Secondary adrenal insufficiency is due to deficient production of ACTH by the pituitary. This usually results from pituitary disease but is occasionally due to hypothalamic disorders. In general, primary adrenocortical insufficiency (Addison’s disease) is associated with inability of the adrenal to produce either cortisol or aldosterone. In addition, there may be cutaneous hyperpigmentation due to pituitary hypersecretion of melanocytic-stimulating hormone (MSH). In secondary adrenal insufficiency, aldosterone secretion is usually sufficient to prevent hyperkalemia, and hyponatremia tends to be less severe. Cutaneous pigmentation does not occur because the pituitary does not produce excess MSH. The major abnormality is lack of cortisol due to deficiency of ACTH. The laboratory picture may simulate inappropriate ADH syndrome.

Differentiation of primary from secondary adrenal insufficiency includes plasma ACTH assay (typically increased levels in primary Addison’s disease and normal or low in pituitary or hypothalamic etiology disease) and in some cases, the prolonged ACTH test. Other tests for pituitary function (metapirone test or CRH test) may be useful in some patients.