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Laparoscopic Adrenalectomy for Patients with Cushing’s Syndrome

Since its description in 1992, laparoscopic adrenalectomy has rapidly become the procedure of choice for unilateral adrenalectomy when the adrenal mass is less than 8 cm in size and there are no frank signs of malignancy (eg. invasion of contiguous structures). The postoperative recovery time and long-term morbidity associated with laparoscopic adrenalectomy are significantly reduced when compared to open adrenalectomy.

Among 2550 laparoscopic adrenalectomy procedures reported in the literature, the most frequent adrenal disorder operated laparoscopically was aldosterone-producing adenoma (36.2%) followed by cortisol-producing cortical adenoma (19.1%), apparent nonfunctioning cortical adenoma (18.2%), and pheochromocytoma (18.0%). However, patients with adrenocorticotropin (ACTH) dependent Cushing’s syndrome who have experienced failed attempts to remove the ACTH-secreting tumor (pituitary or ectopic) are also ideal candidates for one-stage bilateral laparoscopic adrenalectomy. The types of Cushing’s syndrome that can be treated with laparoscopic unilateral or bilateral adrenalectomy are summarized in Table 1.

Table 1. Spectrum of Cushing’s syndrome disorders that may be treated laparoscopically

  • Unilateral adrenalectomy
  • Cortisol-producing adenoma
  • Bilateral partial adrenalectomy
  • Bilateral cortisol-secreting adenomas
  • Bilateral adrenalectomy
  • ACTH-dependent Cushing’s syndrome that failed attempts at removal of ACTH-secreting tumor (pituitary or ectopic)
  • ACTH-independent Cushing’s syndrome caused by primary pigmented nodular adrenal disease or bilateral adrenal macronodular hyperplasia

Advantages of the Laparoscopic Approach

Conventional open adrenalectomy via the anterior or posterior approach requires a large incision to gain access to a relatively small gland. Moreover, the incision used for posterior adrenalectomy, with its associated 12th rib resection and subcostal (T12) nerve retraction, has been associated with various incisional and musculoskeletal problems that may persist long after the operation. These incisional problems, including flank pain, bothersome numbness and loss of muscle tone, are especially pronounced and severe in patients with Cushing’s syndrome because of poor wound healing, laxity of the abdominal wall, obesity, and musculoskeletal complaints associated with the condition.

Laparoscopic adrenalectomy involves making 1 cm incisions through which the laparoscope and tiny operating instruments are inserted. Several different surgical approaches are used, but the most common is called the lateral transabdominal approach where the small incisions are made on the affected side just below the ribs. Since 1995, numerous studies have evaluated the efficacy of laparoscopic adrenalectomy. Benefits over an open procedure include less analgesia requirement, less blood loss, lower complication rate, shorter hospital stay, more rapid return to normal activity, increased patient satisfaction and less late morbidity. Since laparoscopic adrenalectomy is technically more demanding to perform than conventional posterior adrenalectomy and complication rates generally decrease with a surgeon’s experience, laparoscopic adrenalectomies should be performed by endocrine surgeons experienced in the procedure.

At the Mayo Clinic, most patients begin a clear liquid diet the evening of surgery and a regular diet the next day. Patients are encouraged to walk the evening of surgery. Most patients undergoing unilateral adrenalectomy may be dismissed from the hospital on postoperative day 1 or 2. Bilateral adrenalectomy patients and patients who have severe Cushing’s syndrome may require more than a 2-day hospitalization.

Rationale and Clinical Scenarios

Unilateral adrenalectomy: As previously mentioned, laparoscopic adrenalectomy is the procedure of choice for removal of a unilateral cortisol-producing adenoma. However, when a malignancy is suspected from imaging studies, the surgical procedure of choice is the open abdominal incision. Also, very large tumors, greater than 10-12 cm in diameter, may be difficult to remove laparoscopically. The risk of adrenocortical cancer increases proportionately to size.

Bilateral Partial Adrenalectomy: In recent years, a surgical procedure called partial adrenalectomy or adrenal sparing surgery has been used in the rare patient that has cortisol-secreting adenomas on both adrenal glands. Partial bilateral adrenalectomy can usually preserve adrenal function in these patients. Partial bilateral adrenalectomy has been done at the Mayo Clinic for the last 10 years.

Bilateral Adrenalectomy: Bilateral laparoscopic adrenalectomy is an excellent treatment option for ACTH-dependent Cushing’s syndrome after failed pituitary surgery for Cushing’s disease or when the ACTH source cannot be resected or localized as in ectopic ACTH syndrome. To obtain a biological cure in these patients, it is essential that all of the adrenal tissue be removed. Because of the magnification when using a laparoscope, there is actually better visibility of the surgical field, thus decreasing the risk for retained adrenal gland remnants and possible surrounding adrenal rest tissue. Compared to the open approach, bilateral laparoscopic adrenal surgery is associated with much less tissue injury in patients who are immunocompromised and/or are predisposed to delayed wound healing.

Although transsphenoidal surgery for resection of an ACTH-secreting pituitary tumor is the standard of therapy for Cushing’s disease, this surgery is not always successful. Such tumors may invade contiguous structures such as the cavernous sinuses, thus precluding complete resection. Other ACTH-secreting pituitary tumors may be so small that they escape detection and resection at the time of surgery. For these reasons, transsphenoidal surgery is associated with a 20-40% failure rate, even for experienced surgeons. Reoperation carries an increased risk of inducing panhypopituitarism in conjunction with the treatment difficulties and complications associated with the hypercortisolism. Therefore, bilateral adrenalectomy has an important therapeutic role in a significant subset of patients with Cushing’s disease in whom transsphenoidal surgery has failed and would therefore be placed at high risk of panhypopituitarism with additional cranial surgery.

Sellar radiation therapy is not an optimal therapy for Cushing’s disease because its onset of action is slow and its failure rate is unacceptably high. Some degree of pituitary insufficiency is a relatively common side effect, and the mean onset of action is 18 months. Therefore, primary treatment with irradiation is not optimal in patients with clinically significant hypercortisolism and its numerous co-morbidities. Since bilateral laparoscopic adrenalectomy results in immediate cure of hypercortisolism, the role of pituitary irradiation in Cushing’s disease in these patients is limited to the treatment of the small subset of patients with large pituitary tumors (Nelson’s syndrome). In patients with enlarging pituitary tumors, sellar radiation therapy or gamma knife radiosurgery are used to prevent a locally invasive pituitary tumor from further encroaching on surrounding structures.

Patients with the syndrome of ectopic ACTH secretion often have an unresectable or occult source of ACTH secretion. The metabolic manifestations of cortisol excess may appear suddenly and progress rapidly. In these situations, adrenalectomy offers long-term relief from the symptoms associated with cortisol excess. In our experience, most patients with clinically evident ectopic ACTH syndrome have more indolent tumors, such as bronchial or thymic carcinoid tumors, islet cell tumors, or medullary carcinoma of the thyroid. Carcinoid tumors that secrete ACTH may not be apparent even with careful radiological investigation and may take up to 20 years to localize. When the source of ACTH is unresectable or occult, bilateral laparoscopic adrenalectomy is a life-saving treatment option because of the minimal morbidity associated with the procedure, especially when compared with conventional adrenalectomy. Laparoscopic adrenalectomy is also superior to medical therapy in regard to tolerance, efficacy, and safety. The procedure can successfully treat the symptoms of cortisol excess in patients with malignancy and thus offer improved quality of life and effective palliation of symptoms even in patients with disseminated, untreatable malignancy.

Risks of Laparoscopic Adrenalectomy

When performing laparoscopic adrenalectomy, the surgeon sacrifices some tactile sensation, when compared to open surgery, and the small, flat, friable adrenal gland is manipulated with instruments in a two-dimensional plane. The overall complication rate associated with laparoscopic adrenalectomy from a summary of 2550 procedures was 9.5%. Some complications of laparoscopic adrenalectomy include conversion to open adrenalectomy, bleeding, gland fragmentation, wound hematomas, organ injury, incisional hernia, and incisional pain. Nerve root pain has been reported with the posterior laparoscopic adrenalectomy approach. There is risk of violating the tumor capsule and organ damage during manipulation with the laparoscopic instruments. The mean mortality rate for 2550 procedures was 0.2% and the need to convert to an open procedure was 3.6%.

Summary

Laparoscopic adrenalectomy is safe, effective, curative, and shortens hospitalization and convalescence. Laparoscopic adrenalectomy is the procedure of choice for the surgical management of Cushing’s syndrome patients that have cortisol-producing adenomas (unilateral or bilateral), ACTH-dependent Cushing’s syndrome and failed surgery for the removal of the source of ACTH, bilateral primary pigmented nodular adrenal disease, and ACTH-independent bilateral adrenal macronodular hyperplasia. The keys to successful laparoscopic adrenalectomy are appropriate patient selection, knowledge of anatomy, delicate tissue handling, meticulous hemostasis, and experience with advanced laproscopic surgery.

Authors: Dr. William F. Young, Jr., MD and Geoffrey B. Thompson, MD (Summer, 2005)

Editor’s Note: Dr. Young is an Endocrinologist from the Division of Endocrinology, Diabetes, Metabolism, Nutrition and Internal Medicine at the Mayo Clinic, Rochester MN. Dr. Young has been involved in the treatment of Cushing’s patients for many years. Dr. Thompson is a surgeon from the Division of Gastroenterologic and General Surgery at the Mayo Clinic, Rochester, MN. Dr. Thompson has performed over 200 laparoscopic adrenalectomies.

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