous system.

Prolactin at moderately increased levels confers a neuroprotective effect in non-secreting pituitary macroadenomas

“…These studies attribute increased oligodendrocyte proliferation and remyelination after injury to increased PRL levels [ 8 ] and increased white matter volume [ 10 ]. We have previously shown that remyelination is possible after compressive injuries to the anterior visual pathway [ 22 ] and that measures of diffusion known to correlate with myelination are sensitive to varying levels of serum prolactin in a patient with empty-sella syndrome [ 7 ]. Due to PRL’s role in remyelination, this provides another possible mechanism for its protective quality following compressive injuries.…”

“…Pre-operative RNFL measurements have also been shown to predict post-operative visual outcomes for pituitary tumor patients [ 6 ]. These measurements may serve as biomarkers for injury along the visual pathway where thinning indicates ongoing injury and disease progression [ 7 , 24 ]. This allows for RNFL measurements to be used to quantify the efficacy of neuroprotective agents, like PRL.…”

“…All included subjects had ophthalmologic examination data which included RNFL evaluation with SD-OCT–optic disc cube 200 × 200 protocol as described previously [ 7 ]. Measures of RNFL thickness were reported as a function of clock hour position of the fovea and subsequently grouped into anatomical quadrants based on a standard division of the visual field (e.g., for right eyes; superior quadrant: 11 and 1 o’clock; nasal quadrant: 2, 3, and 4 o’ clock; inferior quadrant: 5 and 7 o’ clock; and the temporal quadrant: 8, 9, and 10 o’clock).…”

“…For many patients, decompression of the anterior visual pathway by tumor removal (with surgery) or tumor shrinkage (with medication) can result in rapid visual recovery-although the factors that predict which patients experience recovery and to what extent they will recover remains an active area of investigation. RNFL thickness-a surrogate for retinal ganglion cell axonal health-has been used as a biomarker for indexing various mechanisms of delayed axonal degeneration [4], including white matter injury following anterior visual pathway compression [5][6][7]. Here, we investigate the relation between serum hormone levels of prolactin, RNFL thickness and visual function in a retrospective cohort of pituitary macroadenoma patients.…”

The Kappa Opioid Receptor: Candidate Pharmacotherapeutic Target for Multiple Sclerosis

“…It may also underlie findings that in females with secondary progressive MS treated with domperidone, subjects with higher prolactin levels had reduced disease progression [51]. Prolactin may be generally protective of white matter health [52], and elevated circulating levels of prolactin during sleep have been proposed as potentially mediating the enhanced levels of remyelination during sleep compared to during wakefulness [53,54]. One of the well-known effects of KOR agonists in vivo is to cause significant and reliable increases in circulating prolactin following release from pituitary lactotroph cells.…”