The diagnosis and staging of hypocortisolism in progressing autoimmune adrenalitis

The course of development of hypocortisolism was studied in 20 patients with autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy (APECED) for 1.3-9.3 years during which time the patients underwent at least three 2-h ACTH tests (2hAT). A slow progression of the disease was evident and could be staged. The earliest indicators of incipient failure were subnormality of the 2-h cortisol level alone or with subnormality of the 2-h increment. The increment was then abolished. A normal basal level was maintained longer. Longer forms of the ACTH tests produced normal responses even after the early stages of failure. A constantly elevated ACTH concentration and low cortisol/ACTH ratio in plasma were likewise signs of advanced hypocortisolism. Current criteria of primary hypocortisolism are thus indicators of the late stages of failure only. The presence of circulating adrenocortical antibodies is predictive of hypocortisolism. Some patients had normal 2hAT responses, but antibodies and subnormal cortisol/ACTH ratios. This may represent a state of compensatory activation of the hypothalamic-pituitary-adrenocortical axis.