Octreotide May Act as A Radioprotective Agent in Acromegaly

Landolt, Alex M.; Haller, Dieter; Lomax, N.; Scheib, Stefan; Schubiger, O; Siegfried, J.; Wellis, G.

doi:10.1210/jcem.85.3.6464

Cited by 155 publications

(83 citation statements)

References 6 publications

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“…IGF-I normalization, as compared with the group of patients who had maintained either SA or DA during the period of irradiation. These data point to a putative interference of GH-suppressive treatments on the effectiveness of RxT, and support strongly the preliminary results reported by Landolt and colleagues (28), showing a radioprotective effect of octreotide treatment on RxT outcome. The hypothesis that the reduction of metabolic activity of the tumoral cells caused by the drug could actually lessen the effects of RxT needs to be addressed by prospective studies.…”

Section: Discussionsupporting

confidence: 89%

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Failure of radiotherapy in acromegaly

Cozzi¹,

Barausse²,

Asnaghi

et al. 2001

European Journal of Endocrinology

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Background: Recent data has raised skepticism regarding the long-term effectiveness of radiotherapy (RxT) in acromegaly and its role as an ancillary tool to neurosurgery (Tx). Patients: We evaluated 72 acromegalic patients previously submitted to RxT. Data were discarded in 23 patients, who were lost to follow-up, operated on after RxT or irradiated with techniques different from external conventional fractionated RxT. Among the remaining 49 (five with mixed GH-prolactin adenoma), 34 were irradiated after surgical failure and 15 as primary treatment. A second cycle of RxT was administered in two. Results: (i) GH/IGF-I. After a median follow-up of 14 years (range 3-41), normal age-matched IGF-I levels were reached in eight patients (16%) after 10 years, and GH levels ,2.5 mg/l in six (12%) after 9 years. The rate of persistently pathological hormonal levels was still 90% at 25 years. All patients with GH/IGF-I normalization had undergone irradiation without any antisecretory drug. Neither basal GH nor tumor size affected the outcome of RxT. In three patients (6%) a relapse/worsening occurred. (ii) Tumor size. Tumor shrank after 8.5 years in 24 patients (49%), in nine of whom during GH-suppressive treatment. Tumor shrinkage was not predictive of hormonal normalization. (iii) Side-effects. Hypopituitarism was diagnosed in four patients (selective in three and global in one) and GH deficiency in one. Three patients had neurological side-effects and meningioma was shown in two patients. Conclusion: RxT is unable to cure acromegaly, because it seldom achieves hormonal normalization even after a very prolonged follow-up. Concomitant antisecretory treatment seems to counteract its effects. RxT can still play a role in those patients with large tumor remnants, because of its capacity to shrink tumor size.

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Section: Discussionsupporting

confidence: 89%

“…Five patients (nos 12,20,28,32,38) had been lost to follow-up, i.e. the last evaluation had been performed more than 3 years ago.…”

Section: Follow-upmentioning

confidence: 99%

Failure of radiotherapy in acromegaly

Cozzi¹,

Barausse²,

Asnaghi

et al. 2001

European Journal of Endocrinology

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“…Despite some indications that somatostatin analogues and the GH receptor antagonist could be radioprotective (39,42), we chose to continue medical therapy during the period of radiation in order to limit the time of seriously elevated GH/IGF1. The present study has thus demonstrated that an acceptable treatment outcome can be achieved with FSRT, while the patients were still on medication, which is also in keeping with a demonstrated lack of significant difference between patients treated or not treated with somatostatin analogues (40).…”

Section: Authorsmentioning

confidence: 99%

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

Roug¹,

Rasmussen²,

Juhler³

et al. 2010

European Journal of Endocrinology

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Aim: To evaluate the effect of fractionated stereotactic radiotherapy (FSRT) in acromegaly in a retrospective analysis. Patients and methods: Thirty-four patients (17 females, median 43 years (range 30-74)) with acromegaly were treated with FSRT (conformal dynamic arcing, dose 54 Gy, 27-30 fractions) between January 1998 and April 2007. Of the 34 patients, 32 had undergone transsphenoidal adenotomy, and 28 were on medical therapy before FSRT. Patients on medical therapy continued this during and after the irradiation. The treatment was gradually decreased/withdrawn after careful assessment. Results: Magnetic resonance scanning of the pituitary gland 34 months (median, range 11-95) after irradiation showed stable or reduced volume of the remaining tumour tissue in 31 of 34 patients (91%). Seventeen patients (50%) were biochemically controlled (normalised nadir GH during oral glucose tolerance test and IGF1 !C2 S.D.) 30 months after FSRT (median, range 6-60), and ten of them had true biochemical remission (off medical therapy) 30 months after FSRT (median, range 12-69). Of 28 patients with one or more functioning pituitary axes before irradiation, 8 (29%) developed further deficit of one or two pituitary axes 48 months (median, range 6-102) after FSRT. Of 34 patients, 20 still required medical treatment for acromegaly at the end of this study, mainly those with a short follow-up period after irradiation. Conclusion: The FSRT seems promising in terms of treatment of acromegaly. Longer follow-up is, however, needed to assess the overall efficacy and safety of FSRT for acromegaly.

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“…6 SRLs are often withheld at the time of radiation therapy because of concern that they may be radioprotective, although this finding is controversial, as it is not supported in all studies. 57,59,61 The main limitation for radiotherapy is the development of hypopituitarism, which may occur in up to 50 % of patients after 5 to 10 years. 62,63 Radiationinduced secondary tumors and radionecrosis have been reported in fewer than 2 % of patients undergoing conventional radiotherapy.…”

Section: Radiation Therapymentioning

confidence: 99%

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

Katznelson¹

2015

European Endocrinology

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Acromegaly is an uncommon disorder that, in the vast majority of cases, is the result of a growth hormone (GH)-secreting pituitary adenoma. Because tumors are often macroadenomas at the time of diagnosis, there may be a number of signs and symptoms related to local mass effects, including headache, visual field loss, ophthalmoplegia, and hypopituitarism. Chronic GH and insulin-like growth factor 1 (IGF-1) hypersecretion can lead to soft tissue and bone overgrowth manifestations, medical comorbidities, and accompanying clinical features. Medical comorbidites include arthropathy, cardiomegaly, type 2 diabetes, hypertension, sleep apnea syndrome, and colon polyps. In addition, acromegaly is associated with premature mortality, primarily owing to cardiovascular disease. Appropriate therapy of acromegaly can lead to improvement in these comorbidities and reversal of the premature mortality risk. This current review is an update to the 2012 summary. Diagnosis of AcromegalyThe diagnosis of acromegaly begins with a clinical suspicion by the physician that the patient has this disease. Typical physical examination findings include hand and foot enlargement or facial bone enlargement and acral/soft tissue changes. Of note, subjects usually do not present with a chief complaint related to acral growth. In women, the most common presenting complaint is amenorrhea. 2Biochemical testing involves measurement of GH and IGF-1. GH, produced by the somatotroph cells of the pituitary gland in a pulsatile fashion, circulates and stimulates hepatic secretion of IGF-1. In the recent Endocrine Society guidelines on the approach to acromegaly, it was recommended that a serum IGF-1 level be measured in subjects with acral manifestations. Owing to the lack of agreement between assays and the lack of validated normal ranges for IGF-1, 3,4 the same assay should be used in the same patient for serial measurement. 5A random GH measurement was not considered useful in diagnosis because of the lack of a well-defined normal or safe range, although a markedly elevated random GH level is certainly consistent with the disease. Additionally, in subjects with elevated or equivocal serum IGF-1 concentrations, the recent acromegaly guidelines recommended confirmation of the diagnosis with a lack of suppression of GH to less than 1 mcg/l following an oral glucose load. 6 In a patient with signs and symptoms of acromegaly and an elevated IGF-1 value, an oral glucose tolerance test (OGTT) may not be necessary for diagnosis. In the setting of a clinical suspicion but discordant values, such as an elevated IGF-1 and normal GH value (i.e., suppressible with OGTT), the subject likely has early stage acromegaly. 7After diagnosis of acromegaly, a magnetic resonance imaging (MRI) scan of the sella should be obtained to determine tumor size, location, and invasiveness. Visual field testing is performed if the tumor is touching or compressing the optic chiasm. A thorough ophthalmologic examination should be performed if the patient describes diplopia and the tumo...

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Octreotide May Act as A Radioprotective Agent in Acromegaly

Cited by 155 publications

References 6 publications

Failure of radiotherapy in acromegaly

Failure of radiotherapy in acromegaly

Fractionated stereotactic radiotherapy in patients with acromegaly: an interim single-centre audit

Diagnosis and Management of Acromegaly in 2014 (Update from 2012)

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