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Bilateral Adrenalectomy in 21st Century: When to Use it for Hypercortisolism?

The purpose of this study was to examine existing treatments and outcomes for a variety of pituitary, adrenal, and ectopic tumors in comparison to treatment with a bilateral adrenalectomy (BLA).  Two major sources of research and other medical literature from 1950 through 2015 were searched using six related terms.  The results were analyzed with specific highlight on outcome and recurrence rates.  The authors feel that advances in treatments for Cushing’s, especially over the last decade or so, should cause endocrinologists to consider all options ahead of BLA if appropriate for the patient.

BLAs were first performed through open surgery (anterior laparotomy), then by opening the back and removing the 12th rib (posterior approach), and finally the laparoscopic method that is used today and generally considered the gold standard.  Current Endocrine Society guidelines on diagnosis and treatment of Cushing’s do not recommend BLA as a first line of treatment.  Efficacy of the various pharmaceutical options and radiation as first or second line treatments are well documented in medical literature, but the authors also wanted to look at when BLA is an appropriate choice.  One of the things they found was that side-by-side comparisons are virtually non-existent.  Also complicating things is that there is not enough follow up data on patients past approximately 10 years.

BLA in Acute Hypercortisolism: Because long-term exposure to high levels of cortisol causes complications that are not completely reversible after treatment, the goals are earlier diagnosis and faster control of symptoms.  The more severe the hypercortisolism, the more life-threatening it becomes, especially in patients with psychiatric symptoms.  The literature points to BLA not always being a good option for patients with severe symptoms; instead it seems to point at fast-acting medication that can rapidly lower cortisol but also be adjusted after cortisol control has been achieved.  Monitoring the various drugs available to Cushing’s patients is challenging for doctors and seems to be best suited to expert centers with the knowledge and resources to follow those patients closely and act quickly based on response to medication.

BLA in Chronic Hypercortisolism: Pituitary surgery for Cushing’s Disease is the first line of treatment with an immediate remission rate of 50-80%.  Failed surgery leads to additional choices to make – another surgery, radiation, and/or medication.  BLAs do get recommended under certain circumstances, for example to achieve the “final cure” in patients with multiple failed treatments or patients who are not able to comply with a drug regimen.  Even though a BLA seems fail-proof, there are cases in which patients have experienced recurrence of their hypercortisolism even after having their adrenals removed.

Comparison with Long-Term Treatment with Medical Therapy: The authors focused on data related to the efficacy and tolerance of medical therapy.  They found that overall there is evidence that medical therapies are a safe option and can be maintained on a long-term basis.  Their benefit over BLA is that they do not cause permanent adrenal insufficiency.  There are situations where a BLA might still be the better option; examples include a young woman who would like to get pregnant and a patient who cannot comply with dosing requirements.

Comparison with New Radiotherapy Modalities:  Most studies were based on the Gamma Knife, but the authors felt that similar results would be seen with other forms.  The main advantage of radiation is that the target is clearly defined.  A drawback could be the time it takes to start to see its effects, which is estimated to be 2-4 years.  Patients almost always need medical therapy as a “bridge” while waiting for the radiation to work.  Even so, the low rate of side effects makes radiation a desirable option for some patients who also have success with one of the medical options available.  In the event that radiation doesn’t work, BLA remains an option.

The review concludes that BLA is the most effective definitive treatment for hypercortisolism when surgical removal of the source isn’t possible.  However, several options exist that can change this narrow path for patients who find themselves in experienced hands.  Defining the place of BLA in 21st century hypercortisolism treatment is a challenge that will only get more complex as new drugs currently in the works become available.  These additions to the medicine cabinet are likely to encourage more “wait and see” approaches instead of turning so quickly to BLA.  There are also improvements in radiological methods that are increasing the chances of finding small endocrine tumors in the first place which will hopefully contribute to a shortened average diagnosis time.

Carole Guerin, David Taieb, Giorgio Treglia, Thierry Brue, André Lacroix, Frederic Sebag, Frederic Castinetti.  Society for Endocrinology. 2016 February, Volume 23, Issue 2.  doi: 10.1530/ERC-15-0541

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