A new view on hypocortisolism
Introduction
Since the work of Selye (1936), stress has been associated with an activation of the hypothalamic–pituitary–adrenal (HPA) axis resulting in an increased release of cortisol from the adrenal glands. In recent years, a phenomenon has been described that is characterized by a hyporesponsiveness on different levels of the HPA axis in a number of stress-related states. This phenomenon, termed ‘hypocortisolism’, has been reported in about 20–25% of patients with stress-related disorders such as chronic fatigue syndrome (CFS), chronic pelvic pain (CPP), fibromyalgia (FMS), post-traumatic stress disorder (PTSD), irritable bowel syndrome (IBS), low back pain (LBP), burnout, and atypical depression (Griep et al., 1998, Heim et al., 1998, Heim et al., 2000, Pruessner et al., 1999, Gold and Chrousos, 2002, Gur et al., 2004, Roberts et al., 2004, Rohleder et al., 2004). When hypocortisolemic, all these disorders may share affiliated syndromes characterized by a triad of enhanced stress sensitivity, pain, and fatigue.
Suggesting a common endocrinological pathway characterized by a diminished glucocorticoid efficacy in these disorders, we will discuss the development and mechanisms of hypocortisolism based on animal and human studies. In addition, consequences of a hypocortisolemic stress response on two other bodily systems, the sympathetic nervous system (SNS) and the immune system will be addressed. Finally, we will hypothesize about the rationale of the development of hypocortisolism and its potential protective effects.
Section snippets
The hypocortisolemic symptom triad
Stress-related disorders such as PTSD, FMS, and CFS are usually defined by accentuating one of the symptoms that constitute the symptom triad of high stress sensitivity, fatigue and pain (Heim et al., 2000). While PTSD, for example, is characterized by a high stress sensitivity together with symptoms such as intrusions, tension and increased excitability, FMS is primarily defined by the experience of widespread pain suggesting an enhanced somatosensory sensitivity. CFS, on the other hand,
Mechanisms of hypocortisolism
In all the aforementioned hypocortisolemic disorders, there are several possible patterns of hypocortisolism determined by alterations in different levels of the HPA axis. These alterations of HPA axis are determined by (1) a reduced biosynthesis or release of the respective releasing factor/hormone on different levels of the HPA axis (CRF/AVP from the hypothalamus, ACTH from the pituitary, or cortisol from the adrenal glands) accompanied by a subsequent decreased stimulation of the respective
Hypocortisolism: a developmental model
Several years ago we postulated that hypocortisolism/a hyporeactive HPA axis might develop after prolonged periods of stress together with a hyperactivity of the HPA axis and excessive glucocorticoid release (Hellhammer and Wade, 1993). This proposed time course with changes in HPA axis activity from hyper- to hypocortisolism resembles the history of patients with stress-related disorders who frequently report about the onset of ‘hypocortisolemic symptoms’ (fatigue, pain, stress sensitivity)
Hypocortisolism and the sympathetic nervous system
The HPA axis plays an important role in the regulation of the SNS. CRF seems to increase the spontaneous discharge rate of locus coeruleus (LC) neurons and enhances norepinephrine (NE) release in the prefrontal cortex (Valentino, 1988, Valentino et al., 1993, Smagin et al., 1995), whereas glucocorticoids seem to exert more inhibitory effects on NE release. Results from animal studies with adrenalectomized (ADX) rats have indicated that endogenous glucocorticoids restrain responses such as
Hypocortisolism: protective effects?
Beside the above described negative symptoms associated with hypocortisolism (high stress sensitivity, pain, and fatigue), there is evidence that hypocortisolism may also have protective consequences for the organism. Subsequently, we will illustrate potential beneficial effects of hypocortisolism by giving some examples concerning protection of the mother and the fetus during pregnancy, adaption in order to allow immunologic responses, and prevention from high allostatic load scores.
Assessing
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