Hypothalamic-pituitary-adrenal axis suppression

It is important to remember that adverse effects of topical corticosteroids may be systemic in nature and hypothalamic-pituitary-adrenal axis suppression can occur, especially when high-potency corticosteroids are used. Infants and small children may be more susceptible due to their increased skin sur-face body mass ratio.18 Topical corticosteroids may also cause striae, skin atrophy, acne, telangiectasias, and rosacea.2,10,18 Atrophy can result in thin, fragile, easily lacerated skin. Striae are caused by tearing of dermal connective tissue and are irreversible.18 Due to their significant adverse-effect profile, it has been recommended that no topical corticosteroid be used regularly for more than 4 weeks without review and reassessment.2... 

Topical corticosteroids Monitor for skin thinning, telangiec-tasias, and possible hypothalamic-pituitary-adrenal axis suppression. 

The most common cause of adrenal crisis is abrupt withdrawal of exogenous glucocorticoids in patients receiving chronic treatment that resulted in hypothalamic-pituitary-adrenal-axis suppression. 

If treatment is continued for longer than 2 weeks, a tapering oral schedule should be employed to avoid hypothalamic-pituitary-adrenal axis suppression. 

For a list of the local effects of topical glucocorticoids see separate monograph. The percutaneous absorption of high-potency topical glucocorticoids has been documented, but hypothalamic-pituitary-adrenal axis suppression, leading... 

Duplantier JE, Nelson RP Jr, Morelli AR, Good RA, Kornfeld SJ. Hypothalamic-pituitary-adrenal axis suppression associated with the use of inhaled fluticasone propionate. J Allergy Clin Immunol 1998 102(4 Pt 1) 699-700. 

The percutaneous absorption of high-potency topical glucocorticoids has been documented, but hypothalamic-pituitary-adrenal axis suppression, leading to clinically significant adrenal insufficiency or Cushing s syndrome, is infrequent. Two patients developed adrenal suppression after the unregulated use of betamethasone dipropionate 0.05% ointment (about 80 g/week) or clobetasol 0.05% ointment (up to 100 g/week), obtained without prescription to treat psoriasis (362). 

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). 

Gilchrist FJ, Cox KJ, Rowe R, Horsley A, Webb AK, Jones AM, et al. Itraconazole and inhaled fluticasone causing hypothalamic-pituitary-adrenal axis suppression in adults with cystic fibrosis. J Cyst Fibros July 2013 12(4) 399-402. 

Campbell LS, Chevalier M, Levy RA, Rhodes A. Hypothalamic-pituitary-adrenal axis suppression related to topical glucocorticoid therapy... 

Glucocorticoid doses of less than 7.5 mg/day of prednisone (or its equivalent) for fewer than 3 weeks generally would not be expected to lead to suppression of the hypothalamic-pituitary-adrenal axis. 

However, nicotine also has been shown to stimulate the hypothalamic-pituitary-adrenal axis in rodents, leading to elevated plasma levels of adrenocorticotropic hormone and corticosterone (Andersson et al. 1983 Cam et al. 1979), which are known to exert a wake-promoting effect. However, studies in humans have shown that only intense smoking is able to activate the hypothalamic-pituitary-adrenal axis (Gilbert et al. 1992 Kirschbaum et al. 1992). Nicotine patches, in addition to their use in nicotine suppression and craving, have been used to explore the relationship between sleep and nicotine in human... 

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. ... 

E) Prevention of suppression of the hypothalamic-pituitary-adrenal axis... 

A. Glucocorticoid treatment of rheumatoid arthritis does not eradicate all symptoms, nor does it reverse the degenerative process. Suppression of the hypothalamic-pituitary-adrenal axis is an unwanted side effect of glucocorticoid therapy. While development of a sense of well-being may be attributed to the relief of symptoms, it is not the primary basis for employing the potent glucocorticoids. 

NPY produces a variety of central nervous system effects, including increased feeding (it is one of the most potent orexigenic molecules in the brain), hypotension, hypothermia, respiratory depression, and activation of the hypothalamic-pituitary-adrenal axis. Other effects include vasoconstriction of cerebral blood vessels, positive chronotropic and inotropic actions on the heart, and hypertension. The peptide is a potent renal vasoconstrictor and suppresses renin secretion, but can cause diuresis and natriuresis. Prejunctional neuronal actions include inhibition of transmitter release from sympathetic and parasympathetic nerves. Vascular actions include direct vasoconstriction, potentiation of the action of vasoconstrictors, and inhibition of the action of vasodilators. 

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. 

Hypothalamic-pituitary-adrenal axis function provides one of the most sensitive markers of the systemic activity of inhaled glucocorticoids (35), and suppression can be used as a surrogate marker for adverse effects of inhaled glucocorticoids in other tissues. 

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