Outcome of Gamma Knife Radiosurgery in 82 Patients with Acromegaly: Correlation with Initial Hypersecretion
|
|
- Dayna Wilcox
- 5 years ago
- Views:
Transcription
1 X/05/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 90(8): Printed in U.S.A. Copyright 2005 by The Endocrine Society doi: /jc Outcome of Gamma Knife Radiosurgery in 82 Patients with Acromegaly: Correlation with Initial Hypersecretion Frédéric Castinetti, David Taieb, Jean-Marc Kuhn, Philippe Chanson, Manabu Tamura, Philippe Jaquet, Bernard Conte-Devolx, Jean Régis, Henry Dufour, and Thierry Brue Federation of Endocrinology, Diabetes, Metabolic Diseases and Nutrition (F.C., D.T., P.J., B.C.-D., T.B.), Department of Neurosurgery and Functional Neurosurgery (M.T., J.R., H.D.), and Department of Neurosurgery (H.D.), Hôpital de la Timone, Centre Hospitalier Universitaire de Marseille and Faculté de Médecine, Université de la Méditerranée, Marseille, France; Department of Endocrinology and Metabolic Diseases (J.-M.K.), Centre Hospitalier Universitaire de Rouen, Rouen, France; and Department of Endocrinology and Reproductive Diseases (P.C.), Assistance Publique- Hôpitaux de Paris, Hôpital de Bicêtre and Faculté de Médecine Paris XI, Le Kremlin Bicêtre, France Context: Because surgical and medical therapies of acromegaly all have specific limitations, radiotherapy has been used as an adjunctive strategy. Stereotactic radiosurgery has not yet been widely evaluated. Objective: The objective was to perform an analysis of long-term hormonal effects and tolerance of gamma knife radiosurgery. Design: Eighty-two patients were prospectively studied over a decade, with a mean follow-up of 49.5 months. Setting: All patients were treated at the Department of Functional Neurosurgery of Marseille, France. Patients: The patients included 82 with active acromegaly, of whom 63 had previous transsphenoidal surgery. Intervention: Intervention included radiosurgery using the Leksell Gamma Unit B model. GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists (at least 3 months). Results: Seventeen percent of the patients were in remission without any treatment. Twenty-three percent previously uncontrolled on somatostatin agonists fulfilled the same criteria after gamma knife while maintained on medical treatment. Initial GH and IGF-I levels off somatostatin agonists were significantly higher in uncured than in remission group (P 0.01 and 0.047, respectively). Withdrawal of somatostatin agonists at the time of radiosurgery had no incidence on the outcome. No significant difference was found in success rate whether patients had previously been treated or not. Long-term side effects included complete (n 2) or partial (n 12) hypopituitarism diagnosed 1 7 yr after gamma knife. Conclusions: Gamma knife radiosurgery may represent a therapeutic approach in patients with moderate initial or residual GH hypersecretion. (J Clin Endocrinol Metab 90: , 2005) Main Outcome Measures: Remission was diagnosed when mean First Published Online May 17, 2005 Abbreviations: GK, Gamma-knife radiosurgery; MRI, magnetic resonance imaging. JCEM is published monthly by The Endocrine Society ( endo-society.org), the foremost professional society serving the endocrine community. THE AIMS OF the treatment of acromegaly are to control tumor mass, to decrease hormonal levels of GH and IGF-I, and to alleviate clinical symptoms. Mortality in this disease can be reduced to that of a reference population if GH concentration is less than 1 2 g/liter and IGF-I level is normal (1). Surgery remains the first-line reference treatment, but remission rate ranges from 44 74% because of the high prevalence of invasive tumors (2). Currently available somatostatin agonists control GH and IGF-I excess in about 50 60% of patients (2). The more recent GH antagonist pegvisomant, although usually able to decrease IGF-I levels to the normal range, has no antitumoral effect (3, 4). Postoperative conventional fractionated radiotherapy controls the disease in 5 78% of cases (5, 6) but not before several years. Moreover, complications associated with radiotherapy have limited its usefulness; these include hypopituitarism, cranial nerve neuritis, visual-field defects, possible cognitive disturbances or increased cerebrovascular disorders, radiation-induced gliomas, and delayed brain necrosis (7, 8). The adverse consequences of conventional radiotherapy have been attributed to the inability to accurately deliver adequate doses to a small tumor volume. Such a shortcoming may be addressed by using gamma knife radiosurgery (GK). The hallmark of this procedure is to use cobalt-60 to deliver a single high dose of high-energy beams targeted to stereotactically defined intracranial sites (9, 10). This kind of radiation induces circumscribed cytotoxic effects on both neoplastic and vascular cells (11). Several authors have detailed their experience with GK, with efficacy ranging from 23 90% (12, 13). Most studies reported on short-term effects of GK. Except for a study on few patients (12), no one, to our knowledge, has addressed the long-term effects of GK in acromegaly in terms of efficacy and tolerance and using strict criteria for assessing endocrinological remission. The aim of the present study was to analyze our 10-yr experience with GK in a single radiosurgical center as either 4483
2 4484 J Clin Endocrinol Metab, August 2005, 90(8): Castinetti et al. Radiosurgery in Acromegaly first nonmedical treatment or an adjunctive treatment after transsphenoidal surgery for acromegaly. We thus evaluated the clinical and hormonal outcome in 82 patients, with a mean follow-up of 49.5 months. Patients Patients and Methods A total of 99 patients with active acromegaly were consecutively treated with GK between February 1993 and May 2003 at the Department of Functional Neurosurgery of Hôpital de la Timone (Marseille, France). The diagnosis of acromegaly was based on the association of clinical features of the disease, elevated baseline plasma GH not suppressible less than 1 g/liter after a glucose load, and increased IGF-I levels. Active disease was defined on the basis of GH levels in excess of 2 ng/ml and elevated age-adjusted IGF-I. These patients had been referred from different centers in France (n 89, 23 centers) and abroad (n 10, 6 centers). Each center agreed to monitor the patients outcome according to the standardized investigation described below. Immediate preradiosurgical and postradiosurgical evaluations were performed in the same Endocrinology Department in Marseille. In the present study, we did not analyze data from the 10 patients referred from foreign centers and from seven French patients who were all lost to follow-up. For data analysis, 82 patients were thus entered into this prospective study. Sixty-three of them were treated after unsuccessful transsphenoidal surgery. Two also previously received conventional radiotherapy. Nineteen patients had received only medical treatments (somatostatin or dopamine agonists) before GK in case of unresectable adenomas (such as small intrasellar adenomas with laterosellar extension), of contraindication (due to the patient s general condition), or of refusal of surgery. Only two patients had two consecutive GK. At the time of GK, 42 patients (51.3%) were treated with somatostatin agonists. In the others, the treatment with somatostatin analogs was discontinued at least 3 months or 2 wk before surgery for long-acting and sc forms, respectively. In the only patient treated with cabergoline, treatment was stopped 6 wk before the procedure. Radiosurgical procedure For the radiosurgical procedure, the Gamma Unit B model of the Leksell stereotactic system (Elekta Instruments, Stockholm, Sweden) was used. Irradiation was performed by cross-firing the target region with 201 beams of cobalt-60 distributed within a spherical sector. To delineate the lesion, a Leksell stereotactic head frame was used to perform both magnetic resonance imaging (MRI) and computed tomography scans to minimize metric distortion. For 43 patients treated between February 1993 and July 1997, dose planning was done with the KULA dose-planning software, and, for the 39 remaining patients treated after May 2000, it was done with the more recent Leksell Gamma-Plan system (Elekta Instruments), 18 of them with Automated Positioning System. In each case, the decision to treat by GK was made collectively by the endocrinological, neurosurgical, and radiosurgical teams. Before treatment, the target was delineated by two neurosurgeons. The radiosurgical planning was conducted jointly as part of the GK procedure. The treatment parameters and dose selection varied with the tumor size and the proximity of the tumor to the optic apparatus. Tumor margin was covered within the 50% isodose line (margin dose). Multiple isocenters were used for all of the patients. The prescribed margin dose ranged from Gy according to several factors: tumor volume, distance to the visual pathways, age, and previous treatment with fractionated radiotherapy. In all cases, the dose delivered to the optic chiasm and nerves was less than 9 Gy. In each case, marginal dose and dose delivered to the optic chiasm were recorded. Clinical and hormonal evaluation Each patient had a complete clinical and hormonal evaluation before GK, including ophthalmological evaluation using Goldman s campimetry in the same department (Endocrinology Department, Hôpital de la Timone). Initial pre-gk levels of GH, IGF-I, ACTH, urinary free cortisol, prolactin, LH, FSH, testosterone or estradiol, TSH, and free T 3 and T 4 were determined. The same evaluation was then performed in each center 3 and 6 months after GK, every 6 months during 2 yr, and then yearly. During follow-up, GH and IGF-I levels were determined without any medical therapy or after at least 3 months of discontinuation of the treatment with somatostatin agonists. Results obtained earlier than 3 months or later than 3 months after the last injection of somatostatin agonists were considered as on treatment or off treatment, respectively. All pre-gk evaluations were performed off treatment, and at least one off treatment evaluation was performed during the first year after GK. Subsequently, intervals from 1 3 yr between off-treatment evaluations were decided on by each investigator according to clinical and hormonal evaluations on treatment. Patients were considered in remission if they had a mean GH level of less than 2 g/liter and a normal age-adjusted IGF-I in off-treatment period. Those who were still on somatostatin agonists were considered uncured. Mean GH levels were determined by averaging eight hourly determinations between 0800 and 1500 h. GH and IGF-I concentrations were measured in the same laboratory immediately before and after GK in all patients and at each subsequent time point in the subset of patients (n 42) followed in the Endocrine Department in Marseille. For these assays, the characteristics of the kits used were as follows. Serum GH levels were measured by an immunoradiometric assay (Immunotech, Marseille, France). The sensitivity is 0.05 ng/ml. The intraassay and interassay coefficients of variation are and %, respectively. Serum IGF-I was measured by immunoradiometric assay (Immunotech). The sensitivity is 3 ng/ml. The intraassay and interassay coefficients of variation are and %, respectively. All other determinations in the 22 other centers were done using commercial kits, and normal IGF-I values for each laboratory were taken into account. Gonadotroph deficiency was defined by low plasma testosterone with nonelevated gonadotrophin levels in men, amenorrhea with low plasma estradiol and low or normal gonadotrophins in nonmenopausal women, and a lack of increased gonadotrophins in menopausal women. Corticotroph deficiency was established by subnormal response of cortisol during an insulin tolerance test (peak, 550 nmol/liter). The diagnosis of thyrotroph deficiency was based on low free plasma T 4 level with normal or diminished plasma TSH. Initial pituitary neuroimaging Pituitary imaging was performed by MRI to define dose planning and to evaluate the limits of the lesion. The MRI sequences were coronal postgadolinium T1-weighted spin-echo (SE), T2-weighted SE, and, for most patients, a postgadolinium three-dimensional magnetization prepared acquisition gradient echo sequence. Statistical analysis Data were analyzed by parametric or nonparametric tests. Continuous data with normal distribution were analyzed by t test, and those with uneven distribution were analyzed by Mann-Whitney U test. Categorical data were analyzed by Fisher s exact test. Longitudinal evaluations were performed by Kaplan-Meier method. All statistical tests were two tailed, and P 0.05 was considered significant. Results The patients were followed up for a mean period of 49.5 months (range, months). Long-term effects of GK At the end of the study, 17 patients (20.7%) had GH levels less than 2 ng/ml after an average of 35.3 months, and 21 patients (25.6%) had normal age-adjusted IGF-I after an average of 35.5 months. Based on both criteria, 14 of 82 patients (17%) were considered to be in remission after an average of 36 months (Fig. 1 and Table 1). Thanks to GK, 19 other patients (23%), considered uncured, were controlled by somatostatin agonists, whereas they were not controlled with
3 Castinetti et al. Radiosurgery in Acromegaly J Clin Endocrinol Metab, August 2005, 90(8): FIG. 1. Kaplan-Meier analysis: number of uncured patients based on GH and IGF-I criteria. Remission was diagnosed when mean GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists (at least 3 months). Numbers on the line represent the number of patients who have a follow-up at least equal to the time point. Total mean follow-up in the whole population was 49.5 months. the same treatment before GK. The two patients who had two consecutive GK treatments were not in the remission group. Initial GH and IGF-I levels off somatostatin agonists were significantly higher in uncured patients than in patients in remission. Nevertheless, the mean percentage of GH decrease at mean follow-up (49.5 months) did not differ between the two groups (data not shown). To assess whether previous hormonal evaluations might predict later outcome of the treatment, we compared the percentage of decrease of GH hypersecretion 6 12 months after GK, off somatostatin agonists: no significant difference was observed at these or at any time points. Indeed, as shown on Fig. 2, the profile of GH decrease was similar in both outcome groups, who differed mainly by their initial hormone levels. No significant difference was observed in sex ratio, median age, initial volume of the adenoma (microadenoma or macroadenoma), type of secretion (pure GH or mixed GH and prolactin secretion), or its localization (intracavernous, suprasellar, or laterosellar). No significant difference was found in marginal dose. Interestingly, we also found no significant difference in the outcome of patients who were on or off somatostatin agonists at the time of the GK (Table 2). GK in patients without previous surgical treatment Nineteen patients had GK as a primary nonmedical treatment. In Table 3 are presented the data on patients treated primarily with GK or treated with GK as adjunct of transsphenoidal surgery (n 63). No difference was found between the two groups in terms of sex ratio, marginal dose, prevalence of macroadenomas, mixed or isolated secretion, and initial GH or IGF-I levels. The only difference was median age, reflecting that older patients often had contraindications to transsphenoidal surgery. GK given as a primary TABLE 1. Characteristics of patients in remission (n 14) Sex/age (yr) Volume/secretion/ localization Initial GH/IGF-I (ng/ml) Primary/ adjunctive SSA status Margin dose (Gy) Time to remission (months) Follow-up (months) Complication deficiency 1 F/32 M/GH-PRL/IC 4/330 A On F/33 M/GH-PRL/IS 3.5/709 A On F/53 M/GH-PRL/IC 8.5/641 P Off F/53 M/GH/IC 12/640 A On M/56 M/GH/IC-SS 8/510 A Off F/61 m/gh/ic 2.3/480 P Off TSH 7 F/76 M/GH/IC 7.5/661 P On F/50 M/GH/IC 7.5/433 A Off F/41 M/GH/IC 4.5/367 A Off F/53 M/GH/IC 9/600 A On M/55 M/GH/IC 7/396 P On F/51 M/GH-PRL/IC 4/119 A Off M/54 M/GH-PRL/IC 7.2/350 A On LH/FSH 14 F/40 M/GH/IC 14.8/700 A On Remission was diagnosed when mean GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists (SSA) for at least 3 months. Patient characteristics include sex (F, female; M, male), age, initial volume of adenoma (M, macroadenoma superior to 10 mm; m, microadenoma inferior to 10 mm), secretion (GH, pure GH hypersecretion; GH-PRL, mixed GH-prolactin hypersecretion), localization of the adenoma (IC, intracavernous; IS, intrasellar; SS, suprasellar), initial GH and IGF-I, primary nonmedical treatment (P), and adjunctive treatment (A). SSA status, Patients treated by somatostatin agonists at the time of GK treatment or who had received long-acting SSA less than 3 months before treatment were considered on SSA treatment (On); untreated patients or patients who had received long-acting SSA more than 3 months before GK were considered off SSA treatment (Off). Complication deficiency, Type of new hormonal deficiency appearing after GK.
4 4486 J Clin Endocrinol Metab, August 2005, 90(8): Castinetti et al. Radiosurgery in Acromegaly FIG. 2. Mean GH in remission (n 14) and uncured (n 68) groups. Allocation into each group was based on the following criteria: remission was diagnosed when mean GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists for at least 3 months. Mean GH levels of uncured patients are represented by a broken line with filled squares; mean GH of remission patients is represented by a dotted line with filled circles. SD is shown for each group. Comparisons between groups were performed by ANOVA. treatment or in adjunct of transsphenoidal surgery appears to be similarly effective, resulting in remission in 4 of 19 (21%) and 10 of 63 (16%) patients, respectively. Adverse effects At least one new pituitary deficiency was observed after GK in 14 patients: TSH deficiency in three (1, 3, and 7 yr after GK), ACTH deficiency in three (4, 5, and 6 yr after GK), LH and FSH deficiency in seven (between 5 and 7 yr after GK), and complete hypopituitarism in two (3 and 2 yr after GK). One of these two cases had conventional radiotherapy 10 yr before. The mean margin dose for these 14 patients was 27.5 vs. 26 Gy for patients TABLE 2. Comparison between in remission and uncured groups In remission Uncured P No. of patients Mean age (yr) 50.5 [32 76] 53.5 [21 74] ns Sex ratio (F/M) 11/3 37/31 ns Marginal dose (Gy) 24.2 [15 35] 26 [12 40] ns Macroadenoma 13 (93%) 61 (90%) ns Adenoma with pure GH 9 (64%) 54 (79%) ns hypersecretion Tumor extension Intracavernous ns Suprasellar 1 2 ns Intrasellar 1 6 ns Initial GH (ng/ml) 7.1 [ ] 25.3 [ ] 0.01 Initial IGF-I (ng/ml) 495 [ ] 673 [ ] Patients off SSA at the 6 (43%) 34 (50%) ns time of GK treatment Follow-up (months) 62 [6 108] 50 [8 99] ns Allocation into each group was based on the following criteria: remission was diagnosed when mean GH levels were less than 2 ng/ml and IGF-I was normal for age off somatostatin agonists (SSA) for at least 3 months. Extreme values are between brackets. Sex ratio is presented as number of female (F)/number of male (M) patients. Tumor extension was determined by pretreatment MRI as detailed in Patients and Methods. One patient in the remission group had both suprasellar and cavernous extensions. Percentages indicate the proportion of patients in each subgroup. ns, Nonsignificant. P 0.05 was considered significant. without adverse effects (P 0.05). One patient, previously treated by conventional radiotherapy, presented 1 month after GK (marginal dose, 40 Gy; dose delivered to the optic chiasm, 8 Gy) a trigeminal neuralgia that disappeared under carbamazepine treatment, and, 2 months later, the same patient displayed an impaired central visual field, which was alleviated after 3 months of steroid treatment. Overall, patients in remission (4.7 Gy) or uncured (4 Gy) did not differ in terms of dose delivered to the optic chiasm. Only a few patients had other transient adverse effects, including headaches or vomiting. Discussion When GH hypersecretion persists in patients with acromegaly, the risk of mortality was reported to be up to three to four times higher than that of patients in whom GH secretion is controlled (14 16). Thus, one of the primary aims of the treat- TABLE 3. Comparison between GK as primary nonmedical treatment (without previous surgical treatment) and as adjunctive treatment (after surgical treatment) Primary treatment Adjunctive treatment No. of patients 19 (23%) 63 (77%) Mean age (yr) 62 [35 76] 48 [21 68] 0.01 Sex ratio (F/M) 12/7 36/27 ns Marginal dose (Gy) 30 [20 35] 25 [12 40] ns Macroadenoma 16 (84%) 58 (92%) ns Adenoma with GH 15 (79%) 48 (76%) ns hypersecretion only Initial GH (ng/ml) 15 [2.3 49] 24 [4 240] ns Initial IGF-I (ng/ml) 695 [ ] 640 [ ] ns Patients off SSA at the 10 (53%) 30 (48%) ns time of GK treatment Follow-up (months) 61 [19 99] 50 [6 108] ns In remission 4 (21%) 10 (16%) ns Uncured 15 (79%) 53 (84%) ns Extreme values are between brackets. Sex ratio is presented as number of female (F)/number of male (M) patients. Percentages indicate the proportion of patients in each subgroup. SSA, Somatostatin agonists; ns, nonsignificant. P 0.05 was considered significant. P
5 Castinetti et al. Radiosurgery in Acromegaly J Clin Endocrinol Metab, August 2005, 90(8): ment of acromegaly is to normalize GH and IGF-I levels. For patients to be considered in remission, a recent consensus conference recommended achieving a GH plasma level lower than 2 ng/ml (or a suppressibility 0.3 ng/ml after oral glucose tolerance test) and a normal age-adjusted IGF-I level (17). With reference to these stringent basal GH and IGF-I criteria, 17% of the patients were in remission after an average of 36 months. In addition, based on the same criteria for GH and IGF-I levels, 23% of our patients (n 19) achieved normal values after GK while treated with somatostatin agonists, whereas they were not controlled with the same treatment before. Although some of them might have been found in remission after an appropriate withdrawal of their medical treatment, we considered all of them as uncured. A longer follow-up would obviously be helpful to better evaluate the real effectiveness of GK. In this regard, 36 of our patients had a final off-treatment evaluation less than 36 months after GK, i.e. less than the average time for normalization. In a recent review of currently published series (18), 37.7% of 361 patients reported in 19 studies on 4 68 patients were found to have complete response to GK after a corrected median follow-up of 29 months. These series, however, differed widely in the types of tumors treated, the time between last administration of medical treatment and hormonal evaluation, and the criteria for biological remission, among other factors (9, 12, 13, 19). As underlined by another recent review (20), comparison of results is indeed difficult, mainly because of the variable criteria of cure: in the series with at least 10 patients and a median follow-up of 2 yr, success rates ranged from 20 96%. For example, in the single largest series on 68 patients in 2000 by Zhang et al. (13), patients were considered in remission when GH levels were less than 12 ng/ml, with a reported cure rate of 96%, whereas the second largest series reported a 25% remission rate based on normalization of age- and sex-matched IGF-I (21). In contrast with a recent series with fewer cases (12), we found that initial plasma GH and IGF-I levels were significant predictive factors of outcome. Studies evaluating conventional radiotherapy (22, 23), surgery (24, 25), and somatostatin agonist therapy (26, 27) had also shown a better outcome in acromegalic patients whose pretreatment plasma GH levels were lower. The importance of initial hormonal level was confirmed in our study by the lack of difference in mean percentage of GH decrease between the two groups. In our patients, the final outcome depended mainly on GH and IGF-I initial levels off somatostatin agonists. No difference in the outcome was observed between patients who received somatostatin agonists at the time of GK (20% patients in remission) and those who did not (15% patients in remission). This result does not confirm that of a nonrandomized study by Landolt et al. (28) concluding that the use of octreotide might decrease the efficacy of radiation therapy if used at the time of the procedure. Our results are in accordance with those of a recent study (12). Nevertheless, we share other investigators viewpoint that the treatment should be stopped shortly before GK (9, 13, 29): somatostatin agonist withdrawal indeed allows further comparison of off-treatment GH secretion. In most patients, GK was indicated because transsphenoidal surgery failed to achieve remission. Our study found no significant difference in success rate whether GK was used as primary treatment (16%) or after surgery (21%). When performed in other centers as a primary treatment, GK was mainly used for microadenomas (9, 30). In our study, GK was used as primary treatment for microadenomas or small (10 15 mm) enclosed macroadenoma with laterosellar extension. The overall success rate remains low, in contrast with the study of Zhang et al. (13) in which more than 90% of patients treated with GK as primary nonmedical treatment were in remission. In that study, however, the criteria for remission were not precisely defined. To our knowledge, no other study has tried to compare the efficacy of GK as primary or adjunctive treatment on a large number of patients. As observed in other series, our patients showed no increase in tumor volume (12, 31, 32). Tumor size, however, was not systematically monitored during long-term follow-up because the treatment was not primarily aimed at reducing tumor volume of usually small adenoma remnants. According to a recent review, tumor growth control was obtained in % of patients in all but one series (20). The mean margin dose we used was 25.8 Gy. Higher success rates were observed with higher margin dose but with the drawback of more severe complications (13, 33). The doses used in our center were chosen by comparing the benefits of decreasing GH secretion and the risks of secondary effects, i.e. onset of new pituitary deficiency. Dose prescription was also adapted to the tumor volume, the distance separating the tumor and the visual pathway, the aggressiveness of the disease, and previous treatment. We found a mean time of GH and IGF-I normalization of 36 months. This latency is longer than that in most series evaluating GK in acromegaly (13, 29, 33, 34). This difference can probably be explained by the higher marginal doses used by other researchers. Because GK patients often have lower pretreatment GH concentrations than conventionally treated patients and different types of tumors, it is difficult to compare the rate of decline between GK and conventional radiotherapy. As shown in many studies (12, 16, 35), GK induces far fewer complications than conventional radiotherapy: 82% patients in our series had no side effects after GK vs. less than 50% with conventional radiotherapy in most studies (7, 36). A longer follow-up would probably be useful to better evaluate longterm effects of GK. In the present series, only one severe visual regressive trouble with cavernous syndrome was observed (dose to the optic chiasm, 8 Gy). As recommended previously (37), the dose delivered to the optic chiasm was inferior or equal to 8 Gy in all but one patient. A 9-Gy dose had to be delivered in one case because of the conformation and size of the lesion. In conclusion, after a mean follow-up of more than 4 yr, GK was able to decrease GH and IGF-I concentrations to so-called safe (1) levels in 40% (17% in remission and 23% under somatostatin agonists) of our patients. This treatment was thus helpful in this population who had failed to achieve hormonal control with either surgery alone or a combined treatment of surgery and somatostatin agonists at the time of their irradiation. GK represents a safe and efficacious treatment in welldefined indications: small postsurgical remnants, sufficiently distant from the optic chiasm, and with moderate initial GH hypersecretion. In view of the high rate of IGF-I control obtained with currently available medical therapies, the place of GK in the treatment of acromegaly may, however, need to be redefined in the future. In particular, the cost effectiveness of a
6 4488 J Clin Endocrinol Metab, August 2005, 90(8): Castinetti et al. Radiosurgery in Acromegaly potentially lifelong medical approach will have to be compared in the context of each particular country with an approach that offers long-term remission and possibly cure in a subset of patients with acromegaly. Acknowledgments We thank the following French physicians who referred patients for GK and provided updated information on their outcome: Dr. Jean- Michel Andrieu (Montpellier), Dr. Bernard Aubert (Metz), Prof. Ivan Bachelot (Grenoble), Dr. Catherine Basin (Paris), Prof. Benoit Bataille (Poitiers), Dr. Jean-Gerard Baudet (Le Creusot), Dr. Antoine Bennet (Toulouse), Prof. Xavier Bertagna (Paris), Dr. Basile Bigorie (Meaux), Prof. Philippe Bouchard (Paris), Prof. Didier Dewailly (Lille), Dr. Marie- Laure Dumuis (Paris), Dr. Philippe Emy (Orleans), Dr. Alexandre Fredenrich (Nice), Dr. Philippe Giraud (Angers), Dr. Didier Gouet (La Rochelle), Dr. Edgar Kaloustian (Compiègne), Prof. Véronique Kerlan (Brest), Dr. Albert Martinand (Dijon), Dr. Catherine Mattei (Marseille), Prof. Charles Oliver (Marseille), Dr. Françoise Peillon (Suresnes), Dr. Anne Priou (Avignon), Prof. Eric Renard (Montpellier), Dr. Elisabeth Requeda (Corbeil), Dr. Michel Rodier (Nîmes), Prof. Jean-Louis Sadoul (Nice), Dr. Franck Schilla (Besançon), Dr. Dominique Simon (Paris), Dr. Gilbert Simonin (Marseille), Prof. Antoine Tabarin (Bordeaux), Prof. Bernard Vialettes (Marseille), and all of the coinvestigators of the French Pituitary Society (Club Français de l Hypophyse, Société Française d Endocrinologie). We thank Dr. Vincent Pradel for statistical analysis and Dr. Christine Nicolino for fruitful discussions. Received February 11, Accepted May 5, Address all correspondence and requests for reprints to: Prof. T. Brue, Department of Endocrinology, Hôpital de la Timone, 264 rue St. Pierre, cedex 5, Marseille, France. thierry.brue@mail.ap-hm.fr. References 1. Holdaway IM, Rajasoorya RC, Gamble GD 2004 Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89: Freda PU 2003 How effective are current therapies for acromegaly? Growth Horm IGF Res 13(Suppl A):S144 S Van der Lely AJ, Hutson RK, Trainer PJ, Besser GM, Barkan AL, Katznelson L, Klibanski A, Herman-Bonert V, Melmed S, Vance ML, Freda PU, Stewart PM, Friend KE, Clemmons DR, Johannsson G, Stavrou S, Cook DM, Phillips LS, Strasburger CJ, Hackett S, Zib KA, Davis RJ, Scarlett JA, Thorner MO 2001 Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist. Lancet 358: Trainer PJ, Drake WM, Katznelson L, Freda PU, Herman-Bonert V, van der Lely AJ, Dimaraki EV, Stewart PM, Friend KE, Vance ML, Besser GM, Scarlett JA, Thorner MO, Parkinson C, Klibanski A, Powell JS, Barkan AL, Sheppard MC, Malsonado M, Rose DR, Clemmons DR, Johannsson G, Bengtsson BA, Stavrou S, Kleinberg DL, Cook DM, Phillips LS, Bidlingmaier M, Strasburger CJ, Hackett S, Zib K, Bennett WF, Davis RJ 2000 Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant. N Engl J Med 342: Biermasz NR, Dulken HV, Roelfsema F 2000 Postoperative radiotherapy in acromegaly is effective in reducing GH concentration to safe levels. Clin Endocrinol (Oxf) 53: Barkan AL, Halasz I, Dornfeld KJ, Jaffe CA, Friberg RD, Chandler WF, Sandler HM 1997 Pituitary irradiation is ineffective in normalizing plasma insulin-like growth factor I in patients with acromegaly. J Clin Endocrinol Metab 82: Wass JA 1996 Long-term effects of radiotherapy for acromegaly. Metabolism 45: Barrande G, Pittino-Lungo M, Coste J, Ponvert D, Bertagna X, Luton JP, Bertherat J 2000 Hormonal and metabolic effects of radiotherapy in acromegaly: long-term results in 128 patients followed in a single center. J Clin Endocrinol Metab 85: Jackson IM, Noren G 1999 Role of gamma knife radiosurgery in acromegaly. Pituitary 2: Yamamoto M 1999 Gamma knife radiosurgery: technology, applications, and future directions. Neurosurg Clin N Am 10: Landolt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G 1998 Stereotactic radiosurgery for recurrent surgically treated acromegaly: comparison with fractionated radiotherapy. J Neurosurg 88: Attanasio R, Epaminonda P, Motti E, Giugni E, Ventrella L, Cozzi R, Farabola M, Loli P, Beck-Peccoz P, Arosio M 2003 Gamma-knife radiosurgery in acromegaly: a 4-year follow-up study. J Clin Endocrinol Metab 88: Zhang N, Pan L, Wang EM, Dai JZ, Wang BJ, Cai PW 2000 Radiosurgery for growth hormone-producing pituitary adenomas. J Neurosurg 93(Suppl 3): Swearingen B, Barker 2nd FG, Katznelson L, Biller BM, Grinspoon S, Klibanski A, Moayeri N, Black PM, Zervas NT 1998 Long-term mortality after transsphenoidal surgery and adjunctive therapy for acromegaly. J Clin Endocrinol Metab 83: Abosch A, Tyrrell JB, Lamborn KR, Hannegan LT, Applebury CB, Wilson CB 1998 Transsphenoidal microsurgery for growth hormone-secreting pituitary adenomas: initial outcome and long-term results. J Clin Endocrinol Metab 83: Mahmoud-Ahmed AS, Suh JH, Mayberg MR 2001 Gamma knife radiosurgery in the management of patients with acromegaly: a review. Pituitary 4: Growth Hormone Research Society; The Pituitary Society 2004 Biochemical assessment and long-term monitoring in patients with acromegaly: statement from a Joint Consensus Conference of the Growth Hormone Research Society and The Pituitary Society. J Clin Endocrinol Metab 89: Brada M, Ajithkumar TV, Minniti G 2004 Radiosurgery for pituitary adenomas. Clin Endocrinol (Oxf) 61: Fukuoka S, Ito T, Takanashi M, Hojo A, Nakamura H 2001 Gamma knife radiosurgery for growth hormone-secreting pituitary adenomas invading the cavernous sinus. Stereotact Funct Neurosurg 76: Laws ER, Sheehan JP, Sheehan JM, Jagnathan J, Jane Jr JA, Oskouian R 2004 Stereotactic radiosurgery for pituitary adenomas: a review of the literature. J Neurooncol 69: Laws Jr ER, Vance ML 1999 Radiosurgery for pituitary tumors and craniopharyngiomas. Neurosurg Clin N Am 10: Wass JA 1997 Evidence for the effectiveness of radiotherapy in the treatment of acromegaly. J Endocrinol 155(Suppl 1):S57 S58; discussion S67 S Epaminonda P, Porretti S, Cappiello V, Beck-Peccoz P, Faglia G, Arosio M 2001 Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS) and IGFBP-3 levels in acromegaly. Clin Endocrinol (Oxf) 55: De P, Rees DA, Davies N, John R, Neal J, Mills RG, Vafidis J, Davies JS, Scanlon MF 2003 Transsphenoidal surgery for acromegaly in wales: results based on stringent criteria of remission. J Clin Endocrinol Metab 88: Jenkins PJ, Emery M, Howling SJ, Evanson J, Besser GM, Monson JP 2004 Predicting therapeutic response and degree of pituitary tumour shrinkage during treatment of acromegaly with octreotide LAR. Horm Res 62: McKeage K, Cheer S, Wagstaff AJ 2003 Octreotide long-acting release (LAR): a review of its use in the management of acromegaly. Drugs 63: Newman CB, Melmed S, Snyder PJ, Young WF, Boyajy LD, Levy R, Stewart WN, Klibanski A, Molitch ME, Gagel RF 1995 Safety and efficacy of long-term octreotide therapy of acromegaly: results of a multicenter trial in 103 patients a clinical research center study. J Clin Endocrinol Metab 80: Landolt AM, Haller D, Lomax N, Scheib S, Schubiger O, Siegfried J, Wellis G 2000 Octreotide may act as a radioprotective agent in acromegaly. J Clin Endocrinol Metab 85: Kim SH, Huh R, Chang JW, Park YG, Chung SS 1999 Gamma knife radiosurgery for functioning pituitary adenomas. Stereotact Funct Neurosurg 72(Suppl 1): Hayashi M, Izawa M, Hiyama H, Nakamura S, Atsuchi S, Sato H, Nakaya K, Sasaki K, Ochiai T, Kubo O, Hori T, Takakura K 1999 Gamma knife radiosurgery for pituitary adenomas. Stereotact Funct Neurosurg 72(Suppl 1): Ganz JC, Backlund EO, Thorsen FA 1993 The effects of Gamma knife surgery of pituitary adenomas on tumor growth and endocrinopathies. Stereotact Funct Neurosurg 61(Suppl 1): Mokry M, Ramschak-Schwarzer S, Simbrunner J, Ganz JC, Pendi G 1999 A six-year experience with the post-operative radiosurgery management of pituitary adenomas. Stereotact Funct Neurosurg 72: Martinez R, Bravo G, Burzaco J, Rey G 1998 Pituitary tumors and gamma knife surgery. Clinical experience with more than two years of follow-up. Stereotact Funct Neurosurg 70(Suppl 1): Lim YL, Leem W, Kim TS, Rhee BA, Kim GK 1998 Four years experiences in the treatment of pituitary adenomas with gamma knife radiosurgery. Stereotact Funct Neurosurg 70(Suppl 1): Vance ML, Gamma-knife radiotherapy for pituitary adenomas. Program of the 84th Annual Meeting of The Endocrine Society, San Francisco, CA, 2002, p 27 (Abstract S9-2) 36. Eastman RC, Gorden P, Glatstein E, Roth J 1992 Radiation therapy of acromegaly. Endocrinol Metab Clin North Am 21: Tishler RB, Loeffler JS, Lunsford LD, Duma C, Alexander 3rd E, Kooy HM, Flickinger JC 1993 Tolerance of cranial nerves of the cavernous sinus to radiosurgery. Int J Radiat Oncol Biol Phys 27: JCEM is published monthly by The Endocrine Society ( the foremost professional society serving the endocrine community.
Long-term results of gamma knife surgery for growth hormone producing pituitary adenoma: is the disease difficult to cure?
J Neurosurg (Suppl) 102:119 123, 2005 Long-term results of gamma knife surgery for growth hormone producing pituitary adenoma: is the disease difficult to cure? TATSUYA KOBAYASHI, M.D., PH.D., YOSHIMASA
More informationSomatotroph Pituitary Adenomas (Acromegaly) The Diagnostic Pathway (11-2K-234)
Somatotroph Pituitary Adenomas (Acromegaly) The Diagnostic Pathway (11-2K-234) Common presenting symptoms/clinical assessment: Pituitary adenomas are benign neoplasms of the pituitary gland. In patients
More informationAc r o m e g a ly is an endocrine disorder characterized. A systematic analysis of disease control in acromegaly treated with radiosurgery
Neurosurg Focus 29 (4):E13, 2010 A systematic analysis of disease control in acromegaly treated with radiosurgery Is a a c Ya n g, M.D., Wo n Kim, M.D., An t o n i o De Sa l l e s, M.D., Ph.D., and Marvin
More informationSuccessful use of weekly pegvisomant administration in patients with acromegaly
European Journal of Endocrinology (2009) 161 21 25 ISSN 0804-4643 CLINICAL STUDY Successful use of weekly pegvisomant administration in patients with acromegaly C E Higham, J D J Thomas 1, M Bidlingmaier
More informationGamma knife surgery in management of secretory pituitary adenoma Preliminary evaluation of role, efficacy and safety
International Journal of Clinical Medicine Research 2014; 1(2): 48-56 Published online June 10, 2014 (http://www.aascit.org/journal/ijcmr) Gamma knife surgery in management of secretory pituitary adenoma
More informationAcromegaly: Management of the Patient Who Has Failed Surgery
Acromegaly: Management of the Patient Who Has Failed Surgery Minnesota/Midwest Chapter of the American Association of Clinical Endocrinologists 8 th Annual Meeting October 14, 2017 Mark E. Molitch, M.D.
More informationPegvisomant: an advance in clinical efficacy in acromegaly
European Journal of Endocrinology (2003) 148 S27 S32 ISSN 0804-4643 Pegvisomant: an advance in clinical efficacy in acromegaly Paul M Stewart The University of Birmingham, Queen Elizabeth Hospital, Edgbaston,
More informationRadioterapia degli adenomi ipofisari
Radioterapia degli adenomi ipofisari G Minniti Radiation Oncology, Sant Andrea Hospital, University of Rome Sapienza, and IRCCS Neuromed, Pozzilli (IS) Roma 6-9 Novembre 14 ! Outline " Radiation techniques
More informationAbstract. Introduction
Clinical Features and Outcome of Surgery in 30 Patients with Acromegaly A. Chandna, N. Islam, A. Jabbar, L. Zuberi, N. Haque Endocrinology Section, Department of Medicine, Aga Khan University Hospital,
More informationThis is an author produced version of an article that appears in:
This is an author produced version of an article that appears in: CLINICAL ENDOCRINOLOGY The internet address for this paper is: https://publications.icr.ac.uk/3775/ Published text: M Brada, T V Ajithkumar,
More informationRemission criteria for the follow-up of patients with acromegaly
European Journal of Endocrinology (2004) 150 465 471 ISSN 0804-4643 CLINICAL STUDY Remission criteria for the follow-up of patients with acromegaly Sevim Gullu, Hatice Keles 1, Tuncay Delibasi, Vedia Tonyukuk,
More informationChanging patterns of insulin-like growth factor I and glucose-suppressed growth hormone levels after pituitary surgery in patients with acromegaly
J Neurosurg 97:287 292, 2002 Changing patterns of insulin-like growth factor I and glucose-suppressed growth hormone levels after pituitary surgery in patients with acromegaly ANA LAURA ESPINOSA-DE-LOS-MONTEROS,
More informationEstablishing the relationship between growth hormone. Correlation between GH and IGF-1 during treatment for. acromegaly.
CLINICAL ARTICLE J Neurosurg 126:1959 1966, 2017 Correlation between GH and IGF-1 during treatment for acromegaly Edward H. Oldfield, MD, 1 John A. Jane Jr., MD, 1 Michael O. Thorner, MBBS, DSc, 2 Carrie
More informationACROMEGALY IS A rare disorder usually caused by a
0021-972X/05/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 90(10):5627 5631 Printed in U.S.A. Copyright 2005 by The Endocrine Society doi: 10.1210/jc.2005-0531 Cotreatment of Acromegaly with
More informationHigh and Low GH: an update of diagnosis and management of GH disorders
High and Low GH: an update of diagnosis and management of GH disorders Georgia Chapter-AACE 2017 Laurence Katznelson, MD Professor of Medicine and Neurosurgery Associate Dean of Graduate Medical Education
More informationLeksell Gamma Knife Society
Proceedings of the 9th International Meeting of the Leksell Gamma Knife Society Hong Kong, November 1998 Editors J.C. Ganz, Graz Ph.L. Gildenberg, Houston, Tex. P.O. Franklin, Houston, Tex. 55 figures
More informationIs it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife?
European Journal of Endocrinology (2011) 164 169 178 ISSN 0804-4643 CLINICAL STUDY Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma knife? Josef Marek,
More informationProlactin-Secreting Pituitary Adenomas (Prolactinomas) The Diagnostic Pathway (11-2K-234)
Prolactin-Secreting Pituitary Adenomas (Prolactinomas) The Diagnostic Pathway (11-2K-234) Common presenting symptoms/clinical assessment: Pituitary adenomas are benign neoplasms of the pituitary gland.
More informationCLINICAL REVIEW: A Critical Analysis of Pituitary Tumor Shrinkage during Primary Medical Therapy in Acromegaly
0021-972X/05/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 90(7):4405 4410 Printed in U.S.A. Copyright 2005 by The Endocrine Society doi: 10.1210/jc.2004-2466 CLINICAL REVIEW: A Critical
More informationGamma knife radiosurgery: a safe and effective salvage treatment for pituitary tumours not controlled despite conventional radiotherapy
European Journal of Endocrinology (2009) 161 819 828 ISSN 0804-4643 CLINICAL STUDY Gamma knife radiosurgery: a safe and effective salvage treatment for pituitary tumours not controlled despite conventional
More informationStereotactic radiosurgery for pituitary tumors
Neurosurg Focus 14 (5):Article 10, 2003, Click here to return to Table of Contents Stereotactic radiosurgery for pituitary tumors THOMAS C. WITT, M.D. Department of Neurosurgery, Indiana University Medical
More informationOptimalization and cost management of lanreotide-autogel therapy in acromegaly
European Journal of Endocrinology (2007) 157 571 577 ISSN 0804-4643 CLINICAL STUDY Optimalization and cost management of lanreotide-autogel therapy in acromegaly Pascale Abrams, Orsalia Alexopoulou 1,
More informationMetoclopramide Domperidone. HYPER- PROLACTINAEMIA: the true and the false problems
Modern management of Hyperprolactinaemia Didier DEWAILLY, M.D. Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre, C.H.R.U., 59037 Lille, France 1 Metoclopramide Domperidone
More informationGamma knife stereotactic radiosurgery for acromegaly
European Journal of Endocrinology (2007) 157 255 263 ISSN 0804-4643 CLINICAL STUDY Gamma knife stereotactic radiosurgery for acromegaly Einar Osland Vik-Mo 1, Marianne Øksnes 2, Paal-Henning Pedersen 1,5,
More informationTreating a Growing Problem: A Closer Look at Acromegaly. Lisa Nachtigall, MD (Moderator) Nicholas Tritos, MD, DSc Brooke Swearingen, MD
Treating a Growing Problem: A Closer Look at Acromegaly Lisa Nachtigall, MD (Moderator) Nicholas Tritos, MD, DSc Brooke Swearingen, MD Goal Address key challenges faced by physicians who treat acromegaly
More informationLong-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly
3 Long-term follow-up results of postoperative radiotherapy in 36 patients with acromegaly Nienke R. Biermasz, Hans van Dulken and Ferdinand Roelfsema Departments of Endocrinology and Metabolism (N.B.,
More informationCost-Effectiveness of Somatostatin Analogues for the Treatment of Acromegaly in Colombia
Open Journal of Endocrine and Metabolic Diseases, 2012, 2, 102-106 http://dx.doi.org/10.4236/ojemd.2012.24016 Published Online November 2012 (http://www.scirp.org/journal/ojemd) Cost-Effectiveness of Somatostatin
More informationRadiotherapy approaches to pituitary tumors
Disclosures No relevant disclosures Radiotherapy approaches to pituitary tumors Pituitary Disorders: Advances in Diagnosis and Management Steve Braunstein, MD, PhD UCSF Department of Radiation Oncology
More informationTREATMENT OF ACROMEGALY WITH THE GROWTH HORMONE RECEPTOR ANTAGONIST PEGVISOMANT
TREATMENT OF ACROMEGALY WITH THE GROWTH HORMONE RECEPTOR ANTAGONIST PEGVISOMANT PETER J. TRAINER, M.D., WILLIAM M. DRAKE, M.B., LAURENCE KATZNELSON, M.D., PAMELA U. FREDA, M.D., VIVIEN HERMAN-BONERT, M.D.,
More informationTherapeutic Objectives. Cushing s Disease Surgical Results. Cushing s Disease Surgical Results: Macroadenomas 10/24/2015
Therapeutic Objectives Update on the Management of Lewis S. Blevins, Jr., M.D. Correct the syndrome by lowering daily cortisol secretion to normal Eradicate any tumor that might threaten the health of
More informationThe efficacy of medical treatment in patients with acromegaly in clinical practice
2018, 65 (1), 33-41 Original The efficacy of medical treatment in patients with acromegaly in clinical practice Seo Young Lee 1), Jung Hee Kim 1), 2), Ji Hyun Lee 1), Yong Hwy Kim 2), 3), Hyang Jin Cha
More informationManaging Acromegaly: Review of Two Cases
Managing Acromegaly: Review of Two Cases INDICATION AND USAGE SIGNIFOR LAR (pasireotide) for injectable suspension is a somatostatin analog indicated for the treatment of patients with acromegaly who have
More informationLinear Accelerator Radiosurgery for Pituitary Macroadenomas. BACKGROUND. A prospective study was conducted to assess the efficacy and side
1355 Linear Accelerator Radiosurgery for Pituitary Macroadenomas A 7-Year Follow-Up Study Juergen Voges, MD 1 Martin Kocher, MD 2 Matthias Runge, MD 1 Jorg Poggenborg, MD 3 Ralph Lehrke, MD 1 Doris Lenartz,
More informationManaging Acromegaly: Biochemical Control with SIGNIFOR LAR (pasireotide)
Managing Acromegaly: Biochemical Control with SIGNIFOR LAR (pasireotide) INDICATION AND USAGE SIGNIFOR LAR (pasireotide) for injectable suspension is a somatostatin analog indicated for the treatment of
More informationGH Receptor Antagonist: Mechanism of Action and Clinical Utility
Reviews in Endocrine & Metabolic Disorders 2005;6:5 13 C 2005 Springer Science + Business Media, Inc. Manufactured in The Netherlands. GH Receptor Antagonist: Mechanism of Action and Clinical Utility Sowmya
More informationJMSCR Vol 05 Issue 01 Page January 2017
MEN1, AIP, PRKAR1A and CDKN1B are familial pituitary syndromes found to be associated with four different genes. Pituitary gland is situated in hypophyseal fossa which is bounded supero-laterally by dural
More informationTREATMENT OF CUSHING S DISEASE
TREATMENT OF CUSHING S DISEASE Surgery, Radiation, Medication Peter J Snyder, MD Professor of Medicine Disclosures Novartis Research grant Pfizer Consultant Ipsen Research grant Cortendo Research grant
More informationImpact of Gamma Knife Radiosurgery on the neurosurgical management of skull-base lesions: The Combined Approach
Radiosurgery as part of the neurosurgical armamentarium: Educational Symposium November 24 th 2011 Impact of Gamma Knife Radiosurgery on the neurosurgical management of skull-base lesions: The Combined
More informationSurgical therapeutic strategy for giant pituitary adenomas.
Biomedical Research 2017; 28 (19): 8284-8288 ISSN 0970-938X www.biomedres.info Surgical therapeutic strategy for giant pituitary adenomas. Han-Shun Deng, Zhi-Quan Ding, Sheng-fan Zhang, Zhi-Qiang Fa, Qing-Hua
More information(3) Pituitary tumours
Hypopituitarism Diabetes Insipidus Pituitary tumours (2) Dr T Kemp - Endocrinology and Metabolism Unit - Steve Biko Academic Hospital (3) Pituitary tumours Pituitary microadenoma - intrasellar adenoma
More informationEuropean Journal of Endocrinology (2006) ISSN
European Journal of Endocrinology (2006) 154 467 477 ISSN 0804-4643 CLINICAL STUDY Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term,
More informationStereotactic radiosurgery in pituitary adenomas: long-term single institution experience and role of the hypothalamic-pituitary axis
Jour. of Radiosurgery and BRT, Vol. 0, pp. 1 8 Reprints available directly from the publisher Photocopying permitted by license only 2011 Old City Publishing, Inc. Published by license under the OCP Science
More informationReview Article Gamma Knife Radiosurgery for Acromegaly
Hindawi Publishing Corporation International Journal of Endocrinology Volume 2012, Article ID 821579, 7 pages doi:10.1155/2012/821579 Review Article Gamma Knife Radiosurgery for Acromegaly John D. Rolston
More informationThe primary management of the majority of symptomatic
J Neurosurg 116:1304 1310, 2012 Cranial nerve dysfunction following Gamma Knife surgery for pituitary adenomas: long-term incidence and risk factors Clinical article Christopher P. Cifarelli, M.D., Ph.D.,
More informationGeneral Discussion and Conclusions
16 General Discussion and Conclusions Chapter 16 254 I. Treatm ent of acrom egaly Transsphenoidal surgery Radiotherapy Pre-surgical som atostatin analog treatm ent Som atostatin analog treatm ent Current
More informationRESEARCH ARTICLE. Abstract. Introduction. Materials and Methods
DOI:http://dx.doi.org/10.7314/APJCP.2015.16.13.5279 Outcomes after Linac Based SRS/FSRT for Pituitary Adenomas RESEARCH ARTICLE Outcomes for Pituitary Adenoma Patients Treated with Linac- Based Stereotactic
More informationImaging pituitary gland tumors
November 2005 Imaging pituitary gland tumors Neel Varshney,, Harvard Medical School Year IV Two categories of presenting signs of a pituitary mass Functional tumors present with symptoms due to excess
More informationTABLES. Table 1: Imaging. Congress of Neurological Surgeons Author (Year) Description of Study Classification Process / Evidence Class
TABLES Table 1: Imaging Kremer et al (2002) 2 Study Design: Prospective followed case series. Patient Population: Fifty adult patients with NFPA Study Description: Patients underwent MRI before surgery,
More informationEuropean Journal of Endocrinology (2006) ISSN
European Journal of Endocrinology (2006) 154 213 220 ISSN 0804-4643 CASE REPORT Elevated transaminases during medical treatment of acromegaly: a review of the German pegvisomant surveillance experience
More informationConventional pituitary irradiation is effective in normalising plasma IGF-I in patients with acromegaly
European Journal of Endocrinology (2001) 144 109±116 ISSN 0804-4643 CLINICAL STUDY Conventional pituitary irradiation is effective in normalising plasma IGF-I in patients with acromegaly Bodo Gutt, Christina
More informationPituitary adenomas and menopause
Pituitary adenomas and menopause Iulia Potorac Service d Endocrinologie Université de Liège CHU Liège RESULTATS Clinical case 1-38-year-old patient referred for exploration of premature ovarian failure
More informationPegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl
European Journal of Endocrinology (2005) 153 195 201 ISSN 0804-4643 CASE REPORT Pegvisomant therapy in pituitary gigantism: successful treatment in a 12-year-old girl M Rix, P Laurberg 1, A S Hoejberg
More informationSee the latest estimates for new cases of pituitary tumors in the US and what research is currently being done.
About Pituitary Tumors Overview and Types If you have been diagnosed with a pituitary tumor or worried about it, you likely have a lot of questions. Learning some basics is a good place to start. What
More informationSummary. Introduction ORIGINAL ARTICLE
Clinical Endocrinology (2007) 67, 282 289 doi: 10.1111/j.1365-2265.2007.02878.x ORIGINAL ARTICLE Blackwell Publishing Ltd Long-term (up to 18 years) effects on GH/IGF-1 hypersecretion and tumour size of
More informationMedical Management of Functioning Pituitary Adenoma: An Update
REVIEW ARTICLE Neurol Med Chir (Tokyo) 54, 958 965, 2014 doi: 10.2176/nmc.ra.2014-0239 Online November 29, 2014 Medical Management of Functioning Pituitary Adenoma: An Update Yutaka OKI 1,2 Departments
More informationProfessor Ian Holdaway. Endocrinologist Auckland District Health Board
Professor Ian Holdaway Endocrinologist Auckland District Health Board A land of milk and giants hormonesecreting pituitary tumours I M Holdaway, Endocrinologist, Auckland Acromegaly Prolactinomas Cushing
More informationProcess / Evidence Class. Clinical Assessment / III
Table 2: Endocrine Author Cozzi et al (2009) 1 Study Design: Prospectively followed case series. Fourteen patients had pre-op hypocortisolism. Patient Population: Seventy-two adult patients who underwent
More informationMANAGEMENT OF HYPERGLYCEMIA IN A PATIENT WITH ACROMEGALY TREATED WITH PASIREOTIDE LAR: A CASE STUDY
Case Report MANAGEMENT OF HYPERGLYCEMIA IN A PATIENT WITH ACROMEGALY TREATED WITH PASIREOTIDE LAR: A CASE STUDY Murray B. Gordon, MD, FACE; Kellie L. Spiller, MS ABSTRACT Submitted for publication July
More informationPreoperative octreotide treatment in newly diagnosed acromegalic. patients with macroadenomas increases cure short-term postoperative
J Clin Endocrin Metab. First published ahead of print May 20, 2008 as doi:10.1210/jc.2008-0315 Preoperative octreotide treatment in newly diagnosed acromegalic patients with macroadenomas increases cure
More informationSharon maslovitz Lis Maternity Hospital
Sharon maslovitz Lis Maternity Hospital Case report Chief complaint 27 yo, with PMC @ 31+3w, BCBA twins Complaints of severe rt parietal and retrobulbar headaches Medical background Healthy until 24yo
More informationPituitary Tumors and Incidentalomas. Bijan Ahrari, MD, FACE, ECNU Palm Medical Group
Pituitary Tumors and Incidentalomas Bijan Ahrari, MD, FACE, ECNU Palm Medical Group Background Pituitary incidentaloma: a previously unsuspected pituitary lesion that is discovered on an imaging study
More informationENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA
This is an author produced version of an article that appears in: ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA The internet address for this paper is: https://publications.icr.ac.uk/5974/ Published
More informationIntravenous octreotide test predicts the long term outcom e of treatm ent w ith octreotide-longacting repeatable in active acrom egaly
11 Intravenous octreotide test predicts the long term outcom e of treatm ent w ith octreotide-longacting repeatable in active acrom egaly Nienke R. Biermasz, Alberto M. Pereira, Jan W.A. Smit, Johannes
More informationG Minniti 1, M-L Jaffrain-Rea 2,3, V Esposito 1,4, A Santoro 4, G Tamburrano 5 and G Cantore 1,4. Abstract. Introduction
Evolving criteria for post-operative biochemical remission of acromegaly: can we achieve a definitive cure? An audit of surgical results on a large series and a review of the literature G Minniti 1, M-L
More informationCertain types of tumors, in the CNS and elsewhere,
clinical article J Neurosurg 122:798 802, 2015 Percent reduction of growth hormone levels correlates closely with percent resected tumor volume in acromegaly Lucia Schwyzer, MD, Robert M. Starke, MD, John
More informationEffects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegaly
European Journal of Endocrinology (26) 1 73 78 ISSN 84-4643 CLINICAL STUDY Effects of the long-acting somatostatin analogue Lanreotide Autogel on glucose tolerance and insulin resistance in acromegaly
More informationMedical Management of Growth Hormone-Secreting Pituitary Adenomas
Pituitary 5: 67 76, 2002 C 2003 Kluwer Academic Publishers. Manufactured in The Netherlands. Medical Management of Growth Hormone-Secreting Pituitary Adenomas Michael S. Racine and Ariel L. Barkan Division
More informationPITUITARY: JUST THE BASICS PART 2 THE PATIENT
PITUITARY: JUST THE BASICS PART 2 THE PATIENT DISCLOSURE Relevant relationships with commercial entities none Potential for conflicts of interest within this presentation none Steps taken to review and
More informationPituitary tumors: pathophysiology, clinical manifestations and management
Pituitary tumors: pathophysiology, clinical manifestations and management B M Arafah and M P Nasrallah Division of Clinical and Molecular Endocrinology, Case Western Reserve University and University Hospitals
More informationCase Report Successful Pregnancy in a Female with a Large Prolactinoma after Pituitary Tumor Apoplexy
Case Reports in Obstetrics and Gynecology Volume 2013, Article ID 817603, 4 pages http://dx.doi.org/10.1155/2013/817603 Case Report Successful Pregnancy in a Female with a Large Prolactinoma after Pituitary
More informationJACK L. SNITZER, DO INTERNAL MEDICINE BOARD REVIEW COURSE 2018 PITUITARY
JACK L. SNITZER, DO INTERNAL MEDICINE BOARD REVIEW COURSE 2018 PITUITARY JACK L. SNITZER, D.O. Peninsula Regional Endocrinology 1415 S. Division Street Salisbury, MD 21804 Phone:410-572-8848 Fax:410-572-6890
More informationTumor recurrence or regrowth in adults with nonfunctioning pituitary adenomas using GH replacement therapy
Tumor recurrence or regrowth in adults with nonfunctioning pituitary adenomas using GH replacement therapy N. C. van Varsseveld C. C. van Bunderen A. A. M. Franken H. P. F. Koppeschaar A. J. van der Lely
More informationResearch paper. *Authors with equal contribution
HORMONES 2016, 15(2):224-234 Research paper Beneficial effect of dose escalation and surgical debulking in patients with acromegaly treated with somatostatin analogs in a Romanian tertiary care center
More informationAcromegaly: a challenging condition to diagnose and manage. C. L. Chik, MD, PhD, FRCPC University of Alberta, Edmonton
Acromegaly: a challenging condition to diagnose and manage C. L. Chik, MD, PhD, FRCPC University of Alberta, Edmonton Acromegaly: a challenging condition to diagnose and manage? Objectives: n Know the
More informationSomatostatin Analog and Estrogen Treatment in a Tall Girl
Clin Pediatr Endocrinol 1995; 4 (2): 163-167 Copyright (C) 1995 by The Japanese Society for Pediatric Endocrinology Somatostatin Analog and Estrogen Treatment in a Tall Girl Toshiaki Tanaka, Mari Satoh,
More informationMonitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant?
Clinical Endocrinology (2009) 71, 166 170 doi: 10.1111/j.1365-2265.2009.03556.x CLINICAL QUESTION Monitoring of acromegaly: what should be performed when GH and IGF-1 levels are discrepant? Pamela U. Freda
More informationCase report. Open Access. Abstract
Open Access Case report Hyperthyroidism unmasked several years after the medical and radiosurgical treatment of an invasive macroprolactinoma inducing hypopituitarism: a case report Luca Foppiani 1 *,
More informationClinical experiences and success rates of acromegaly treatment: the single center results of 62 patients
Evran et al. BMC Endocrine Disorders 2014, 14:97 RESEARCH ARTICLE Open Access Clinical experiences and success rates of acromegaly treatment: the single center results of 62 patients Mehtap Evran *, Murat
More informationPITUITARY ADENOMAS. Effective Date: August, 2012
CLINICAL PRACTICE GUIDELINE CNS-00 PITUITARY ADENOMAS Effective Date: August, 2012 The recommendations contained in this guideline are a consensus of the Alberta Provincial CNS Tumour Team synthesis of
More informationClinical Commissioning Policy: Pegvisomant for acromegaly as a third-line treatment (adults)
Clinical Commissioning Policy: Pegvisomant for acromegaly as a third-line treatment (adults) Reference: NHS England: 16050/P NHS England INFORMATION READER BOX Directorate Medical Operations and Information
More informationEvidence Based Medicine for Gamma Knife Radiosurgery. Metastatic Disease GAMMA KNIFE SURGERY
GAMMA KNIFE SURGERY Metastatic Disease Evidence Based Medicine for Gamma Knife Radiosurgery Photos courtesy of Jean Régis, Timone University Hospital, Marseille, France Brain Metastases The first report
More informationPasireotide Long-Acting Repeatable (Signifor) for acromegaly first and second line
Pasireotide Long-Acting Repeatable (Signifor) for acromegaly first and second line December 2010 This technology summary is based on information available at the time of research and a limited literature
More informationEui Hyun Kim. Department of Medicine The Graduate School, Yonsei University
Immediate postoperative growth hormone level and early postoperative oral glucose tolerance test as predictive tools for the long-term surgical remission in acromegaly Eui Hyun Kim Department of Medicine
More informationClinical Commissioning Policy Proposition: Stereotactic radiosurgery/ radiotherapy for the treatment of pituitary adenomas [Adults]
Clinical Commissioning Policy Proposition: Stereotactic radiosurgery/ radiotherapy for the treatment of pituitary adenomas [Adults] Reference: NHS England 1603 First published: TBC Prepared by NHS England
More informationGLMS CME- Cell Group 5 10 April Greenlane Medical Specialists Pui-Ling Chan Endocrinologist
GLMS CME- Cell Group 5 10 April 2018 Greenlane Medical Specialists Pui-Ling Chan Endocrinologist Pituitary case one Mrs Z; 64F Seen ORL for tinnitus wax impaction MRI Head Pituitary microadenoma (3mm)
More informationPreoperative Short-term Administration of Octreotide for Facilitating Transsphenoidal Removal of Invasive
Preoperative Short-term Administration of Octreotide for Facilitating Transsphenoidal Removal of Invasive Growth Hormone-secreting Macroadenomas Eiji TACHIBANA, Kiyoshi SAITO, and Jun YOSHIDA, Nagoya University
More informationGamma Knife radiosurgery Pituitary adenomas
Gamma Knife radiosurgery Pituitary adenomas Introduction Pituitary adenomas represent one of the most common types of intracranial tumors. While their macroscopic appearance and anatomical location are
More informationEfficacy and Safety of Cabergoline as First Line Treatment for Invasive Giant Prolactinoma
J Korean Med Sci 2009; 24: 874-8 ISSN 1011-8934 DOI: 10.3346/jkms.2009.24.5.874 Copyright The Korean Academy of Medical Sciences Efficacy and Safety of Cabergoline as First Line for Invasive Giant Prolactinoma
More informationOtolaryngologist s Perspective of Stereotactic Radiosurgery
Otolaryngologist s Perspective of Stereotactic Radiosurgery Douglas E. Mattox, M.D. 25 th Alexandria International Combined ORL Conference April 18-20, 2007 Acoustic Neuroma Benign tumor of the schwann
More informationRadiosurgery by Leksell gamma knife. Josef Novotny, Na Homolce Hospital, Prague
Radiosurgery by Leksell gamma knife Josef Novotny, Na Homolce Hospital, Prague Radiosurgery - Definition Professor Lars Leksell The tools used by the surgeon must be adapted to the task and where the human
More informationAccepted Preprint first posted on 4 February 2010 as Manuscript EJE FRACTIONATED STEREOTACTIC RADIOTHERAPY IN PATIENTS WITH ACROMEGALY.
Page 1 of 25 Accepted Preprint first posted on 4 February 2010 as Manuscript EJE-09-1045 FRACTIONATED STEREOTACTIC RADIOTHERAPY IN PATIENTS WITH ACROMEGALY. INTERIM SINGLE CENTRE AUDIT By Roug S 1, Rasmussen
More informationMaternal and fetal effects of acromegaly on pregnancy. Clinical Practice and Drug Treatment.
International Journal of Advanced Biotechnology and Research (IJBR) ISSN 0976-2612, Online ISSN 2278 599X, Vol-7, Issue-3, 2016, pp952-960 http://www.bipublication.com Review Article Maternal and fetal
More informationDosimetry, see MAGIC; Polymer gel dosimetry. Fiducial tracking, see CyberKnife radiosurgery
Subject Index Acoustic neuroma, neurofibromatosis type 2 complications 103, 105 hearing outcomes 103, 105 outcome measures 101 patient selection 105 study design 101 tumor control 101 105 treatment options
More informationClinical Policy: Pasireotide (Signifor LAR) Reference Number: CP.PHAR.332 Effective Date: Last Review Date: Line of Business: Medicaid
Clinical Policy: (Signifor LAR) Reference Number: CP.PHAR.332 Effective Date: 03.01.17 Last Review Date: 11.17 Line of Business: Medicaid Coding Implications Revision Log See Important Reminder at the
More informationPreliminary Experience with 3-Tesla MRI and Cushing s Disease
TECHNICAL NOTE Preliminary Experience with 3-Tesla MRI and Cushing s Disease LouisJ.Kim,M.D., 1 Gregory P. Lekovic, M.D., Ph.D., J.D., 1 William L.White, M.D., 1 and John Karis, M.D. 2 ABSTRACT Because
More informationPituitary Tumors: Unsual Situations
Pituitary Tumors: Unsual Situations Michigan Chapter of AACE 2018 Annual Meeting September 22, 2018 Mark E. Molitch, M.D. Northwestern University Feinberg School of Medicine Chicago, Illinois USA Mark
More informationImaging The Turkish Saddle. Russell Goodman, HMS III Dr. Gillian Lieberman
Imaging The Turkish Saddle Russell Goodman, HMS III Dr. Gillian Lieberman Learning Objectives Review the anatomy of the sellar region Discuss the differential diagnosis of sellar masses Discuss typical
More informationEndocrinological Outcome Among Treated Craniopharyngioma Patients
Endocrinological Outcome Among Treated Craniopharyngioma Patients Afaf Al Sagheir, MD Head & Consultant, Section of Endocrinology/Diabetes Department of Pediatrics KFSH&RC Introduction Craniopharyngiomas
More informationPegvisomant-induced cholestatic hepatitis with jaundice in a patient with
Page of Accepted Preprint first posted on March 00 as Manuscript EJE-0-000 Pegvisomant-induced cholestatic hepatitis with jaundice in a patient with Gilbert s syndrome Ignacio Bernabeu, Jose Cameselle-Teijeiro,
More informationPituitary for the General Practitioner. Marilyn Lee Consultant physician and endocrinologist
Pituitary for the General Practitioner Marilyn Lee Consultant physician and endocrinologist Pituitary tumours Anterior/posterior pituitary Extension of adenoma upwards/downwards/sideways Producing too
More information