[Cushing's disease with negative imaging in adults]

In more than one third of patients with Cushing's disease, pituitary MRI does not identify a microadenoma. The diagnostic approach should be as rigorous as possible in patients with ACTH-dependent Cushing's syndrome, to obtain a definitive diagnosis. Improved pituitary MRI techniques, including dynamic sequences, optimal T1-weighted spin-echo MRI protocol, MRI technique of spoiled gradient recalled acquisition in the steady state, and using a 3-tesla magnet, improved the tumor detection rate, parallel to the performance of endocrine dynamic tests (CRH stimulation, desmopressin stimulation and high-dose dexamethasone suppression tests). When a pituitary tumor is not convincingly identified, inferior petrosal sinus sampling remains the gold standard for diagnosis, and recently, new approaches (simultaneous prolactin measurement) could improve its sensitivity and specificity. Transsphenoidal surgery is the first-line treatment, with remission rates similar to those of patients with preoperative positive MRI. However, medical therapies play an important role after surgical failure or in a search for the onset of a visible tumor, especially with development of new drugs targeting the pituitary gland.