Clinical investigation: brain
Stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas after prior adrenalectomy

Presented at the 5th International Stereotactic Radiosurgery Society Congress, Las Vegas, NV, 2001.
https://doi.org/10.1016/S0360-3016(02)02975-9Get rights and content

Abstract

Purpose: To review the results of stereotactic radiosurgery for patients with adrenocorticotropic hormone (ACTH)-producing pituitary adenomas after bilateral adrenalectomy.

Methods and Materials: Eleven patients with ACTH-producing pituitary adenomas after bilateral adrenalectomy underwent radiosurgery between 1990 and 1999. Nine patients had documented tumor growth, hyperpigmentation, and elevated ACTH levels (median 920 ng/mL) at the time of radiosurgery. Five of these patients had tumor enlargement despite prior fractionated radiotherapy (median dose 50 Gy). Two patients were treated prophylactically within 1 month of their adrenalectomies to prevent future tumor growth. The median follow-up was 37 months (range 22–74).

Results: Tumor growth control was achieved in 9 patients (82%); 2 patients had had continued tumor growth after radiosurgery. The ACTH levels decreased a median of 66% (range −99% to +27%); 4 patients had normal ACTH levels. Three patients had radiation-related complications, including diplopia (n = 2), ipsilateral blindness (n = 1), testosterone/growth hormone deficiency (n = 1), and asymptomatic temporal lobe radiation necrosis (n = 1): all had received prior radiotherapy. One patient who had undergone three prior resections and radiotherapy died 59 months after radiosurgery despite two additional attempts at tumor resection.

Conclusion: Although our experience is limited, it appears that radiosurgery provides tumor control for most patients with ACTH-producing pituitary adenomas who have undergone bilateral adrenalectomy.

Introduction

Most patients with Cushing’s disease achieve biochemical remission after transsphenoidal surgery 1, 2. However, some patients have persistent adenoma causing adrenocorticotropic hormone (ACTH) overproduction and require repeated pituitary surgery (3), fractionated radiotherapy (RT) (4), or stereotactic radiosurgery 5, 6, 7. As an alternative to these adjuvant pituitary treatments, bilateral adrenalectomy can be performed to cure hypercortisolism 8, 9. The aggressive biologic nature of a subset of ACTH-secreting pituitary adenomas has been well-documented and termed Nelson syndrome 10, 11. The pituitary tumors in patients with Nelson syndrome may transform into pituitary carcinomas with the capacity for extracranial spread 12, 13. Fractionated RT has been reported to be protective against the development of Nelson syndrome after bilateral adrenalectomy 9, 14, 15. However, other studies have detected little benefit from RT for these patients 16, 17. In this report, we outline our 12-year experience with stereotactic radiosurgery for patients with ACTH-producing pituitary adenomas who have also undergone bilateral adrenalectomy.

Section snippets

Patients

Twelve female patients with ACTH-producing pituitary adenomas having bilateral adrenalectomy underwent radiosurgery at our center between March 1990 and June 1999. One patient died 3 months after radiosurgery of myocardial infarction and was excluded from additional analysis. The characteristics of the remaining 11 patients are detailed in Table 1. All patients had undergone ≥1 pituitary procedures (range 1–3). The median patient age was 42 years (range 26–76).

Radiosurgery and follow-up

All procedures were performed

Results

The tumor size remained stable (n = 6) or decreased (n = 3) in 9 (82%) of 11 patients. Two patients had tumor enlargement after radiosurgery. One patient had partial tumor coverage (18.5 cm3) and a tumor margin dose of 12 Gy. The second patient had complete tumor coverage (11.8 cm3) and a tumor margin dose of 16 Gy. This tumor appeared decreased in size until 39 months after the procedure, but then showed progressive enlargement. Both patients had Nelson syndrome (ACTH level 920 and 11,000

Discussion

Stereotactic radiosurgery provides biochemical remission of Cushing’s disease in >50% of treated patients 5, 6, 7. Sheehan et al. (7) reviewed 43 patients with Cushing’s disease treated between 1990 and 1998. In all patients, prior transsphenoidal surgery had failed. Twenty-seven patients (63%) had normal 24-h urinary free cortisol excretion at 12 months after radiosurgery. The authors argued that the ability of radiosurgery to provide endocrine normalization for a large proportion of patients

References (21)

  • J.B Tyrrell et al.

    Cushing’s diseaseTherapy of pituitary adenomas

    Endocrinol Metab Clin North Am

    (1994)
  • E.R Laws et al.

    Radiosurgery for pituitary tumors and craniopharyngiomas

    Neurosurg Clin North Am

    (1999)
  • B.H Wolffenbuttel et al.

    Beneficial gamma-knife radiosurgery in a patient with Nelson’s syndrome

    Clin Neurol Neurosurg

    (1998)
  • G.T Tindall et al.

    Cushing’s diseaseResults of transsphenoidal surgery with emphasis on surgical failures

    J Neurosurg

    (1990)
  • R.B Friedman et al.

    Repeat transsphenoidal surgery for Cushing’s disease

    J Neurosurg

    (1989)
  • J Estrada et al.

    The long-term outcome of pituitary irradiation after unsuccessful transsphenoidal surgery in Cushing’s disease

    N Engl J Med

    (1997)
  • M Degerblad et al.

    Long-term results of stereotactic radiosurgery to the pituitary gland in Cushing’s disease

    Acta Endocrinol

    (1986)
  • C Höybye et al.

    Adrenocorticotrophic hormone-producing pituitary tumors12- to 22-year follow-up after treatment with stereotactic radiosurgery

    Neurosurgery

    (2001)
  • J.M Sheehan et al.

    Radiosurgery for Cushing’s disease after failed transsphenoidal surgery

    J Neurosurg

    (2000)
  • S.K Nagesser et al.

    Long-term results of total adrenalectomy for Cushing’s disease

    World J Surg

    (2000)
There are more references available in the full text version of this article.

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