Adrenal insufficiency (AI) patients who are deprived of regular steroid replacement therapy rapidly become unwell. However, the interval for which AI patients might safely be withdrawn from steroid medication for clinical purposes, such as re-assessment of adrenal reserve, is largely a matter of speculation, since it would be difficult to construct an ethical trial on this matter. Valuable insights into this dilemma can be gained from the case studies of an early clinical research trial on the development of synthetic desoxy-corticosterone acetate (DOCA), (Thorn et al. J Clin Invest 1939).
In 1938, 8 patients with primary AI were stabilised on once-daily doses of injected DOCA (average dose 18 mg, range 1030 mg). This was then substituted with placebo, with the intention to withdraw all patients for 72 h. DOCA therapy had to be re-introduced more rapidly for over half the patients due to their rapid deterioration. Placebo was not attempted with one patient due to the rapid onset of adrenal crisis when his previous adrenal extract therapy had been withdrawn. Of the 7 patients who received placebo, one became acutely unwell within 24 h and was resumed on DOCA. Another 3 patients became unwell within 48 h. The remaining 3 patients received placebo injections for the full 72 h, although marked diuresis, weight loss, anorexia, loss of strength, lowered blood pressure, increased renal excretion of sodium and lowered serum sodium were observed. Of the 3 patients who remained stable for 72 h on placebo, one continued to receive 15 g p.d. salt supplementation.
Two patients had signs of active tuberculosis infection, but this did not correlate with their relative tolerance for steroid withdrawal; one became acutely unwell within 24 h where the other remained stable for 72 h. Neither did salt supplementation or DOCA dosage requirements correlate with the degree of stability during steroid withdrawal.
In conclusion, AI patients demonstrate varying degrees of tolerance for steroid withdrawal with placebo substitution, but most can be anticipated to deteriorate markedly within 2472 h.