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Preserved Adrenocortical Function After Laparoscopic Bilateral Adrenal Sparing Surgery for Hereditary Pheochromocytoma¹

Department of Nephrology and Hypertension (H.P.H.N., B.U.B.), Department of Gastroenterology and Endocrinology (M.R.), Albert-Ludwigs-University, D-79106 Freiburg, Germany; Department of Pediatrics (R.E.), Maximilian-University, D-80337 Munich, Germany; Department of Urology (G.J.) Leopold-Franzens-University, A-6020 Innsbruck, Austria

Address correspondence and requests for reprints to: Professor Dr. H. P. H. Neumann, Medizinische Universitätsklinik, Hugstetter Straße 55, D-79106 Freiburg, Germany. E-mail: Neumann{at}mm41.ukl.uni-freiburg.de

	Abstract

Top Abstract Introduction Patients and Methods Results Discussion References

 
Background: Familial pheochromocytoma, increasingly diagnosed in asymptomatic subjects with inherited syndromes such as multiple endocrine neoplasia type 2 and Von Hippel-Lindau disease, is frequently bilateral and multifocal, but very rarely malignant. Therefore, bilateral adrenalectomy and subsequent lifelong steroid replacement, with its attendent side effects, is not desirable. Minimally invasive adrenal sparing surgery by means of laparoscopy was explored for the treatment of bilateral pheochromocytoma. We report on the cure rate and adrenocortical function in a series of patients treated accordingly.

Patients and methods: Four patients (three male, one female, ages 9–60 yr) with hereditary bilateral adrenal pheochromocytoma were treated by laparoscopic surgery in an organ sparing fashion. Postoperatively, all patients were reevaluated for complete tumor removal and for adrenocortical function.

Results: Two to 24 months after surgery, all patients were normotensive, had normal sodium potassium, glucose, aldosterone, renin, and cortisol serum concentrations, 24-h excretion of norepinephrine, epinephrine, and vanillylmandelic acid. Abdominal magnetic resonance imaging (n = 3) and computed tomographic scan (n = 1) disclosed no remnant or relapsing tumor tissue. ACTH stimulation testing resulted in normal cortisol responses.

Conclusion: By adrenal sparing laparoscopic surgery not only bilateral pheochromocytoma can be successfully removed, but also adrenocortical function preserved. This may become the treatment of choice for familial pheochromocytoma.

	Introduction

Top Abstract Introduction Patients and Methods Results Discussion References

 
BILATERAL adrenal pheochromocytoma is typically found as an inherited condition, for example, as a component tumor of either multiple endocrine neoplasia type 2 or Von Hippel-Lindau disease (1, 2). Classical therapy of bilateral pheochromocytoma results in complete adrenalectomy followed by life-long steroid replacement. Such patients usually receive a fixed daily steroid dosage, which could result in undertreatment during stress situations and possibly over-replacement with premature osteoporosis, hypertension, and diabetes after many years (3, 4). For these reasons, we developed the concept of adrenal sparing surgery, and recently reported the excellent outcome of these patients (5). Because patients with bilateral pheochromocytoma require a large transabdominal access, we now extended the concept of an adrenal sparing approach to minimally invasive surgery by means of laparoscopy. We here report the endocrine data of the first four patients treated accordingly.

	Patients and Methods

Top Abstract Introduction Patients and Methods Results Discussion References

 
The four patients were diagnosed in Freiburg (n = 3) and Munich (n = 1). Surgical treatment was performed in the Department of Urology in Innsbruck. The essential data and findings are presented in Table 1. All patients had Von Hippel-Lindau disease with bilateral adrenal pheochromocytomas, and three had, in addition, one to two extraadrenal pheochromocytomas. Two patients had had previous surgery for pheochromocytoma, patient no. 1, 41 yr ago, for left adrenal, and patient no. 4, 3 yr ago, for thoracic pheochromocytoma.

	Results

Top Abstract Introduction Patients and Methods Results Discussion References

 
All four patients were reinvestigated 2–24 months after operation. They had returned to normal life 14–24 days postoperatively. All were normotensive and had normal ranges of serum sodium, potassium, glucose, and 24-h catecholamine excretion. Magnetic resonance imaging excluded tumor rests in patients 1, 2, and 3, and CT in patient 4. Baseline hormone concentrations were normal in the patients postoperatively (Table 2), and serum cortisol concentrations responded normally to exogenous ACTH demonstrating maintained adrenocortical function (Fig. 1).

View larger version (98K): [in this window] [in a new window]   Figure 1. Graph demonstrating normal response to 250 µg iv ACTH1–24 test (250 µg iv ACTH1–24) in patients after bilateral adrenal sparing surgery. The lower normal limit after stimulation is indicated by the dashed line.

	Discussion

Top Abstract Introduction Patients and Methods Results Discussion References

Within a short period of time, minimally invasive surgery using endoscopic techniques has been adopted by numerous medical centers worldwide and has gained wide acceptance among endocrine surgeons for the resection of adrenal tumors (10). Although prospective, randomized studies are lacking, laparoscopic adrenalectomy seems to be associated with a significantly shorter hospital stay, less postoperative narcotic use, increased patient satisfaction and reduced late morbidity (11). However, the laparascopic procedure was associated with longer operation time and higher costs (6). Laparoscopic surgery is now recommended for benign adrenal lesions not exceeding 6 cm in diameter, whereas larger and potentially malignant adrenal masses should be removed by open surgery (10).

In bilateral pheochromocytoma which occurs mainly in Von Hippel-Lindau disease or in multiple endocrine neoplasia type 2, both, conventional and laparoscopic adrenalectomy result in permanent adrenal insuffiency requiring life long steroid replacement therapy. This may have serious health implications including osteoporosis due to chronic hydrocortisone oversubstitution, impaired quality of life and symptoms of hypoandrogenism in women due to missing adrenal androgen production. We therefore offered patients with hereditary pheochromocytoma adrenal sparing surgery as an alternative to a total adrenalectomy, avoiding steroid dependency. Because malignancy is extremely rare in familial pheochromocytoma and does not pose a major problem, we considered this approach to be safe. Since 1985, we have treated 39 patients accordingly, including 14 patients with bilateral pheochromocytoma (5). All patients were cured from pheochromocytoma. Of the patients who underwent bilateral surgery, only one became chronically steroid dependent. These data show that open adrenal sparing surgery is a rather safe procedure and preserves adrenocortical function in most of the patients. This approach may be particularly justified in patients with bilateral or hereditary pheochromocytoma.

We now show that adrenal sparing surgery can also be performed using laparoscopic minimally invasive surgery. Because of the magnification provided by the endoscope, laparoscopy has the advantage of allowing better visualization of small vessels than open surgery, thus permiting meticulous preparation during resection. There is an increased risk of hypertensive crisis during partial adrenalectomy, as the adrenal vein cannot be ligated. Indeed, an instant increase in blood pressure has always been observed when the adrenal gland is approached. Nevertheless, hypertension could be easily controlled by pharmacological means in our studies and in the literature (8). Obviously, pretreatment with an alpha-blocker is very effective, and direct manipulation of the pheochromocytoma is tolerated without previous ligation of the adrenal vein.

Adrenocortical function was maintained in all patients as documented by normal ACTH stimulation tests. The time of follow-up is still to short to draw conclusions concerning the rate of pheochromocytoma recurrence, but for technical reasons it should not be higher than after open adrenal sparing surgery, with one recurrence in 29 patients after 6 yr mean follow-up (5). A disadvantage of the technique is the long operation time (mean, 8 hr). This is longer than the mean operation time of 6.5 hr in a recently published series of patients undergoing bilateral laparoscopic adrenalectomy (12) and considerably longer than that of open bilateral adrenalectomy. However, operation time was increased in our series due to extra-adrenal pheochromocytomas in 3 of 4 patients, which were removed in the same session successfully. On the other hand, even long operative times do not increase morbidity substantially, but recovery is essentially decreased after laparascopy as compared to open surgery (8, 11). Finally, patients will increasingly prefer laparascopic adrenal operations because of the excellent cosmetic results.

In summary, we show that bilateral laparoscopic and adrenal sparing surgery is technically feasable and maintains adrenocortical function in patients with hereditary pheochromocytoma. This approach should be considered especially in young patients who may otherwise face life long steroid replacement therapy.

	Footnotes

 
¹ This work was supported by the Center of Clinical Research of the University of Freiburg.

Received February 24, 1999.

Revised April 14, 1999.

Accepted April 16, 1999.

	References

Top Abstract Introduction Patients and Methods Results Discussion References

 

1. Neumann HPH, Berger DP, Sigmund G, et al. 1993 Pheochromocytomas, multiple endocrine neoplasia type 2 and von Hippel-Lindau disease. N Engl J Med 329:1531–1538.
2. Eng C. 1996 RET proto-oncogene in multiple endocrine neoplasia type 2 and Hirschsprung’s disease. N Engl J Med 335:943–951.
3. Oelkers W. 1996 Adrenal insuffiency. N Engl J Med 335:1206–1212.
4. Zelissen PM, Croughs RJM, Van Rijk PP, et al. 1994 Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison disease. Ann Intern Med 120:207–210.
5. Neumann HPH, Bender BU, Reincke M, et al. 1998 Adrenal sparing surgery for phaeochromocytoma. Brit J Surg,86 :94–97.
6. Janetschek G, Altarac S, Finkenstedt D, Gasser R, Bartsch G. 1996 Technique and results of laparoscopic adrenalectomy. Eur Urol 30:475–479.
7. Janetschek G, Lhotta K, Gasser R, et al. 1997 Adrenal-sparing laparoscopic surgery for aldosterone-producing adenoma. J Endourol 11:145–148.
8. Janetschek G, Finkenstedt G, Gasser R, et al. 1998 Laparoscopic surgery for pheochromocytoma: adrenalectomy, partial resection, excision of paragangliomas. J Urol 160:1248–1254.
9. Gagner M, Lacroix A, Bolte E. 1992 Laparoscopic adrenalectomy in Cushing syndrome and pheochromocytoma. N Engl J Med 327:1033 (Letter).
10. Wells SA, Merke DP, Cutler GB, et al. 1998 Therapeutic controversy: The role of laparoscopic surgery in adrenal disease. J Clin Endocrinol Metab 83:3041–3049.
11. Thompson GB, Grant CS, van Heerden J, et al. 1997 Laparoscopic vs. open posterior adrenalectomy. A case control study of 100 patients. Surgery 6:132–136.
12. Wells SA, Merke DP, Cutler Jr GB, Norton JA, Lacroix A. 1998 Therapeutic controversy: The Role of Laparoscopic Surgery in Adrenal Disease. Five-year experience with laparoscopic adrenalectomy at Hotel-Dieu in Montreal. J Clin Endocrinol Metab83 :3041–3049.

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