Mean GH Values Research Articles

Native-tissue pelvic organ prolapse (POP) repair with perineorrhaphy for level III support results in reduced genital hiatus size and improved quality of life in sexually active and inactive patients

Introduction and hypothesisRecent findings address the importance of Level III defects with increased genital hiatus being associated with pelvic organ prolapse (POP), correlated with Level I defects and strongly related to POP recurrence. We hypothesised that concomitant perineorrhaphy in POP repair reduces genital hiatus (gh) and increases perineal body (pb), that gh would be larger with number of vaginal deliveries and that patients’ QOL was not different comparing sexually active vs inactive patients with overall judgement of cure comparable to the literature at evaluation. MethodsRetrospective observational study including consecutive patients with indications for posterior repair and Level III support between 2016 and 2018. Concomitant perineorrhaphy was indicated due to complaints of wide introitus or genital hiatus of ≥ 3.5 cm. Primary objective was to compare pre- and postoperative gh and pb according to POP-Q. Secondary objectives were preoperative gh and pb values by parity, POMs obtained with P-QOL/D comparing sexually active vs inactive patients, and subjective judgement of cure according to EGGS system. ResultsIn n = 121 patients, mean gh value was reduced postoperatively by 29.5 % (31 ± 6 vs 44 ± 10 mm, p < 0.001), mean pb value increased by 25.5 % (47 ± 8 vs 35 ± 8 mm, p < 0.001). Influence of parity on preoperative gh (p = 0.020), but not pb values (p = 0.119) was observed. All P-QOL/D domain scores improved significantly postoperatively without differences seen in sexually active vs inactive patients. EGGS responses indicated partial/full goal achievement in 90 % and cure in 87 %. ConclusionsIn the study cohort, perineorrhaphy as concomitant in POP repair led to Level III support reflected by decreased genital hiatus size. Functional QOL was improved regardless of sexual activity status and the majority of patients reported partial or full cure.

MON-LB047 GH Values in Serum and Blood Spots on Filter Paper Samples in Infants until 60 Days of Life by Electrochemiluminescence (ECLIA)

Congenital Growth Hormone Deficiency (GHD) in newborn is an infrequent condition, which can cause threat to life due mainly to hypoglycemia that begins in the first week of life. Severe neonatal GHD needs a fast diagnosis and the substitution with recombinant human GH because of the risk the morbi-mortality. A GH basal level (whether random or associated with spontaneous hypoglycemia) that distinguishes infants with GHD from those with GH sufficiency in the neonatal period is not conclusive. Few data have been reported about the GH measurements in serum and dried blood spots on filter paper samples in healthy neonates born appropriate for gestational age (AGA). Aims: To compare and correlate the GH values in serum and blood spots on filter paper samples in infants until 60 days of life. To establish GH reference values in healthy newborn until 15 days of life. To analyzed the correlation between GH concentrations in serum and blood spot and with hormones of the hypothalamic-pituitary-gonadal and adrenal axis. Subjects and methods: We analyzed 301 serum and whole blood spots samples obtained from AGA neonates between 2-60 days of life (2-15 days n=216, 16-30 days n=65 and 31-60 days n=20 (F: 154, M: 147). GH concentrations were measured by ECLIA Roche C600, which is calibrated against the 2nd International Standard Code 98/574 in serum as well as eluted from filter paper samples. The mean and SD GH value, P 5.0 and P 95.0 were calculated. The statistical analysis was performed by Spearman correlation coefficient. Results: 2-5 days: serum GH (ng/mL) mean value (SD): 20.81(15.8); P5: 6.30, P95: 42.30; 6-15 days: mean GH value 8.78 (4.34); P5: 3.29, P95: 15.19; 16-30 days: mean GH value: F: 10.55 (4.58), M: 7.72 (3.75) and 31-60 days: mean GH value: F: 4.67 (2.75), M 6.82 (4.57). Blood spots GH (ng/mL) mean value (SD): 2-5 days: 17.58 (9.95); P5: 5.68, P95: 33.60; 6-15 days: mean GH value: 10.31 (5.88), P5: 3.0, P95: 21.02; 16-30 days: mean GH value: F: 10.41 (6.01), M: 10.99 (7.78) and 31-60 days: mean GH value: 7.02 (5.25), M 9.12 (8.08). The Spearman correlation obtained between both techniques in parallel measurements was r2=0.85 (p< 0.0001). Conclusions: In agreement with different reports, our results showed high average GH levels in the first few days of life. Human GH secretion is pulsatile from the very beginning, however, newborn screening card spotted with blood during the first week of life, when neonatal hypersomatotropism is present, provides such high levels that, even at the nadir of GH pulsatility a basal value could contribute to detect GHD accurately. The good correlation obtained between both type of samples would indicate that the measurement of GH in dried blood spot samples is an appropriate and reliable method which can be incorporated in the diagnosis of neonatal GHD. The newborn screening samples may be a valuable resource for retrospectively assessing GH sufficiency if this neonatal window has passed. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

SUN-085 Assessing the Impact of Disease Activity on Clot Formation and Lysis in Patients with Acromegaly

Introduction: Data from previous studies suggest increased thrombogenic potential in patients with acromegaly, with higher levels of fibrinogen and a degree of impaired fibrinolysis, which may be contributing to the increased cardiovascular risk associated with acromegaly. However, it remains unclear whether these hemostatic abnormalities reverse in patients with disease remission. Patients and Methods: We conducted a cross-sectional study in 40 patients with acromegaly. The patients were divided into two groups based on the Endocrine Society criteria for disease remission (GH<1mcg/L and IGF-1 within the reference range) at the time of the study. We measured fibrinogen using the Clauss method and also analyzed clot formation and lysis using a validated turbidimetric assay. Results: Twenty-two patients with active acromegaly (Group 1; mean age 51±13 years) and 18 with disease remission (Group 2; mean age 55±13 years) were assessed. There was no difference in the two groups with regards to age, gender distribution, BMI, fat mass (as measured by bioimpedance), skinfold thickness, total cholesterol and HbA1c. Mean GH and IGF-1 values were significantly higher in the group with active acromegaly (2.6±2.4 vs. 0.5±0.5 mcg/L, p<0.001 and 163±105% vs. 73±23% of upper limit of normal, p<0.001 respectively). Mean duration of disease remission in Group 2 was 9.4±6 years. Patients in remission had more prolonged lag time for the initiation of clot formation (571±68 vs. 514±72 sec, p=0.02), however maximum clot optic density was similar in the two groups (Group 1: 0.40±0.12 vs. Group 2: 0.35±0.14 arbitrary units, p=0.26). Additionally, no statistical difference was found in the lysis times in the two groups (mean time from maximum clot formation to 50% lysis was 24.5±18.7 min in Group 1, compared with 34.4±25.3 min in Group 2; p=0.16). Fibrinogen levels were also similar (Group 1: 3.9±1.6 mg/ml vs. Group 2: 3.2±1.5 mg/ml; p=0.2). Duration of active disease was associated with higher fibrinogen levels (coefficient 0.06, p=0.03), while duration of disease remission was associated with longer lag time for clot formation (coefficient 5.0, p=0.015). Disease status was another predictor of lag time for clot formation, with active acromegaly being associated with shorter lag time (coefficient -56.5, p=0.016). Conclusions: We were not able to demonstrate any significant differences in the clot structure properties between patients with active acromegaly and those with disease remission. This may be due to a type II statistical error due to the relatively small sample size or suggest that hemostatic abnormalities described in other studies persist, despite biochemical control of acromegaly. The presence of active disease and the overall duration of this, appear to be associated with increased potential for clot formation in patients with acromegaly.

Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time.

To describe the course of growth hormone response to growth hormone releasing hormone (GHRH) plus arginine provocative test in children with idiopathic short stature (ISS) and to evaluate the role of peak time. A retrospective study was performed analyzing 344 GHRH plus arginine provocative tests performed in children and adolescents with short stature. Serum GH levels were measured at four-time points (T0', T30', T45' and T60') and GH peak was defined as the maximum value at any time point. Mean (T30'-T60') GH value and area under the curve (AUC) were calculated. When analyzing the time of peak at the provocative test, the most frequent peak time was T45' (53.8%) in the ISS group, with no differences in gender, age, and pubertal stage. Analyzing GHD subjects, the most frequent time of peak was T30 (50%). Analyzing the whole population, the GH T0' levels were significantly lower in subjects with the GH peak at T45' than those with the GH peak at T30' (1.7±2.0 vs. 3.2±4.0, p<0.001). In subjects with GH peak at T45', the value of GH peak, AUC and mean GH were significantly higher than in those with GH peak at T30' and T60'. A direct correlation was found between the value of GH peak and growth velocity SDS (r=0.127, p=0.04) and a negative one between GH peak and GH level at T0' (r=-0.111, p=0.04), even when adjusted for gender, age, pubertal stage and BMI Z score. The time peak at 45min seems to be associated with a better response to the test considering GH peak, mean and AUC. Patients with a GH peak at 30min more probably could have a derangement in GH secretion showing worst growth pattern and/or a GH deficiency and should be carefully observed.

Somatostatin Is Essential for the Sexual Dimorphism of GH Secretion, Corticosteroid-Binding Globulin Production, and Corticosterone Levels in Mice

Distinct male and female patterns of pituitary GH secretion produce sexually differentiated hepatic gene expression profiles, thereby influencing steroid and xenobiotic metabolism. We used a fully automated system to obtain serial nocturnal blood samples every 15 minutes from cannulated wild-type (WT) and somatostatin knockout (Sst-KO) mice to determine the role of SST, the principal inhibitor of GH release, in the generation of sexually dimorphic GH pulsatility. WT males had lower mean and median GH values, less random GH secretory bursts, and longer trough periods between GH pulses than WT females. Each of these parameters was feminized in male Sst-KO mice, whereas female Sst-KO mice had higher GH levels than all other groups, but GH pulsatility was unaffected. We next performed hepatic mRNA profiling with high-density microarrays. Male Sst-KO mice exhibited a globally feminized pattern of GH-dependent mRNA levels, but female Sst-KO mice were largely unaffected. Among the differentially expressed female-predominant genes was Serpina6, which encodes corticosteroid-binding globulin (CBG). Increased CBG was associated with elevated diurnal peak plasma corticosterone in unstressed WT females and both sexes of Sst-KO mice compared with WT males. Sst-KO mice also had exaggerated ACTH and corticosterone responses to acute restraint stress. However, consistent with their lack of phenotypic signs of excess glucocorticoids, cerebrospinal fluid concentrations of free corticosterone in Sst-KO mice were not elevated. In summary, SST is necessary for the prolonged interpulse troughs that define masculinized pituitary GH secretion. SST also contributes to sexual dimorphism of the hypothalamic-pituitary-adrenal axis via GH-dependent regulation of hepatic CBG production.

AB0647 Arthritis in systemic lupus erythematosus: A patient’s perspective

BackgroundJoint involvement in systemic lupus erythematosus (SLE) is common and occurs in over 80% of patients. Even if traditionally considered mild and non erosive, joint involvement may cause chronic pain,...

Clinical and metabolic characteristics of acromegalic patients with high IGF1/normal GH levels during somatostatin analog treatment

Divergence between GH and IGF1 values are often reported in treated acromegalic patients, but the mechanisms of this discrepancy have not been completely explored. To evaluate the frequency of divergence between GH and IGF1 values and identify the role of clinical and metabolic factors in treated patients with acromegaly, according to the latest criteria of Cure published in July 2010. Retrospective study of patients' records between October 2002 and March 2008. Patients were grouped according to their mean GH and IGF1 values as 'controlled' (normal GH and IGF1), 'divergent' (high IGF1 and normal GH) and 'uncontrolled' (high GH and IGF1), and compared with respect to their clinical characteristics and metabolic markers. Patients (n=104) were grouped as 'controlled' (n=20), 'divergent' (n=43) and 'uncontrolled' (n=41). More patients in the divergent group (93%) and uncontrolled group (98%) were treated with somatostatin analogs than in the controlled group (65%; P=0.001 for the comparison of the three groups). Patients in the divergent group had higher fasting blood glucose (0.94 g/l (interquartile range: 0.83-1.17)) and systolic blood pressure (130 mmHg (120-140) compared with the controlled group (0.84 g/l (0.80-0.92); P=0.017) and 120 mmHg (interquartile range: 110-130; P=0.029). In patients with divergent IGF1/GH levels, fasting glucose and GH were both strongly associated with IGF1. Totally 41% of treated acromegalic patients had a high IGF1 and normal GH level. In these divergent patients treated with somatostatin analogs, these clinical and metabolic parameters might either play a causal role or be a marker for disease activity.

Assessment of the Magnitude of Growth Hormone Hypersecretion in Active Acromegaly: Reliability of Different Sampling Models

The pulsatility of GH secretion in acromegaly poses difficulty in ascertaining true daily GH milieu in patients with this disease. Intensive GH sampling [every 10-20 (Q10-20) min for 24 h] is not practical in clinical practice. Our objective was to ascertain reliability of abbreviated sampling protocols to reflect true 24-h mean GH concentrations in patients with acromegaly. An analysis of previously obtained plasma GH profiles was performed. The analysis was performed at the General Clinical Research Center at the University of Michigan. A total of 115 GH profiles obtained in 94 patients with active acromegaly were examined. Frequent blood sampling, i.e. Q10-20 min for 24 h, was performed. Concordance of 24-h mean GH concentrations derived from Q10- to 20-min samplings with abbreviated GH sampling schedules was performed. The study was planned after data collection. All abbreviated schedules of GH sampling correlated well with the true 24-h plasma GH means (i.e. Q10- to 20-min sampling) (R = 0.93-0.98; P < 0.0001 for all). In the GH range more than 20 microg/liter, only 5 and 9-h means had R values more than 0.9. Single GH concentrations less than 1 microg/liter had a positive predictive value of only 0.29, and those with less than 2.5 microg/liter had a positive predictive value of 0.67 vs. their corresponding 24-h mean GH values of the same magnitude. The intensity of GH sampling in patients with acromegaly may vary depending on the nature of the required information. Investigators and clinicians should be aware of the limitations of the abbreviated GH sampling protocols in acromegaly.

Ensaios para a medida de hormônio do crescimento (GH) e IGF-I: aspectos metodológicos e suas implicações no diagnóstico e seguimento da acromegalia

Growth hormone quantification in serum is essential for confirming or ruling out its excess. The absence of clinical criteria sufficiently sensitive to evaluate the treatment success enables GH as the key diagnostic procedure and for that, its measurements must be done in a reliable way and must allow uniform interpretation. Several different biochemical criteria for remission have been suggested in the past, including a random GH measurement less than 2.5 microg/l, mean GH value from a day curve less than 2.5 microg/l, nadir GH value after an oral glucose tolerance test (OGGT) less than 1.0 microg/l and a normal age-related IGF-I level. The importance of adequate treatment is highlighted by data indicating that lowering GH levels to less than 2.5 microg/l reverses the premature mortality of acromegaly. With the advances of ultrasensitive assays for GH measurement, strictest remission criteria to determine remission or cure were necessary. In this review, we describe the changes of assay methodology and its consequences in serum GH results and cut off point values to define activity and remission of acromegaly.

Two hour mean GH is not superior to basal GH for the follow-up of acromegalic patients treated with Octreotide LAR ®

Background GH secretion, in acromegaly, is characterized by increased basal levels, as well as by increased frequency and amplitude of pulses. Evaluation of disease activity during follow-up of treated patients is frequently done with mean GH levels, although there is no established protocol for sample collection. Objective Determine mean GH value of 5 blood samples collected 30 min apart for 2 consecutive hours in the follow-up of acromegalic patients treated with octreotide LAR. Methods Ninety-one GH curves of 44 patients (25 women) were evaluated as were the respective IGF-I values (basal). Normal IGF-I for age and sex was considered standard for control of disease activity. Correlations between basal and mean GH were studied as were correlations between both values and %IGF-I above the upper limit of reference values (%ULRV). Results Median age of the group was 45.5 years (range 28–73). Twenty-five patients (56.8%) had previous surgery and 7 (15.9%) had both surgery and radiotherapy. A positive correlation was found between mean and basal GH ( r = 0.953; p < 0.001). Both basal and mean GH were correlated to %ULRV ( r = 0.645 and 0.661; p < 0.001 for both). In only 3 of the 91 curves (3.3%) there were discordances between basal GH and IGF-I, however the latter was concordant with mean GH. In 3 other curves there was concordance between basal GH and IGF-I although the latter was discordant with mean GH. Conclusions There was no benefit to perform GH curves with the present protocol. It may be due to our established outpatient follow up protocol. The use of more complex protocols and the cost of multiple GH assays should be acknowledged, and probably reserved for patients with basal GH levels between 1 and 5 μg/L with discordant GH and IGF-I.

IGF-I/IGF-binding protein-3 combination improves insulin resistance by GH-dependent and independent mechanisms.

IGF-I has been shown to enhance insulin sensitivity in patients with type I and type II diabetes. IGF-I suppresses GH, and this raises the question of whether its ability to enhance insulin sensitivity is mediated solely through a reduction in GH's antiinsulin actions. This study was conducted to determine whether administration of a GH receptor antagonist to patients with acromegaly and insulin resistance would result in improvement in insulin sensitivity and whether IGF-I had any additional insulin-sensitizing effects over and above those induced by its ability to suppress GH secretion. Five patients with active acromegaly were treated for 2 wk with a GH receptor antagonist. The GH receptor antagonist was effective, as IGF-I fell 65%, and mean GH values rose 42%. Mean fasting insulin fell from 39 +/- 6 to 30 +/- 7 micro U/ml, and this was accompanied by a 9% decrease in fasting glucose. After treatment the insulin sensitivity index was 2.7 +/- 1.0 x 10(-4)/min. micro U/ml compared with a baseline value of 1.65 +/- 0.8 x 10(-4)/min. micro U/ml (P < 0.015). Subsequently, the subjects were treated with the receptor antagonist plus IGF-I/IGF-binding protein-3 given by sc injection (1 mg/kg daily). After 2 wk of the combined treatment, fasting insulin fell from 49 +/- 9 to 29 +/- 7 micro U/ml, and fasting glucose fell by 14%. The insulin sensitivity index improved to 4.34 +/- 1.3 x 10(-4)/min. micro U/ml, which was significantly greater than the value obtained after treatment with the GH antagonist alone. Although only a limited number of subjects were studied, the results strongly suggest that IGF-I has insulin-sensitizing actions that are independent of its ability to suppress GH secretion. These findings necessitate further studies into the non-GH-related mechanism by which IGF-I enhances insulin sensitivity.

Acromegaly with apparently normal GH secretion: implications for diagnosis and follow-up.

The biochemical diagnosis of acromegaly is conventionally based on elevated plasma GH levels that fail to suppress after an oral glucose load. We studied 16 newly diagnosed patients with acromegaly with normal mean plasma GH but elevated age and gender-adjusted plasma IGF-I concentrations (476 +/- 29 microg/liter, mean +/- SE). Plasma GH was sampled every 10 min for 24 h, and an oral glucose tolerance test was performed. The control group included 46 healthy subjects. All patients had 24-h mean GH values that overlapped with those of the healthy controls. Mean plasma GH was less than 2.5 microg/liter in 12 patients. Patients had higher 24-h nadir GH values than healthy controls (P < 0.001). During the oral glucose tolerance test, nadir plasma GH was less than 1 micro g/liter in eight patients. Plasma IGF-I normalized in 11 of 14 patients after transsphenoidal surgery. Four patients with normal IGF-I after transsphenoidal surgery were restudied. Mean and nadir GH decreased in all of them. In our experience in many patients with acromegaly, the diagnosis could be missed if only the existing GH-based criteria are used. Revised GH criteria in combination with plasma IGF-I should be used for the diagnosis and follow-up of acromegaly.

Efficacy of the New Long-Acting Formulation of Lanreotide (Lanreotide Autogel) in the Management of Acromegaly

Lanreotide Autogel is a new long-acting aqueous preparation of lanreotide for the treatment of acromegaly and is administered by deep sc injection from a small volume, prefilled syringe. The aim of this study was to evaluate the efficacy and safety of this new long-acting formulation in a large population of acromegalic patients previously responsive to lanreotide 30 mg, im (sustained release microparticle formulation). Lanreotide Autogel was administered by deep sc injection every 28 d to 107 patients (54 males and 53 females; mean age, 54 ± 1.2 yr). All patients had been treated with lanreotide (30 mg) for at least 3 months before study entry and had a mean GH level less than 10 ng/ml after at least 4 subsequent im injections every 14 d (48%), 10 d (32%), or 7 d (20%). Treatment was switched from lanreotide 30 mg injected every 14, 10, or 7 d to 60, 90, or 120 mg lanreotide Autogel, respectively, every 28 d. After three fixed dose injections of lanreotide Autogel, mean lanreotide levels were similar to those obtained at steady state with lanreotide 30 mg. During lanreotide Autogel treatment, the control of acromegalic symptoms was comparable with that previously achieved during lanreotide 30 mg treatment. After 3 injections of lanreotide Autogel, mean GH (2.87 ± 0.22 ng/ml) and IGF-I (317 ± 15 ng/ml) values were comparable with those recorded at the end of lanreotide 30 mg treatment (GH, 2.82 ± 0.19 ng/ml; IGF-I, 323 ± 16 ng/ml). GH levels below 2.5 ng/ml and age-/sex-normalized IGF-I were achieved in 33% and 39% of patients during lanreotide 30 mg and lanreotide Autogel treatment, respectively. Diarrhea, abdominal pain, and nausea were reported by 38%, 22%, and 18% of patients during lanreotide 30 mg treatment and by 29%, 17%, and 9% of patients, respectively, during lanreotide Autogel treatment. In conclusion, this clinical study shows that lanreotide Autogel is at least as efficacious and well tolerated as lanreotide 30 mg. This new long-acting lanreotide formulation, lanreotide Autogel, which is administered from a small volume, prefilled syringe by deep sc injection, is therefore likely to improve the acceptability of medical treatment for patients requiring long-term somatostatin analog therapy.

Predictors of the outcome of surgical treatment in acromegaly and the value of the mean growth hormone day curve in assessing postoperative disease activity.

Acromegaly is associated with increased morbidity and mortality unless serum GH levels are persistently less than 5 mU/L ( approximately 2 ng/mL) after treatment. Transsphenoidal surgical resection is the best available treatment for restoring GH to such "safe" levels; however, criteria for the assessment of the response to treatment are not uniform. To determine the clinically most useful method of assessing disease activity postoperatively and identify predictors of a favorable response to surgical treatment, we have analyzed 67 patients with acromegaly who underwent transsphenoidal surgery between 1993 and 1998. We used three different definitions of a satisfactory or safe response: 1) a postoperative mean GH less than 5 mU/L obtained from averaging five serum GH values obtained throughout one day; 2) a random single GH less than 5 mU/L; or 3) a serum insulin-like growth factor I (IGF-I) level within the normal range. Relying on a single GH measurement alone, 9 of the 23 patients with a single postoperative mean GH level less than 5 mU/L obtained at least one GH value of more than 5 mU/L (false positive rate, 28%) and 8 of the patients with a postoperative mean GH value of more than 5 mU/L obtained a single GH value of less than 5 mU/L (false negative rate, 15%). Postoperatively, a significant increase in the fluctuation of random GH values around the mean was observed in patients who were rendered safe (coefficient of variation, from 26 +/- 2% to 53 +/- 6%; P < 0.001) compared with patients with persistence of inadequately controlled disease. However, 13% (3 of 23) of patients with mean postoperative GH levels of less than 5 mU/L had elevated serum IGF-I levels postoperatively, and 17% (8 of 44) of patients with mean serum GH levels more than 5 mU/L had postoperative IGF-I levels within the normal range. There was no difference in the rate of agreement between mean GH less than 5 mU/L and normalization of IGF-I in relation to the interval since operation when IGF-I levels were measured. Preoperative tumor size and pretreatment mean GH levels were the major determinants of the outcome of surgery, as patients who were rendered safe had significantly lower preoperative mean GH levels than patients who were not cured (median, 31 mU/L vs. 78.5 mU/L, P < 0.01). IGF-I levels were weakly correlated with tumor size and could not be used to predict the patients who would be rendered safe. Preoperative PRL levels were higher in patients who failed to achieve a surgical satisfactory outcome [498 mU/L (187-857) vs. 196 mU/L (136-315), P < 0.01]. In summary, although single random GH values and IGF-I values are both significantly correlated with mean GH levels, they should not be used as an alternative to averaging several GH values to assess disease activity, because of the pulsatile nature of GH secretion and the multiple factors that may influence serum IGF-I. Because significant discrepancies occur, particularly postoperatively, mean GH levels remain the more reliable indicator of surgical outcome and disease activity. As there is considerably more evidence relating long-term prognosis to serum GH levels than to IGF-I and discrepancies occur between GH levels and IGF-I, we suggest that mean serum GH levels and single IGF-I levels, measured early in the postoperative period, are currently the best biochemical guide to the adequacy of surgery and, hence, the need for further treatment.

Results of a two-year treatment with slow release lanreotide in acromegaly.

In this open sequential study we evaluated the long-term effectiveness and tolerability of the i.m. administration of slow release lanreotide 30 mg (SRL) in 18 acromegalics (7 M/11 F, age 50.9+/-12.7 yr). Baseline mean GH and IGF-1 levels were 15.8+/-6.6 ng/ml and 702+/-74 ng/ml, respectively. Four hours, 1, 7, and 14 days after SRL, mean GH levels were 8.9+/-5.9 (p < 0.005), 11.4+/-6.9 (p < 0.05), 9.1+/-4.5 (p < 0.05), and 9.1+/-4.1 ng/ml (p < 0.05), respectively; and the IGF-1 values at 1, 7, and 14 days were 624+/-77 (p < 0.05), 555+/-83 (p < 0.001), and 467+/-58 ng/ml (p < 0.0001), respectively. Four hours after SRL administration GH was < 2.5 ng/ml in 11 patients and decreased 85% of the basal value, without normalizing, in another case. In the following 2 weeks, 7 and 2 patients maintained GH < 2.5 ng/ ml or < 50% of baseline; 3 and 2 of them attained IGF-1 values in the normal range or < 50% of basal levels. A patient developed acute pancreatitis after the injection of the drug and therefore stopped the treatment. Another patient did not continue SRL, and she was turned on octreotide, s.c. administered (OCT), because only the latter treatment ameliorated significantly the headache. In 16/18 patients the treatment was continued until the 24th month. SRL was administered every 14 days until the 24th month in 3 cases, whereas in 13 patients the dose schedule was increased every 10 days since the 7th month because they did not normalize serum GH and IGF-1 levels. In these 16 patients baseline GH and IGF-1 levels were 10.0+/-2.5 ng/ml and 671+/-75 ng/ml, respectively. At the 1st, 3rd, and 6th month of treatment mean GH levels fell to 5.4+/-1.4 (p < 0.05), 5.3+/-1.8 (p < 0.05), and 5.0+/-1.6 (p < 0.05) ng/ml, respectively; and IGF-1 declined to 511+/-87 (p < 0.005), 565+/-85 (p < 0.05), and 525+/-94 (p < 0.01) ng/ml, respectively. Throughout the first semester GH was < 2.5 ng/ml in 5 patients and decreased > 50% in another three. IGF-1 levels normalized in 3/5. Throughout the following 18 months of treatment, mean GH (3.4+/-1.0 ng/ml) and IGF-1 (413+/-75 ng/ml) values decreased significantly in comparison with both the baseline concentrations (GH p < 0.01, IGF-1 p < 0.001) and the levels measured during the 1st semester of treatment (GH p < 0.05, IGF-1 p < 0.001). GH remained < 2.5 ng/ml in 11 patients, and in 8/11 cases IGF-1 fell in the normal range. Serum GH and IGF-1 levels decreased by more than 50% of baseline levels in 2 other cases. At MRI, pituitary adenoma was no longer evident in one patient previously treated with OCT and significantly decreased in another patient previously treated with surgery plus radiotherapy, as well as in a patient previously untreated. During treatment the percentage of patients complaining of headache and fatigue decreased significantly (chi2, p < 0.05 and p < 0.0005, respectively). Overall, the headache (p < 0.005), arthralgia (p < 0.05), and paresthesia (p < 0.01) ameliorated significantly. Ultrasound scan showed gallbladder sludge or sand-like stones in 5/11 patients. This study, which is one of the longest surveys on a relatively large series of acromegalics treated with SRL, confirms the long-term effectiveness of this drug for the treatment of patients with active acromegaly. SRL decreases significantly GH and IGF-1 in most cases and induces the shrinkage of the pituitary tumor in some patients previously either untreated or both treated for acromegaly. SRL improves significantly clinical symptoms and it is well tolerated.

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.

Late-Night Snacking Decreases Nocturnal Secretion of Growth Hormone

The effect of snacking before going to sleep on the nocturnal secretion of GH was investigated in 7 children with non-GH deficiency short stature. Each child was tested on two nights: on one night, the child ate a snack before going to bed, but on the other night, the child did not. Serum GH concentrations were measured every 20 min during the first 3 h of sleep. GH concentrations in urine collected the following morning were also examined. Mean and maximum serum GH values, and urinary GH concentrations were lower in all of the children when they had eaten a snack before going to bed.

Differential impact of age, sex steroid hormones, and obesity on basal versus pulsatile growth hormone secretion in men as assessed in an ultrasensitive chemiluminescence assay.

A chemiluminescence-based GH assay with 30- to 100-fold increased sensitivity recently disclosed combined basal and pulsatile GH secretion in men. However, how age, sex steroid hormones, and obesity singly and jointly influence the basal vs. pulsatile modes of GH release is not known. We used the foregoing assay (detection threshold, 0.002-0.005 microgram/L) and high sensitivity and specificity (> or = 90% each) deconvolution analysis to quantitate basal and pulsatile GH secretion from 24-h serum GH concentration profiles in 26 healthy lean and obese men, whose ages spanned 18-63 yr and whose percentage body fat ranged from 12-47%. Concentrations of serum insulin-like growth factor I (IGF-I), IGF-I-binding protein-1 (IGFBP-1), and IGFBP-3 were related to specific measures of basal or pulsatile GH release. We observed that mean (24-h) serum GH concentrations embraced a 140-fold range from 0.013-1.8 micrograms/L and were related negatively to age (r = -0.50; P < 0.01), percentage body fat (r = -0.620; P < 0.01), and their interaction (r = -0.610; P < 0.01). In contrast, testosterone was a robustly positive statistical determinant of mean serum GH values (r = 0.628; P = 0.0006). Stepwise multivariate regression analysis disclosed that percentage body fat alone and jointly with the serum testosterone concentration controlled, respectively, 38% and 50% of the total variability in GH levels (P = 0.0013 and P = 0.0008). As assessed by deconvolution analysis, GH secretory burst mass was negatively related to percentage body fat (r = -0.621; P < 0.01) and positively to serum testosterone (r = 0.529; P = 0.0054). The calculated half-life of GH correlated positively with serum estradiol (r = 0.447; P = 0.032), and negatively with percentage body fat (r = -0.437; P = 0.048). Basal GH secretion rates were negatively related to serum estradiol (r = -0.485; P = 0.016). In contrast, GH secretory burst frequency and duration were unrelated to age, percentage body fat, or sex steroids. The fraction of total GH secreted in bursts was negatively correlated with the body mass index (r = -0.540; P < 0.01). Serum IGF-I concentrations were positively related to total pulsatile GH secretion (r = 0.690; P = 0.0011) and negatively to age (r = -0.597; P = 0.007) and percentage body fat (r = -0.611; P = 0.009).(ABSTRACT TRUNCATED AT 400 WORDS)

Serum lipoproteins in acromegaly before and 6-15 months after transsphenoidal adenomectomy.

Acromegaly is a rare disorder characterized by over-secretion of GH, most often because of a pituitary adenoma. The disease is associated with disturbances in lipoprotein metabolism and an increased cardiovascular mortality. The aim of the present study was to investigate whether treatment of acromegaly results in changes in serum concentrations of lipids and apolipoproteins, including lipoprotein(a) (Lp(a)). Fourteen patients with clinical features of acromegaly and increased GH secretion were studied 1-10 months before and 6-15 months after transsphenoidal adenomectomy in an open study. Three patients had diabetes mellitus before surgery and two of these patients had normalized serum glucose levels post-operatively. Mean and baseline plasma GH levels were determined from 24-hour GH profiles. Serum samples were taken in the morning after an overnight fast. All patients were normocholesterolaemic, and four patients were hypertriglyceridaemic before treatment. Mean plasma GH levels decreased from 34.5 +/- 7.4 to 2.1 +/- 0.4 mU/l (mean +/- SEM). Serum IGF-I, insulin and free T3 levels decreased and serum SHBG concentrations increased post-operatively. There was no effect of treatment on serum cholesterol concentrations, but serum triglyceride concentrations decreased. Serum apolipoprotein (apo) B and apoE levels were unaffected by treatment. Serum apoA-I levels increased and Lp(a) levels decreased post-operatively. Successful treatment of acromegaly, resulting in normal mean GH values (< 5 mU/l) and/or normal responsiveness to TRH, have beneficial effects on serum lipoproteins with increased serum apoA-I levels and decreased serum levels of triglycerides and Lp(a). These effects seem to be independent of improvement in glucose tolerance, since patients with diabetes mellitus before surgery and normal fasting blood glucose levels post-operatively had similar lipoprotein responses to treatment as those with normal fasting blood glucose levels before surgery.

Slow release lanreotide treatment in acromegalic patients previously normalized by octreotide.

Several clinical studies reported the efficacy of the long-acting SRIH analog, octreotide (Octreotide, Sandoz) in the treatment of acromegaly. Recently, another SRIH analog (BIM 23014, Ipsen Biotech) was shown to decrease plasma GH levels in acromegalic patients. The recent availability of a long-acting formulation of BIM 23014 [slow release (SR) lanreotide] could avoid the inconveniences associated with either repeated sc injections or continuous sc infusions. In this study, we compared the clinical and biochemical efficacies of both drugs in a cohort of 19 acromegalic patients, considered initially as responsive to octreotide and sequentially treated with octreotide (3 sc injections of 100-200 micrograms/day) for 12 months and with SR lanreotide (30 mg, im, every 10 or 14 days) for 6 months. Before octreotide treatment, baseline plasma GH (mean +/- SE of 8 hourly samplings) was 29.0 +/- 10.0 micrograms/L and was lowered to 3.2 +/- .2 micrograms/L during the first 7 h after the first 100-micrograms sc octreotide administration. After 12 months of treatment with octreotide, 14 of 19 patients (74%) were considered normalized, as their mean individual GH profiles and insulin-like growth factor-I (IGF-I) values were within the normal range. After octreotide withdrawal for 1 week, plasma GH and IGF-I levels rose to 18.3 +/- 4.8 and 4.1 +/- 0.4 U/mL, respectively. The first 30-mg SR lanreotide im injection produced an acute suppression of plasma GH levels (mean GH value during the 7 h after the injection, 3.0 +/- 0.4 micrograms/L), not different from results previously observed after the first octreotide injection. After 3 months of treatment with 30 mg SR lanreotide every 14 days, normalization of baseline GH and IGF1 levels was achieved in 6 of 19 patients. Ten patients, who did not achieve normal GH levels, subsequently received a 30-mg SR lanreotide injection every 10 days. Among them, normalization of GH and IGF-I levels occurred in 7 of 10 patients after 3 months of such a regimen. After 6 months of SR lanreotide treatment, 13 of 19 patients (68%) were considered normalized, with mean GH and IGF-I values, respectively, of 3.1 +/- 0.4 micrograms/L and 1.5 +/- 0.1 U/mL. The overall tolerance of both drugs (glucose homeostasis and gallstone formation) was similar.(ABSTRACT TRUNCATED AT 400 WORDS)