Guest terry jackon1 Posted July 1, 2002 Report Share Posted July 1, 2002 Entrez-PubMed--National Library of Medicine--I think May 2002 Commentary: Exogenous glucocorticoids influence adrenal function, but assessment can be difficult ? Peter Hindmarsh, reader in paediatric endocrinology. Cobbold Laboratories, Middlesex Hospital, London W1T 3AA Inhaled glucocorticoids are considered the most effective anti-inflammatory drugs for patients with asthma.1 Adrenal insufficiency has been documented in children with asthma receiving high dose inhaled glucocorticoids. ?Drake et al's report raises several issues about clinical management of hypoglycaemia. The first is how a child presenting to an emergency unit with hypoglycaemia should be managed. It is important to realise that hypoglycaemia is not in itself a diagnosis, and a low blood glucose concentration should trigger further rapid biochemical evaluation before being corrected. A minimum biochemical profile should include growth hormone, cortisol, insulin, lactate, and pyruvate, measured in a blood sample drawn at the time of hypoglycaemia. The second issue is specifically related to treatment with inhaled glucocorticoids. All the children in Drake et al's report received high dose inhaled glucocorticoids. These show dose dependent suppression of adrenal function. ?In such a situation it could be argued that exogenous glucocorticoids are simply replacing endogenous production. If that is so, how did the children in this report become hypoglycaemic? One possibility is that the hypoglycaemia resulted from another disease process. Alternatively the duration of action of the inhaled glucocorticoid in these patients is less than expected. Generally an evening dose of inhaled glucocorticoid suppresses the endogenous secretion of cortisol until any time after 6 am, although there is great variation. ?Whether such suppression reflects adequate circulating concentrations of inhaled glucocorticoid is unclear, but there is the distinct possibility that at certain times of the early morning or at least before the next dose is due people lack endogenous or exogenous glucocorticoid. Furthermore, occasional non-compliance in patients receiving excessive glucocorticoids should be considered, as any non-compliance with treatment compromises them. Consideration also needs to be given to how patients receiving high dose inhaled glucocorticoids deal with situations such as intercurrent infections or trauma. In patients with adrenal insufficiency the replacement dose of glucocorticoid is doubled, and similar advice may pertain to those receiving high dose inhaled glucocorticoids. The third issue is how individuals receiving inhaled glucocorticoids should be monitored for hypothalamic-pituitary-adrenal activity. Urinary free cortisol concentrations have been measured to this end, but they are poor discriminators of adrenal underactivity. Cortisol appears in the urine only when the circulating carrier proteins are saturated, which requires high circulating cortisol concentrations, as in Cushing's disease. As such adrenal status should not be monitored on the basis of urinary cortisol concentrations in patients receiving inhaled glucocorticoids. A better approach is to estimate 24 hour secretion rates of total cortisol and cortisol metabolites as derived from gas chromatography-mass spectroscopy. Another approach has been to assess morning serum cortisol concentrations, usually by obtaining a blood sample at either 8 am or 9 am. Such measurements are also poor discriminators, although when values are undetectable cortisol can be considered absent. Low values do not necessarily indicate insufficiency. This is because cortisol secretion is pulsatile and superimposed on the circadian rhythm. The increase in serum cortisol concentrations in the morning can take place at any time between 4 am and 6 am, so that the morning peak may be detected in normal individuals between 6 am and 9 am. This means that in normal individuals the serum cortisol concentrations at 8 am or 9 am may be low as they are on the descending limb of what was a much higher pulse of cortisol in the circulation. Rather than list other estimates of cortisol secretion it is perhaps better to consider the two pieces of information required by clinicians. Firstly, what is the day to day production rate of endogenous glucocorticoids? This can best be measured by evaluating the cortisol and cortisol metabolites in the urine with gas chromatography-mass spectroscopy. Secondly, what is the response of the hypothalamic-pituitary-adrenal axis in periods of stress? The answer can be obtained either from tests such as insulin induced hypoglycaemia, which is problematic in children, or from a low dose Synacthen test. ? ? Quote Link to comment Share on other sites More sharing options...
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