No adverse reactions are anticipated from substitution therapy with physiologic doses. Short-term hydrocortisone therapy even at high dose is generally harmless.
In long-term high dose therapy, adverse reactions occur frequently. Hydrocortisone has the same adverse reactions as other glucocorticoids. It also has a mineralocorticoid effect. Hydrocortisone causes adrenocortical insufficiency in long-term high dose therapy. Therefore, stress, e.g. surgery or infection, can cause hypotension, hypoglycemia, or even death, unless the steroid dose is increased to adjust to the stress. Glucocorticoid withdrawal syndrome will follow abrupt withdrawal of long-term steroid therapy.