The condition requires lifelong substitution unless contra-lateral gland recovers, which is seen within 6 months up to 2 years (maximum 4-5 years); time to recovery mostly depends on CS etiology, it is shorter in younger patients and it seems independent of sex, pre-operative symptoms and levels of cortisol or ACTH; after adrenal surgery of one side, CS may persist in cases of ECS or CD[109,110]. Here, POMC is linked to Cowden syndrome 1.