ESPE Yearbook of Paediatric Endocrinology

Brief summary: This study investigated the brain structure in young adult patients with autoimmune Addison’s disease (AAD). It found that patients with AAD had a 4.3% smaller total brain volume but no major differences in subcortical structures compared to healthy controls.

Both short- and long-term disruptions in cortisol concentrations and rhythmicity affect brain structure development. Animal studies have shown that both pre- and postnatal disturbances in cortisol affect neuronal growth, dendritic arborization and long-term potentiation, although the effects depend on glucocorticoid (GC) dose, brain region and developmental time-window. In addition to affecting structural development, cortisol is involved in memory formation, selective attention and learning, and further helps to control sleep, motivation, mood and fear. These complex processes require precisely regulated GC concentrations, in which the dynamic hormonal oscillations under natural conditions are crucial. Disruption of the natural cortisol secretion and the chronic effect of hormone replacement therapy may thus affect brain function and brain structure in individuals with primary adrenal insufficiency.

This study investigated for the first time brain structure in young adult patients with autoimmune Addison’s disease (AAD) (n=52, age 19–43 years) compared to healthy controls (n=70). T1 and diffusion weighted images were acquired on a 3 Tesla magnetic resonance imaging scanner for estimation of grey matter and white matter microstructure. The association between brain structure and disease related factors, self-reported executive function problems and performance on executive function tests were also explored.

Individuals with AAD had a 4.3% smaller total brain volume but no major differences were identified in subcortical structures compared to controls. A higher GC replacement dose was associated with reduced total brain volume (without ventricles) entailing a reduction of 0.73% TBV for every mg/m²/day increase in GC dose. A higher dose was also associated with smaller volume of the left rostral anterior cingulate cortex, left lingual gyrus and right supramarginal gyrus. A higher daily GC replacement dose in mg/m²/day was associated with better performance on one of the visuo-spatial working memory tasks (Span Board forward) (B=0.28, P=0.030).

In contrast to patients with CAH, relatively young patients with AAD do not have major structural brain disturbances in grey matter regions or in white matter microstructure except for a smaller total brain volume (at the same level of magnitude as in CAH). The less substantial structural changes in AAD are consistent with the finding that patients performed within the normal range on a variety of cognitive tasks, although females were previously reported to experience problems with executive function in daily life. The association between GC dose and brain volume requires follow-up studies.