| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Studies |
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
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
To evaluate the long-term hormonal and metabolic effects of radiotherapy in acromegaly, a retrospective analysis was undertaken studying 128 patients followed for 11.5 ± 8.5 yr (mean ± SD) in a single center. The preradiation GH levels decreased as a function of time to 50% at 2 yr, 20% at 5 yr, and 10% at 10 yr. 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 associated with suppression of GH below 2 µg/L during an oral glucose tolerance test and normalization of IGF-I levels in 9 of 10 patients. Preradiation GH levels was the sole factor that could predict 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% of the patients (37 of 47; mean follow-up, 15.0 ± 11.3 yr).
In the 32 patients presenting with diabetes mellitus, improvement of glucose tolerance was associated with lower GH levels after treatment (35 ± 78 µg/L in the group of 13 patients still presenting diabetes; 9 ± 12 µg/L in the group of 4 patients with glucose intolerance; 5 ± 8 µg/L in the 14 patients with normal glucose tolerance; P = 0.04). Ten years after termination of radiotherapy gonadotroph, thyreotroph and corticotroph deficiencies were observed in 80%, 78%, and 82% of the patients, respectively.
In conclusion, conventional radiotherapy can reduce GH levels below the optimal level of 2.5 µg/L and normalize IGF-I levels in acromegaly. However, the incidence of late hypopituitarism is high, and the delay to obtain this safe GH secretory status can be long, depending on the preradiation GH level. These parameters should be considered when adjuvant therapy is needed after surgery.
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Acromegaly is associated with increased morbidity and mortality rates (7, 8, 9, 10). The mortality rate is at least twice the normal value and is due to cardiovascular, respiratory, and malignant diseases (10, 11). Over the past few years, it has been shown that the mortality rate is normal in acromegalic patients whose posttreatment basal GH levels were reduced to less than 2.5 µg/L (5, 8, 10).
Radiotherapy has consistent, but delayed, effects on GH secretion in acromegaly; basal plasma GH levels decrease to less than 5 µg/L in 56–70% of patients 10 yr after radiotherapy (12, 13, 14). Only a few studies have evaluated the effects of radiotherapy on GH levels using a basal GH level of less than 2.5 µg/L, suppression of GH during oral glucose tolerance test (OGTT), and normalized insulin-like growth factor I (IGF-I) levels as the criteria for cure (5, 15, 16, 17). Indeed, a recent study questioned the efficacy of radiotherapy in lowering IGF-I levels (17).
To determine the long-term outcome in patients treated with pituitary irradiation, we retrospectively reviewed the records of 128 acromegalic patients followed at the Cochin Hospital who underwent pituitary radiotherapy, in most cases after unsuccessful surgery. The effect of radiotherapy was assessed using the classic criterion of cure, a basal GH level below 5 µg/L; the more stringent criterion, a basal GH level below 2.5 µg/L; along with suppression of GH during an OGTT. We also reported the long-term effect of radiotherapy on IGF-I levels in a subset of patients. The influence of control of GH secretion on glucose tolerance in patients presenting with diabetes was also studied. In this study we show that radiotherapy is an effective treatment for the long-term control of GH hypersecretion resulting in a decrease in basal GH below 2.5 µg/L, suppression of post-OGTT GH, and normalization of IGF-I in 61–79% of patients after 15 yr.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
We identified all patients with acromegaly seen at the Department of Endocrinology of Cochin Hospital between 1951 and 1998. Of a total of 389 patients, 128 underwent pituitary irradiation before or during 1996 as part of their treatment and were therefore selected for this study. Radiotherapy followed unsuccessful surgical resection of a pituitary adenoma by transsphenoidal or by transfrontal approach in 104 patients. In the remaining 24 patients, radiotherapy was the primary treatment, either alone (13 patients) or followed by surgical resection (11 patients).
Pituitary irradiation procedure
A mean dose of 52 ± 8.5 Gray units (Gy) at the International Commission on Radiation Units and Measurements prescription point was given with a daily administration of 1.8 Gy, 5 days/week. Seventy-eight of the 128 patients were treated at the Curie Institute, and the remaining patients were treated at various other centers.
A variety of treatment techniques were employed at the Curie Institute.
Different beam energies were used: 1.25 megavolt (MV) 
-rays from a
60Co source in the early years of the study
(between 1960 and 1980) and 5-, 15-, or 23-MV X-rays produced by linear
accelerator latter. The target volume was defined on lateral and
anterior simulation films guided by radiological and surgical findings,
and more recently (1994) with contrast-enhanced computed tomography
scans for conformal treatment planning procedures. Most of the patients
were treated with a combination of three coplanar fields (two lateral
and one anterior), and more rarely a fourth posterior field was used to
spare temporal lobes (18).
Endocrine evaluation
For basal GH measurement, a single fasting value or the mean value from two fasting samples obtained in the morning is reported. For GH measurements during OGTT, 75 g glucose were given orally, and GH assays were performed on the plasma samples collected after 0 and 60 min of the OGTT. OGTT-derived GH levels below 2 µg/L were considered normal (19). Most GH measurements (90%) were assayed in the nuclear medicine laboratory of Cochin Hospital 1) by RIA using a rabbit polyclonal antibody (lower limit of delectability, 1 µg/L) between 1966 and 1984 (20), 2) by RIA using the CIS-Bio International kit (Gif-sur-Yvette, France) between 1984 and 1990, and 3) by immunoradiometric assay (IRMA) using the CIS-Bio International kit (lower limit of detectability, 0.04 µg/L) thereafter. Correlation analysis between RIA and IRMA GH assays showed a 10% higher GH level for a sample assayed with IRMA compared to the RIA assay.
Plasma IGF-I concentrations were measured by RIA as previously reported (21), IGF-I was separated from its binding proteins using an INCSTAR Corp. kit (Stillwater, MN) with Sep-Pak column extraction or gel filtration before 1993 (21) and acid/ethanol extraction using the Nichols Institute Diagnostics diagnostic kit (San Juan Capistrano, CA) thereafter. For plasma IGF-I, results are expressed as a percentage of the upper limit of the normal age- and sex-adjusted range. Patients who had radiotherapy followed by surgery were excluded from the analysis of GH levels after surgery. For patients receiving medical therapy (bromocriptine or somatostatin analogs) after radiotherapy, only plasma GH levels measured after medication withdrawal were included in the analysis.
Diabetes mellitus, impaired glucose tolerance, and normal carbohydrate tolerance were diagnosed according to the criteria proposed by the National Diabetes Data Group of the NIH (22).
Endocrine testing after radiotherapy included basal hormone measurement associated in most cases with dynamic testing. Hypopituitarism was defined as clinical and biochemical evidence of pituitary dysfunction or requirement for hormone replacement. Gonadotropic deficiency was defined as low plasma testosterone and low or normal gonadotropin levels in men, amenorrhea with low plasma estradiol and low or normal gonadotropin levels in nonmenopausal women, and nonincreased levels of gonadotropins in menopausal women. Corticotropic deficiency was established by subnormal cortisol response to synthetic ACTH or by subnormal response of 11-deoxycortisol or urinary 17-hydroxycorticosteroids after a metyrapone test. Thyreotroph deficiency was defined as low total or free plasma T4 with normal or diminished plasma TSH.
Statistical analysis
Changes in the biological variables were described using means and SDs. Due to the nonnormal distribution of several variables and the small numbers of subjects in certain groups of interest, nonparametric statistical methods were used to examine relationships between variables when appropriate (Wilcoxon test and Kruskal-Wallis ANOVA). Two-tailed P values were used, and values below 0.05 were considered to indicate significance.
The rates of cure were analyzed by life-table analysis (Kaplan-Meier). The prognostic values of factors (measured on entry) on cure were investigated using log-rank tests. Cox’s proportional hazards models were used to study the effects of several factors simultaneously and to adjust for the potential confounding effect of the delay between time of onset of symptoms and time of entry into the study.
The relationship between GH decrease and follow-up duration was assessed using random effects linear models (23). These models permitted us 1) to provide estimations of mean parameters of a polynomial (intercepts, slopes, etc.), and 2) to test null hypotheses, that these parameters are equal to 0, within the group of patients as a whole. For each model tested, residuals were checked for normality, and their squares were averaged (to give the mean squared error) for assessing the goodness of fit (24). Restricted maximum likelihood was used as the optimal criterion to fit the data. All computations were performed using the SAS package (SAS Institute, Inc., Cary, NC) (25).
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The average age of the 128 patients (65 women and 63 men) was
36.5 ± 11.3 yr (mean ± SD) at the time of
diagnosis of acromegaly. The mean duration of acromegaly before
diagnosis was 7.1 ± 5.2 yr. Surgery alone decreased plasma GH
from 52 ± 64 to 30 ± 70 µg/L. At the time of
radiotherapy, the average age of patients was 38.9 ± 11.2 yr, and
plasma GH was 36 ± 70 µg/L. The average duration of follow-up
after irradiation was 11.5 ± 8.5 yr. During the interval between
radiotherapy and decreased GH levels, 56 patients were treated with
bromocriptine (45 patients) or somatostatin analogs (11
patients; Table 1
).
|
Two years after radiotherapy, 25% of patients had basal GH below
5 µg/L; this increased to 48%, 65%, and 79% of patients at 5, 10,
and 15 yr, respectively (Fig. 1 and Table 2). Basal GH levels less than 2.5 µg/L were reached in 7% of the
patients at 2 yr, 35% at 5 yr, 53% at 10 yr, and 66% at 15 yr (Fig. 2). Suppression of GH during OGTT was
seen in 15% of the patients at 2 yr, 39% at 5 yr, 54% at 10 yr, and
61% at 15 yr (Fig. 3).
|
|
|
|
High preradiation GH values predicted a longer delay of cure (defined by basal GH <2.5 µg/L; P = 0.008). Patients with a basal GH value greater than 20 µg/L at the time of irradiation were significantly less likely to reach basal GH levels below 2.5 µg/L during long-term follow-up and had a decrease of 63% of a probability of cure compared to patients with preradiation GH value below 20 µg/L. No statistically significant relationship was found between disease persistence and sex, age, acromegaly duration before diagnosis, or dose of irradiation.
Rate of decrease in GH levels
As the delay of normalization of GH depends on the initial GH
value, efficacy of radiotherapy was expressed as a percent decrease in
plasma GH during follow-up. Plasma GH declined gradually to
approximately 50% of the preradiation value at 2 yr, 20% of the
preradiation value at 5 yr, and 10% of the preradiation value at 10 yr
(Fig. 4).
|
To validate the criteria of cure used (basal GH <2.5 µg/L), we analyzed the relation among basal GH levels, GH nadir during OGTT, and IGF-I. Of the 701 measurements made, basal GH levels below 2.5 µg/L were associated with GH suppression below 2 µg/L after OGTT in 89% of cases, whereas basal GH levels below 5 µg/L were associated with GH suppression in only 56% of the cases. Basal GH values below 2.5 µg/L were associated with normal IGF-I in 90% of the 195 simultaneous measurements. Of the OGTT-derived GH levels below 2 µg/L, 90% of them were associated with normal IGF-I levels. Thus, basal GH less than 2.5 µg/L is generally the best parameter associated with suppression of GH during OGTT and normal IGF-I levels.
Long-term effects of radiotherapy on IGF-I levels
Analysis of IGF-I measurements at late follow-up for subjects followed for at least 5 yr after irradiation was possible for 47 of the 128 patients. At a mean follow-up after radiotherapy of 15.0 ± 11.3 yr, 37 of these patients (79%) had normal IGF-I levels. In the group of patients with normal IGF-I values, the mean GH plasma level was 1.9 ± 2.1 µg/L. In the remaining 10 patients with persistent high IGF-I levels, the mean plasma GH level was 7.8 ± 4.5 µg/L (P < 0.05, for comparison between the two groups). The last IGF-I assay during the 5 yr after radiotherapy was normal in only 25% of the patients (6 of 24), but this percentage increased dramatically thereafter: 60% (12 of 20) in the 5- to 10-yr period after radiotherapy, and 96% (23 of 24) during the 10- to 20-yr period after radiotherapy.
Analysis of the 37 patients not still receiving medical treatment showed that at a mean follow-up after radiotherapy of 15.4 ± 10.9 yr, 30 of these patients (81%) had normal IGF-I levels. In this group, the mean GH plasma level was 1.9 ± 2.2 µg/L, whereas in the persistent high IGF-I level group, the mean GH plasma level was 8.5 ± 4.9 µg/L (P = 0.001). Taking into account only the 30 patients in whom IGF-I was assayed after 1993 by the Nichols Institute Diagnostics diagnostic kit did not change the results, as 23 of them (77%) had normal IGF-I levels.
Influence of the control of acromegaly on glucose tolerance
The improvement of glucose tolerance paralleled the decrease in plasma GH concentration. In the 32 diabetic patients, the basal GH value was 125 ± 456 µg/L (range, 0.75–2400 µg/L) at diagnosis of diabetes. After a mean follow-up period of 7.5 ± 4.1 yr (range, 1.4–11.6 yr), 13 patients were still diabetic (group 1), 4 patients had impaired glucose tolerance (group 2), and 14 patients had normal glucose tolerance (group 3). The mean GH values were 35 ± 78 µg/L for group 1, 9.47 ± 12 µg/L for group 2, and 5.69 ± 8 µg/L for group 3. The difference among the 3 groups was significant (P = 0.04). The majority of diabetic patients (group 1) had persistently uncontrolled secretion of GH; 80% and 90% of these patients had basal GH levels greater than 5 µg/L and GH greater than 2.5 µg/L, respectively. In contrast, patients whose glucidic tolerance was normalized (group 3) had basal GH levels below 5 µg/L in 71% of the cases and basal GH below 2.5 µg/L in 50% of cases.
Incidence of hypopituitarism and other complications
In the postoperative period and before radiotherapy, gonadotropic insufficiency was present in 48% of the patients, whereas thyrotropic and corticotropic insufficiency were observed in 30% and 28% of the patients, respectively. The prevalence of hypopituitarism increased progressively after radiotherapy; 2 yr after pituitary irradiation, gonadotropic deficiency was present in 61% as well as thyrotropic deficiency, and corticotropic deficiency was observed in 60% of the patients. Ten years after radiotherapy, 80% of the patients had gonadotropic deficiency, thyrotropic insufficiency was observed in 78% of the cases, and corticotropic deficiency was present in 82%.
Four patients (3%) presented with a neurological event that was diagnosed by computed tomographic scan and/or magnetic resonance imaging as potential cerebral necrosis linked to radiotherapy. In all cases radiotherapy was performed between 1970 and 1975, and the neurological complications occurred 10–19 yr latter. An impairment of visual field was observed in four patients (3%) during the postradiotherapy follow-up. In these cases, imaging investigation revealed an empty sella that could take part in these alterations.
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The major effects of radiotherapy were seen during the first 5 yr after treatment, with a continuous gradual fall in GH apparent after 10 and 15 yr, as previously reported (12, 26, 27). Plasma GH declined to 50% of the preradiation values at 2 yr and to 20–25% at 5 yr. Most prior studies have used GH concentrations below 5 µg/L as the definition of acromegaly cure. Approximately 25–40% of patients have GH levels below 5 µg/L 5 yr after radiotherapy, reaching 30–70% at 10 yr (13, 16, 28, 29, 30). Evidence is now accumulating that this classical criterion is not sufficiently stringent (31). A pragmatic approach has found that GH levels below 2.5 µg/L are necessary to suppress the morbidity and increased mortality associated with this disease (5, 8, 10). Using this strict criterion the proportions of cured patients in our series were 35%, 53%, and 66% at 5, 10, and 15 yr, respectively. Our results show an improvement over those reported in a recent small study with 25% (7 of 28) and 21% (4 of 19) of patients with GH levels below 2.5 µg/L at 5 and 10 yr (16). The efficacy of radiotherapy is best measured by the GH fall during follow-up, as the time for GH normalization depends upon the preradiation GH value (15). The differences in cure rates between series may be due to differences in preradiotherapy GH levels. Here, we confirm that the likely success of radiotherapy is predicted by pretreatment GH values, with a cut-off GH value of 20 µg/L.
The post-OGTT GH level is also a recognized criterion for evaluating the effect of treatment in acromegaly (15, 19, 32, 33). Plasma GH levels fluctuate widely, and oral glucose loading suppresses secretory bursts of GH (34). Our data show a good consistency among safe baseline GH (<2.5 µg/L), suppressed post-OGTT GH (<2 µg/L), and normal IGF-I levels. Thus, a basal GH level less than 2.5 µg/L is a simple and valid criterion of control of acromegaly. In contrast, only half of the basal GH measurements below 5 µg/L are associated with suppressed post-OGTT GH. A more thorough evaluation of basal GH secretion with serial samples over a 24-h period does not provide additional information, as outcome assessment based on basal GH levels (single measurement or mean of two measurements) correlates well with post-OGTT GH levels (4). On the other hand, the simultaneous use of basal GH, nadir GH after OGTT, and IGF-I levels to evaluate cure in an acromegalic patient might be required, because discrepancy among these three parameters could be observed even with the use of a sensitive GH IRMA (35).
Few studies have evaluated the effects of radiotherapy on IGF-I levels. In the first study reported, radiotherapy apparently failed to normalize plasma IGF-I levels despite the reduction of GH levels; only 2 of 38 patients reached normal IGF-I levels while not receiving drugs after a mean follow-up period of 6.8 ± 0.8 yr, whereas 65% of patients (11 of 17) had random GH levels below 5 µg/L after 5 yr (17). The reason for such a disappointing decrease in IGF-I levels after radiotherapy remains unknown. However, a more recent study found that 42% (19 of 45) of patients had normal IGF-I levels without additional medical therapy at a mean follow-up of 6.7 yr after irradiation therapy (5). Here we show that 79% of the patients had age- and sex-adjusted normal IGF-I levels at the last point of follow-up (mean, 15 yr) after radiotherapy with a concomitant mean basal GH level of 1.9 ± 2.1 µg/L. However, the relatively small number of subjects in these studies and the numerous IGF-I assays used in Barkan’s study and our study make it hard to draw final conclusions.
Diabetes mellitus is observed in 19–30% of acromegalic patients (36, 37), and its prevalence in our study was 25%. Diabetes contributes to the reduced survival of acromegalic patients (9). Here we show that reduction in GH levels after radiotherapy correlated with improvement of glucose tolerance (26, 36).
Hypopituitarism is an unavoidable side-effect of radiotherapy. Its frequency increases with longer follow-up, reaching 38–70% at 10 yr (12, 13, 28). Prior surgery increases the risk of postirradiation hypopituitarism (38). We observed a high rate of hypopituitarism occurring in about 80% of the patients at 10 yr (78% thyroid insufficiency, 82% adrenal insufficiency, 80% gonadal insufficiency). Radiotherapy rarely has other side-effects, with low incidence of damage to the optic nerves, brain necrosis, and second brain tumors (13, 29). Little is known, however, about the long-term effect of pituitary irradiation on neuropsychological functions (39, 40). It is likely that the improvement in irradiation methods will further reduce the incidence of such complications.
Since the introduction of somatostatin analogs for the treatment of acromegaly, there has been controversy over the indications for radiotherapy after unsuccessful surgery (19, 41, 42). Somatostatin analogs decrease GH and IGF-I levels to normal in about 60% of patients, but they are not curative, and their high cost in a long-term therapy should be considered (19). Nevertheless, even when radiotherapy is performed, somatostatin analogs are clearly useful until the full effects of radiotherapy occur. The kinetics of the decrease of GH levels after radiotherapy, as described here, allow us to predict when medical treatment should be stopped to assess the effect of radiotherapy.
In conclusion, we show that radiotherapy is an effective treatment for the long-term control of GH hypersecretion resulting in a decrease in basal GH below 2.5 µg/L, suppression of post-OGTT GH, and normalization of IGF-I in 61–79% of patients after 15 yr. Radiotherapy is useful after unsuccessful pituitary surgery, particularly for acromegalic patients with large and infiltrating tumors and for patients not controlled by medical treatment. However, the long delay required in some patients before optimal control of GH hypersecretion (that could be partly predicted using the preirradiation GH level) and the high prevalence of hypopituitarism must be taken into account when choosing irradiation therapy for treatment of acromegaly.
|
Acknowledgments |
|---|
Received March 3, 2000.
Revised July 3, 2000.
Accepted July 7, 2000.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE</ |
