Fig. 9.6 The hypothalamo–pituitary–adrenal axis in primary and secondary adrenocortical insufficiency. In primary adrenocortical insufficiency, circulating ACTH levels are elevated because of the negative feedback effects of low circulating cortisol. In secondary adrenocortical insufficiency, low circulating ACTH levels result from either hypothalamic or pituitary disease; as a consequence, cortisol levels are low.