Corticosteroid-induced adrenal

Grabner W. Zur induzierten NNR-Insuffizienz bei chirur-gischen Eingriffen. [Problems of corticosteroid-induced adrenal insufficiency in surgery.] Fortschr Med 1977 95(30) 1866-8. 

Children Children may be more susceptible to topical corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing syndrome than adults because of a larger skin surface area to body weight ratio. 

Kyriazopoulou V, Parparousi O, Vagenakis AG. Rifampicin-induced adrenal crisis in Addisonian patients receiving corticosteroid replacement therapy. J Clin Endocrinol Metab 1984 59(6) 1204-6. 

In patients with longstanding hypothyroidism and those with ischemic heart disease, rapid correction of hypothyroidism may precipitate angina, cardiac arrhythmias, or other adverse effects. For these patients, replacement therapy should be started at low initial doses, followed by slow titration to full replacement as tolerated over several months. If hypothyroidism and some degree of adrenal insufficiency coexist, an appropriate adjustment of the corticosteroid replacement must be initiated prior to thyroid hormone replacement therapy. This prevents acute adrenocortical insufficiency that could otherwise arise from a thyroid hormone-induced increase in the metabolic clearance rate of adrenocortical hormones. 

When corticosteroids are administered for more than 2 weeks, adrenal suppression may occur. If treatment extends over weeks to months, the patient should be given appropriate supplementary therapy at times of minor stress (two-fold dosage increases for 24-48 hours) or severe stress (up to ten-fold dosage increases for 48-72 hours) such as accidental trauma or major surgery. If corticosteroid dosage is to be reduced, it should be tapered slowly. If therapy is to be stopped, the reduction process should be quite slow when the dose reaches replacement levels. It may take 2-12 months for the hypothalamic-pituitary-adrenal axis to function acceptably, and cortisol levels may not return to normal for another 6-9 months. The glucocorticoid-induced suppression is not a pituitary problem, and treatment with ACTH does not reduce the time required for the return of normal function. 

In patients with normal adrenals, ACTH was used to induce the endogenous production of cortisol to obtain similar effects. However, except when the increase in androgens is desirable, the use of ACTH as a therapeutic agent has been abandoned. Instances in which ACTH was claimed to be more effective than glucocorticoids were probably due to the administration of smaller amounts of corticosteroids than were produced by the dosage of ACTH. 

In its acute stages, benzene toxicity appears to be due primarily to the direct effects of benzene on the central nervous system, whereas the peripheral nervous system appears to be the target following chronic low-level exposures. In addition, because benzene may induce an increase in brain catecholamines, it may also have a secondary effect on the immune system via the hypothalamus-pituitary-adrenal axis (Hsieh et al. 1988b). Increased metabolism of catecholamines can result in increased adrenal corticosteroid levels, which are immunosuppressive (Hsieh et al. 1988b). 

Adrenocorticotropic hormone derives from the anterior pituitary in response to the leptin-or stress-induced anorexigenic, hypothalamic CRH. Corticotropin (like enkephalins and MSHs) derives from a precursor polypeptide pro-opiomelanocortin. Corticotropin induces the catabolic adrenal cortex corticosteroid cortisol and the mineralocorticoid aldosterone (Chapter 11) and is an important regulator of immune responses including chemotaxis and phagocytosis. Corticotropin acts via GPCRs to activate Gas and increase cAMP in anterior pituitary cells. 

Secondary adrenal insufficiency most commonly results from exogenous corticosteroid use, leading to suppression of the hypothalamic-pituitary-adrenal axis and decreased release of ACTH, resulting in impaired androgen and cortisol production. Mirtazapine and progestins (e.g., medroxyprogesterone acetate, megestrol acetate) have also been reported to induce secondary adrenal insufficiency. Secondary disease typically presents with normal mineralocorticoid concentrations. 

Concerns about adverse effects from topical steroids have resulted in restrictions of its use on certain anatomic areas and its use in children. Both health care providers and patients lack of confidence in the safety of topical corticosteroid use has resulted in undertreatment and nonadherence. The potential for adverse effects with these products depends a variety of factors. The concentration applied, the amount applied, how often it is applied, and for how long it is applied can be important factors to consider. Long-term topical corticosteroid use primarily results in cutaneous abnormalities such as skin atrophy, striae, hypopigmentation, and steroid-induced acne. Systemic effects, namely hypothalamic-pituitary-adrenal axis suppression, growth retardation, and other adrenal abnormalities have been reported and thus have resulted in limiting topical steroid use in children (Table 97-2). - ... 

It has been shown that several monocyte-derived cytokines can act on the hypothalamic-pituitary-adrenal axis, stimulating adrenal cells to release corticosteroid hormones (B31, N2). Injection of IL-6 into rats results in an increase in concentrations of ACTH in the plasma (N2). IL-6 can also act directly on adrenal cells to induce corticosteroid release (S4, S5). IL-6 interacts with a number of cytokines to enhance the growth and differentiation of multipotent progenitor, erythroid, myeloid, and megakaryocytic cells (RIO, Rll, S60). 

---