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The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 10 3419-3426
Copyright © 1998 by The Endocrine Society

Original Studies

Long-Term Mortality after Transsphenoidal Surgery and Adjunctive Therapy for Acromegaly1

Brooke Swearingen, Fred G. Barker, II, Laurence Katznelson, Beverly M. K. Biller, Steven Grinspoon, Anne Klibanski, Nicole Moayeri, Peter McL. Black2 and Nicholas T. Zervas

Neuroendocrine Clinical Center (B.S., L.K., B.M.K.B., S.G., A.K., N.T.Z.), Neurosurgical Service, Departments of Surgery (B.S., F.G.B., N.M., P.McL.B., N.T.Z.), and Medicine (L.K., B.M.K.B., S.G., A.K.), Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Brooke Swearingen, M.D., ACC 331, Massachusetts General Hospital, Fruit Street, Boston, Massachusetts 02114.

To analyze the long term outcome after multimodality therapy for acromegaly, a retrospective review was performed on 162 patients who underwent transsphenoidal surgery at Massachusetts General Hospital between 1978 and 1996. The surgical cure rate for microadenomas was 91%, that for macroadenomas was 48%, and it was 57% overall. The surgical cure rate was significantly dependent on tumor size, but was not dependent on age or sex. An improvement in the surgical cure rate was noted over the course of the review, from 45% before 1987 to 73% since 1991. Long term follow-up was obtained in 99% of U.S. residents (149 of 151), with a mean follow-up period of 7.8 yr. Adjuvant radiation and/or pharmacological therapy was given to 61 patients. Of the entire group, 83% (124 of 149) were in biochemical remission as determined by normalization of serum insulin-like growth factor I levels or by GH suppression after oral glucose tolerance testing at last contact or at death. The recurrence rate was 6% at 10 yr and 10% at 15 yr after surgery in those patients who initially met the criteria for surgical cure. The 10-yr survival rate was 88%, and there were 12 deaths at postoperative intervals of 2–12 yr, with the most common cause of death being cardiovascular disease. A Cox proportional hazards model showed that patient-years with persistent disease carried a 3.5-fold [95% confidence interval (CI), 1.0–12; P = 0.02] relative mortality risk compared to those patient-years in remission. A Poisson person-years regression analysis showed no significant difference in survival between those 86 patients cured at operation and an age- and sex-matched sample from the U.S. population [standardized mortality ratio (SMR), 0.84; 95% CI, 0.3–2.2; P = 0.35]. A similar analysis on the entire group of 149 patients showed no significant difference in survival from that in a control sample (SMR, 1.16; 95% CI, 0.66–2.0; P = 0.3). Mortality risk for patient-years with persistent active disease after unsuccessful treatment vs. that in the U.S. population sample remained increased (SMR, 1.8; 95% CI, 0.9–3.6; P = .05). This analysis suggests that the decreased survival previously reported to be associated with acromegaly can be normalized by successful surgical and adjunctive therapy.




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A. Colao, D. Ferone, P. Marzullo, and G. Lombardi
Systemic Complications of Acromegaly: Epidemiology, Pathogenesis, and Management
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S.M. Shalet
Biochemical Monitoring of Disease Activity after Surgery for Acromegaly
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 492 - 494.
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P. U. Freda, A. T. Nuruzzaman, C. M. Reyes, R. E. Sundeen, and K. D. Post
Significance of "Abnormal" Nadir Growth Hormone Levels after Oral Glucose in Postoperative Patients with Acromegaly in Remission with Normal Insulin-Like Growth Factor-I Levels
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 495 - 500.
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O. Serri, C. Beauregard, and J. Hardy
Long-Term Biochemical Status and Disease-Related Morbidity in 53 Postoperative Patients with Acromegaly
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 658 - 661.
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I. M. Holdaway, R. C. Rajasoorya, and G. D. Gamble
Factors Influencing Mortality in Acromegaly
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A. Mukherjee, J. P. Monson, P. J. Jonsson, P. J. Trainer, and S. M. Shalet
Seeking the Optimal Target Range for Insulin-Like Growth Factor I during the Treatment of Adult Growth Hormone Disorders
J. Clin. Endocrinol. Metab., December 1, 2003; 88(12): 5865 - 5870.
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F. G. Barker II, A. Klibanski, and B. Swearingen
Transsphenoidal Surgery for Pituitary Tumors in the United States, 1996-2000: Mortality, Morbidity, and the Effects of Hospital and Surgeon Volume
J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4709 - 4719.
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D. R. Clemmons, K. Chihara, P. U. Freda, K. K. Y. Ho, A. Klibanski, S. Melmed, S. M. Shalet, C. J. Strasburger, P. J. Trainer, and M. O. Thorner
Optimizing Control of Acromegaly: Integrating a Growth Hormone Receptor Antagonist into the Treatment Algorithm
J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4759 - 4767.
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P. De, D. A. Rees, N. Davies, R. John, J. Neal, R. G. Mills, J. Vafidis, J. S. Davies, and M. F. Scanlon
Transsphenoidal Surgery for Acromegaly in Wales: Results Based on Stringent Criteria of Remission
J. Clin. Endocrinol. Metab., August 1, 2003; 88(8): 3567 - 3572.
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A. Colao, L. Spinelli, P. Marzullo, R. Pivonello, M. Petretta, C. Di Somma, G. Vitale, D. Bonaduce, and G. Lombardi
High Prevalence of Cardiac Valve Disease in Acromegaly: An Observational, Analytical, Case-Control Study
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R. N. Clayton
Cardiovascular Function in Acromegaly
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Modern treatment of acromegaly
Postgrad. Med. J., April 1, 2003; 79(930): 189 - 194.
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A. Ben-Shlomo and S. Melmed
The Role of Pharmacotherapy in Perioperative Management of Patients with Acromegaly
J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 963 - 968.
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J. J. Kopchick, C. Parkinson, E. C. Stevens, and P. J. Trainer
Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly
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J. S. Bevan, S. L. Atkin, A. B. Atkinson, P.-M. Bouloux, F. Hanna, P. E. Harris, R. A. James, M. McConnell, G. A. Roberts, M. F. Scanlon, et al.
Primary Medical Therapy for Acromegaly: An Open, Prospective, Multicenter Study of the Effects of Subcutaneous and Intramuscular Slow-Release Octreotide on Growth Hormone, Insulin-Like Growth Factor-I, and Tumor Size
J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4554 - 4563.
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S. Melmed, F. F. Casanueva, F. Cavagnini, P. Chanson, L. Frohman, A. Grossman, K. Ho, D. Kleinberg, S. Lamberts, E. Laws, et al.
Guidelines for Acromegaly Management
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4054 - 4058.
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J. Ayuk, S. E. Stewart, P. M. Stewart, and M. C. Sheppard
Long-Term Safety and Efficacy of Depot Long-Acting Somatostatin Analogs for the Treatment of Acromegaly
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4142 - 4146.
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P. J. Trainer
Acromegaly--Consensus, What Consensus?
J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3534 - 3536.
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E. V. Dimaraki, C. A. Jaffe, R. DeMott-Friberg, W. F. Chandler, and A. L. Barkan
Acromegaly with Apparently Normal GH Secretion: Implications for Diagnosis and Follow-Up
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P. U. Freda
Somatostatin Analogs in Acromegaly
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3013 - 3018.
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A. C. F. Costa, A. Rossi, C. E. Martinelli Jr., H. R. Machado, and A. C. Moreira
Assessment of Disease Activity in Treated Acromegalic Patients Using a Sensitive GH Assay: Should We Achieve Strict Normal GH Levels for a Biochemical Cure?
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3142 - 3147.
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C. Parkinson, W. D. J. Ryder, and P. J. Trainer
The Relationship between Serum GH and Serum IGF-I in Acromegaly Is Gender-Specific
J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5240 - 5244.
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J. Kreutzer, M. L. Vance, M. B. S. Lopes, and E. R. Laws Jr.
Surgical Management of GH-Secreting Pituitary Adenomas: An Outcome Study Using Modern Remission Criteria
J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4072 - 4077.
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S. Melmed
CLINICAL PERSPECTIVE: Acromegaly and Cancer: Not a Problem?
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 2929 - 2934.
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D. C. Danila, J. N. S. Haidar, X. Zhang, L. Katznelson, M. D. Culler, and A. Klibanski
Somatostatin Receptor-Specific Analogs: Effects on Cell Proliferation and Growth Hormone Secretion in Human Somatotroph Tumors
J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 2976 - 2981.
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A. Colao, A. Cuocolo, P. Marzullo, E. Nicolai, D. Ferone, A. M. Della Morte, R. Pivonello, M. Salvatore, and G. Lombardi
Is the Acromegalic Cardiomyopathy Reversible? Effect of 5-Year Normalization of Growth Hormone and Insulin-Like Growth Factor I Levels on Cardiac Performance
J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1551 - 1557.
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A. J. van der Lely, A. F. Muller, J. A. Janssen, R. J. Davis, K. A. Zib, J. A. Scarlett, and S. W. Lamberts
Control of Tumor Size and Disease Activity during Cotreatment with Octreotide and the Growth Hormone Receptor Antagonist Pegvisomant in an Acromegalic Patient
J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 478 - 481.
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S. R. Peacey, A. A. Toogood, J. D. Veldhuis, M. O. Thorner, and S. M. Shalet
The Relationship between 24-Hour Growth Hormone Secretion and Insulin-Like Growth Factor I in Patients with Successfully Treated Acromegaly: Impact of Surgery or Radiotherapy
J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 259 - 266.
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N. R. Biermasz, H. van Dulken, and F. Roelfsema
Ten-Year Follow-Up Results of Transsphenoidal Microsurgery in Acromegaly
J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4596 - 4602.
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G. Barrande, M. Pittino-Lungo, J. Coste, D. Ponvert, X. Bertagna, J. P. Luton, and J. Bertherat
Hormonal and Metabolic Effects of Radiotherapy in Acromegaly: Long-Term Results in 128 Patients Followed in a Single Center
J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3779 - 3785.
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N. R. Biermasz, H. van Dulken, and F. Roelfsema
Long-Term Follow-Up Results of Postoperative Radiotherapy in 36 Patients with Acromegaly
J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2476 - 2482.
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J. S. Powell, S. L. Wardlaw, K. D. Post, and P. U. Freda
Outcome of Radiotherapy for Acromegaly Using Normalization of Insulin-Like Growth Factor I to Define Cure
J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 2068 - 2071.
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P. J. Trainer, W. M. Drake, L. Katznelson, P. U. Freda, V. Herman-Bonert, A.J. van der Lely, E. V. Dimaraki, P. M. Stewart, K. E. Friend, M. L. Vance, et al.
Treatment of Acromegaly with the Growth Hormone-Receptor Antagonist Pegvisomant
N. Engl. J. Med., April 20, 2000; 342(16): 1171 - 1177.
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R. D. Utiger
Treatment of Acromegaly
N. Engl. J. Med., April 20, 2000; 342(16): 1210 - 1211.
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A. Giustina, A. Barkan, F. F. Casanueva, F. Cavagnini, L. Frohman, K. Ho, J. Veldhuis, J. Wass, K. von Werder, and S. Melmed
Criteria for Cure of Acromegaly: A Consensus Statement{dagger}
J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 526 - 529.
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H.E. Turner and J.A.H. Wass
Modern approaches to treating acromegaly
QJM, January 1, 2000; 93(1): 1 - 6.
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M. R. DRANGE, N. R. FRAM, V. HERMAN-BONERT, and S. MELMED
Pituitary Tumor Registry: A Novel Clinical Resource
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 168 - 174.
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N.J.L. Gittoes, M.C. Sheppard, A.P. Johnson, and P.M. Stewart
Outcome of surgery for acromegaly--the experience of a dedicated pituitary surgeon
QJM, December 1, 1999; 92(12): 741 - 745.
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P. U. Freda and S. L. Wardlaw
Diagnosis and Treatment of Pituitary Tumors
J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 3859 - 3866.
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R N Clayton, P M Stewart, S M Shalet, and J A H Wass
Pituitary surgery for acromegaly
BMJ, September 4, 1999; 319(7210): 588 - 589.
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S. Melmed
Tight Control of Growth Hormone: An Attainable Outcome for Acromegaly Treatment
J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3409 - 3410.
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