Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders

Inclusion Criteria: * Primary or secondary chronic adrenal insufficiency, previously or newly diagnosed. * ACTH-dependent or ACTH-independent Cushing's Syndrome diagnosis during active disease (new diagnosis or recidivating). * Signed informed consent to participate in the study. Exclusion Criteria: \- acute adrenal insufficiency; * clinical or laboratory signs of significant respiratory, hepatobiliary, or pancreatic disease; * pregnancy; * severe infections, surgery, trauma requiring hospitalization within 3 months before study entry; * any active blood or rheumatic disorders, and active liver disease in the previous 5 years; * clinically significant chronic kidney disease; * severe psychiatric diseases; * history of neoplasms in the last 5 years (except for adrenal or pituitary adenoma in Cushing Syndrome, pituitary adenoma or related neolpasms in secondary adrenal insufficiency); * heart disease with a class III or class IV functional capacity; * BMI greater than 40 kg/m²; * use of medication that interferes with cortisol metabolism within 1 month before study entry; * treatment with systemic Glucocorticoid (GC) therapy other than hydrocortisone (HC), or cortisone acetate (CA); (except for the exogenous glucocorticoid cohort) * alcoholism and/or drug addictions; * night-shift workers; * use of melatonin, antipsychotic medications, estroprogestinic preparations Additional inclusion criteria introduced by Protocol Amendment Version 2.1 (approved 2026): Adults with obesity (BMI ≥30 kg/m²), with or without metabolic syndrome. Adults initiating systemic glucocorticoid therapy for non-endocrine conditions, including respiratory or rheumatologic disorders. Additional control participants, including euthyroid individuals with benign nodular thyroid disease, according to the amended protocol.