Zelissen and colleagues' [1] impressive sample of 91 patients receiving glucocorticoid replacement therapy for Addison disease confirm our long-held suspicion that long-term treatment with standard replacement doses of glucocorticoids may induce bone loss. The authors suggested that the correct determination of the dose required for glucocorticoid replacement is empiric. They stated that "for practical purposes, the correct dose is the lowest possible dose that allows the patient to feel well without producing symptoms of hypocortisolism"

Physicians now routinely use sensitive serum thyroid-stimulating hormone assays to carefully monitor levothyroxine replacement [2]. Treatment of adrenal insufficiency has advanced only slightly compared with treatment of hypothyroidism because thyroid insufficiency is relatively common and adrenal insufficiency is rare. Also, no single available test is adequate for monitoring adrenal hormone replacement therapy, which is more complicated than thyroid hormone replacement therapy.

We have proposed a practical assessment of glucocorticoid and mineralocorticoid adequacy in patients with adrenal insufficiency [3] that can be done during working hours in the office by using widely available adrenal function studies (Table 1). Two years' experience with this protocol has convinced us that the quality of patients' lives can be improved in most instances with appropriate dose adjustments.

Both the total glucocorticoid dose and the way in which this dose is distributed over the 24-hour period are important. Perhaps peak serum cortisol levels, along with 24-hour urine free cortisol determinations, would be more closely correlated with bone density than the levels reported by the authors for total glucocorticoid daily dose.

Zelissen and colleagues should provide the impetus for clinicians to base adrenal replacement doses on the results of modern endocrine function studies, which are the standard for thyroid replacement therapy.