Features of Cushing's SyndromeCognitive Function and Cerebral Assessment in Patients Who Have Cushing's Syndrome
Section snippets
Loss of brain volume in endogenous Cushing's syndrome
Previous pathologic and imaging studies suggested that some morphologic anatomic modifications did occur in the brain of patients who have CS. The authors first wish to point out that the terminology cerebral atrophy has been used widely in the literature for the description of morphologic changes observed in the brain of patients who have CS. Considering the facts that cell atrophy or cell loss has not been demonstrated pathologically and that the observed changes are potentially reversible,
Reversibility of loss of brain volume after correction of hypercortisolism
Data on the anatomic outcome of apparent cerebral atrophy following correction of hypercortisolism are limited. The authors re-evaluated 22 patients who had CS at 39.7 ± 34.1 months after achieving eucortisolism. The subjective score of apparent brain volume loss, the third ventricle diameter, and the bicaudate diameter improved (see Fig. 1) [6] but did not reach the normal control group values (see Fig. 1). The objective parameters of brain volumes progressively improved but did not reach a
Loss of brain volume in exogenous Cushing's syndrome
Synthetic GCs are used widely, and their systemic adverse effects are well known. Their impact on brain volume, however, largely remains unrecognized. A few reports underlined the association of supraphysiologic administration of exogenous GCs with apparent brain atrophy. Bentson et al [8] studied a population less than 40 years old that had a diagnosis of cerebral atrophy and found that approximately 10% of them were on chronic GC therapy. Pharmacologic doses of GCs also were related to
Cerebral magnetic resonance spectroscopy in Cushing's syndrome
Patients affected by endogenous and exogenous CS were studied by proton magnetic resonance spectroscopy (MRS) of the brain. Thirteen untreated patients who had endogenous CS, including seven who had pituitary corticotroph adenomas and six who had primary adrenal disease, were examined in the frontal, thalamic, and temporal areas, and compared with 40 normal control subjects. A statistically significant decrease in the choline to creatine ratio (Cho/Cr) was measured in the frontal (−24%) and
Pathophysiology of glucocorticoids on brain
Corticosteroid hormones enter the brain compartment and bind to intracellular receptors. Two receptor subtypes mediate GC actions: GC receptors (GRs) and mineralocorticoid receptors (MRs). GRs are distributed widely in cerebral neurons and glial cells, whereas MRs are expressed highly in limbic brain areas such as the hippocampus. MRs bind corticosterone with an affinity 10-fold higher than GRs. Thus, low basal corticosterone levels predominantly occupy high-affinity MRs, whereas GRs can be
What are the mechanisms underlying loss of brain volume in Cushing's syndrome?
The pathogenesis of loss in brain volume induced by chronic GC excess is probably multi-factorial [18]. Previous animal and in vitro studies examined the effects of GCs on the morphology and survival of neurons on the brain; it must be mentioned that this work has been conducted mainly on hippocampus cells. Woolley et al [21] reported that treatment of young adult rats with exogenous corticosterone for 3 weeks induced atrophy of the apical dendrites of CA3 pyramidal neurons, whereas a longer
Psychiatric disorders associated with Cushing's syndrome
Psychiatric disturbances have been associated with the exogenous administration of large amounts of steroid hormones. A substantial body of evidence suggests that depression is a major and life-threatening complication of CS [36]. In a summary of 12 studies involving 330 patients up to 1980 [37], it was observed that 45% of CS patients were depressed or suicidal. Subsequent studies used a standardized assessment of depression by specific diagnostic criteria. In his study, Haskett [38] obtained
Cognitive functions in Cushing's syndrome
Although several investigations conducted in recent years have stressed the numerous effects of GCs on cognition, studies specifically studying CS and its effects on the cognitive processes are few. As mentioned earlier, Starkman et al [4] found a significant correlation between the severity of the hypercortisolism and the extent of hippocampal formation atrophy, and a correlation with the severity of the accompanying verbal learning and memory deficits in patients who have CS (this work used
Acknowledgments
The authors wish to express their gratitude to Mrs. Josée Baker for her secretarial assistance in preparing the manuscript.
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2016, PsychoneuroendocrinologyCitation Excerpt :The detection of GC receptors in the prefrontal cortex suggests that this brain area may be susceptible to atrophy when GC levels are elevated. Our observations agree with the data from the literature showing that the neuropsychological effects of hypercortisolism may not be fully reversible, although partial recovery does take place (Mauri et al., 1993; Forget et al., 2002; Starkman et al., 2003; Bourdeau et al., 2005; Merke et al., 2005; Hook et al., 2007). There are few data on the anatomical outcomes of apparent cerebral atrophy following correction of hypercortisolism, but we now know that the brain is a resilient structure that is capable of reversing structural changes (for a review, see Andela et al., 2015).