Glucocorticoid atrophy

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. 

Immunotoxicity of organotin compounds is not mediated by stress-induced release of glucocorticoids, since adrenalectomy did not prevent development of thymus atrophy (Seinen Willems, 1976). Also, adrenal weights were unaffected in these studies. 

The potential hyperactivation of the HPA axis in mood disorders has been revisited in recent years, in large part due to the growing recognition of the specific brain areas in which atrophy (loss), a neuroplastic event, may be present in many patients. To what extent these findings of atrophy represent the sequelae of the biochemical changes (for example, in glucocorticoid levels) accompanying repeated affective episodes, remains to be fully elucidated. 

This suggestion receives support from the observation that chronic stress or glucocorticoid administration has been demonstrated to produce atrophy and death of vulnerable hippocampal neurons in rodents and primates. Furthermore, MRI studies have revealed reduced hippocampal volumes in patients with Cushing s disease... 

Sapolsky, R. M. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch. Gen. Psych. 57 925-935,... 

The exogenous administration of glucocorticoids can result in hypothalamic-pituitary-adrenal axis (HPA) suppression, which may subsequently lead to adrenal atrophy The degree of adrenal suppression is dependent on the dosage, duration, frequency, time, and route of administration of the specific glucocorticoids. At least one patient who received prednisone for neurological symptoms developed Cushing s syndrome. ... 

The atrophied changes of the thymolymphatic system is thought to be in part due to the high levels of plasma glucocorticoids in malnutrition (M12, S4, S12). In accordance with this view is the observation that protein-deficient rats had a very marked increased uptake of 1,2- H2-... 

As mentioned previously, glucocorticoids promote apoptosis and reduce survival, differentiation, and proliferation of a number of inflammatory cells. While there is an increase in the number of polymorphonuclear leukocytes in the circulation, corticosteroids cause the involution and atrophy of all lymphoid tissue and decrease the number of circulating lymphocytes. The striking lymphocytopenia is caused in large part by an inhibition of lymphocyte proliferation, although diminished growth with preferential accumulation of cells in the Gi-phase of the cell cycle is followed by cell death. These effects are mainly mediated by alterations in cytokine production and action. 

Other side effects include acne, striae, truncal obesity, deposition of fat in the cheeks (moon face) and upper part of the back (buffalo hump), and dysmenorrhea. Topical administration may produce local skin atrophy. In patients with AIDS who are treated with glucocorticoids, Kaposi s sarcoma becomes activated or progresses more rapidly. 

Interestingly, while peripheral neuroendocrine function appears normal in patients with panic disorder, decreased basal cortisol concentrations have been reported in most studies in PTSD patients. This relative hypocortisolism occurs in the context of increased feedback inhibition of the HPA axis (see Yehuda, 2000). However, a dissociation between central and adrenocortical (re)activity has been found in animal models of severe early-life stress as well as in abused children and women, suggesting that adrenal dysfunction may, at least in part, contribute to hypocortisolism in PTSD. In the face of hypocortisolism, it seems surprising that hippocampal atrophy is one of the most prominent findings in patients with PTSD, including adult survivors of childhood abuse with PTSD (see Newport and Nemeroff, 2000). While increased glucocorticoid sensitivity of hippocampal cells may play a role in the development of hippocampal atrophy, another potential mechanism may involve toxic effects of markedly increased cortisol responses to everyday stress in patients with PTSD. 

Long-term treatment with glucocorticoids can cause cerebral atrophy (44). 

Prednicarbate is a topical glucocorticoid that seems to have an improved benefit-harm balance, as has been shown in 24 healthy volunteers (7 men, 17 women, aged 25-49 years) in a double-blind, randomized, placebo-con-trolled study of the effects of prednicarbate, mometasone furoate, and betamethasone 17-valerate on total skin thickness over 6 weeks (175). On day 36, total skin thickness was reduced by a mean of 1% in test fields treated with vehicle the relative reductions were 13,17, and 24% for prednicarbate, mometasone furoate, and betamethasone 17-valerate respectively. There were visible signs of atrophy or telangiectasia in two subjects each with betamethasone 17-valerate and mometasone furoate, but not with prednicarbate or its vehicle. 

Withdrawal symptoms disappear if the glucocorticoid is resumed, but as a rule they will in any case vanish spontaneously within a few days. More serious consequences can ensue, however, in certain types of cases and if adrenal cortical atrophy is severe. In patients treated with corticoids for the nephrotic syndrome and apparently cured, the syndrome is particularly likely to relapse on withdrawal of therapy if the adrenal cortex is atrophic (SEDA-3,305). In some cases, acute adrenocortical insufficiency after glucocorticoid treatment has actually proved fatal. It is advisable to withdraw long-term glucocorticoid therapy gradually so that the cortex has sufficient opportunity to recover. Table 5 lists methods of... 

Intra-articular and periarticular administration Local injections of glucocorticoids into and around the joints can have a dramatic therapeutic effect, but the catabolic effect can have serious consequences, including adverse effects on joint structure (461) and on local tendons, subcutaneous atrophy, and possibly osteonecrosis. Provided the state of the joint is carefully inspected before any new injection is given, and the interval between the injections is not less than 4 weeks, the risk seems to be small enough to justify treatment in invalidating cases (SEDA-3, 307). 

Hickson RC, Marone JR. Exercise and inhibition of glucocorticoid-induced muscle atrophy. Exerc Sport Sci Rev. 1993 21 135-167. 

LaPier TK Glucocorticoid-induced muscle atrophy. The role of exercise in treatment and prevention. J Cardiopulm Rehabil. 1997 17 76-84. 

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