Hormonal and Metabolic Effects of Radiotherapy in Acromegaly: Long-Term Results in 128 Patients Followed in a Single Center
Gaëlle Barrande,
Myriam Pittino-Lungo,
Joël Coste,
Dominique Ponvert,
Xavier Bertagna,
Jean Pierre Luton and
Jérôme Bertherat
Service des Maladies Endocriniennes et Métaboliques (G.B.,
M.P.L., X.B., J.P.L., J.B.), Département de Biostatistique
(J.C.), Hôpital Cochin, and Service de Radiothérapie
(D.P.), Institut Curie, 75014 Paris, France
Address all correspondence and requests for reprints to: Prof. Jean Pierre Luton, M.D., Service des Maladies Endocriniennes et Métaboliques, Hôpital Cochin, 27 rue du Fg. St. Jacques, 75014 Paris, France. E-mail:
jean-pierre.luton{at}cch.ap-hop-paris.fr
Conventional radiotherapy is usually indicated in acromegalywhen
surgery fails to normalize GH secretion. However, the benefitsof
radiotherapy are delayed. This has raised questions aboutthe potency
of this treatment for reaching the safe GH levelof 2.5 µg/L and for
normalizing insulin-like growth factorI (IGF-I) levels, both of which
are currently recommended asthe therapeutic goal.
To evaluate the long-term hormonal and metabolic effects of
radiotherapyin acromegaly, a retrospective analysis was undertaken
studying128 patients followed for 11.5 ± 8.5 yr (mean ±
SD)in a single center. The preradiation GH levels
decreased asa function of time to 50% at 2 yr, 20% at 5 yr, and 10%
at 10yr. Basal GH levels below 2.5 µg/L were obtained in 7%of the
patients at 2 yr, 35% at 5 yr, 53% at 10 yr, and 66%at 15 yr. A
basal GH level below 2.5 µg/L was associatedwith suppression of GH
below 2 µg/L during an oral glucosetolerance test and normalization
of IGF-I levels in 9 of 10patients. Preradiation GH levels was the
sole factor that couldpredict the delay in GH fall to below 2.5 µg/L
(P = 0.008).At the last follow-up, IGF-I levels
were normalized in 79% ofthe patients (37 of 47; mean follow-up,
15.0 ± 11.3 yr).
In the 32 patients presenting with diabetes mellitus, improvementof
glucose tolerance was associated with lower GH levels aftertreatment
(35 ± 78 µg/L in the group of 13 patientsstill presenting
diabetes; 9 ± 12 µg/L in the groupof 4 patients with glucose
intolerance; 5 ± 8 µg/Lin the 14 patients with normal glucose
tolerance; P = 0.04).Ten years after termination of
radiotherapy gonadotroph, thyreotrophand corticotroph deficiencies
were observed in 80%, 78%, and82% of the patients,
respectively.
In conclusion, conventional radiotherapy can reduce GH levelsbelow the
optimal level of 2.5 µg/L and normalize IGF-Ilevels in acromegaly.
However, the incidence of late hypopituitarismis high, and the delay
to obtain this safe GH secretory statuscan be long, depending on the
preradiation GH level. These parametersshould be considered when
adjuvant therapy is needed after surgery.
This article has been cited by other articles:
M. Sherlock, R. C. Reulen, A. A. Alonso, J. Ayuk, R. N. Clayton, M. C. Sheppard, M. M. Hawkins, A. S. Bates, and P. M. Stewart ACTH Deficiency, Higher Doses of Hydrocortisone Replacement, and Radiotherapy Are Independent Predictors of Mortality in Patients with Acromegaly
J. Clin. Endocrinol. Metab.,
November 1, 2009;
94(11):
4216 - 4223.
[Abstract][Full Text][PDF]
K Mullan, C Sanabria, W P Abram, E M McConnell, H C Courtney, S J Hunter, D R McCance, H Leslie, B Sheridan, and A B Atkinson Long term effect of external pituitary irradiation on IGF1 levels in patients with acromegaly free of adjunctive treatment
Eur. J. Endocrinol.,
October 1, 2009;
161(4):
547 - 551.
[Abstract][Full Text][PDF]
F. Castinetti, M. Nagai, I. Morange, H. Dufour, P. Caron, P. Chanson, C. Cortet-Rudelli, J.-M. Kuhn, B. Conte-Devolx, J. Regis, et al. Long-Term Results of Stereotactic Radiosurgery in Secretory Pituitary Adenomas
J. Clin. Endocrinol. Metab.,
September 1, 2009;
94(9):
3400 - 3407.
[Abstract][Full Text][PDF]
S. Melmed, A. Colao, A. Barkan, M. Molitch, A. B. Grossman, D. Kleinberg, D. Clemmons, P. Chanson, E. Laws, J. Schlechte, et al. Guidelines for Acromegaly Management: An Update
J. Clin. Endocrinol. Metab.,
May 1, 2009;
94(5):
1509 - 1517.
[Abstract][Full Text][PDF]
C. B d'Alva, G. Abiven-Lepage, V. Viallon, L. Groussin, M. A. Dugue, X. Bertagna, and J. Bertherat Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess
Eur. J. Endocrinol.,
November 1, 2008;
159(5):
641 - 647.
[Abstract][Full Text][PDF]
M. Losa, L. Gioia, P. Picozzi, A. Franzin, M. Valle, M. Giovanelli, and P. Mortini The Role of Stereotactic Radiotherapy in Patients with Growth Hormone-Secreting Pituitary Adenoma
J. Clin. Endocrinol. Metab.,
July 1, 2008;
93(7):
2546 - 2552.
[Abstract][Full Text][PDF]
L. Nachtigall, A. Delgado, B. Swearingen, H. Lee, R. Zerikly, and A. Klibanski Changing Patterns in Diagnosis and Therapy of Acromegaly over Two Decades
J. Clin. Endocrinol. Metab.,
June 1, 2008;
93(6):
2035 - 2041.
[Abstract][Full Text][PDF]
E. O. Vik-Mo, M. Oksnes, P.-H. Pedersen, T. Wentzel-Larsen, E. Rodahl, F. Thorsen, T. Schreiner, S. Aanderud, and M. Lund-Johansen Gamma knife stereotactic radiosurgery for acromegaly
Eur. J. Endocrinol.,
September 1, 2007;
157(3):
255 - 263.
[Abstract][Full Text][PDF]
S. Melmed Acromegaly
N. Engl. J. Med.,
December 14, 2006;
355(24):
2558 - 2573.
[Full Text][PDF]
E. R. Schwarz, P. Jammula, R. Gupta, and S. Rosanio A Case and Review of Acromegaly-Induced Cardiomyopathy and the Relationship Between Growth Hormone and Heart Failure: Cause or Cure or Neither or Both?
Journal of Cardiovascular Pharmacology and Therapeutics,
December 1, 2006;
11(4):
232 - 244.
[Abstract][PDF]
P. J. Jenkins, P. Bates, M. N. Carson, P. M. Stewart, J. A. H. Wass, and on behalf of the UK National Acromegaly Register S Conventional Pituitary Irradiation Is Effective in Lowering Serum Growth Hormone and Insulin-Like Growth Factor-I in Patients with Acromegaly
J. Clin. Endocrinol. Metab.,
April 1, 2006;
91(4):
1239 - 1245.
[Abstract][Full Text][PDF]
G. Minniti, V. Esposito, M. Piccirilli, A. Fratticci, A. Santoro, and M.-L. Jaffrain-Rea Diagnosis and management of pituitary tumours in the elderly: a review based on personal experience and evidence of literature
Eur. J. Endocrinol.,
December 1, 2005;
153(6):
723 - 735.
[Abstract][Full Text][PDF]
A. L. Barkan, P. Burman, D. R. Clemmons, W. M. Drake, R. F. Gagel, P. E. Harris, P. J. Trainer, A. J. van der Lely, and M. L. Vance Glucose Homeostasis and Safety in Patients with Acromegaly Converted from Long-Acting Octreotide to Pegvisomant
J. Clin. Endocrinol. Metab.,
October 1, 2005;
90(10):
5684 - 5691.
[Abstract][Full Text][PDF]
M Rix, P Laurberg, A S Hoejberg, and B Brock-Jacobsen Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl
Eur. J. Endocrinol.,
August 1, 2005;
153(2):
195 - 201.
[Abstract][Full Text][PDF]
F. Castinetti, D. Taieb, J.-M. Kuhn, P. Chanson, M. Tamura, P. Jaquet, B. Conte-Devolx, J. Regis, H. Dufour, and T. Brue Outcome of Gamma Knife Radiosurgery in 82 Patients with Acromegaly: Correlation with Initial Hypersecretion
J. Clin. Endocrinol. Metab.,
August 1, 2005;
90(8):
4483 - 4488.
[Abstract][Full Text][PDF]
J. Bertherat, V. Contesse, E. Louiset, G. Barrande, C. Duparc, L. Groussin, P. Emy, X. Bertagna, J.-M. Kuhn, H. Vaudry, et al. In Vivo and in Vitro Screening for Illegitimate Receptors in Adrenocorticotropin-Independent Macronodular Adrenal Hyperplasia Causing Cushing's Syndrome: Identification of Two Cases of Gonadotropin/Gastric Inhibitory Polypeptide-Dependent Hypercortisolism
J. Clin. Endocrinol. Metab.,
March 1, 2005;
90(3):
1302 - 1310.
[Abstract][Full Text][PDF]
A. F. Muller, J. J. Kopchick, A. Flyvbjerg, and A. J. van der Lely Growth Hormone Receptor Antagonists
J. Clin. Endocrinol. Metab.,
April 1, 2004;
89(4):
1503 - 1511.
[Full Text][PDF]
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.
[Abstract][Full Text][PDF]
R. Cozzi, R. Attanasio, M. Montini, G. Pagani, G. Lasio, S. Lodrini, M. Barausse, M. Albizzi, D. Dallabonzana, and A. M. Pedroncelli Four-Year Treatment with Octreotide-Long-Acting Repeatable in 110 Acromegalic Patients: Predictive Value of Short-Term Results?
J. Clin. Endocrinol. Metab.,
July 1, 2003;
88(7):
3090 - 3098.
[Abstract][Full Text][PDF]
R. Attanasio, P. Epaminonda, E. Motti, E. Giugni, L. Ventrella, R. Cozzi, M. Farabola, P. Loli, P. Beck-Peccoz, and M. Arosio Gamma-Knife Radiosurgery in Acromegaly: A 4-Year Follow-Up Study
J. Clin. Endocrinol. Metab.,
July 1, 2003;
88(7):
3105 - 3112.
[Abstract][Full Text][PDF]
Z Merza Modern treatment of acromegaly
Postgrad. Med. J.,
April 1, 2003;
79(930):
189 - 194.
[Abstract][Full Text][PDF]
J. J. Kopchick, C. Parkinson, E. C. Stevens, and P. J. Trainer Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly
Endocr. Rev.,
October 1, 2002;
23(5):
623 - 646.
[Abstract][Full Text][PDF]
L. Groussin, E. Jullian, K. Perlemoine, A. Louvel, B. Leheup, J. P. Luton, X. Bertagna, and J. Bertherat Mutations of the PRKAR1A Gene in Cushing's Syndrome due to Sporadic Primary Pigmented Nodular Adrenocortical Disease
J. Clin. Endocrinol. Metab.,
September 1, 2002;
87(9):
4324 - 4329.
[Abstract][Full Text][PDF]
