Pituitary Tumor Volume Research Articles

Does partial surgical tumour removal influence the response to octreotide‐LAR in acromegalic patients previously resistant to the somatostatin analogue?

To compare the intrapatient response to the same dose of slow-release octreotide (OCT-LAR) before and after noncurative surgery in acromegalic patients who did not attain disease control after primary treatment with OCT-LAR. Prospective clinical study. Eleven acromegalic patients (eight men, aged 42.45 +/- 11.15 years, 10 macroadenomas) received OCT-LAR (20 mg, n = 1; 30 mg, n = 10) every 28 days as the primary treatment (1stOCT-LAR) for 11.3 +/- 4.2 months, without IGF-I normalization. They were subsequently submitted to surgery without cure and were then treated with the same dose of OCT-LAR for 8.0 +/- 6.5 months (2ndOCT-LAR). GH and IGF-I serum concentrations were obtained under basal conditions as well as during treatment. Pituitary tumour volume was assessed by magnetic resonance imaging (MRI) of the sella. IGF-I was also expressed as a percentage of the upper limit of the normal age- and sex-matched range (%ULNR IGF-I). After 1stOCT-LAR, there was a decrease in GH levels (P = 0.003) and %ULNR IGF-I (P = 0.009) compared to baseline (B), but no IGF-I normalization. Tumour shrinkage was observed in eight of 10 patients with macroadenomas (median 63.7%, range 24.5-75.5%). After surgery, mean levels of GH and %ULNR IGF-I were lower than those at baseline (P = 0.0004 and P = 0.003, respectively), but not when compared to values during 1stOCT-LAR (P = 1.000 and P = 0.957, respectively). MRI confirmed surgical tumour removal (median 64%, range 4.9-96.6%) in eight of the 10 patients. Comparing the 2ndOCT-LAR results with postsurgical results, there were no significant decrease in %ULNR IGF-I (P = 0.061) and GH levels (P = 0.414). Nine patients (82%) achieved IGF-I normalization. The degree of surgical tumour reduction did not correlate with IGF-I normalization (P = 0.794). When comparing the results between 1stOCT-LAR and 2ndOCT-LAR, there was a decrease, albeit not statistically significant, in serum GH levels (P = 0.059) and a significant decrease in %ULNR IGF-I (P = 0.011). Using strict criteria (same patient, same drug, same dose) our results strongly suggest that the surgical reduction of tumour mass can improve the outcome of OCT-LAR treatment in acromegalic patients resistant to primary therapy with SA.

Treatment of acromegaly with the GH receptor antagonist pegvisomant in clinical practice: Safety and efficacy evaluation from the German Pegvisomant Observational Study

The GH receptor antagonist pegvisomant is a highly effective new treatment option in acromegaly. The German Pegvisomant Observational Study (GPOS) was started to monitor long-term safety and efficacy of pegvisomant as prescribed in clinical practice. GPOS is an observational, multi-center, surveillance study, which comprises non-interventional data collection. Of the 229 patients included in the study, 90.4% had previous pituitary surgery, 43.2% were treated by radiation therapy, and 94.3% had previous medical therapy for acromegaly that had been discontinued mainly due to persistent IGF-I elevation or side effects. The intention-to-treat population included 177 patients with at least one post-baseline efficacy measurement. IGF-I levels decreased from 1.75+/-0.91-fold the upper limit of normal at baseline to 1.05+/- 0.62 at the 6-month visit, 0.96+/-0.60 at the 12-month visit, and to 0.89+/-0.41-fold after 24 months (P<0.0001). Mean duration of pegvisomant therapy was 51.8+/-35.8 weeks (median=51.9 weeks). IGF-I was normalized in 64.4% at 6 months with a median dose of 15.0 mg/day, in 70.9% at 12 months, and in 76.3% at 24 months. Fasting glucose levels improved from 114.4+/-45.9 to 101.5+/- 42.8 mg/dl after 6 months (P<0.01) and to 100.6+/-33.2 mg/ml after 12 months (P<0.01). General physical condition measured by specific signs and symptoms score improved significantly. Adverse events occurring in >1% were injection site reactions in 7.4%, elevated liver enzymes (>3 times of normal) in 5.2% (3.1% spontaneously normalized during continued treatment), reported increase of pituitary tumor volume in 5.2% (which was verified in 3.1%), and headache in 1.7%. Pegvisomant is generally well tolerated with a safety profile similar to that reported in clinical trials and can effectively reduce IGF-I in patients with acromegaly refractory to conventional therapy.

Intrasellar pressure and tumor volume in pituitary tumor: relation study

To determine if there was a relationship between intrassellar pressure (ISP) and pituitary tumor volume. Between August 2002 and May 2004, 60 patients aged between 13 and 75 years old (39 males), having a pituitary adenoma were submitted to an endoscope transseptal approach. During the surgery and before tumor resection, 2 mm of the sellas floor were removed and a 1.5 mm dural opening made to place a transducer into the pituitary adenoma. The transducer was connected to a pressure monitor. The intrasellar pressure, ranged from 2-51 mmHg and was measured based on the classification of Hardy-Vezina. The most elevated was in the type II macro adenomas with 32.6 mmHg, sharply superior to the value of a normal intracranial pressure. These values showed that the macroadenomas confined to the sella, without destruction of the floor and integrity of the diaphragm, type II of Hardy-Vezina, presented a value of ISP much higher than intra-extrasellar macroadenoma's.

Glucose Homeostasis and Safety in Patients with Acromegaly Converted from Long-Acting Octreotide to Pegvisomant

In clinical practice, patients with acromegaly may be switched from therapy with long-acting somatostatin analogs to pegvisomant. The effect of changing therapies on glucose homeostasis and safety has not been reported. The objectives of this study were to monitor changes in IGF-I levels, glycemic control, and safety, particularly liver function and tumor size. This was a multicenter, open-label, 32-wk trial study. The study was performed at outpatient clinics. Fifty-three patients with acromegaly previously treated with octreotide long-acting release (LAR) participated in this study. Pegvisomant (10 mg/d) was initiated 4 wk after the last dose of octreotide LAR and was adjusted based on serum IGF-I concentrations at wk 12, 20, and 28. The main outcome measures were changes in IGF-I, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose, and safety during the first 12 wk after conversion. At the end of pegvisomant treatment, IGF-I was normalized in 78% of patients. At wk 32, median fasting glucose concentration and HbA1c were reduced (-1.4 mmol/liter and -0.4%, respectively; both P < or = 0.0001) in the study population. Improvements in glycemic control occurred in patients with normal IGF-I concentrations at wk 4 [n = 15; fasting glucose, -1.7 mmol/liter (P < or = 0.0001); HbA1c -0.2% (P = 0.03)]. Decreases in fasting glucose and HbA1c levels were observed in patients with and without diabetes. HbA1c was reduced by more than 1.0% in patients with diabetes. Median pituitary tumor volume did not change, although tumor volume increased in two patients with macroadenomas. Conversion from octreotide LAR to pegvisomant was safe and well tolerated. Improved glycemic control indicates that pegvisomant should be considered in patients with acromegaly and diabetes.

Treatment of acromegaly with octreotide‐LAR: extensive experience in a Brazilian institution

Somatostatin analogues have become the mainstay of the medical treatment of acromegaly. The aim of our study was to evaluate the efficacy and tolerability of octreotide-LAR (OCT-LAR) treatment in acromegalic patients. Prospective open trial. Eighty acromegalic patients (46 women; 18-80 years) were treated with OCT-LAR. Mean +/- SD duration of follow-up was 16.6 +/- 6.6 months (6-24 months). Twenty-eight patients received OCT-LAR as primary treatment. The target was to achieve normal IGF-I levels. Clinical activity was evaluated by symptom score and fasting samples for GH and IGF-I serum concentrations, obtained under basal conditions as well as during treatment. Pituitary tumour volume was assessed by magnetic resonance imaging of the sella. A tumour volume reduction of at least 25% was considered significant. Clinical improvement was attained in most patients. Fifty-nine (74%) of them attained mean GH < 2.5 ng/ml and 33 (41%) achieved normal IGF-I by the 24th month of treatment. GH and IGF-I control increased throughout treatment. Regarding the 46 patients treated for at least 12 months there was a significant decrease of GH and IGF-I levels by the third month compared to basal levels, persisting with no subsequently variation. In the patient group that achieved normal serum IGF-1 during treatment (controlled group: n = 43) 20 patients maintained normal levels up to the latest follow-up, whereas 23 of them once again showed altered serum IGF-1-values of some measurements during follow-up, despite dose maintenance or elevation. Baseline percentage of the upper limit of IGF-I normal range, GH levels by the third month and length of treatment were predictive factors of IGF-I normalization. Tumour shrinkage occurred in 76% of primary patients. Among 21 diabetic patients, four worsened and five improved glycaemic control, based on glycated haemoglobin. One previously intolerant patient progressed to overt diabetes. Nine patients developed gall bladder sludge, other nine patients acquired microlithiasis and one patient developed gallstone pancreatitis. OCT-LAR is an effective agent in alleviating symptoms, suppressing GH, normalizing IGF-I and inducing tumour shrinkage in many acromegalic patients. Overall, OCT-LAR is well tolerated and should be recommended for nonsurgically cured acromegalics, and also be considered as primary therapy for selected cases, mainly for those with a low probability of surgical cure.

Predicting Therapeutic Response and Degree of Pituitary Tumour Shrinkage during Treatment of Acromegaly with Octreotide LAR

Background/Aims: The efficacy of transsphenoidal surgery in the treatment of patients with acromegaly is largely dependent on tumour size. A reduction in pituitary tumour volume by medical therapy might therefore improve subsequent surgical cure rates. This study prospectively determined the effects of the depot somatostatin analogue octreotide LAR on pituitary tumour size, GH and IGF-I levels and clinical symptoms in a cohort of previously untreated patients with acromegaly. Methods: Six patients newly diagnosed with acromegaly (mean age 53 years; range 42–76 years) received intramuscular octreotide LAR every 28 days for 6 months. The initial dose of LAR was 20 mg, but increased to 30 mg after the initial 3 injections if mean GH levels were >5 mU/l. Prior to commencing LAR therapy, each patient received 3 injections of subcutaneous octreotide (50, 100 and 200 µg) in a randomized order on separate days, and the serum GH response was measured. Pituitary tumour volume was calculated from MRI or computed tomography scans at baseline, then 3 and 6 months after initiation of treatment, and assessed by a ‘blinded’ radiologist in random order. At baseline, 4 patients had a macroadenoma and 2 patients had a microadenoma. For the latter, the whole gland volume was measured. Results: Serum GH levels decreased from 29.6 ± 19.2 mU/l (mean ± SD) at baseline to 12.1 ± 10.5 mU/l at 3 months and 10.4 ± 9.3 mU/l at 6 months. Three patients achieved a mean serum GH level of <5 mU/l. In these patients, the serum GH had declined to <5 mU/l in response to a single 100 µg subcutaneous octreotide injection. Serum IGF-I levels decreased by a mean of 45 ± 7.4%. Tumour volume decreased in all patients: mean baseline volume 2,175 mm³ (range 660–6,998) decreasing to 1,567 mm³ (range 360–4,522) at 3 months (p < 0.05) and 1,293 mm³ (range 280–4,104) at 6 months (p < 0.002). The mean percentage decrease in size was 29% (range –54 to +4%) at 3 months (p < 0.02) and 47% (range 21–97%) at 6 months (p < 0.002). There was no statistically significant correlation between GH response and tumour shrinkage. Conclusions: A single test dose of subcutaneous octreotide may be useful in predicting the subsequent efficacy of octreotide LAR. Octreotide LAR results in significant shrinkage of pituitary tumours of newly diagnosed patients with acromegaly. Whether its administration to such patients for 6–12 months can improve the efficacy of subsequent transsphenoidal surgery will require further study.

The GH receptor antagonist Pegvisomant in the treatment of acromegaly

Understanding the mechanisms by which growth hormone (GH) interacts with its receptor has led to the design of compounds that function as GH receptor antagonists. One such compound has been conjugated to polyethylene glycol (PEG) to produce a drug, pegvisomant, which has been extensively investigated as a treatment for acromegaly and is now available for clinical use in the United States and Europe. Studies have shown that the drug is able to normalise circulating concentrations of insulin-like growth factor I (IGF-I), the principal mediator of GH action, in 97% of patients with active acromegaly, as well as improve the symptoms and signs associated with GH excess. Unlike other medical therapies, pegvisomant does not have as its target the somatotroph pituitary tumour responsible for excess GH secretion. All patients have therefore undergone regular surveillance imaging to ensure that interruption of the GH/IGF-I feedback loop is not associated with accelerated tumour growth. Overall, there is no evidence that pegvisomant therapy is associated with an increase in pituitary tumour volume but periodic radiological surveillance is clearly mandatory. The fact that pegvisomant does not act on other endocrine systems has facilitated careful dissection of many of the metabolic consequences of GH excess and documentation of the effect of GH receptor blockade. Active acromegaly is associated with a variety of metabolic derangements, including abnormal lipoprotein metabolism, accelerated cortisol metabolism and insulin resistance (IR). In this talk, particular focus will be given to insulin resistance and glucose homeostasis, which are believed to be important contributory factors in the increased cardiovascular morbidity and mortality associated with acromegaly. Although the IR of acromegaly is well documented, it does not, per se, predict glucose tolerance, as measurements of insulin sensitivity (IS) are equivalent in patients with or without carbohydrate intolerance. Compensatory β-cell hyperfunction is seen in patients with normal glucose tolerance but not in those with diabetes mellitus. The effect of somatostatin analogs on glucose tolerance is complex and unpredictable; glucose tolerance improves in some patients by virtue of better control of the GH-IGF-I axis but often worsens by virtue of inhibition of pancreatic insulin release. No published data exist regarding the effect of cabergoline on IR and glucose tolerance, although experience with bromocriptine would suggest that dopamine agonists improve glycaemic control in proportion to the degree of control of GH hypersecretion. Significant decreases in plasma glucose and insulin concentrations have been observed in acromegalic patients treated with pegvisomant; and there are anecdotal reports of patients with acromegaly and diabetes treated with pegvisomant in whom it has been necessary to reduce the dose of oral hypoglycemic agents. However, to date, studies of pegvisomant have included a substantial proportion of patients with complete or partial OT resistance, such that the improvements in IS may, in part, have been consequent upon better biochemical control of acromegaly. No randomised, comparative studies of pegvisomant and SST are currently available, although preliminary data from a recent observational study of patients converted from depot OT to pegvisomant suggest that treatment with pegvisomant may be associated with improved IS and overall glucose tolerance.

Pituitary volume and headache: size is not everything.

Pituitary tumors are commonly associated with disabling headache. The accepted mechanisms for headache are dural stretch and cavernous sinus invasion. To determine if there is a relationship between pituitary tumor size and the report of headache. We prospectively studied 63 patients who were initially seen with pituitary tumors. Clinical headache scores, pituitary tumor volume, and the extent of cavernous sinus invasion were obtained for each patient. The prevalence of headache was 70%. There was no positive correlation the between clinical headache score and pituitary volume (r = -0.32, P =.01, Spearman rank correlation). There was also no association between cavernous sinus invasion and headache. There was a strong association between pituitary-associated headache and a family history of headache (chi(2) = 8.36, P =.004). These data suggest that a pituitary tumor-associated headache may not simply be a structural problem. Other factors such as family history of headache, and the endocrine activity of the tumor may be equally important determinants of headache. Elucidating these mechanisms will aid in the treatment of these patients and further our understanding of other headache syndromes.

Medical management of thyrotropin-secreting pituitary adenomas.

Thyrotropin-secreting pituitary tumors (TSH-omas) are a rare cause of hyperthyroidism and account for less than 1% of all pituitary adenomas. It is however noteworthy that the number of reported cases tripled in the last years as a consequence of the routine use of ultrasensitive immunometric assays for measuring TSH levels. Contrary to previous RIAs, ultrasensitive TSH assays allow a clear distinction between patients with suppressed and those with non-suppressed circulating TSH concentrations, i.e. between patients with primary hyperthyroidism (Graves' disease or toxic nodular goiter) and those with central hyperthyroidism (TSH-oma or pituitary resistance to thyroid hormone action). Failure to recognize the presence of a TSH-oma may result in dramatic consequences, such as improper thyroid ablation that may cause the pituitary tumor volume to further expand. The medical treatment of TSH-omas mainly rests on the administration of somatostatin analogs, such as octreotide and lanreotide. In fact, administration of dopamine agonists failed to persistently block TSH secretion in almost all patients and caused tumor shrinkage only in those with combined hypersecretion of TSH and PRL. On the contrary, somatostatin analogs were effective in reducing TSH and alpha-subunit secretion in more than 90% of cases with consequent normalization of FT4 and FT3 levels and restoration of the euthyroid state in the majority of them. In about one third of patients, a clear shrinkage of tumor mass and vision improvement could be demonstrated. Tachyphylaxis, cholelithiasis and carbohydrate intolerance occurred in a minority of treated patients. Whether somatostatin analog treatment may be an alternative to surgery and/or irradiation in patients with TSH-oma remains to be established. Nonetheless, the long-acting somatostatin preparations represent a useful tool for long-term treatment of such a rare pituitary tumors.

Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist

Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days. Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis. Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353). Pegvisomant is an effective medical treatment for acromegaly.

Mdm2 and the p53 pathway in human pituitary adenomas.

Studies on pituitary tumours have failed to identify mutations in the tumour suppressor gene p53 suggesting that the protein identified is wild type. p21(WAF--1) is a downstream effector of p53 which promotes growth arrest. Mdm2 (mouse double minute) is a protein induced by wild type p53 and forms an autoregulatory feedback loop suppressing wild type p53 activity. The purpose of this study was to examine a group of pituitary tumours for expression of p53 and its two downstream effector proteins p21(WAF--1) and mdm2 and to compare this with their radiological invasive status and proliferative potential as assessed by Ki-67 expression. Sixty-nine tumours removed at transsphenoidal surgery were examined by immunocytochemistry using antibodies against p53, p21(WAF--1), mdm2 and Ki-67 (MIB-1). The invasive status of the tumours was determined from the preoperative CT/MRI scans. p53 was expressed in 42 of 69 (61%) pituitary adenomas but there was no relationship with either pituitary tumour invasive status (P = 0.71) or volume (P = 0.33). p53 expression correlated, however, with the proliferative state of the tumours as assessed by the MIB-1 labelling index (P = 0.0065). Invasive tumours had a higher growth fraction than non-invasive ones (P = 0.027). p21(WAF--1) was expressed in the nuclei of 58/69 (84%) pituitary adenomas and its expression correlated with that of p53 (r = 0.26, P = 0.03). Mdm2 was expressed in the cytoplasm of 46/69 (67%) tumours and this correlated with the nuclear staining for p53 (P = 0.022) while nuclear staining was seen in 32/69 (46%) tumours but this did not correlate significantly with nuclear p53 staining (P = 0.096). These results suggest that p53, p21(WAF--1) and mdm2 are all expressed in pituitary tumours suggesting that the p53 protein detected by immunocytochemistry is wild type. Expression of p53 is associated with tumours which have a higher proliferative status. The p53 activity is probably the result of upstream signals of local stresses mediated through either genetic change, cytokines, hypoxia or hormonal factors. Our results suggest, however, that the downstream pathway mediated through the activities of p21(WAF--1) and mdm2 may be dysfunctional in these tumours.

Results of somatostatin receptor scintigraphy do not predict pituitary tumor volume- and hormone-response to ocreotide therapy and do not correlate with tumor histology.

The value of somatostatin receptor scintigraphy (SRS) to predict the effect of somatostatin analog therapy on pituitary adenomas is not clear, due to the use of different radiopharmaceuticals (123I-Tyr3-octreotide and 111In-pentetreotide) and the small number of patients in previous studies. We used 111In-pentetreotide scintigraphy in 49 patients in order to (i) correlate SRS results with basal tumor volume as well as volume- and hormone-response to 3 months of octreotide therapy (Oct-Tx). (ii) identify tumor remnants after incomplete surgery and (iii) evaluate any correlation with immuno histology. Twenty-five patients had a GH-secreting adenoma (GH-A, 15 prior to intended surgery, 10 with persistent/recurrent disease after previous therapy). Twenty-four patients had a clinically non-functioning adenoma (NF-A). For SRS, planar and single photon emission computer tomographic images (SPECT) were recorded 4 h and 24 h post injection. SRS grading was as follows: GO, no uptake: G1, uptake comparable to normal pituitary; G2, increased uptake: G3, very intense uptake. G2/3 was seen in 8/25 GH-A and in 12/24 NF-A. Pretreatment tumor volume (magnetic resonance imaging (MRI) tended to be related to 111In-pentetreotide uptake in GH-A with a tumor visible on MRI (G0/1 (n = 10) vs G2/3 (n = 8): 3.6 +/- 1.9 vs 10.5 +/- 6.5 cm3 (mean +/- S.E.), P = 0.051), but not in NF-A (G0/1 (n = 12) vs G2/3 (n = 12): 17.0 +/- 10.1 vs 14.3 +/- 3.6 cm3). SRS did not identify a tumor remnant in the 7 MRI-negative patients with persistent post-operative acromegaly. Basal GH (6-h profile) and IGF-1 in GH-A did not correlate with SRS results (G0/1 (n = 17) vs G2/3 (n = 8), GH: 32.3 +/- 18.2 vs 29.3 +/- 7.4 micrograms/l IGF-I: 851 +/- 80 vs 1038 +/- 153 micrograms/l). During Oct-Tx of GH-A neither tumor shrinkage nor GH suppression was related to SRS results. In 6 NF-A classified as gonadotropinomas (by their plasma glycoprotein hormone or alpha-subunit concentrations, basally and/or in response to TRH) 111In-pentetreotide uptake was not different from that of the non-gonadotropin/non-secreting adenomas. SRS results were not related to the immunohistological subtype in 22 GH-A (monohormonal mixed somatotrope/lactotrope, plurihormonal) or in 22 NF-A (null-cell adenomas, gonadotropinomas silent hormonal adenomas). We conclude that 111In-pentetreotide SRS reflects tumor volume poorly in GH-A and not at all in NF-A. It does not predict the effect of Oct-Tx on the volume of both GH-A and NF-A, nor on the GH concentration in GH-A. 111In-pentetreotide SRS is unable to identify post-operative tumor remnants not visible on MRI.

Three year follow-up of acromegalic patients treated with intramuscular slow-release lanreotide.

Somatostatin analogs are an alternative treatment to pituitary surgery and radiotherapy in acromegalic patients. Recently, a depot long-lasting formulation of slow release (SR) lanreotide has been shown to be effective in the short-term control of GH hypersecretion in acromegalic patients. We report the long-term follow-up of a cohort of 22 acromegalic patients treated with SR lanreotide during 1-3 yr. Thirteen females and 9 males, age 51 +/- 3 yr, presented with macroadenomas (n = 12), microadenomas (n = 8), or empty sella (n = 2). Seven patients previously had undergone a partial surgical removal of their adenomas, and 21 of them had mean plasma GH levels less than 5 micrograms/L during a previous octreotide treatment. According to GH values recorded after 3 months of twice monthly 30 mg SR lanreotide im injection, SR lanreotide was administered every 14 days (n = 13) or every 10 days (n = 9). At the 6-month visit, mean GH values were 5 micrograms/L or less in 68% and 2.5 micrograms/L or less in 27% of patients, and these results remained unchanged during the 1-3 yr follow-up period. During SR lanreotide treatment, the mean insulin-like growth factor I (IGF-I) concentrations remained in the normal range in 63% of patients. No escape from the treatment occurred in any of the cases. A significant decrease of the pituitary tumor volume was observed in 3 (13%) patients. The main side effect consisted of minor digestive problems during 48 h after each injection and was reported by 13 patients. Biannual gallbladder echographies revealed the occurrence of gallstones in 4 (18%) patients. In conclusion, these data confirm the efficacy and the tolerance of the long-term SR lanreotide administration (30 mg im every 10-14 days) in the control of acromegaly.

Intramuscular injections of slow-release lanreotide (BIM 23014) in acromegalic patients previously treated with continuous subcutaneous infusion of octreotide (SMS 201-995)

Nine acromegalic patients (five females and four males), mean age 50 +/- 4 years, presented macroadenomas (N = 7), microadenoma (N = 1) or normal computed tomography scans (N = 1). Patients were treated with continuous subcutaneous infusion of octreotide (range 200-600 micrograms/day). Following a washout period of 7 days, the patients were injected im with 30 mg slow-release lanreotide every 10 days for the first month and then twice monthly. In case of elevated growth hormone (GH) levels at 3 months, the patients were injected every 10 days for the next three months. Plasma GH and insulin-like growth factor I (IGH-I) decreased in all patients during octreotide treatment. After 6 months of octreotide treatment, seven patients were considered as well controlled (mean 8 h GH < 5 micrograms/l, IGF-I normal) whereas in two patients the mean 8-h GH and/or IGF-I levels remained increased. Serum GH and IGH-I increased after octreotide withdrawal. In one patient, serum GH and IGF-I increased during slow-release lanreotide administration and injections were stopped after 45 days. After 3 months of lanreotide, three patients were well controlled while in five patients GH or IGF-I levels were not normalized. At 6 months, five patients were injected twice monthly and three patients had one injection every 10 days. Six patients were well controlled and in two patients the mean 8-h GH level remained increased. The pituitary tumor volume decreased by 20-30% in two patients during octreotide, as well as in one other during slow-release lanreotide therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

The sensitivity of growth hormone secretion to medical treatment in acromegalic patients: influence of age and sex.

We investigated the relationship between age, sex, pituitary tumour volume, serum GH, PRL and IGF-I levels with the responsiveness of GH to TRH, bromocriptine and octreotide in patients with acromegaly. We performed a retrospective study. Correlations were determined between all variables using univariate regression analysis. One hundred previously untreated acromegalic patients were studied (60 males (age 23-76; mean 49 years) and 40 females (age 25-83; mean 51 years)). We studied tumour volume, fasting morning circulating levels of GH, PRL and IGF-I, mean 24-hour circulating GH levels and the acute GH responses to TRH, bromocriptine and octreotide. Tumour size was related to serum and mean 24-hour GH levels, but not to IGF-I. Circulating IGF-I and GH levels were related only for the group of patients whose fasting and unsuppressed GH level was 80 mU/l (40 micrograms/l) or less. Older patients tended to have lower circulating GH and IGF-I levels. There was a close similarity in the responsiveness of tumorous GH secretion to TRH, bromocriptine and octreotide. An elevated serum PRL level predicted a stronger inhibitory response of bromocriptine on GH. The sensitivity of GH release to octreotide was highest in elderly (especially male) acromegalics, as well as in patients with lower IGF-I levels. Hormone secretion by GH secreting pituitary tumours, as well as circulating IGF-I levels, tend to be lower in elderly patients. These tumours are more sensitive to octreotide, especially in elderly male patients. This suggests that octreotide might be used especially successfully as a primary medical therapy in elderly, male acromegalics.