Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is the most investigated biological risk marker in functional somatic disorders (FSDs), such as chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS). Our aim was to assess whether there is an association between basal hypocortisolism and FSD and to identify potential moderators of this association. Meta-analysis on 85 studies revealed that although basal cortisol levels were generally lower in FSD subjects compared to controls, this association did not reach statistical significance (SMD −0.07, 95% CI −0.17 to 0.04, p = 0.241). However, when the three FSD were assessed separately, statistically significant basal hypocortisolism was observed in CFS subjects compared to controls (SMD −0.14, 95% CI −0.28 to 0.00, p = 0.047), but not in FM or IBS. When all potential moderators were entered into a meta-regression analysis, only type of FSD and female gender were significant independent predictors of basal hypocortisolism. In conclusion, we did not find evidence to consider all three main FSD as hypocortisolemic disorders, as significant reduction in basal cortisol compared to healthy controls was only found in CFS and in females with FM, but not in IBS.

Research highlights
► Functional somatic disorders are often referred to as hypocortisolemic disorders.
► In this meta-analysis, we compared cortisol levels of patients with controls.
► Hypocortisolism was only observed in subjects with chronic fatigue syndrome.
► Hypocortisolism was not observerd in subjects with fibromyalgia or irritable bowel syndrome.
► Meta-regression revealed that female gender independently predicts hypocortisolism.