Adrenal-Sparing Surgery Better for Pheochromocytoma

Becky McCall

May 26, 2015

DUBLIN — Adrenal-sparing surgery enables half of patients with multiple endocrine neoplasia type 2 (MEN2) and bilateral pheochromocytoma to gain 10 years without adrenal insufficiency yet still have a rate of tumor recurrence similar to those who undergo classical adrenalectomy.

The results of this large international study indicate that adrenal-sparing surgery should be the surgical approach of choice to reduce adrenal insufficiency associated with classical adrenalectomy, said Dr Frederic Castinetti, from Aix-Marseille University, Marseille, France, who presented the findings here at the recent European Congress of Endocrinology (ECE) 2015.

"With adrenal-sparing surgery, patients gain 10 years without adrenal insufficiency with no increased risk of having secondary lesions," he pointed out.

Avoiding adrenal insufficiency is clearly important in MEN2, where more than 50% of the patients will develop bilateral pheochromocytoma by age 50, Dr Castinetti explained. "Given a life expectancy of around 70 years worldwide, this could mean adrenal insufficiency for more than 30 years.

"We want to improve quality of patients' lives because they can live a long time with adrenal insufficiency if bilateral surgery is carried out," he stressed in an interview with Medscape Medical News. In contrast, "if surgery leaves even a small piece of adrenal tissue then patients are not insufficient and should have normal function."

However, he highlighted that adrenal-sparing surgery does run the risk of recurrence of pheochromocytoma, "but this might not happen until at least 10 years postsurgery. If recurrence occurs then a patient can have bilateral adrenal surgery when it becomes symptomatic. At this point, the patient will become adrenally insufficient."

Asked to comment, Dr Wouter de Herder, professor of endocrine oncology, Erasmus University, the Netherlands, said Dr Castinetti's work shows "that adrenal-sparing surgery has real advantages, especially with regard to postponing total corticosteroid dependence and…total adrenalectomy for 10 years.

"I think this is an important issue, and there is a clear benefit for patients associated with this, due to the huge morbidity and mortality in patients on cortisone-replacement therapies."

This was the first detailed presentation of these findings to endocrinologists at a medical meeting but the study was published 2014 (Lancet Oncol. 2014; 15:648–655).

Adrenal-Sparing Surgery vs Classical Adrenalectomy

Pheochromocytoma originates in the inner section of the adrenal gland, known as the medulla — all of the tumors in the study were the result of MEN2, an inherited autosomal dominant syndrome that can lead to a number of different tumors in the endocrine glands.

Pheochromocytoma may be symptomatic but is almost always benign. The surgical approach has conventionally been bilateral adrenalectomy, even in the presence of a single pheochromocytoma to minimize the risk of tumor recurrence, but then patients may suffer from Addison's disease–like symptoms, requiring lifelong corticosteroid treatment.

But in past years, surgeons have started to perform organ-sparing surgery that, while meaning a risk of recurrence, leaves patients with some adrenal function.

"The therapeutic and surgical approach to pheochromocytoma needs to take into account the risk of recurrence, in comparison with the gain in terms of adrenal function," explained Dr Castinetti.

As such, Dr Castinetti and his colleagues from institutions across Europe, China, America, and India initiated a retrospective study to determine whether adrenal-sparing surgery is safe and effective in MEN2 patients with pheochromocytoma.

They drew on data from 1210 patients in 20 countries and 30 centers, who were followed between the years 1968 and 2013. Of these, 563 had pheochromocytoma at last follow-up who had unilateral tumors (218) and underwent adrenalectomy (181) or adrenal-sparing surgery (32) or had bilateral tumors (345) and had adrenalectomy (257) or adrenal-sparing surgery (82). Some patients in each group refused surgery.

The primary aim of the retrospective analysis was to compare tumor recurrence rate in patients after adrenal-sparing surgery or adrenalectomy as well as cortical function as a measure of adrenal insufficiency over time.

Adrenal-Sparing Surgery: Similar Recurrence Rate but Retains Function

Overall, 79% (438 of 552) of operated patients underwent adrenalectomy, and 21% (114) had adrenal-sparing surgery. Pheochromocytoma recurrence occurred in 3% (four of 153) of the operated glands following adrenal-sparing surgery with a follow-up of 6 to 13 years, compared with 2% (11 of 717) of glands removed by adrenalectomy (P = .57).

"Because patients were found to have a 2% risk of recurrence in classical bilateral surgery, this implies that surgery might have been incomplete," said Dr Castinetti. Although an endocrinologist, not a surgeon, he said he understands that "if you operate on the right side, some of the adrenal gland can move behind the vena cava, and recurrence can occur in this tissue."

Assessment of postoperative adrenal insufficiency (or steroid dependence) showed that normal cortical function was found in 0% of patients who underwent classical bilateral adrenalectomy (257). However, 57% (47 of 82) of patients with bilateral pheochromocytoma who underwent adrenal-sparing surgery had normal cortical function.

Dr Castinetti cautioned that, after approximately 20 years, nearly all patients who have adrenal-sparing surgery would have recurrence of pheochromocytoma, and he stressed the fact that patients treated this way should be made aware of the need for a prolonged follow-up after 10 years.

"But in this study, these patients gained 10 years without adrenal insufficiency, and this was a significant benefit," he emphasized. "By way of comparison, even when patients are educated in how to manage steroid therapy [after adrenalectomy], they can still have adrenal crises, which left untreated can be fatal."

In conclusion, Dr Castinetti said that adrenal-sparing surgery should be the first-line treatment in patients with MEN2.

And the results of adrenal-sparing surgery are improved by endoscopy (laparoscopy or retroperitoneoscopy), which should be considered the gold standard for the approach to MEN2 pheochromocytoma, he added.

"Most importantly, these results show that adrenal-sparing surgery will make 50% of your patients with bilateral pheochromocytoma gain 10 years without adrenal insufficiency."

Dr Castinetti and Dr de Herder have declared no relevant financial relationships.

European Congress of Endocrinology 2015. May 18, 2015. Abstract


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