Approach to the Cushing's Disease Patient with Persistent/Recurrent Hypercortisolism after Pituitary Surgery

Although it is the ideal treatment, pituitary surgery is not always successful, and success is not always lasting. Close surveillance, clinical and biological, will detect immediate failure or late recurrence. The reason must be thoroughly explored with the somewhat dogmatic rule that the patient should be offered the best surgery in expert hands, and a repeat surgical attempt must be systematically discussed. When repeat pituitary surgery is not indicated or has failed, then comes the difficult task to choose between a number of options directed toward different targets: directly suppress tumor ACTH by pituitary radiotherapy (conventional or stereotaxic) or with medications (somatostatin analog such as pasireotide, or dopaminergic drug such as cabergoline), directly suppress adrenocortical activity with medications (inhibitors of adrenal steroidogenesis such as ketoconazole or metyrapone, or the adrenolytic Lysodren), or by surgery (bilateral adrenalectomy), and finally oppose peripheral cortisol action with the antiglucocorticoid mifepristone. No single option is ideal, able to provide at the same time a high success rate and a rapid onset of action, to restore a normal pituitary adrenal axis, and to have good tolerability. Close follow-up and thorough evaluation of the cortisolic status will eventually dictate a switch in treatment options and/or combination strategies over time. The tumor status and its possible oncogenic threat, the severity of the hypercortisolism, and the patient perspectives (wish of fertility) are among the major parameters that can help a multidisciplinary approach toward the best option.

Learning Objectives

Upon completion of this educational activity, participants shouldbe able to:

  • Lead healthcare team (surgeon, pathologist, and radiologist) to evaluate immediate and long-term outcome of pituitary surgery, anticipate the probability of recurrence and analyze the reasons for immediate failure or late recurrence.
  • Select best therapeutic option to control cortisol oversecretion and/or actions in patients with persistent Cushing's disease, considering time to action, success rate, possible adverse events and specific problems for each therapy option.
  • Appropriately monitor patient, along with the specific outcome of the selected option, and sequentially modify or combine several therapeutic options as necessary.

Additional Information

Target Audience: 
Clinical researcher
Scientific researcher
Nurse/Nurse practitioner
Physician assistant
Allied health professional
Competency Area: 
Patient Care and Procedural Skills
Medical Knowledge
Topic Area: 
General Endocrinology
Neuroendocrinology and Pituitary
Level of Outcomes: 
Level 1 (Participation)
Level 2 (Satisfaction)
Level 3A (Learning: Declarative Knowledge (Knows))
Level 3B (Learning: Procedural Knowledge (Knows How))
Level 4 (Learning: Competence (Shows How))
Activity summary
Available credit: 
  • 1.00 AMA PRA Category 1 Credits
  • 1.00 CME Certificate of Participation
Course opens: 
Course expires: 

Disclosure Policy

Authors, editors, and Endocrine Society staff involved in planning this JCEM Journal-based CME activity are required to disclose to The Endocrine Society and to learners any relevantfinancial relationship(s) of the individual or spouse/partner that have occurred within the last12 months with any commercial interest(s) whose products orservices are discussed in the CME content. The Endocrine Societyhas reviewed all disclosures and resolved all identifiedconflicts of interest.

The following author reported relevant financial relationships:

Xavier Y. Bertagna, M.D., Ph.D., has received research grant fundings from- and occasionally served on advisory boards for HRA Pharma, Ipsen, and Novartis.

The following author reported no relevant financial relationships:

Laurence Guignat, M.D., has no relevant financial relationships.

The following JCEM Editors reported relevant financial relationships:

The Editor-in-Chief, Leonard Wartofsky, M.D., is a Consultant for Asurogen, Genzyme, and IBSA, and is on the Speaker's Bureau for Genzyme. Kenneth Burman, M.D., is a Consultant for Medscape and UpToDate; a Reviewer for the Endocrine Fellows Foundation; and has received Institutional Grants for Research from Amgen, Eisei, and Pfizer. Samuel Dagogo-Jack, M.D., is a Consultant for Merck and Novo Nordisk; a Grantee for the American Diabetes Association, AstraZeneca, Boehringer Ingelheim, National Institutes of Health, and Novo Nordisk; and a Grant Reviewer for the American Diabetes Association and National Institutes of Health. Silvio Inzucchi, M.D., is a Consultant/Advisor for Boehringer Ingelheim, Genentech, Janssen, Merck, and Takeda; has DSMB Activity with Amgen, Esai, and Gilead; and receives CME support from Abbott, Amylin, Boeringher-Ingelheim, Merck, and Takeda. Kieren Mather, M.D., received an Investigator-initiated Grant from Novo Nordisk. Lynnette Nieman, M.D., is an Author/Editor for UpToDate, and receives Research Support from HRA-Pharmaceutical.

The following JCEM Editors reported no relevant financial relationships: Paolo Beck-Peccoz, M.D.; David Ehrmann, M.D.; David Handelsman, Ph.D.; Michael Kleerekoper, M.D.; Merrily Poth, M.D.; Constantine Stratakis, M.D.

Endocrine Society staff associated with the development of contentfor this activity reported no relevant financial relationships.

Acknowledgement of Commercial Support

JCEM Journal-based CME activities are not supported by grants, other funds, or in-kind contributions from commercial supporters.

Available Credit

  • 1.00 AMA PRA Category 1 Credits
  • 1.00 CME Certificate of Participation