One of the reasons that hydrocortisone is the preferred treatment for primary adrenal insufficiency (PAI) is because it has both glucocorticoid (GC) and mineralocorticoid (MC) activity. As a short-acting agent, it can be administered in 2-3 daily divided doses that can mimic the circadian pattern of endogenous cortisol secretion (i.e., early morning peak and bedtime nadir).
Prednisone and prednisolone have similar GC and MC effects but are intermediate-acting, so are considered second-line agents for PAI.
In contrast, methylprednisolone and dexamethasone have strong GC effects but minimal MC effects, as shown in this table. As such, when these agents are used in patients with PAI, it’s recommended to add fludrocortisone for MC replacement because virtually all patients with PAI have MC deficiency.
Dexamethasone is the recommended GC for patients hospitalized for COVID with severe symptoms, but acceptable alternatives according to the IDSA include methylprednisolone and prednisone; WHO also adds hydrocortisone as an option.