Hypothalamic-pituitary-adrenal abnormalities

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). - ... 

ALTERED BARRIER FUNCTION In many dermatological diseases, such as psoriasis, the stratum comeum is abnormal, and barrier function is compromised. In these settings, percutaneous absorption may be increased to the point that standard drag doses can result in systemic toxicity (e.g., hypothalamic-pituitary-adrenal axis suppression can result from systemic absorption of potent topical glucocorticoids). 

It is now generally accepted that emotional/psychological stress stimulates the sympathetic nervous system, which in turn can lead to abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis [7]. During normal or abnormal times the HPA axis serves as a communicator between nervous, immune and endocrine systems. Thus, during stressful conditions abnormal secretions occur that can produce a variety of adverse effects upon various health states [7,8]. 

Concentrations of hypothalamic and anterior pituitary peptides and adrenal glucocorticoids are measured accurately and at low concentrations in body fluids using immunoassay and instrumental methods. Relying on basal hormone concentrations for confirmmg adrenocortical dysfunction, however, can be problematic because of the episodic and circadian secretion of the hormones that regulate the HPA axis. For example, some individuals have an abnormality of the HPA axis, but still maintain basal cortisol and ACTH secretion within die reference interval of the normal population. Dynamic testing of the HPA axis helps define abnormalities that are not reflected in basal hormone secretion. 

NR4A1 nullizygous mice have no discernible phenotype and display no abnormalities in hypothalamic regulation, pituitary fundion, adrenal steroidogenesis [53], and in thymic and peripheral T cell death [54], indicating a functional redundancy among NR4A nuclear receptors. 

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