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Objective: Inoperable and metastatic pheochromocytomas and paragangliomas (PPGLs) present a therapeutic challenge with current treatment options being limited to radiolabelled meta-iodo-benzyl-guanidine (MIBG) and systemic chemotherapy. Peptide receptor radionuclide therapy (PRRT) seems to be a promising option for these patients with few studies reporting favourable response. This systematic review was conducted to evaluate the efficacy and safety of PRRT in patients with advanced PPGLs., Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in PubMed, Scopus and Embase were made using relevant keywords and articles up to May 2019 were included. Data on efficacy and toxicity were extracted from the individual articles, and pooled estimates were generated using meta-analysis., Results: Twelve articles consisting of 201 patients with advanced PPGLs were included. Overall, treatment with PRRT achieved an objective response rate of 25% (95% CI: 19%-32%) and a disease control rate of 84% (95% CI: 77%-89%). Clinical and biochemical responses were seen in 61% and 64% of the patients, respectively. Among the PRRTs, similar tumour response rates were noted for 90 Y-yttrium- and 177 Lu-lutetium-based agents. Treatment-related adverse effects were minimal with grade 3/4 neutropenia, thrombocytopenia, lymphopenia and nephrotoxicity observed in 3%, 9%, 11% and 4% of the patients, respectively. Treatment discontinuation was noted in five out of 102 patients., Conclusions: Peptide receptor radionuclide therapy is a safe and efficacious treatment option for advanced PPGLs and may be considered a viable alternative to chemotherapy and I- 131 MIBG., (© 2019 John Wiley & Sons Ltd.)

Acromegaly is a chronic disorder usually diagnosed late in the disease evolution. Such delayed diagnosis, together with the inability to achieve the treatment goals of normalizing biochemical disease markers and controlling tumour mass may result in substantial morbidity and mortality. Somatostatin analogues (SSA) are accepted as first-line medical therapy or as second-line therapy in patients undergoing unsuccessful surgery and are considered a cornerstone in the treatment of acromegaly. However, because a high percentage of patients experience SSA medical treatment failure, the identification of biomarkers associated with a successful or unsuccessful response to all classes of medical therapy would help in the choice of treatment and potentially allow for a quicker normalization of biochemical parameters. The current treatment algorithms for acromegaly are based upon a "trial-and-error" approach with additional treatment options provided when disease is not controlled. In many other diseases, therapeutic algorithms have been evolving towards personalized treatment with the medication that best matches individual disease characteristics, using biomarkers that identify therapeutic response. Additionally, a personalized approach to complementary treatment of comorbidities present in the acromegalic patient is also required. This review will discuss the development of a potential treatment algorithm for acromegaly addressing the biochemical control of the disease as well of its associated comorbidities, under a personalized approach based upon markers of prognostic and predictive significance, such as tumour size, MRI adenoma signal, GH value after acute octreotide test, granular adenoma pattern, Ki-67, somatostatin receptor phenotype, aryl hydrocarbon-interacting protein expression, gsp mutations, RAF kinase activity, E-cadherin and beta-arrestin-1., (© 2015 John Wiley & Sons Ltd.)

Objective: Impaired physical performance is a disturbing complication of acromegaly. We aimed to evaluate the role of regular exercise in amelioration of the impaired physical performance in acromegaly., Methods: Patients with acromegaly were divided into two groups according to their participation in a prescheduled programme of exercise. Participants in the study group were exercised 3 days a week for 3 consecutive months. Exercise tolerance was evaluated by maximal oxygen consumption (VO2 max) and time (T) taken to complete the Bruce protocol, muscle flexibility by the sit and reach test (SRT) and muscle strength by the hand grip strength test (HGST). Concomitantly, anthropometric assessment was performed using body mass index (BMI), waist-to-hip ratio (WHR), skinfold measurements from 8 points, percentage body fat (PBF), fat mass (FM) and lean body mass (LBM)., Results: After 3 months of exercise, VO2 max and T were higher in cases that exercised than in cases that did not (P = 0.004 and P = 0.001). Over 3 months, within the exercise group, VO2 max and T of the Bruce protocol increased (P = 0.003 and P = 0.004) and heart rate during warming decreased (P = 0.04). SRT increased within the exercise group after 3 months (P = 0.004). HGSRT did not change significantly (right P = 0.06 and left P = 0.2). The sum of skinfolds, BMI, WHR and LBM remained stable over the study period (P = 0.1, P = 0.08, P = 0.3 and P = 0.09). PBF decreased slightly and FM decreased significantly over 3 months (P = 0.05 and P = 0.03)., Conclusion: Even short-term exercise may improve impaired physical performance, muscle activity and disturbed body fat composition in acromegaly., (© 2014 John Wiley & Sons Ltd.)

Current guidelines do not recommend the routine use of somatostatin analogue pretreatment prior to surgery in patients with growth hormone-secreting pituitary tumours. In theory, presurgical use of somatostatin analogues should improve metabolic control and reduce soft tissue swelling, leading to improved anaesthetic outcomes. Shrinkage of tumours prior to surgery might also improve surgical remission rates. Hence, this article addresses the question: Should all patients with acromegaly receive a somatostatin analogue prior to surgery? Clinical trials published before December 2013 were reviewed, although literature in this area remains relatively deficient. We conclude: (i) On the basis of limited data available, somatostatin analogue pretreatment does not improve anaesthetic or immediate postoperative outcomes (i.e. hospital stay, rates of surgical complications and postoperative pituitary dysfunction). (ii) Somatostatin analogues should be considered in all patients with growth hormone-secreting macroadenomas, including invasive macroadenomas, when the overall surgical remission rate for macroadenomas at the treating centre is below 50%. Four recent RCTs have demonstrated increased rates of surgical remission using such an approach. (iii) When deemed appropriate, patients should be treated with somatostatin analogues for at least 3 months before surgery; there is currently no evidence that treatment beyond 6 months provides any additional benefit. Patients with minimally invasive macroadenomas are those most likely to benefit in terms of improved surgical remission., (© 2014 John Wiley & Sons Ltd.)

Background: Macroadenomas causing acromegaly are cured surgically in only around 50% of patients. Primary medical treatment with somatostatin analogues has been suggested to be a means of treating patients with a potentially poor surgical outcome. Previous retrospective studies have also suggested that surgical debulking of pituitary tumours causing acromegaly improves control by somatostatin analogues. No prospective study using lanreotide has been carried out thus far to assess whether this is the case., Objective: We carried out a prospective study to assess whether surgical debulking of pituitary macroadenomas causing acromegaly improved the subsequent control of acromegaly by the somatostatin analogue lanreotide., Patients and Methods: We treated 26 consecutive patients [10 males and 16 females--median age 53.5 years (range 22-70)] with macroadenoma causing acromegaly unselected for somatostatin response for 16 weeks with lanreotide, maximizing GH and IGF-I suppression, if necessary, by incremental dosing. Surgical resection was carried out and the patients were re-assessed off medical treatment at 16 weeks following surgery. Those with nadir GH > 2 mU/l in the oral glucose tolerance test (OGTT) and a mean GH in the GH day curve (GHDC) > 5 mU/l were subsequently restarted on lanreotide and the responses were assessed at the same time points as during the preoperative lanreotide treatment., Results: GH values fell on lanreotide treatment and prior to surgery they were considered 'safe' (mean GH in GHDC < 5 mU/l) in eight patients (30.7%). After surgery, they were 'safe' in 18 patients (69.2%). The figures for normal IGF-I were 11 (42.3%) before surgery and 23 (88.5%) after surgery. After surgery, six patients had nadir GH > 2 mU/l in the OGTT and 'unsafe' GH levels (mean GH in GHDC > 5 mU/l); on re-exposure to lanreotide, GH levels fell in all patients and at the end of 16 weeks postsurgery, they were 'safe' in three of them (50%) (P < 0.05). Pituitary tumour volume was also assessed prospectively, preoperatively on lanreotide and showed a mean fall of 33.1%. Eighty-three percent of patients had > 20% shrinkage., Conclusions: In this first prospective study using lanreotide, surgical debulking of pituitary tumours causing acromegaly improved subsequent postoperative control by the somatostatin analogue lanreotide. Surgery should, therefore, be considered in patients with macroadenoma causing acromegaly, even if there is little prospect of surgical cure. Lanreotide causes significant pituitary tumour shrinkage in the majority of patients.

Background: Somatostatin analogues have been used successfully for the treatment of acromegaly but no randomized studies have compared the effects of lanreotide Autogel (LAN) and octreotide acetate long-acting repeatable (OCT)., Objective: To compare the effect of LAN and OCT for the treatment of acromegaly in a randomized study design., Material and Methods: Twelve acromegalic patients were included and 10 patients completed treatment with LAN or OCT for 6 months and were then switched to the opposite treatment modality for 6 months without a washout period in a randomized crossover design. GH and IGF-I profiles, clinical and biochemical evaluations were performed at 0, 4, 6, 10 and 12 months., Results: After 6 months of treatment, five patients had GH levels < 0.38 microg/l during both therapies. The remaining patients had GH levels > 0.38 microg/l during both LAN and OCT treatment. Four patients had normalized IGF-I levels during both treatment regimes. Two patients on LAN and one on OCT had normalized IGF-I levels during one treatment and not during the other. In three patients, IGF-I levels were elevated during both therapies. Four patients developed palpable nodules, two patients on LAN and two patients on OCT. Gastrointestinal complaints were seen in three patients during both therapies, in three patients only during LAN, and in one patient only during OCT. Two patients were withdrawn from the study because of serious adverse effects during LAN. After the study period, four patients preferred LAN and six patients preferred OCT treatment., Conclusion: The effects of LAN and OCT therapy on GH and IGF-I levels were comparable, but 3/10 patients had different treatment efficacies and 6/10 had different side-effect profiles during the LAN and OCT treatment. These results indicate that a change from LAN to OCT or vice versa may be beneficial in some patients with treatment failure or side-effects.

Objective: Lanreotide Autogel 120 mg (ATG120; Ipsen S.p.A, Milan, Italy) is a high-dose, sustained-release aqueous gel formulation, supplied in a prefilled syringe and given by deep subcutaneous injection. The aim of this study was to compare efficacy and tolerability of ATG120 given every 4-8 weeks with those of octreotide LAR (o-LAR) given every 4 weeks. DESIGN PATIENTS AND INTERVENTION: A phase III multicentre Italian open clinical study of 23 acromegalic patients (15 female, 8 male). All patients had received o-LAR for 6-18 months and, after 3 months wash out, ATG120 was given every 6 weeks for a total of four injections (Period 1). Then the interval between ATG120 injections was adjusted according to three different schemes: every 4, 6 or 8 weeks depending on GH levels (GH > 2.5 microg/l; 1 < GH

Context: The role of somatostatin analogues (SSTa) in the treatment of acromegaly., Objective: To evaluate the antihormonal and antitumour efficacy of long-term (up to 18 years) primary treatment with SSTa in patients with GH-secreting pituitary adenoma responsive to SSTa., Design: An open, prospective, single-centre, clinical study., Patients: Thirty-six acromegalic patients, aged 17-75 years (postoral glucose tolerance test GH > 1 microg/l, increased IGF-1 for age and sex), were monitored in a single centre and treated with SSTa as first-line therapy. The mean pretreatment GH level was 13.5 +/- 3.1 microg/l, and IGF-1 (as a percentage of the value over the normal range) was 302 +/- 26%. The patients had macroadenoma (n = 25), microadenoma (n = 8) or empty sella turcica (n = 3). The mean duration of treatment was 8 years (range 3-18 years). Hormonal and morphological monitoring was undertaken after 6 months, and then the patients were followed annually., Results: After 1 year, the mean GH and IGF-1 levels had reduced considerably (GH: 2.4 +/- 0.3 microg/l; IGF-1; 174 +/- 14%, P < 0.01), and they continued to decrease over 10 years, with a mean GH level of 1.6 +/- 0.1 microg/l and IGF-1 of 123 +/- 18% (P = 0.02). GH < 2 microg/l, normal IGF-1, or both were observed in 25 (70%), 24 (67%) and 21 (58%) patients, respectively. The mean reduction in tumour volume was 43% (range 13-97%) and shrinkage > 20% was obtained in 21 patients (72%). SSTa treatment was well tolerated with few digestive or metabolic side-effects., Conclusion: Long-term (up to 18 years) treatment with SSTa used as first-line therapy is effective from both an antihormonal and antitumour perspective, and is well tolerated in acromegalic patients.

Background: Acromegaly is associated with hypertrophic cardiomyopathy, hypertension and subsequent congestive heart failure. Impairment of cardiac function has also been associated with growth hormone deficiency (GHD). B-type natriuretic peptides (BNPs) have emerged as strong diagnostic and prognostic risk markers. They are cardioprotective hormones that compensate heart disease by promoting natriuresis and modulation of cardiac hypertrophy in response to volume expansion and ventricular wall stretch., Objective: To investigate N-terminal pro-BNP (NT-proBNP) in patients with GH disturbances before and after treatment, and in healthy gender- and age-matched controls., Subjects and Methods: Ten acromegalic patients (age 48 +/- 12 years) and 10 patients with GHD (age 41 +/- 14 years) were studied. None had symptoms or signs of cardiovascular disease except for hypertension. Serum NT-proBNP was measured before and 3, 6, 12 and 24 months after treatment., Results: Baseline NT-proBNP was lower in acromegalic patients [median (interquartile range) 24.3 (17.8-33.0) pg/ml] than in 20 healthy matched controls [57.9 (35.4-92.2) pg/ml; P < 0.001]. NT-proBNP increased during treatment (P = 0.002), concomitant with a decrease in IGF-I (P < 0.001). After 3 months of treatment NT-proBNP peaked, with a fourfold increase to 96.4 (57.8-113.2) pg/ml. NT-proBNP did not differ in patients with GHD compared with controls (P = 0.19), and did not change during treatment (P = 0.39)., Conclusion: Untreated patients with acromegaly had low NT-proBNP levels that increased fourfold after treatment. This is in contrast to other conditions with cardiac hypertrophy. Further studies are required to determine the significance of this novel finding in relation to acromegalic cardiac disease.

Background: Limited data are available on clinical presentation and treatment strategy in patients with GH-secreting adenomas with onset in adolescence., Objective: To report results of diagnosis and treatment in adolescents with GH and IGF-I excess., Design: Analytical, observational, retrospective., Subjects: Thirteen patients (five females and eight males, age 15-20 years) all with macroadenoma (two extrasellar, 11 invasive)., Main Outcome Measures: Height, body mass index (BMI), GH and IGF-I levels, tumour volume at diagnosis and after treatment., Interventions: Transsphenoidal surgery, octreotide subcutaneous (OCT, 0.3-0.8 mg/day), octreotide-LAR i.m. (LAR, 20-30 mg/q28 days), lanreotide i.m. (LAN, 60-90 mg/q28 days), bromocriptine (BRC, 5 mg/day), cabergoline (CAB, 1-2 mg/week)., Results: Concomitant hyperprolactinaemia was found in eight patients (61.5%). All girls presented with amenorrhoea, which was associated with galactorrhoea in two patients; all boys presented with symptoms of tumour mass compression such as visual disturbance or headache; two girls also had these symptoms. Height at diagnosis was above the 97th centile in four of five girls and in six of eight boys. None of the patients had altered lipid profile while homeostasis model assessment of insulin resistance (HOMA-IR; 2.8 +/- 0.9) and beta-cell function (HOMA-beta, 207.6 +/- 98.1%) were higher than predicted (1% and 100%, respectively). First-line treatment was surgery in two patients and somatostatin analogues associated with dopaminergic drugs in 11 patients. None of the patients operated on were cured while six of 11 patients receiving pharmacotherapy (6-24 months) were controlled. In these six, tumour volume was reduced by 51.0 +/- 25.2% (median 51.5%). As second-line treatment, all the 11 patients treated with somatostatin analogues underwent surgical removal of their tumours. Surgery was successful in four patients and second-line pharmacotherapy in six patients. One patient was lost at follow-up and two patients maintained active acromegaly despite different treatment schedules; both patients were then treated with radiotherapy. At the last follow-up, there was a significant decrease in insulin levels, HOMA-IR and HOMA-beta without any change in lipid profile., Conclusions: The clinical presentation of GH-secreting adenomas in adolescent girls is associated with menstrual disturbances and in boys with symptoms of mass effects; tall stature is characteristic in both. First-line treatment with depot somatostatin analogues followed by surgery and then by a second course of somatostatin analogues was successful and safe in 11 of 13 patients.

Background: The prevalence of gallstones (GS) is increased in acromegaly and further increased by somatostatin analogue (SA) therapy. The incidence is reported at 10-63%, but they are often asymptomatic and rarely require definitive management. Evidence suggests discontinuation of SA may precipitate acute biliary problems., Objective: To determine the frequency of symptomatic gallstones in patients treated with SA., Design: Retrospective analysis of prospectively followed patients in our centre., Results: Fifty patients (30 male, mean age 54 +/- 16 years) were on treatment with SA on 1 January 2003. Fifteen (11 male, mean age 50 +/- 17 years) have since discontinued SA with three proceeding to develop acute cholecystitis and two, biliary colic necessitating cholecystectomy. Three of the five had abnormal liver enzymes at or within 3 months of symptomatic presentation. Two of the remaining 35 patients experienced biliary colic necessitating cholecystectomy. These data indicate a highly significant increase in acute biliary problems on discontinuing SA (5 in 27.67 patient 'off-treatment' years vs. 2 in 299 patient treatment years, chi(2), P < 0.0001). All seven patients experiencing problems were male (P = 0.01)., Conclusion: This analysis demonstrates the high incidence of symptomatic GS following SA withdrawal, particularly in men. Although liver enzymes were raised no common abnormality was evident to aid as a predictor of future symptoms. We recommend all patients due to stop SA be forewarned of the risk of acute biliary problems. Further work is required to confirm if there is a gender-related difference in the incidence of acute biliary problems on discontinuing SA therapy.

Objective and Design: Depot somatostatin analogues are well accepted as either adjuvant or primary therapy for acromegaly, and their long dosage intervals facilitate adherence to treatment. Our objective was to evaluate whether lanreotide Autogel 120 mg, every 4-8 weeks, was as effective in controlling acromegaly as lanreotide microparticles 30 mg, every 1-2 weeks. PATIENTS DESIGN AND MEASUREMENTS: Patients who had used lanreotide microparticles 30 mg, >or= 2 months prestudy, and had responded to treatment were recruited to this open, prospective, multicentre phase III trial. Three to five injections of lanreotide Autogel 120 mg were administered. Lanreotide Autogel 120 mg was injected every 4, 6 or 8 weeks in patients previously receiving lanreotide microparticles every 7, 10 or 14 days, respectively. GH and insulin-like growth factor (IGF)-1 levels were assessed one dosing interval after the final injections., Results: Ninety-eight patients were enrolled and 93 completed. Steady-state GH concentrations demonstrated similar efficacy between the formulations (upper 95% confidence interval of the quotient, 77.7%). Mean (SE) GH levels were lower with lanreotide Autogel than with lanreotide microparticles (3.8 (0.5) vs 4.3 (0.5) ng/ml; P < 0.001). GH levels < 2.5 ng/ml were observed in 54% and 46% of patients; 40% and 35% having GH < 2.5 ng/ml and normalized IGF-1 with lanreotide Autogel and microparticles, respectively. Symptoms were controlled better with lanreotide Autogel and treatment was well accepted., Conclusions: Lanreotide Autogel 120 mg every 4-8 weeks, is at least as effective and as well tolerated in acromegaly as lanreotide microparticles 30 mg injected every 7-14 days.

Objective: To investigate the pharmacokinetic profile of a prolonged release, aqueous Autogel formulation of the somatostatin analogue lanreotide (Lan-ATG)., Design: A phase II, randomized, double-blind study, during which patients received 60, 90 or 120 mg Lan-ATG for four fixed administrations at 28-day intervals., Patients: A total of 18 patients with acromegaly were recruited; six patients were randomized to each treatment., Measurements: Lanreotide minimum concentration (C(min)), maximum serum concentration (C(max)) and area under the concentration-time curve during a dosing interval (AUC(tau)) were assessed after a single dose and at steady state (ss). Serum GH and IGF-1 levels were assessed before each administration and at the end of the study., Results: After a single administration, dose proportionality for C(min,1), C(max) and AUC(tau) was demonstrated statistically. After repeated administrations, Lan-ATG exhibited linear pharmacokinetics over the dose range and ss values of C(min), C(max) and AUC(tau) increased in a dose-dependent, linear manner. Mean C(max,ss) values were only two- to fourfold greater than C(min,ss) values, and there was good control over the entire release profile. Serum levels of GH and IGF-1 declined over the course of the study and acromegaly symptoms improved. The treatment was well tolerated., Conclusions: Lan-ATG showed linear pharmacokinetic profiles over the three dose levels after both single and repeated dosing, no initial burst effect and good control over the entire release profile. Despite the absence of dose adaptation, four injections of Lan-ATG were effective in lowering serum levels of GH and IGF-1.

Unlabelled: :GH and IGF-I secretion is related to gender and age., Objective: To evaluate the impact of gender and gonadal status on the long-term sensitivity to the somatostatin analogues depot octreotide long-acting release (OCT-LAR) and lanreotide (LAN)., Patients: Seventy-three patients with active acromegaly (37 women, median age 34 years; 36 men, median age 38 years) who had not previously been treated with somatostatin analogues were studied: 24 women and 23 men were newly diagnosed; 22 men (61.1%) and 17 women (45.9%) had hypogonadism (P=0.28). Exclusion criteria were age >45 years, follow-up less than 12 months, mixed GH/PRL-secreting adenomas. Study design Observational, analytical, retrospective. Outcome measures (1) Disease control measured as serum GH< 2.5 microg/l and IGF-I normal for age and gender; (2) reduction in tumour volume graded as absent (< 25%), mild (25-50%) and notable (>50%). Results Basal GH, but not IGF-I, levels were higher in women than in men both in the entire series and in 'de novo' patients (97.8+/- 42.2 vs. 71.1+/- 32.6 microg/l, P=0.021). After 12 and 24 months of treatment, respectively, disease control was achieved similarly in men (57.1 and 86.7%) and women (48.6 and 86.7%). Hypogonadal men had longer disease duration than eugonadal men (P=0.022), without any difference in the other parameters. No difference was found between eugonadal and hypogonadal women. Eugonadal men had a smaller tumour volume at baseline than eugonadal women (1396+/- 794 vs. 2896+/- 2871 mm(3), P=0.025). In men undergoing testosterone replacement and withdrawal, there was no change in GH and IGF-I levels after 12 and 24 months of treatment with either LAR or LAN. In the seven women receiving oestro-progestinic replacement, after 24 months of LAR or LAN treatment GH levels were higher during replacement than at withdrawal and IGF-I levels were lower during replacement than withdrawal. Tumour volume decreased significantly in both women and men without any difference between them: the percentage tumour shrinkage in men and women was similar either after 12 (34.4+/-24.4 vs. 40.7+/-22.5%, P=0.38) or 24 months of treatment (58.5+/- 17.4 vs. 56.1+/- 23.6%, P=0.75). Similarly, there was no difference in tumour volume between hypogonadal and eugonadal women and men., Conclusions: The results of this study demonstrate that long-term responsiveness to OCT-LAR is similar in women and men. Care should be taken in women with acromegaly and hypogonadism treated with somatostatin analogues and oral oestro-progestinic as in this case GH levels are higher while IGF-I levels are lower than after the somatostatin analogues alone.

Background: The long-acting depot somatostatin analogues [octreotide LAR (LAR) and lanreotide (LAN)] are among the most effective available medical therapies for acromegaly. However, published data on a biochemical test suitable for predicting the responsiveness to these depot agents are lacking., Aim: To investigate the value of an acute octreotide suppression test (OST) in predicting the responses to treatment with long-acting somatostatin analogues in patients with active acromegaly., Patients and Methods: Thirty patients with active acromegaly [mean GH in GH day curve (GHDC) > 5 mU/l] were subjected to an OST [hourly GH measurements for 6 h following 100 microg subcutaneous (s.c.) octreotide]. Subsequently, 14 patients were treated with LAR, 10 with LAN and 6 received both drugs at different times. The final response to treatment was evaluated when the subjects had achieved 'safe' GH levels (mean GH < 5 mU/l) or after receiving the maximal dose of each drug (maximum duration of treatment 6 months)., Results: The nadir GH values during the OST were 2.6 +/- 2.5 mU/l (mean +/- SD, range 0.2-8.7) with a percentage fall of 84.8 +/- 15.7% (mean +/- SD, range 26-99%) from the baseline levels (26.2 +/- 31.5 mU/l, mean +/- SD). All the patients except one showed a decrease of greater than 50%. The mean time to achieve the nadir GH value was 3.8 +/- 1.6 h (mean +/- SD, range 1-6). The nadir GH levels showed a positive correlation with both pre-treatment (i.e. before commencing LAN or LAR) GH values during the GHDC (r = 0.63, P < 0.01) and IGF-I levels (r = 0.56, P < 0.05). The nadir GH values during the OST showed a positive correlation with the achieved mean GH levels in patients treated with LAR (r = 0.66, P < 0.01) but not in the ones treated with LAN. The criterion of GH < 5.25 mU/l during the OST had sensitivity 100%, specificity 80%, positive predictive value (PPV) 94% and negative predictive value (NPV) 100% in predicting achievement of 'safe' GH levels in patients treated with LAR. A less optimal prognostic profile was obtained for subjects treated with LAN with the criterion of GH < 6.05 mU/l during the OST providing sensitivity 92%, specificity 67%, PPV 92% and NPV 67%. The above cut-off GH levels had a PPV of only 77% and 60% in predicting normalization of IGF-I on treatment with LAR or LAN, respectively., Conclusions: The OST is a reliable tool for the selection of patients with active acromegaly who will achieve 'safe' GH levels on therapy with LAR. Its prognostic profile is less optimal for patients treated with LAN. If GH values during the test fall < 5.25 mU/l (in case of LAR treatment) or < 6.05 mU/l (in case of LAN treatment), there is a 92-94% chance of subsequently achieving 'safe' GH levels after up to 6 months treatment with either of these agents.

Background: Somatostatin analogues (SA) are currently the mainstay in the medical treatment of acromegaly. However, even high doses of depot SA for prolonged periods do not achieve GH-IGF-I normalization in some patients. Even though some data were reported about the addition of cabergoline, a long-acting dopamine agonist (DA), to SA in resistant patients, definite data are still lacking., Design: Prospective open trial., Patients: In 19 acromegalic patients with active disease (34-82 years old, seven males, 12 females) resistant to chronic (9-12 months) depot SA (octreotide-LAR, 30 mg/28 days in 13 patients, lanreotide, 60 mg/28 days intramuscularly in six patients) cabergoline was added (combined treatment). In these patients, SA treatment had partially relieved GH and IGF-I hypersecretion but no patient had achieved 'safe' GH and normal IGF-I-values. Eight patients had PRL levels greater than 15 micro g/l (range 16-60 micro g/l; 1 micro g = 21.2 mIU). Immunohistochemistry (IHC) was positive for PRL in four out of eight operated patients., Results: The addition of cabergoline, using the minimal effective and the maximal tolerated dose (range 1-3.5 mg/week), decreased GH from 6.6 +/- 0.9 to 4.6 +/- 0.6 micro g/l (P = 0.018), and IGF-I from 552 +/- 44 to 428 +/- 54 micro g/l (P = 0.019) after 6 months (median, range 3-18 Months). Combined treatment decreased GH to < 2.5 micro g/l in four patients (21%) and normalized IGF-I for age in eight patients (42%). It obtained a decline of both GH and IGF-I (-49 +/- 7%, and -47 +/- 5%, respectively) in nine patients (47%), and a partial improvement in six (32%) patients (GH decreased by 43 +/- 8% in four, and IGF-I by 35-38% in two patients). No change was observed in two patients, and worsening in two other patients. Results were not dependent on PRL status (serum levels or IHC). Combined treatment was well tolerated., Conclusions: The addition of cabergoline to depot SA-resistant acromegalic patients is effective, not dependent on PRL values and normalizes IGF-I levels in 42% of patients. The association of long-acting DA and SA deserves a more relevant role in the therapeutical algorithm of acromegaly.

Objective: Somatostatin analogue treatment is first-line medical therapy for acromegaly. This study compared the efficacy and tolerability of titrated doses of the long-acting somatostatin analogue preparation lanreotide Autogel with fixed doses and with lanreotide prolonged release (PR) 30 mg microparticles., Patients: Patients entering the initial study had received a diagnosis of active acromegaly within the previous 5 years., Design: This open, comparative, multicentre study was a 1-year extension of a previous trial during which patients with acromegaly had switched from lanreotide PR 30 mg microparticles injected intramuscularly every 7, 10 or 14 days, for at least 3 months, to one of three fixed doses of lanreotide Autogel (120, 90, or 60 mg every 28 days, respectively). In this extension study, patients continued to receive 60, 90, or 120 mg of lanreotide Autogel by deep subcutaneous injection every 28 days for 1 year. Doses could be titrated at entry or after four or eight injections, according to the GH/IGF-I response (dose increased if GH > 2.5 micro g/l, or decreased if GH < 1 micro g/l with normal IGF-I)., Measurements: Mean +/- SEM GH and IGF-I concentrations were analysed and gallbladder echography performed at weeks 0, 16, 32, and 48. Acromegaly symptoms were recorded monthly and tolerance and side-effects were monitored throughout the study., Results: In total, 130 patients entered this extension phase. After 1 year of treatment with titrated doses of lanreotide Autogel, mean GH (2.4 +/- 0.2 micro g/l) and IGF-I (287 +/- 12 micro g/l) concentrations were significantly lower than with lanreotide microparticles (GH, 2.8 +/- 0.2 micro g/l, P < 0.001; IGF-I, 332 +/- 15 micro g/l, P < 0.01) or with fixed-dose lanreotide Autogel (GH, 3.0 +/- 0.2 micro g/l, P < 0.001; IGF-I, 310 +/- 14 micro g/l, P = 0.02). GH hypersecretion was reduced to

Objective: Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty-four active acromegalic patients were studied in order to determine the long-term effects of octreotide-LAR and SR-lanreotide on insulin sensitivity and carbohydrate metabolism., Design: Prospective study., Patients: We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50.7 +/- 12.7 years, body mass index (BMI) 30.1 +/- 4.8 (kg/m2)., Measurements: All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy., Results: Acromegalic patients showed low M-values in respect to the control group at baseline (P<0.05), followed by a significant improvement after 6 months of therapy (P<0.005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P<0.05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P<0.05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4.7 +/- 0.6% and 5.1 +/- 0.5%, basal and after six months, respectively, P<0.005)., Conclusion: In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy.

Objective: The objective of this open study of 104 patients was to determine whether the somatostatin analogue lanreotide shrinks GH-secreting adenomas and to identify the predictive factors of a significant tumour volume reduction (> 20%)., Patients: A total of 104 previously untreated and newly diagnosed acromegalic patients received the prolonged release (PR) formulation of lanreotide (lanreotide 30 mg, one intramuscular injection every 10 days) for either 1 (n = 84), 2 (n = 13), or 3 or more (n = 7) months before transsphenoidal surgery., Measurements: Pituitary tumour volumes, tumour extension grade and possible cavernous sinus invasion were assessed in blinded conditions by a centralized team of radiologists. Factors such as demographics, tumour characteristics, GH and IGF-I levels were evaluated as possible predictive factors of a significant tumour volume reduction. The clinical activity and random GH, IGF-I, IGFBP-3, PRL, TSH, free T4 and lanreotide levels serum concentrations were measured under basal conditions and in the 10 days before surgery. All analyses were done in a centralized laboratory. The tolerability of preoperative PR lanreotide and the surgical outcome at the 6th month after surgery were assessed., Results: The presurgical treatment improved the symptoms of acromegaly and induced a statistically significant reduction of GH, IGF-I and IGFBP-3. Despite the short duration of the preoperative lanreotide 30 mg treatment, IGF-I levels were normalized in 25% of patients. A statistically significant reduction in tumour volume (P < 0.001) was observed. The median value of the differences was -152 mm3. A reduction in tumour volume was observed in 66% of patients and was > 20% in 29% of all patients included. Both the univariate analyses and the logistic regression model demonstrated that a positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of a significant tumour shrinkage (odds ratio of 7.8, 95% confidence interval 1.6-37.1). Preoperative PR lanreotide did not modify the expected soft consistence of the tumour. The main adverse events consisted of minor gastrointestinal problems. Univariate analyses revealed that younger age, higher GH and IGF-I levels at diagnosis, higher preoperative tumour volume, more than one tumour extrasellar extension and the presence of cavernous sinus invasion were statistically significant determinants of persistent disease at the 6th month after surgery. The multivariate analysis revealed that higher IGF-I levels at diagnosis and the preoperative cavernous sinus invasion were each statistically significant prognostic factors of persistent disease., Conclusions: A short administration of preoperative lanreotide 30 mg induced a statistically significant shrinkage of GH-secreting pituitary adenomas where this reduction was > 20% of the pretreatment value in 29% of the whole population. Among the factors considered was the fact that positive hormone response to preoperative lanreotide 30 mg was the sole predictive factor of this significant tumour volume reduction.

The case of a 33-year-old-woman with Multiple Endocrine Neoplasia Type 1 (MEN1) syndrome and acromegaly due to ectopic growth hormone-releasing hormone (GHRH) secretion by a thymic carcinoid tumour is reported. Immunohistochemistry revealed positive immunoreactivity for GHRH, vasoactive intestinal polypeptide, somatostatin and alpha-subunit in the tumour cells. A previously undescribed new germ line mutation of the MEN1 protein gene was revealed.

Background and Objective: The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy., Patients and Methods: Twenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant., Results: Biochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively)., Conclusions: This study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.

Background: The recent introduction of the depot somatostatin analogues octreotide LAR and lanreotide represent major advances in the medical treatment of acromegaly. However, it is uncertain whether the recommended dose intervals of 4 weeks and 10-14 days, respectively, are applicable to all patients., Aims: To determine the optimum intervals between depot injections of either octreotide LAR and lanreotide for the suppression of serum GH and IGF-I in patients with acromegaly. Twenty-seven patients with acromegaly were randomly allocated to receive either three injections at 4 week intervals of octreotide LAR (n = 18) or five injections at 14 day intervals of lanreotide (n = 11); two patients participated in both arms. Prior to the first injection, at 4 and 6 weeks after the last injection of LAR, and at 10, 14 and 21 days after the last injection of lanreotide, serum mean GH and IGF-I levels were measured., Results: In the LAR-treated group, at 4 and 6 weeks after the third injection 13 patients (72%) and 12 patients (67%), respectively, had a mean GH < 5 mU/l. IGF-I was normalized in 12 and 11 patients at these times. In the lanreotide-treated group, five (45%), four (36%) and three (27%) patients, respectively, had a GH < 5 mU/l at 10, 14 and 21 days after the last injection and eight, six and five patients had a normal serum IGF-I., Conclusion: There is marked variability in individual patient responses to depot somatostatin analogues. The establishment of optimal drug intervals requires careful assessment. For octreotide LAR many patients may be as adequately controlled with 6 weekly injections as with 4 weekly injections. It is important to measure serum GH profiles at intervals after initiating therapy with these drugs to individualize doses for each patient and hence minimize cost.

Background and Objective: The most effective option for the medical treatment of patients with acromegaly is the use of somatostatin analogues. Long-acting depot formulations for intramuscular injection of two somatostatin analogues have recently become available: octreotide acetate LAR (Sandostatin LAR, Novartis Pharma AG) and lanreotide SR (Somatuline, Ipsen Biotech). We wished to compare efficacy of octreotide LAR and lanreotide SR in acromegalic patients., Patients and Methods: A group of 125 patients with acromegaly (67 females; mean age, 47 years; 59 patients had previous pituitary irradiation) from 26 medical centres in France, Spain and Germany were studied. Before the study, all patients had been treated with intramuscular injections of lanreotide SR (mean duration, 26 months) at a dose of 30 mg which was injected every 10 days in 64 and every 14 days in 61 patients, respectively. All patients were switched from lanreotide SR to intramuscular injections of 20 mg of octreotide LAR once monthly for three months. In order to obtain efficacy and safety data of lanreotide SR under study conditions, it was decided to randomly assign at day 1, in a 3 : 1 ratio, the time point of the treatment switch; 27 of the patients were randomly assigned to continue the lanreotide SR treatment for the first 3 months of the study (group A); they were on octreotide LAR 20 mg from month 4-6. The other 98 patients were assigned to be switched to treatment with octreotide LAR 20 mg at day 1 (group B). In group B patients, octreotide LAR treatment was continued until month 6, with an adjustment of the dose based on GH levels obtained at month 3., Results: The mean GH concentration decreased from 9.6 +/- 1.3 mU/l at the last evaluation on lanreotide SR to 6.8 +/- 1.0 mU/l after three injections of octreotide LAR (P < 0.001). The percentages of patients with mean GH values < or = 6.5 mU/l (2.5 microg/l) and < or = 2.6 mU/l (1.0 microg/l) at the last evaluation on lanreotide SR were 54% and 14%, and these values increased after 3 months treatment with octreotide LAR to 68% and 35% (P < 0.001), respectively. IGF-I levels were normal in 48% at the last evaluation on lanreotide SR and in 65% after 3 months on octreotide LAR (P < 0.001). Patients with pre-study pituitary irradiation had lower mean GH and IGF-I concentrations. But the effects of the treatment change did not differ between the irradiated and the nonirradiated patients. In general both drugs were well tolerated., Conclusion: Octreotide LAR 20 mg administered once monthly was more effective than lanreotide SR 30 mg administered 2 or 3 times monthly in reducing GH and IGF-I in patients with acromegaly.

Background: A major cause of morbidity and functional disability in acromegaly is represented by axial and peripheral arthropathy., Objective: The effect of a 12-month treatment with lanreotide (LAN) on arthropathy in 12 untreated acromegalic patients has been evaluated. Twelve healthy subjects served as controls., Study Design: Open prospective., Study Protocol: Articular cartilage thickness of shoulder, wrist and knee, as well as the size of the heel tendons, was measured by ultrasonic (USG) examination before, monthly for the first 3 months and quarterly thereafter, during treatment with 60-90 mg/month of LAN. The achievement of safe GH and IGF-I levels was considered when fasting GH was below 5 mU/l and IGF-I levels were normalized for age., Results: Before treatment, thickening of shoulder, wrist and knee cartilages, and of heel tendons, was found in all patients compared with controls (P < 0.01). During the first 3 months of LAN treatment, a significant decrease in circulating GH (from 86.8 +/- 19.8 to 25.6 +/- 9.8 mU/l) and IGF-I levels (from 624 +/- 47.8 to 412.2 +/- 44.5 microg/l) was observed. Overall, a slight decrease was noted in all the articular sites examined, but it reached statistical significance only at the right shoulder (P < 0. 001). However, a notable improvement of joint pain and active and passive articular mobility were recorded in all patients, as well as of weakness, soft tissue swelling, hyperhydrosis and headache. After 6 months of LAN treatment, a further significant decrease was observed at the level of the right shoulder (P < 0.01) and the right knee (P < 0.01). Eight patients achieved safe GH and IGF-I levels. After 12 months of LAN treatment, a significant decrease was observed at the level of all the articular sites examined (P < 0.01), as well as at the level of both heel tendons (P < 0.01). Safe GH and IGF-I levels were achieved in all but one of the patients who, similarly, had a significant decrease in shoulder, wrist and both heel tendon thicknesses. The thickness reduction of right shoulder cartilage, a non-weight-bearing joint, was significantly greater than that observed at the level of the right and left knee cartilages and heel tendons (37.4 +/- 4.4% vs. 18 +/- 6.1%, 19.3 +/- 4.4%, 16.5 +/- 4.2%, and 13.7 +/- 5.5%, respectively, P < 0.01). No difference was found in thickness decrease of all sites examined between the eight patients achieving safe GH levels after 3-6 months, and the remaining four patients, or between patients with estimated disease duration below (n = 6) or above 10 years (n = 6)., Conclusions: Improvement in articular and periarticular soft tissue hypertrophy of the shoulder and wrist, two non-weight-bearing joints, but also of the knees, two weight-bearing joints, and heel tendons, was obtained by suppressing GH and IGF-I levels for 12 months with LAN treatment, although complete reversal of joint thickening was not achieved. Since no difference in the response to treatment, in terms of joint size decrease, was found between patients with short or long disease duration, treatment longer than 12 months may be needed to reverse the acromegalic arthropathy completely.

Background and Objective: Two long-acting depot somatostatin analogues have recently been licensed for the treatment of acromegaly. We wished to assess the effectiveness of both these drugs in suppressing mean GH to a target of < 5 mU/l in patients with acromegaly unselected for responsiveness to octreotide, and also to compare the effects of both drugs, Methods: We prospectively studied 10 unselected patients with acromegaly who were treated first with lanreotide (LAN) and then octreotide LAR (LAR) following a washout period. The target for therapy was to achieve mean GH less than 5 mU/l., Results: Five (50%) patients achieved mean GH < 5 mU/l on lanreotide 30 mg every 10 days, and 7 out of 9 (77.8%) achieved this level when the dose frequency was increased to every 7 days. On 20 mg octreotide LAR, 6 (60%) patients achieved the target mean GH and a further 2 (80%) when the dose was increased to 30 mg. Normalization of IGF-1 occurred in 5/9 (55.6%) patients who received lanreotide and 7/10 (70%) of those who received octreotide LAR. There was a significant difference in mean GH attained on the 2 drugs. The patients' mean GH was significantly lower when treated with octreotide LAR 20 mg every 4 weeks compared with lanreotide 30 mg every 10 days (P = 0.037). Maximal suppression of mean GH with 30 mg octreotide LAR or 7 day dosing of lanreotide was significantly greater on octreotide LAR (P < 0.02)., Conclusions: At current dose recommendations, lanreotide and octreotide LAR are both effective in lowering mean GH to 'safe' (< 5 mU/l) levels in 80% patients but octreotide LAR treatment leads to significantly lower mean GH.

Objective: We analysed the effects of 6-months' treatment with octreotide s.c. and lanreotide-SR on circulating GH and IGF-I levels in acromegaly., Design: Open retrospective study., Patients: Thirty-eight patients with active acromegaly (plasma IGF-I levels greater than 2 standard deviations for age-matched controls and increased serum GH levels not suppressible by oral glucose load) were studied. All patients received s.c. octreotide at a dose of 150-600 microg/day for six months as first therapy and subsequently, lanreotide i.m., 30-60 mg either at 14 or 10 day intervals, for 6 months. A 3 months' washout was applied before starting lanreotide treatment., Measurements: Mean serum GH levels (from three samples), IGF-I, and clinical examination were performed before and 30, 60, 90 and 180 days after octreotide and lanreotide treatments. Safety tests, HbA1c and, thyroid function were evaluated every three months., Results: Circulating GH and IGF-I levels were significantly reduced (P < 0.001) after one, three and six months of both octreotide and lanreotide treatment. The absolute values were lower and the percent decrease in serum GH levels obtained after octreotide treatment was significantly greater, at all scheduled assessments, than after lanreotide (P < 0.01). Serum IGF-I levels during octreotide were significantly lower only after the first month of therapy (P < 0.01)., Conclusions: Our study shows that octreotide s.c. is able to induce an earlier reduction in IGF-I levels and a more marked reduction in GH levels than lanreotide. However, after six months of therapy the number of patients with safe GH levels and normal IGF-I age-matched levels, was similar with both drugs. Therefore we suggest that octreotide treatment be preferentially used in the short-term presurgical treatment, while lanreotide can be used in chronic therapy when better compliance is necessary.

Objective: Previous studies have shown that somatostatin analogues such as octreotide and lanreotide are effective in suppressing GH and IGF-I levels in acromegaly, but the mode of administration and the frequency of injections were inconvenient for the patients. We have evaluated the effects of a new slow-release (SR), long-acting formulation of lanreotide, a somatostatin analogue, on clinical, biochemical and safety responses in acromegaly., Design: We studied the effects of SR-lanreotide 30 mg administered intramuscularly twice or three times monthly for 6 months. Ten patients were studied, in whom acromegaly was confirmed by clinical features,mean GH > 5 mU/l, and failure to suppress GH to < 2 mU/l after a 75-g oral glucose load., Measurements: Subjective improvement in clinical symptoms of acromegaly was graded and recorded. Any adverse reactions were noted. Plasma GH levels were measured every 10 min for one hour from 08300930h; fasting IGF-I levels were determined at 0830h; GH, glucose and insulin responses to oral glucose loading were measured at 0,30,60,90 and 120 minutes from 0930 to 1130h. Baseline measurements were carried out and repeated at 3 and 6 months. Biliary ultrasonography was performed at baseline and 6 months., Results: GH levels in the 10 patients decreased from 26.8 12.0 (mean SEM) to 12.7 7.0 mU/l at 3 months (P = 0.04) and 9.8 5.0 mU/l at 6 months (P = 0.06). Fasting IGF-I levels decreased from 123.2 27.0 to 73.5 13.0 nmol/l at 3 months (P = 0.01), and increased slightly to 97.4 31.0 nmol/l (P = 0.05) but remained below baseline levels at 6 months. Five patients achieved good control (GH < 5 mU/l) at 3 months. In the remaining 5 patients the dose frequency was increased to every 10 days and one achieved good control. IGF-I levels normalized in 3 and 5 patients at 3 and 6 months, respectively. Fasting insulin levels and peak insulin after an oral glucose load did not change significantly at 3 months but decreased from 11.7 2.0 to 7.8 3.3 mU/l (P = 0.05) and 106.2 24.6 to 53.3 14.3 mU/l (P = 0.04) at 6 months, respectively. There was no significant change in fasting glucose at 3 or 6 months. Most patients reported clinical improvement in acromegalic symptoms. No major adverse events were reported, but mild to moderate gastrointestinal symptoms were recorded after the initial injections. One patient developed asymptomatic gallstones at 6 months., Conclusions: This slow-release formulation of lanreotide given either twice or thrice monthly was well tolerated, more convenient for patients, effective in controlling and alleviating the symptoms of acromegaly, as well as suppressing GH and IGF-I levels, and had no detrimental effects on carbohydrate tolerance in acromegaly.