Glucocorticoid excess

Insulin is a powerful anabolic hormone but it is unlikely that insulin deficiency causes skeletal muscle atrophy by direct action on muscle fibers (as opposed to neurogenic atrophy) except in chronic untreated cases. There is however a close parallel between the catabolic states induced by glucocorticoid excess and by insulin deficiency. Moreover, impaired insulin action is implicated in other endocrine myopathies as a contributory cause of muscle wasting. Both acromegaly and thyrotoxicosis are associated with insulin resistance due to a postreceptor defect, and secondary hyperparathyroidism due to hypophosphatemia also gives rise to insulin insensitivity. 

Cushing s syndrome and other glucocorticoid excess states... 

Patients with Cushing s syndrome owing to endogenous or exogenous glucocorticoid excess typically present with similar clinical manifestations. 

Kletsas, D., Pratsinis, H., Gioni, V., Pilichos, K., Yiacoumettis, A. M., and Tsagarakis, S. (2007). Prior chronic in vivo glucocorticoid excess leads to an anabolic phenotype and an extension of cellular life span of skin fibroblasts in vitro. Ann. N. Y. Acad. Sci. 1100, 449-454. 

A study has been undertaken to clarify whether glucocorticoid excess affects endothelium-dependent vascular relaxation in glucocorticoid treated patients and whether dexamethasone alters the production of hydrogen peroxide and the formation of peroxynitrite, a reactive molecule between nitric oxide and superoxide, in cultured human umbilical endothelial cells (7). Glucocorticoid excess impaired endothelium-dependent vascular relaxation in vivo and enhanced the production of reactive oxygen species to cause increased production of peroxynitrite in vitro. Glucocorticoid-induced reduction in nitric oxide availability may cause vascular endothelial dysfunction, leading to hypertension and atherosclerosis. 

The benefit of glucocorticoid therapy is often limited by several adverse reactions, including cardiovascular disorders such as hypertension and atherosclerosis. Plasma volume expansion due to sodium retention plays a minor role, but increased peripheral vascular resistance, due in part to an increased pressor response to catecholamines and angiotensin II, plays a major role in the pathogenesis of hypertension induced by glucocorticoid excess. However, the molecular mechanism remains unclear. 

Iuchi T, Akaike M, Mitsui T, Ohshima Y, Shintani Y, Azuma H, Matsumoto T. Glucocorticoid excess induces superoxide production in vascular endothelial cells and elicits vascular endothelial dysfunction. Circ Res 2003 92 81-7. 

Rieu I, Sornet C, Grizard J, Dardevet D. Glucocorticoid excess induces a prolonged leucine resistance on muscle protein synthesis in old rats. Exp Gerontol. 2004 39 1315-1321. 

BAP is increased in metabolic bone diseases, including osteoporosis, osteomalacia and rickets, hyperparathyroidism, renal osteodystrophy, and thyrotoxicosis, and in individuals with acromegaly, bony metastases, glucocorticoid excess, Paget s disease, and other disorders with increased bone formation." ... 

Hyperfunction of the adrenal cortex produces clinical syndromes of glucocorticoid excess, mineraiocorticoid excess, and androgen excess... 

Sasano H, Okamoto M, Sasano N. Immunohistochemical study of cytochrome P-450 IIB hydroxylase in human adrenal cortex with mineralo- and glucocorticoid excess. Virchows Arch A Pathol Anat Histopathol. 1988 413 313-318. 

Some antifungal drugs such as ketoconazole (see Chapter 48) inhibit CYPs and thereby block the synthesis of steroid hormones, including testosterone and cortisol. Because they may induce adrenal insufficiency and are associated with hepatotoxicity, these drugs generally are not used to inhibit androgen synthesis, but sometimes are employed in cases of glucocorticoid excess. 

Soldatos G, Sztal-Mazer S, Woolley I, Stockigt J. Exogenous glucocorticoid excess as a result of ritonavir-fluticasone interaction. IntemMedJ (2005) 35, 67-8. 

Dose relation Growth hormone deficiency and glucocorticoid excess are associated with an increased risk of fragility fractures. In a cross-sectional study of glucocorticoid overreplacement on the prevalence of vertebral fractures in 51 men (mean age 55, range 23-81 years) with hypopituitarism and growth hormone deficiency, replaced in 21... 

It is important not to confuse nutritional deficiency with endocrinological d Z5function. Diabetes is caused by insuhn deficiency or resistance, resulting in uncontrolled fluctuations in blood glucose. Cushings disease is caused by glucocorticoid excess. Blindness may be caused by vitamin A deficiency, and osteomalacia (not osteoporosis) may be caused by vitamin D deficiency. Hypothyroidism is usually caused by a defect in thyroid function, but can also be due to a dietary deficiency of iodine. 

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