Lack of delayed neurocognitive side effects of Gamma Knife radiosurgery in acromegaly: the Later-Ac study.

INTRODUCTION: Persistent growth hormone hypersecretion can be observed in roughly 50% of patients operated for somatotroph adenomas, requiring additional treatments. Despite its proven antisecretory efficacy, the use of Gamma Knife radiosurgery (GK) is limited probably due to the lack of data on long-term side effects, including potential cognitive consequences. METHODS: The LATe Effects of Radiosurgery in Acromegaly study was a cross-sectional exposed/unexposed non-randomized study. The primary objective was to determine the long-term neurocognitive effects of GK focusing on memory, executive functions, and calculation ability. Exposed patients had been treated by GK for acromegaly at least 5 years before inclusion. Unexposed patients (paired for age) had to be cured or controlled at last follow-up without any radiation technique. Patients of both groups were cured or controlled at the last follow-up. RESULTS: Sixty-four patients were evaluated (27 exposed and 37 unexposed). Mean follow-up after GK was 13 ± 6 years (including 24 patients followed for at least 10 years). While up to 23.8% of the patients of the whole cohort presented at least one abnormal cognitive test, we did not observe any significant difference in neurocognitive function between both groups. During the follow-up, 11 patients presented at least one new pituitary deficiency (P = 0.009 for thyroid-stimulating hormone deficiency with a higher rate in exposed patients), two presented a stroke (1 in each group), and one presented a meningioma (12 years after GK). CONCLUSIONS: While GK exposes patients to a well-known risk of pituitary deficiency, it does not seem to induce long-term cognitive consequences in patients treated for acromegaly.

Intensity-modulated Radiotherapy for Pituitary Somatotroph Adenomas.

OBJECTIVE: To summarize our experience in the treatment of pituitary somatotroph adenomas by fractionated intensity-modulated radiotherapy (IMRT), describe the treatment outcomes, and determine predictors. METHODS AND MATERIALS: Patients with pituitary somatotroph adenoma treated by IMRT in our institution from August 2009 to January 2019 were reviewed. A total of 113 patients (37 male) were included in this study. The median age was 33 years (range 12-67 years). A total of 112 patients had not achieved complete remission after surgery, and 1 patient was treated by radiotherapy (RT) alone because she refused to surgery. The median growth hormone level was 8.6 ng/mL (range 2-186 ng/mL) and the median insulin-like growth factor (IGF)-1 level was 732 ng/mL (range 314-1485 ng/mL) pre-RT. The radiation doses to clinical target volume were usually 50-56 Gy in 25 to 30 fractions and to gross tumor volume were 60.2 Gy in 28 fractions while simultaneous integrated boost-IMRT used. After RT, the patients were followed up with endocrine testing every 6 to 12 months and magnetic resonance imaging annually. Endocrine complete remission was defined as a normal sex- and age-adjusted IGF-1 level without any pituitary suppressive medications. The outcomes including endocrine remission and new hypopituitarism after RT were recorded. The median follow-up time was 36 months (range 6-105.5 months). RESULTS: The endocrine complete remission rates of IGF-1 at 1, 2, 3, and 5 years were 6%, 22.8%, 48.6%, and 74.3%, respectively. The median time to complete remission was 36.2 ±â€…3.8 months. The tumor control rate was 99% during the follow-up. The overall incidence of RT-induced hypopituitarism was 28.3% at the last follow-up. Univariate and multivariate analysis demonstrated that tumor sizes before RT, pre-RT IGF-1 level, and age significant predicted the endocrine remission. CONCLUSIONS: IMRT is a highly effective treatment for pituitary somatotroph adenoma. Endocrine remission rate, tumor control rate, the median time to remission and hypopituitarism incidence are similar to stereotactic radiosurgery. Age and IGF-1 level before RT were significant predictive factors in endocrine remission.

The Impact of Insulin-Like Growth Factor Index and Biologically Effective Dose on Outcomes After Stereotactic Radiosurgery for Acromegaly: Cohort Study.

BACKGROUND: Stereotactic radiosurgery (SRS) is a safe and effective treatment for acromegaly. OBJECTIVE: To improve understanding of clinical and dosimetric factors predicting biochemical remission. METHODS: A single-institution cohort study of nonsyndromic, radiation-naïve patients with growth hormone-producing pituitary adenomas (GHA) having single-fraction SRS between 1990 and 2017. Exclusions were treatment with pituitary suppressive medications at the time of SRS, or <24 mo of follow-up. The primary outcome was biochemical remission-defined as normalization of insulin-like growth factor-1 index (IGF-1i) off suppression. Biochemical remission was assessed using Cox proportional hazards. Prior studies reporting IGF-1i were assessed via systematic literature review and meta-analysis using random-effect modeling. RESULTS: A total of 102 patients met study criteria. Of these, 46 patients (45%) were female. The median age was 49 yr (interquartile range [IQR] = 37-59), and the median follow-up was 63 mo (IQR = 29-100). The median pre-SRS IGF-1i was 1.66 (IQR = 1.37-3.22). The median margin dose was 25 Gy (IQR = 21-25); the median estimated biologically effective dose (BED) was 169.49 Gy (IQR = 124.95-196.00). Biochemical remission was achieved in 58 patients (57%), whereas 22 patients (22%) had medication-controlled disease. Pre-SRS IGF-1i ≥ 2.25 was the strongest predictor of treatment failure, with an unadjusted hazard ratio (HR) of 0.51 (95% CI = 0.26-0.91, P = .02). Number of isocenters, margin dose, and BED predicted remission on univariate analysis, but after adjusting for sex and baseline IGF-1i, only BED remained significant-and was independently associated with outcome in continuous (HR = 1.01, 95% CI = 1.00-1.01, P = .02) and binary models (HR = 2.27, 95% CI = 1.39-5.22, P = .002). A total of 24 patients (29%) developed new post-SRS hypopituitarism. Pooled HR for biochemical remission given subthreshold IGF-1i was 2.25 (95% CI = 1.33-3.16, P < .0001). CONCLUSION: IGF-1i is a reliable predictor of biochemical remission after SRS. BED appears to predict biochemical outcome more reliably than radiation dose, but confirmatory study is needed.

Fractionated radiotherapy and radiosurgery in acromegaly: analysis of 352 patients from the German Acromegaly Registry.

BACKGROUND: If biochemical control of acromegaly is not achieved by operation and medication, radiotherapy may be indicated. OBJECTIVE: To describe fractionated radiotherapy (FRT) and stereotactic radiosurgery (SRS) regarding excess of IGF-1 and pituitary function. DESIGN AND METHODS: A retrospective analysis of 352 patients (4126 patient-years) from the German Acromegaly Registry was performed. Follow-up was 1.0-45.1 years after radiotherapy. Therapeutic success was defined by low or normal IGF-1 according to center-specific reference ranges without (= remission) or on (= controlled disease) suppressive medication. RESULTS: Time between radiotherapy and last follow-up was 13.0 ± 8.2 years for FRT (n = 233) and 8.9 ± 5.0 years for SRS (n = 119, P < 0.001). Median (IQR) basal growth hormone before radiotherapy was 6.3 (2.9-16.2) ng/mL for FRT and 3.5 (1.8-6.9) ng/mL for SRS (P < 0.001). Mean time in uncontrolled state was 3.0 years after FRT and 2.1 years after SRS (95% CI for the difference is 0.1 to 1.6 years, P = 0.021). The 10-year calculated remission rate was 48% for FRT and 52% for SRS (95% CI for the difference is -18 to 26% age points, P = 0.74) and the respective controlled disease rate was 23 and 26%. The odds ratio for adrenocorticotropic or thyreotropic insufficiency was 0.54 (95% CI: 0.30-1.00, P = 0.049) in SRS compared to FRT patients. CONCLUSION: Both after FRT and SRS about 75% of patients with acromegaly are in remission or controlled after 10 years. A slightly faster achievement of target values was observed after SRS. The rate of pituitary insufficiency in FRT patients is significantly higher.

Internal carotid artery aneurysms diagnosed after stereotactic radiosurgery for a growth hormone-secreting pituitary adenoma: a case report and literature review.

Radiation therapy is associated with the subsequent development of cerebral aneurysms; however, stereotactic radiosurgery (SRS)-associated aneurysm cases have not been well documented, with only 18 cases reported to date. We present a case of intracranial aneurysms with the rupture occurring 20 years after SRS for a growth hormone-producing pituitary adenoma. This is the first report of aneurysms diagnosed following transsphenoidal surgery and SRS for pituitary adenoma. We believe that the aneurysm reported here is a consequence of the SRS treatment, and thus this may be a very rare long-term complication following radiation treatments.

Radiotherapy and pasireotide treatment of a growth hormone producing pituitary tumor in a diabetic dog.

An 8-year-old castrated male border terrier dog was diagnosed with acromegaly resulting from a growth hormone secreting pituitary tumor. Sixteen daily fractions of radiation therapy were delivered followed, approximately 1 year later, by administration of pasireotide. The aforementioned treatment was considered effective and should be further evaluated in similar cases.

Radiothérapie et traitement au pasiréotide pour une tumeur pituitaire produisant une hormone de croissance chez un chien diabétique. Un chien Terrier-Border castré âgé de 8 ans a été diagnostiqué avec de l'acromégalie découlant d'une tumeur pituitaire secrétant une hormone de croissance. Seize fractions quotidiennes de radiothérapie ont été administrées et ont été suivies, environ un an plus tard, de l'administration du pasiréotide. Le traitement précédemment mentionné a été considéré efficace et devrait être étudié de plus près dans des cas similaires.(Traduit par Isabelle Vallières).

Stereotactic radiation therapy for the treatment of functional pituitary adenomas associated with feline acromegaly.

BACKGROUND: Conventional fractionated radiotherapy has been shown to be partially effective for management of pituitary tumors in cats that cause acromegaly and diabetes mellitus (DM), but, the efficacy and safety of stereotactic radiation therapy (SRT) as a treatment for acromegalic cats has not been described. HYPOTHESIS: Stereotactic radiation therapy is an effective and safe treatment for controlling acromegaly associated with pituitary adenomas in cats. Additionally, SRT-treated acromegalic cats with DM will experience a decrease in insulin requirements after radiation therapy. ANIMALS: Fifty-three client-owned cats referred to Colorado State University for SRT to treat pituitary tumors causing poorly controlled DM secondary to acromegaly. METHODS: Retrospective study of cats treated for acromegaly with SRT between 2008 and 2016 at Colorado State University. Diagnosis of acromegaly was based on history, physical examination, laboratory results, and cross-sectional imaging of the pituitary. Signalment, radiation protocol, insulin requirements over time, adverse effects, and survival were recorded. RESULTS: Median survival time was 1072 days. Of the 41 cats for which insulin dosage information was available, 95% (39/41) experienced a decrease in required insulin dose, with 32% (13/41) achieving diabetic remission. Remission was permanent in 62% (8/13) and temporary in 38% (5/13) cats. Median duration to lowest insulin dose was 9.5 months. Of the treated cats, 14% developed hypothyroidism and required supplementation after SRT. CONCLUSIONS: Stereotactic radiation therapy is safe and effective for treating cats with acromegaly. Cats treated with SRT have improved survival time and control of their DM when compared to previously reported patients treated with non-SRT.

Postoperative Gamma Knife Radiosurgery for Cavernous Sinus-Invading Growth Hormone-Secreting Pituitary Adenomas.

OBJECTIVE: We aimed to determine the long-term effects of Gamma knife radiosurgery (GKS) on remnants in the cavernous sinus (CS) after transsphenoidal surgery (TSS) for acromegaly and to identify its possible adverse effects. METHODS: Thirty patients who had remnant tumors only inside the CS after TSS and who consequently underwent GKS were included. They were followed for a median period of 47 months after GKS with regular hormonal and radiologic examinations. RESULTS: The mean tumor volume and margin dose irradiated by GKS was 3.7 cm3 and 26.2 Gy, respectively. Radiologic tumor control was identified in all patients, and no tumor regrowth or recurrent tumors were identified. For 14 patients who achieved endocrinologic remission, the median duration from GKS until remission was 35 months. The actuarial rates of remission at 2, 5, and 10 years were 7.1%, 43.6%, and 65.6%, respectively. The degree of decrease in the nadir GH level in the OGTT at 6 months after GKS was a statistically significant predictor of remission. Newly developed hypopituitarism frequently developed in a time-dependent manner. Radiation necrosis developed in 4 patients with relatively large remnant volumes. CONCLUSIONS: GKS is an effective adjuvant treatment option for remnant tumors inside the CS after TSS. Maximal surgical resection, leaving minimal volume of remnants only inside the CS, allows the safe and sufficient delivery of a radiation dose to tumors, thereby increasing the possibility of remission. However, the risk of new hypopituitarism and radiation necrosis should be considered when tumors inside the CS are treated with GKS.

Bevacizumab for Radiation Induced Optic Neuritis Among Aggressive Residual/Recurrent Suprasellar Tumors: More Than a Mere Antineoplastic Effect.

BACKGROUND: Angiogenesis and vascular endothelial growth factor (VEGF) have recently been implicated in animal and clinical models of radiation-induced optic nerve, retinal, and brain necrosis. Although there are isolated case reports of anti-VEGF therapy with bevacizumab for management of radiation-induced brain necrosis, there are little data defining its role in radiation-induced optic nerve damage. PATIENTS AND METHODS: This study included patients with a sellar-suprasellar tumor who underwent intensity-modulated or Gamma Knife radiotherapy and developed radiation-induced optic neuritis (RION) refractory to 3 weeks of glucocorticoid therapy who received bevacizumab 5 mg/kg intravenously as initial dose, followed by subsequent doses of 10 mg/kg. RESULTS: Here we report 3 patients with sellar-suprasellar lesions undergoing conventional radiation therapy (2 cases) or Gamma Knife surgery (1 case) who had benefitted from anti-VEGF therapy following radiation-induced optic nerve damage. CONCLUSIONS: Early bevacizumab therapy in steroid-refractory RION shows gratifying results.

Management of aggressive growth hormone secreting pituitary adenomas.

Aggressive GH-secreting pituitary adenomas (GHPAs) represent an important clinical problem in patients with acromegaly. Surgical therapy, although often the mainstay of treatment for GHPAs, is less effective in aggressive GHPAs due to their invasive and destructive growth patterns, and their proclivity for infrasellar invasion. Medical therapies for GHPAs, including somatostatin analogues and GH receptor antagonists, are becoming increasingly important adjuncts to surgical intervention. Stereotactic radiosurgery serves as an important fallback therapy for tumors that cannot be cured with surgery and medications. Data suggests that patients with aggressive and refractory GHPAs are best treated at dedicated tertiary pituitary centers with multidisciplinary teams of neuroendocrinologists, neurosurgeons, radiation oncologists and other specialists who routinely provide advanced care to GHPA patients. Future research will help clarify the defining features of "aggressive" and "atypical" PAs, likely based on tumor behavior, preoperative imaging characteristics, histopathological characteristics, and molecular markers.

Long-term results of hypofractionated stereotactic radiotherapy with CyberKnife for growth hormone-secreting pituitary adenoma: evaluation by the Cortina consensus.

The aim of the present study was to evaluate the safety and feasibility of hypofractionated stereotactic radiotherapy (SRT) with CyberKnife for growth hormone-secreting pituitary adenoma (GH-PA). Fifty-two patients with GH-PA were treated with hypofractionated SRT between September 2001 and October 2012. Eight patients had clinically silent GH-PA and 44 were symptomatic. Only 1 patient was inoperable. The other patients had recurrent or postoperative residual tumors on MRI. All patients had received pharmacotherapy prior to SRT with a somatostatin analog, dopamine agonist, and/or GH receptor antagonist. The marginal doses were 17.4-26.8 Gy for the 3-fraction schedule and 20.0-32.0 Gy for the 5-fraction schedule. Endocrinological remission was assessed by the Cortina consensus criteria 2010 (random GH <1 ng/ml or nadir GH after an oral glucose tolerance test <0.4 ng/ml and normalization of age- and sex-adjusted insulin-like growth factor-1). The median follow-up period was 60 months (range 27-137). The 5-year overall survival, local control, and disease-free survival rates were 100, 100, and 96 %, respectively. Nine patients (5 clinically silent and 4 symptomatic patients) satisfied the Cortina criteria without receiving further pharmacotherapy, whereas the remaining 43 patients did not. No post-SRT grade 2 or higher visual disorder occurred. Symptomatic post-SRT hypopituitarism was observed in 1 patient. CyberKnife hypofractionated SRT is safe and effective when judged by imaging findings for GH-PA. However, it may be difficult to satisfy the Cortina consensus criteria in most symptomatic patients with SRT alone. Further investigations of optimal treatments are warranted.

Growth hormone-secreting macroadenoma of the pituitary gland successfully treated with the radiolabeled somatostatin analog (90)Y-DOTATATE: case report.

Pituitary tumors causing acromegaly are usually macroadenomas at the time of diagnosis, and they can grow aggressively, infiltrating surrounding tissues. Difficulty in achieving complete tumor removal at surgery can lead toward a strong tendency for recurrence, making it necessary to consider a means of treatment other than those currently used such as somatostatin analogs (SSAs), growth hormone (GH) receptor antagonist, surgical removal, and radiotherapy. The purpose of this paper is to describe a patient diagnosed with an aggressive, giant GH-secreting tumor refractory to medical therapy but ultimately treated with the radiolabeled somatostatin analog (90)Y-DOTATATE. A 26-year-old male with an invasive macroadenoma of the pituitary gland (5.6 × 2.5 × 3.6 cm) and biochemically confirmed acromegaly underwent 2 partial tumor resections: the first used the transsphenoidal approach and the second used the transcranial method. The patient received SSAs pre- and postoperatively. Because of the progression in pituitary tumor size, he underwent classic irradiation of the tumor (50 Gy). One and a half years later, the patient presented with clinically and biochemically active disease, and the tumor size was still 52 mm in diameter (height). Two neurosurgeons disqualified him from further surgical procedures. After confirming the presence of somatostatin receptors in the pituitary tumor by using (68)Ga-DOTATATE PET/CT, we treated the patient 4 times with an SSA bound with (90)Y-DOTATATE. After this treatment, the patient attained partial biochemical remission and a reduction in the tumor mass for the first time. Treatment with an SSA bound with (90)Y-DOTATATE may be a promising option for some aggressive GH-secreting pituitary adenomas when other methods have failed.

Long-term Outcome After Fractionated Radiotherapy for Pituitary Adenoma: The Curse of the Secretory Tumor.

OBJECTIVES: To determine the influence of secretory status on long-term outcome after fractionated radiotherapy (RT) for gross residual pituitary adenoma. MATERIALS AND METHODS: This is a retrospective study of 116 consecutively treated patients who met the following inclusion criteria: tissue diagnosis of pituitary adenoma, visible tumor at the time of RT, treatment with fractionated RT, and imaging follow-up of ≥2 years. Hypersecretion of growth hormone, adrenocorticotrophic hormone, prolactin, or thyroid-stimulating hormone was documented in 30 patients (26%). The RT dose in most (78%) patients was 45 Gy at 1.8 Gy per fraction. The major outcome endpoint is clinical and biochemical control, meaning no growth on follow-up scans and normalization of hypersecretion, if present before RT. RESULTS: Long-term tumor control was outstanding for nonsecretory tumors: 96% at 10 years. There was a major drop in the control rate of secretory tumors: 10-year clinical and biochemical control was 62% (P<0.0001 vs. 96%). Multivariate analysis confirmed secretory status as the only independent prognostic factor (variables analyzed were sex, age, tumor size, RT dose, and secretory status). CONCLUSIONS: Secretory pituitary adenomas have a worse prognosis than nonsecretory tumors after 45 to 50 Gy of conventionally fractionated RT. As a result of this finding, our plan is to increase the intensity of RT in secretory tumors, but our data did not evaluate this approach. The treatment guidelines that we currently use in pituitary adenoma are as follows. Radiosurgery (20 to 30 Gy) is our first-choice treatment of a secretory tumor that cannot be completely resected. When treating gross residual pituitary adenoma with fractionated RT, we use the following dose schedules: Nonsecretory: 45 Gy at 1.8 Gy/fraction, once-daily fractionation. Secretory: 54 Gy at 1.8 Gy/fraction once daily or 55.2 Gy at 1.2 Gy/fraction with twice-daily treatment.

Long-term results of fractionated stereotactic radiotherapy as third-line treatment in acromegaly.

The treatment of acromegaly is based on surgery, drugs, and radiotherapy as a third-line option. Fractionated stereotactic radiotherapy (FSRT) is a new technique with a need for long-term evaluation. The purpose of the study was to evaluate long-term results of FSRT in acromegaly. Overall, 34 patients [sex ratio 1.12, age 45 (5-65) years] with a pituitary adenoma of 24.5 (9-76) mm including 20 invasive tumors were treated by radiotherapy in fractionated stereotactic conditions delivering 50 gy in 27 sessions. Baseline growth hormone (GH) and IGF1 levels were 18 (±14.5) and 632.6 (±339) µg/L, respectively. Indications of FSRT were failure of surgery and drug treatments (n = 30) or contraindication/refusal of surgery (n = 4). Hormonal control was defined by normal age- and sex-adjusted IGF1. Remission was defined by hormonal control after withdrawal of drugs for a minimum of three consecutive months. Data were analyzed in SPSS software with a significance level at p < 0.05. After a mean follow-up of 152 months, hormonal control was achieved in 33 patients (97 %) with withdrawal of drugs in 13 patients (38.2 %) without any recurrence. Factors found to be significantly associated to remission in a multivariate Cox regression were lower baseline hormone levels (GH and IGF1) and smaller tumor size. Tumor control was achieved in all patients. Acquired hypopituitarism after radiotherapy was the main side effect reported with a rate of 39 %. FSRT seems to be an effective and well tolerated third-line treatment of acromegaly, particularly adapted to macro adenomas treatment.

Giant GH-secreting pituitary adenomas: management of rare and aggressive pituitary tumors.

OBJECTIVES: Patients with acromegaly usually harbor macroadenomas measuring between 10 and 30 mm in maximal diameter. Giant (adenoma size ≥40 mm) GH-secreting pituitary tumors are rarely encountered and the aim of this study is to analyze different methods for managing them. DESIGN AND METHODS: We have identified 34 patients (15 men and 19 females) with giant adenomas among 762 subjects (4.5%) with acromegaly in our records, and characterized their clinical characteristics and response to treatment. RESULTS: Mean age at diagnosis was 34.9±12.5 years (range, 16-67 years). Mean adenoma size was 49.4±9.4 mm (range, 40-80 mm); 30 adenomas showed cavernous sinus invasion and 32 had suprasellar extension. Twenty-nine (85%) patients had visual field defects. Mean baseline IGF1 was 3.4±1.8×ULN. All patients except one underwent pituitary surgery (one to three procedures), but none achieved hormonal remission following first surgery. Among the 28 subjects with visual disturbances, 14 recovered post-operatively and 13 improved. Treatment with somatostatin analogs was given to all patients after surgical failure. Six achieved remission, nine others were partially controlled (IGF1<1.5×ULN; 3/9 when combined with cabergoline), and 17 did not respond (two were lost). Nine patients were treated with pegvisomant, alone (n=4) or in combination with somatostatin analogs (n=5); five are in remission and two are partially controlled. Pasireotide-LAR achieved hormonal remission in one of the six patients. Currently, after a mean follow-up period of 8.9 years, 17 patients are in biochemical remission, eight are partially controlled, and seven are uncontrolled (two were lost to follow-up). CONCLUSIONS: Giant GH-secreting adenomas are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission.

Peptide receptor radionuclide therapy for aggressive atypical pituitary adenoma/carcinoma: variable clinical response in preliminary evaluation.

PURPOSE: There are limited treatment options for progressive atypical pituitary adenomas and carcinomas. Peptide receptor radionuclide therapy that targets somatostatin receptors has recently been proposed as a potential treatment option. The theoretical rationale for efficacy is elegant but evaluation of outcomes in the first patients treated for this indication is required to assess whether further study is warranted. METHODS: We performed a case review of the three pituitary patients we have treated with (177)Lutetium DOTATATE in our institution (two atypical adenomas, one carcinoma) and dosimetric analysis of the radiation uptake in one patient. RESULTS: Treatment was well tolerated. One patient with slowly progressive pituitary carcinoma has stable disease 40 months after completing the planned 4 cycles of treatment. Two patients with rapidly progressive atypical adenomas terminated treatment early due to continued disease progression. Dosimetric evaluation revealed inhomogenous uptake across the tumour (1.3-11.9 Gy with one cycle). CONCLUSION: We have found mixed results in our first 3 patients with stable disease achieved only in the patient with the more slowly progressive tumour. As only a limited number of centres offer Peptide receptor radionuclide therapy, a formal study with prospective data collection may be feasible and if carried out should include dosimetric evaluation of absorbed dose.

[Abnormalities of carbohydrate metabolism in acromegaly]. / Alteraciones del metabolismo hidrocarbonado en la acromegalia.

BACKGROUND AND OBJECTIVE: Carbohydrate metabolism (CHM) is impaired in over 50% of acromegalic patients. Natural history of acromegaly and treatment modalities may impact in a different way on CHM. We assessed CHM alterations in acromegaly and their relationship with clinical features and treatment options. PATIENTS AND METHOD: Retrospective study with 55 patients with acromegaly. Age, sex, body mass index (BMI), tumor size, insulin growth factor type 1 (IGF-1) levels and the presence of impaired fasting glucose (IFG) or diabetes mellitus (DM) were analyzed before and after surgery or medical treatment. RESULTS: There were 30 men and 25 women. Mean age was 50 ± 17 years and mean BMI was 27.9 ± 3.8 Kg/m(2). Impaired CHM was found in 50.9% (n = 28) (DM in 27% and IFG in 24%). In diabetic patients, we found no differences in age, sex, BMI and IGF-1 levels between IFG/DM and patients without CHM impairment. However, IFG/DM patients had macroadenomas more commonly. In diabetic patients, glycosylated hemoglobin (HbA1c) decreased after surgery from 7.6 to 6.7% and after somatostatin analogues from 7.1 to 6.6%; in patients on pegvisomant we observed a significant reduction of HbA1c: from 9.8 to 5.6% (P < .005). Furthermore, only in the pegvisomant group, insulin and/or oral agents had to be lowered. CONCLUSIONS: Up to 50% of patients with active acromegaly have CHM impairment which correlates with tumor size. Only pegvisomant is associated with significant improvement in glycemic control and a reduction in hypoglycemic treatment.

Acromegaly: a single centre's experience of stereotactic radiosurgery and radiotherapy for growth hormone secreting pituitary tumours with the linear accelerator.

Primary treatment for growth-hormone secreting pituitary adenomas usually involves surgery, with treatment options for recurrent and persistent disease including repeat surgery, medication and radiation therapy. The majority of previously published series for radiation therapy in acromegaly in the past 20 years have been based on Gamma-Knife (Elekta, Stockholm, Sweden) surgery. To our knowledge, we present the largest series of linear accelerator-based treatment for this disease, with a review of 121 patients treated at our institution; since 1990, 86 patients underwent stereotactic radiosurgery (SRS), 10 patients underwent fractionated stereotactic radiotherapy (FSRT), and for the purposes of comparison we also reviewed 25 patients who underwent conventional radiotherapy prior to 1990. Tumour volume control in all three groups was excellent and consistent with previously reported literature - only three of 86 (4%) patients undergoing SRS had a documented increase in tumour size, and none of the patients undergoing FSRT had a documented increase in size following a median follow-up of 5.5 and 5.1 years for SRS and FSRT, respectively. Target growth hormone levels of <2.5 ng/mL were met by 12 of 86 (14%) of the SRS group, and by two of 10 (20%) in the FSRT group. Target insulin-like growth factor-1 levels of age and sex matched controls were achieved in 16 of 86 patients (18.6%) post-SRS and five of 10 patients (50%) post-FSRT. New hormonal deficits requiring replacement therapy were identified in 17 of 86 (19.8%) patients post-SRS which is consistent with previously published radiosurgical series. Identified non-hormonal morbidity was low (<5%).

[Optimization of the medical treatment for acromegaly]. / Optimización del tratamiento médico de la acromegalia.

Somatostatin analogues are the cornerstone in the first-line and adjuvant (postsurgical) therapy in patients with acromegaly. These drugs highly effectively decrease serum concentrations of growth hormone (GH) and insulin-like growth factor type I (IGF-I), as well as pituitary adenoma size. However, in approximately one third of patients response to these agents is unsatisfactory. The optimization of the medical therapy for acromegaly can be accomplished by modifying the dose or the interval of administration of somatostatin analogues or by combining other pharmacological agents. Increasing the dose or frequency of administration is followed by an additional decrease in GH and IGF-I levels in a significant percentage of patients. These changes are not accompanied by a relevant increase in the number or severity of adverse events. Combined treatment with somatostatin analogues and pegvisomant has been shown to significantly reduce serum IGF-I levels in patients with inadequate control of disease activity. The addition of cabergoline to somatostatin analogue therapy is accompanied by a further decrease in IGF-I levels that is independent of serum prolactin concentrations.