The clinical and biochemical manifestations of secondary adrenocortical insufficiency are not well defined in the medical literature. This study was designed to determine the clinical and laboratory features suggesting the diagnosis of adrenal insufficiency in 15 chronic ACTH deficiency patients during low and normal cortisol states. Except for fatigue and weakness, the characteristic clinical manifestations of primary adrenal insufficiency occurred rarely. ACTH deficiency did not significantly modify blood glucose, serum calcium, sodium, potassium and differential white blood cell count. However, serum T4 was lower (65 +/- 19 vs 95 +/- 21 nmol/l, p less than 0.001) during cortisol deficiency, while T3 was higher (2.4 +/- 0.67 vs 2.0 +/- 0.60 nmol/l, p less than 0.001). Furthermore, rT3 decreased significantly during hypocorticism (0.27 +/- 0.07 vs 0.18 +/- 0.07 nmol/l, p less than 0.001). The T4/T3 ratio was significantly lower than the normal in 15 out of the 17 episodes of ACTH deficiency (29 +/- 12.5 vs 57 +/- 9.4, p less than 0.0001). We conclude that the increase in T3 and decrease in T4 levels are associated with chronic secondary adrenocortical insufficiency. This laboratory feature could be due, at least in part, to the increased peripheral conversion of T4 to T3 during cortisol deficiency.