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Letters to the Editor |
Department of Endocrinology The Queen Elizabeth Hospital Woodville, South Australia 5011
To the editor:
I read with considerable interest the paper by Nordenstrom et al. (1) describing a clinical case where administration of oral cortisone acetate produced an unusually high ratio of cortisone to cortisol (THE/THF) urinary metabolites and failed to suppress hyperadrenalism due to an underlying 21-hydroxylase enzyme deficiency. The patient, however, responded to either oral prednisolone or hydrocortisone with a accompanying significant decrease in the THE/THF ratio. These findings led the authors to suggest a deficiency of the 11ß-hydroxydehydrogenase enzyme with respect to hepatic 11-oxoreductase activity. However, studies (2, 3, 4) have previously documented clinical cases where a decreased conversion of cortisone to cortisol is proposed, with the same general urinary corticosteroid metabolic pattern described by Nordenstrom et al. (1). As well, Raven et al. (5) have reported that the adrenocortical 11ß-hydroxylase blocking agent metyrapone also decreases 11-oxoreductase activity with respect to metabolism of exogenous hydrocortisone.
The difference between our original findings (2, 4) and those of Nordenstrom et al. (1) is that essentially the same THE/THF ratio resulted whether oral cortisone acetate or hydrocortisone was administered and while dexamethasone suppressed hyperadrenalism, ongoing treatment, even at a low daily dose of 0.25 mg caused the patient to develop cushingoid features. Taylor et al. (3) also found a marked increase in the ratio of urinary prednisone to prednisolone metabolites (compared with controls) after oral administration of either prednisone or prednisolone and extensive plasma conversion of prednisone to prednisolone.
The failure of cortisone acetate to effect adrenal suppression is inconsistent with the fact that a defect of 11-oxoreductase activity of this magnitude would also lead to an extremely rapid clearance of plasma hydrocortisone. For example, Taylor et al. (3) reported that in their patient the plasma half-life of prednisolone decreases more than 4-fold compared with controls. Also, in Fig. 1 of the article by Nordenstrom et al., administration of prednisolone appears to have minimal effect on plasma levels of 17-hydroxyprogesterone while hydrocortisone causes both a rapid and marked decrease. Two questions, therefore, arise: what degree of suppression (if any) does cortisone acetate achieve and is prednisone also ineffective?
Unfortunately, Nordenstrom et al. (1) do not
provide an estimate of the variability of the THE/THF ratio for
hydrocortisone treatment, given the high variability of this ratio
during cortisone acetate therapy (mean, 13.6; range, 7–24). Assessment
of the urinary equilibrium set-point of the 11ß-hydroxydehydrogenase
enzyme is further complicated by use of the THE/THF ratio rather than
the cortisol metabolic ratio (6), which includes the
contribution of 5
-THF. While in adults the urinary excretion of THF
is typically greater than 5-THF, the situation is often reversed in
young children.
Whether the corticosteroid metabolic abnormality in the case described by Nordenstrom et al. (1) is the same as that previously reported (2, 3, 4) is presently unclear. Extra information is obviously necessary, particularly with respect to plasma and urinary concentrations of cortisol after cortisone acetate and hydrocortisone treatment, and the efficacy of suppression with prednisone.
Received November 12, 2000.
References
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