Endocrine Abstracts (2019) 65 OC2.1 | DOI: 10.1530/endoabs.65.OC2.1

Differential effects of subcutaneous pulsatile versus oral hydrocortisone replacement therapy on fMRI resting state and task based emotional processing in patients with primary adrenal insufficiency

Georgina Russell1, Konstantinos Kalafatakis1, Jamie Thakrar1, Elizabeth Hudson1, Lina Alim1, Nicola Marchant1, Russell Thirard1, Jonathan Brooks1, Jade Thai1, Catherine Harmer2 & Stafford Lightman1


1University of Bristol, Bristol, UK; 2University of Oxford, Oxford, UK


Background : Patients with primary adrenal insufficiency (PAI) describe significant impairments in quality of life. Current replacement regimes are non-physiological. Animal studies indicate that pulsatile presentation of endogenous glucocorticoids is critical for normal transcriptional and behavioural responses. Healthy volunteer work also shows that pattern of glucocorticoid presentation alters cognitive and emotional processing.

Objective: To assess the effects of glucocorticoid presentation on cognition and emotional processing in patients with PAI

Methods: The Pulses study (ISRCTN67193733) was a 6-week Double-blind placebo control cross over trial of standard three-time daily oral hydrocortisone to continuous pulsatile subcutaneous in PAI secondary to Addison’s (AD) and Congenital Adrenal Hyperplasia (CAH) (N=21, AD 17/CAH 4). Secondary outcome measures of resting state and task based (Facial Expression Recognition Task – FERT) functional magnetic resonance imaging (fMRI) are discussed. Whole brain and region of interest (ROI) analysis based on known cortisol sensitivity and involvement in emotional processing was performed. Washout range 6 weeks-1 year. Total daily dose of hydrocortisone was the same on both arms (range 20–40 mg).

Results: Righthanded N=13 female AD only; fsl analysis detected differential activation between treatment arms. Task based whole brain analysis under fearful condition – Middle Frontal Gyrus, Precentral Gyrus, Superior Frontal Gyrus, Supplementary Motor Cortex, Anterior Cingulate Gyrus and Paracingulate Gyrus. ROI analysis under fearful condition – insula and amygdala. Resting state fMRI ROI analysis dorsal striatum and insula.

Conclusions: The Pulses trial confirms safety and tolerability of subcutaneous hydrocortisone pump treatment. No subjects dropped out due to trial related issues. fMRI detected differentially activated executive control regions that are important in cognitive and emotional processing. This gives an early indicator that cortisol dynamics impact on cognition and emotional processing and should be considered in glucocorticoid based therapeutics.