Cortisol impairment

Cortisol-Cortisone Conversion. Under normal conditions, this equilibrium slightly favors the oxidized compound. Similarly, the conversion of corticosterone to 11-deoxycorticosterone is also mediated by the liP-hydroxysteroid dehydrogenase enzyme system and requites NAD(P) /NAD(P)H. This conversion is especially important both in the protection of the human fetus from excessive glucocorticoid exposure, and in the protection of distal nephron mineral ocorticoid receptors from glucocorticoid exposure (14). The impairment of this conversion is thought to result in hypertension associated with renal insufficiency (15). 

Aluru, N. aud Vijayau, M.M. (2006). Aryl Hydrocarbou receptor activatiou impairs cortisol respouse to stress in Rainbow Trout by disrupting the rate-hmiting steps in steroidogenesis. ii rfocri o/ogy 147, 1895-1903. 

Hontela, A., Rasmussen, J.B., and Andet, C. et al. (1992). Impaired cortisol stress response in fish from environments polluted by PAHs, PCBs, and Mercury. A rchives of Environmental Contamination and Toxicology 22, 278-283. 

Chronic elevation of corticosteroids has been shown to impair cognitive processes and have neurotoxic effects (Sheline et al. 1996 de Kloet et al. 1999). The cumulative effects of elevated cortisol levels are associated with cognitive impairments in human aging (Lupien et al. 1999). Thus, the cognitive and neuroprotective effects of ginkgo may be partly mediated through its neuroendocrine effects. 

Lupien SJ, Nair NP, Briere S, Maheu F, Tu MT, Lemay M, McEwen BS, Meaney MJ. (1999). Increased cortisol levels and impaired cognition in human aging implication for depression and dementia in later life. Rev Neurosci. 10(2) 117-39. 

Endocrine effects Statins interfere with cholesterol synthesis and lower circulating cholesterol levels and, as such, might theoretically blunt adrenal or gonadal steroid hormone production. Small declines in total testosterone with no commensurate elevation in LH have been noted with the use of fluvastatin. Pravastatin showed inconsistent results with regard to possible effects on basal steroid hormone levels atorvastatin, lovastatin, rosuvastatin, and simvastatin did not reduce basal plasma cortisol concentration or basal plasma testosterone concentration or impair adrenal reserve. Appropriately evaluate patients who display clinical evidence of endocrine dysfunction. Exercise caution when administering HMG-CoA reductase inhibitors with drugs that affect steroid levels or activity, such as ketoconazole, spironolactone, and cimetidine. 

Abnormality in the regulatory feedback mechanism may explain the overactivity of the HPA axis seen in depressed patients, since a lack of dexam-ethasone suppression of cortisol secretion is observed (Carroll et al., 1981). In addition, despite a hypercortisolaemia, depressive patients generally do not demonstrate Cushingoid features, possibly because of a reduction in the function of corticosteroid receptors. It has therefore been hypothesised that the primary abnormality in depression may thus be an impairment of corticosteroid receptor function (Barden et al., 1995). 

As a possible consequence of direct neurotoxic effects of sustained hypercortisolism, hippocampal atrophy has now repeatedly been reported for depressed patients (Sheline et ah, 1996 Bremner et al., 2000a). Hippocampal atrophy may be associated with disinhi-bition of CRF secretion and further increases in cortisol secretion, which in turn may further damage the hippocampus. Impaired inhibition of the HPA axis is also evidenced by nonsuppression of cortisol by dexame-thasone and decreased GR numbers in depressed patients both findings parallel those in maternally separated rats. 

Medical illness or medication side effects may directly affect cognition virtually all classes of medication have been implicated. In adult patients, glucocorticoids can impair memory at relatively low doses (Keenan et ah, 1995 Newcomer et ah, 1999), as there are postulated effects on hippocampal neurons. Newcomer et ah, (1999) have reviewed the literature on illnesses in adults in which memory inversely correlates with cortisol levels, such as in Cushing s disease, Alzheimer s dementia, schizophrenia, and depression. There is no similar literature on the pediatric population. The risk of memory impairment puts chronic steroid treatment, such as that seen in certain pediatric rheumatologic disorders and severe asthmatics, for example, into a different perspective, however. Documentation of memory both before and during chronic steroid treatment might help determine detrimental effects in the pediatric population. 

Individuals with chronic liver disease may have disorders of fluid and electrolyte balance, including ascites, edema, and effusions. Alterations of whole body potassium induced by vomiting and diarrhea, as well as severe secondary aldosteronism, may contribute to muscle weakness and can be worsened by diuretic therapy. The metabolic derangements caused by metabolism of large amounts of ethanol can result in hypoglycemia, as a result of impaired hepatic gluconeogenesis, and in ketosis, caused by excessive lipolytic factors, especially increased cortisol and growth hormone. 

Cortisol deficiency results in impaired renal function (particularly glomerular filtration), augmented vasopressin secretion, and diminished ability to excrete a water load. 

In healthy individuals undergoing acute stress, there was specifically impaired retrieval of declarative long-term memory for a word list, suggesting that cortisol-induced impairment of retrieval may add significantly to the memory deficits caused by prolonged treatment (94). 

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