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Original Studies |
Divisions of Endocrinology, Metabolism, and Internal Medicine (A.V., W.F.Y.) and Gastroenterology and General Surgery (G.B.T., C.S.G., J.A.v.H., D.R.F.), Mayo Clinic and Foundation, Rochester, Minnesota 55905
Address all correspondence and requests for reprints to: William F. Young, M.D., Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905. E-mail: wyoung{at}mayo.edu
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Abstract |
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Bilateral laparoscopic adrenalectomy performed for the treatment of ACTH-dependent Cushing’s syndrome was attempted in 19 patients at our institution between 1995 and 1998. Conversion to an open procedure was required in three patients. All patients who underwent bilateral laparoscopic adrenalectomy were subsequently followed to assess the outcome of this intervention.
Twelve patients with pituitary-dependent Cushing’s syndrome and four with ectopic ACTH syndrome underwent successful bilateral laparoscopic adrenalectomy. All patients experienced resolution of the signs and symptoms (e.g. proximal myopathy, hirsutism, and emotional lability) of Cushing’s syndrome as well as weight loss, improved glucose tolerance, and improved control of blood pressure. No residual cortisol secretion was detected in the patients.
Bilateral laparoscopic adrenalectomy is a safe and effective treatment for Cushing’s syndrome when the ACTH-secreting neoplasm cannot be removed.
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Introduction |
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Since its description by Gagner (6) and Higashihara (7) 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 (e.g. invasion of contiguous structures). Laparoscopic adrenalectomy has been shown to decrease the length of hospitalization, the length of recovery, and perioperative complications (8, 9, 10, 11, 12, 13, 14). In addition, incisional or musculoskeletal complaints are rarely associated with the procedure. Expanding the laparoscopic approach to bilateral laparoscopic adrenalectomy is a reasonable alternative for the treatment of ACTH-dependent Cushing’s syndrome after failed pituitary surgery (Cushing’s disease) or when the ACTH source cannot be resected or localized (ectopic ACTH syndrome). Herein we review our experience with bilateral laparoscopic adrenalectomy for patients with ACTH-dependent Cushing’s syndrome.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The medical records and operative notes were reviewed for data
extraction and for gathering information about clinical follow-up
through July 2000. Seven patients who had not undergone postoperative
follow-up at the Mayo Clinic were asked to complete a questionnaire,
which is detailed in Table 1
. This
follow-up study was approved by the institutional review board of the
Mayo Foundation.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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. The mean duration of disease
before presentation was 3 yr (range, 6 months to 10 yr). Before
adrenalectomy, medical therapy with ketoconazole was attempted in
four patients and with aminogluthetimide in two. Only one patient was
able to tolerate medical therapy for longer than a month; nevertheless,
adequate control of cortisol secretion was not achieved in this
patient.
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Laparoscopic adrenalectomy was successfully performed transabdominally, with the patient in the lateral decubitus position. Twelve patients had Cushing’s disease, and four had ectopic ACTH secretion. Four of the patients had previously had abdominal surgery (hysterectomy, n = 1; umbilical hernia repair, n = 1; appendectomy, n = 2). The average weight of each adrenal was 9.3 g, and the mean operating time was 252 min (range, 160–360 min). The length of the hospital stay ranged from 2–5 days (mean, 2.7 days). Except for a patient who had a deep vein thrombosis 1 month after dismissal, there were no postoperative complications, allowing dismissal to home care.
All 16 patients in the series had resolution of the signs and symptoms attributed to hypercortisolism (e.g. proximal myopathy, hirsutism, and emotional lability) within 6 months of adrenalectomy. Over the period of follow-up, patients experienced an average weight loss of 13 kg.
Five patients had an increased fasting plasma glucose concentration (>5.8 mmol/L), and two of these patients had overt diabetes mellitus (>7 mmol/L) at presentation. Improved glucose tolerance was observed postoperatively, and on follow-up evaluation none had an increased fasting plasma glucose concentration. Similar improvements were noted in blood pressure control. Of five patients with hypertension, only one required continued antihypertensive therapy postoperatively.
Five patients with residual pituitary tumor encroaching on structures
such as the cavernous sinus or the optic chiasm received some form of
pituitary irradiation in an effort to prevent development of the
Nelson-Salassa syndrome. Two patients (one at another institution)
received traditional pituitary irradiation, and three others received
-knife therapy to the pituitary area. The Nelson-Salassa syndrome
has not developed in any patient during the relatively short period of
follow-up.
For the purposes of our study, a morning serum cortisol concentration was measured after the patients were asked to refrain from taking replacement therapy the previous evening. No residual cortisol secretion was detected in any of the patients.
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Discussion |
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Although transsphenoidal surgery is the standard of therapy for Cushing’s disease, resection of an ACTH-secreting pituitary tumor is not always possible. 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 (15, 16, 17, 18). Reoperation carries an increased risk of inducing panhypopituitarism in conjunction with the treatment difficulties and complications associated with the condition. 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 who would be placed at high risk of panhypopituitarism with additional cranial surgery.
Pituitary irradiation is unsuitable as primary therapy for Cushing’s disease because its onset of action is slow, and its failure rate is unacceptably high (19). A more recent series suggested that the outcome of radiotherapy after failed transsphenoidal surgery is far more favorable than previously thought (20). However, 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 multiple associated comorbidities.
As laparoscopic adrenalectomy allows rapid normalization of cortisol concentrations, the role of pituitary irradiation in Cushing’s disease is limited to the treatment of the Nelson-Salassa syndrome. Sellar radiation therapy is used to prevent a locally invasive pituitary tumor from further encroaching on surrounding structures and may potentially be combined with bilateral laparoscopic adrenalectomy to prevent development of the Nelson-Salassa syndrome in patients with residual pituitary tumor after rendering the patient eucortisolemic.
Patients with the syndrome of ectopic ACTH secretion often have an unresectable or occult source of ACTH secretion (21). The metabolic manifestations of cortisol excess appear suddenly and progress rapidly. The typical Cushing’s habitus may be absent. In these situations, adrenalectomy offers long-term relief from the symptoms associated with cortisol excess. Although, small cell lung cancer is the malignancy most frequently associated with ectopic ACTH secretion, few develop the stigmata of 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 (21). In contrast to the typical patient with ectopic ACTH syndrome, carcinoid tumors that secrete ACTH may not be apparent even with careful radiological investigation (21, 22). Bilateral laparoscopic adrenalectomy is a potential treatment option when the source of ACTH is unresectable or occult 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 tolerability, 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.
The adrenal enzyme inhibitors, aminogluthetimide, metyrapone, and ketoconazole, are used most commonly to treat Cushing’s syndrome medically. However, complete blockade of adrenal steroid synthesis is achieved only transiently; ACTH levels increase and override the blockade, requiring additional increases in the dosage of enzyme inhibitor. Furthermore, the incidence of patient intolerance and side-effects (e.g. gynecomastia and liver enzyme abnormalities) of these medications is high. Few patients are able to tolerate long-term therapy with aminogluthetimide, metyrapone, or ketoconazole. Also, to prevent an Addisonian crisis in patients receiving adrenal enzyme inhibitors, glucocorticoid and mineralocorticoid replacement may be necessary.
Since the description of laparoscopic adrenalectomy (6, 7), various researchers have described their experience with bilateral laparoscopic adrenalectomy for the treatment of Cushing’s syndrome (23, 24, 25, 26, 27). Increased experience with the technique has resulted in a decreased conversion rate to open adrenalectomy as well as a decreased incidence of pancreatitis and intra- or perioperative hemorrhage. None of these complications was observed in our series, and biochemical cure of Cushing’s syndrome was achieved.
The availability of this optimized approach to bilateral adrenalectomy raises several questions (28). Should all patients with ACTH-dependent Cushing’s syndrome selected for adrenalectomy undergo a laparoscopic procedure? The low morbidity of laparoscopic adrenalectomy compared with conventional open adrenalectomy would argue in favor of earlier referral for adrenalectomy in some patients. Cases of failure after the first transsphenoidal operation may be managed by laparoscopic adrenalectomy instead of a second transsphenoidal surgery. Similarly, laparoscopic adrenalectomy can be recommended for patients with ectopic ACTH syndrome if imaging of the thorax, abdomen, and pelvis fails to show any obvious source of ACTH. Our demonstration of the biochemical success and safety of the procedure points to an increasing role of laparoscopic adrenalectomy in the treatment of Cushing’s syndrome.
Received September 22, 2000.
Revised November 27, 2000.
Revised December 18, 2000.
Accepted December 22, 2000.
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References |
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