Dexamethasone interpretation

It is sometimes necessary to suppress the production of ACTH to identify the source of a particular hormone or to establish whether its production is influenced by the secretion of ACTH. In these circumstances, it is advantageous to use a very potent substance such as dexamethasone because the use of small quantities reduces the possibility of confusion in the interpretation of hormone assays in blood or urine. For example, if complete suppression is achieved by the use of 50 mg of cortisol, the urinary 17-hydroxycorticosteroids will be 15-18 mg/24 h, since one third of the dose given will be recovered in urine as 17-hydroxycorticosteroid. If an equivalent dose of 1.5 mg of dexamethasone is used, the urinary excretion will be only 0.5 mg/24 h and blood levels will be low. 

Interpretation In normal subjects, serum cortisol concentration is suppressed to 2 pg/dL or less after administration of 1 mg of dexamethasone. Most patients with Cushing s syndrome do not show adequate suppression, and 0800 hours cortisol concentrations are usually >10pg/dL. Serum cortisol >2pg/dL may also be seen in cases of stress, obesity, infection, acute or chronic illness, alcohol abuse, severe depression, oral contraceptive use, pregnancy, estrogen therapy, failure to take the dexamethasone, or treatment with phenytoin or phenobarbital (enhancement of dexamethasone metabolism). 

Interpretation Normal subjects have suppressed serum and urinary free cortisol concentrations on day 4 to <50% of baseline values serum cortisol at 2000 hours on day 1 should be one third of the value at 0800 hours. Patients with Cushing s syndrome usually do not show diurnal rhythmicity and do not show suppression with low-dose dexamethasone. Those patients taking phenytoin or phenobarbital, or both, metabolize dexamethasone more rapidly than do normal subjects and may not show suppression. 

Interpretation Most patients with Cushing s syndrome show a suppression of baseline cortisol concentration of at least 50%. If suppression is <50%, the test should be repeated with 8 to 24 mg of dexamethasone. 

The use of dexamethasone interferes with the interpretation of clinical response to treatment. For example, corticosteroid use interferes with the resolution of fever. Thus all infants and children are recommended to undergo a repeat lumbar puncture after 24 to 48 hours of treatment to verify CSF sterilization. ... 

The interpretations on the controls of two other well-studied enzymes in tissue culture may be mentioned. Nebert and Gelboin [130] using hamster fibroblasts, and the induction by benzanthracene of microsomal aryl hydroxylase, found that the inducer appeared to cause an increase in mRNA synthesis of the hydroxylase even if protein synthesis was blocked by inhibitors it was therefore concluded that the induction occurred at the level of transcription. In contrast, Tomkins et al. [131], using rat hepatoma cells induced with dexamethasone phosphate to form tyrosine-x-KG-amino transferase (TAT), concluded that the inducer acted at the level of translation to antagonize the action of a repressor. This conclusion was based on the fact that, when actinomycin D at the very high concentration of 5 //g/ml was given several hours after the induction, an enhanced synthesis of the enzyme occurred. To... 

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