Prevalence of adrenal insufficiency and glucocorticoid use in pediatric pseudotumor cerebri syndrome

Authors: HOYOS-MARTINEZ, ALFONSO - Baylor College Of Medicine; HORNE, VINCENT - Baylor College Of Medicine; WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC); SHAH, VEERAL - University Of Cincinnati

Submitted to: Journal of Neuro-Ophthalmology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/5/2020
Publication Date: 10/26/2020
Citation: Hoyos-Martinez, A., Horne, V.E., Wood, A.C., Shah, V. 2020. Prevalence of adrenal insufficiency and glucocorticoid use in pediatric pseudotumor cerebri syndrome. Journal of Neuro-Ophthalmology. https://doi.org/10.1097/WNO.0000000000001111.
DOI: https://doi.org/10.1097/WNO.0000000000001111

Interpretive Summary: Pseudotumor cerebri syndrome (PTCS) occurs far more often in people with obesity than in their normal weight counterparts. The causes of PTCS are not well known, but if they could be identified may help improve health by (1) helping better identify who is at risk so these individuals could be screened and monitored; (2) giving clues what interventions to prevent PTCS may be effective; and (3) helping better understand the pathophysiological sequelae of obesity. A few isolated case reports have suggested that reduced adrenal function may be a risk factor, yet no large cohort study has examined this relationship. Therefore, we conducted a chart review of all children with PTCS who also had their cortisol measured (a measure of adrenal functioning) and presented at Texas Children's Hospital (TCH). We found that 75% had cortisol levels either indicative of insufficient adrenal functioning, or suggesting that they were at-risk for insufficient adrenal functioning. Once we confirmed that reduced adrenal functioning was prevalent in children with PTCS, we were interested in what could have caused this problem, and examined the role of topical corticosteroids. Adrenal functioning is reduced after prolonged exposure to systemic steroids (those taken orally or administered intravenously), and hence the use of these is minimized where possible. The emerging literature provides strong support for the notion that topical corticosteroids (administered on the skin, through the nose, or inhaled) can have similar effects as systemic steroids if used for an extended period. Yet, knowledge of the problems of topical corticosteroids is not well integrated into current clinical practice – their use is not minimized and they are available over the counter (without prescription). In our chart review, the majority of those in the insufficient (70%) or at-risk (80%) adrenal functioning groups were exposed to topical, nasal, or inhaled glucocorticoids (a form of steroid) but not systemic steroids. Based on this finding, we concluded that poor adrenal functioning is prevalent in PTCS, and among those with PTCS the use of topical corticosteroids (in the absence of systemic corticosteroids) is high. Given that obesity is a strong risk factor for PTCS, our study suggests that more research is needed to examine whether the use of topical corticosteroids in children with overweight and obesity should be considered more carefully.

Technical Abstract: The pathophysiology underlying pseudotumor cerebri syndrome (PTCS) is complex and not well understood. There are clear differences between PTCS in adults and pediatrics. Few and isolated case reports have suggested that adrenal function may be involved, yet no large cohort study has examined this relationship. We conducted a retrospective single-center study of children who presented with a diagnosis of PTCS and had cortisol testing measured between January 2010 and September 2019. We included all subjects meeting the revised PTCS diagnostic criteria after the chart review. Based on morning, random or 1-µg cosyntropin stimulated cortisol levels, adrenal functioning was classified as: (1) insufficient (peak cortisol <16 ug/dL and AM cortisol <5 ug/dL), (2) at risk (peak cortisol 16-20 ug/dL, AM cortisol 5-13 ug/dL, or random <13 ug/dL), or (3) sufficient (peak cortisol >20 ug/dL and AM or random cortisol >13 ug/dL). A total of 398 individuals were reviewed, and 64 were included for analysis. Of these, 40.6% were men, of mixed race and ethnicity with a mean age of 10.5 (SD 4.7) years. Of these, 23% and 52% had insufficient or at-risk cortisol levels. The majority of those in the insufficient (70%) or at-risk (80%) groups were exposed to topical, nasal, or inhaled glucocorticoids but not systemic. Only 60% and 12% of those with PTCS with insufficient or at-risk cortisol testing, respectively, underwent definitive testing with a stimulation test. Glucocorticoid use and hypocortisolism are prevalent in PTCS and need consideration as a potential underlying cause. Most children had insufficient or at-risk cortisol levels, and many did not undergo further testing/workup. Children who present with PTCS, particularly young, males should be evaluated for adrenal insufficiency and its risk factors, including nonsystemic steroids. Prospective studies are necessary to further evaluate the effect of cortisol in relation to pediatric PTCS.