Purpose
The aim of this study was to evaluate the somatotroph axis in a large series of patients with prolactinoma to verify the prevalence of silent acromegaly in this population.
Methods
A hundred ...and forty-four patients were enrolled in a multicenter study: 90 were already on cabergoline (CAB) and enrolled in a cross-sectional arm (group A) with random PRL, GH and IGF-I determination on treatment (≥ 3 months), whereas 54 untreated patients were enrolled at diagnosis in a prospective arm (group B) with PRL, GH and IGF-I measurement before and after 6 and 12 months of treatment. In the presence of high IGF-I, CAB was withdrawn for 3 months and GH, IGF-I, PRL and GH during an oral Glucose Tolerance Test (OGTT) were obtained.
Results
High IGF-I levels (ULN 1.01–1.56) were observed in 9 patients (6.25%, 5F). After CAB withdrawal, IGF-I levels normalized in 5/9 patients, GH was < 0.4 ng/ml after OGTT in 7/9 cases or at random GH determination in one case. After CAB re-introduction, IGF-I levels re-increased in a single case. Overall, a single young female patient harboring a macroadenoma in group A was diagnosed with silent acromegaly and underwent successful transsphenoidal removal of a GH/PRL-secreting adenoma.
Conclusion
The prevalence of silent acromegaly in prolactinomas (0.7%) is lower than previously reported and OGTT is helpful to recognize silent acromegaly. We suggest that the somatotroph axis should be evaluated at diagnosis in all cases and not systematically during follow-up.
Purpose
Somatostatin receptor ligands (SRL) are the first-line medical treatment for acromegaly. Gallbladder alterations are one of most important SRL side effect, but according to some authors ...growth hormone hypersecretion itself is a risk factor for gallstones. This single center, longitudinal retrospective study evaluated the incidence and the predictors of biliary adverse events (BAE) in acromegaly during SRL therapy and their response to ursodeoxycholic acid (UDCA).
Methods
91 acromegaly patients with indication to SRL were enrolled. Evaluations of acromegaly activity (GH, IGF-I, IGF-I/ULN) and metabolic profile were collected before starting treatment, yearly during follow-up and at BAE onset. In patients developing BAE we searched for predictors of UDCA effectiveness.
Results
61.5% of patients developed BAE (58.9% cholelithiasis; 41.1% only sludge). IGF-I and IGF-I/ULN proved to be positive predictor of BAE, which occur about 5 years after SRL starting. None of metabolic markers proved to be associated with BAE. Only five patients (5.5%) underwent cholecystectomy for symptomatic cholelithiasis. 71% of patients started UDCA treatment, achieving regression of BAE in 60% of cases (88% in patients developing only sludge and 30% in patients affected by cholelithiasis, p < 0.001). BMI and obesity were negative predictors of UDCA efficacy. In 50% of the subjects BAE resolved after 36 months of therapy with a lower rate if cholelithiasis was present.
Conclusion
Biliary stone disease is a frequent SRL adverse event, although it is often symptomless. Ultrasound follow-up mainly in the first 5 years of therapy, early UDCA starting and proper lifestyle represent a valid strategy in their detection and management.
The central goal of this study was to identify the primary mechanisms triggering steroid atrophy. Adaptations of soleus (Sol) and vastus lateralis (VL) muscles of C57BL/6 female mice were studied ...following 3, 7 and 15 days of daily intraperitoneal injection (5 mg kg
day
) of dexamethasone (dEx) (chronic treatment) and 1, 3 and 10 hours after a single dEx injection (acute treatment). In the chronic treatment, analyses were performed 24 hours after the last injection. Gene expression of major components of the intracellular signalling pathways controlling mass and metabolism were assessed. Analyses were repeated following dEx and unacylated ghrelin (uAG) (100 μg kg
day
), co-administration. We found a significant VL fibres atrophy after 7 (13%) and 15 (28%) days and a Sol fibres atrophy (23%) after 15 days of dEx treatment. The acute treatment showed, in both muscles, several responses in most signalling pathways, among which the enhanced gene expression of Murf-1 (6-fold change in VL and 3-fold in Sol) and myostatin (6-fold change in VL and 20-fold in Sol). In Sol, uAG administration was able to fully counteract muscle atrophy and Murf-1 upregulation, but not the upregulation of myostatin, suggesting a causal relationship between muscle atrophy and Murf-1. Results indicate that: a) the primary mechanism triggering steroid atrophy is an early transient activation of Murf-1; b) uAG inhibits Murf-1 induction counteracting steroid atrophy. The present work contributes to the understanding of the complexity of the muscle response to glucocorticoids.
In this article, we present the draft genome sequence of Metabacillus niabensis strain 4T19T (= CSUR Q2603 T = DSM 17723 = JCM 16399 = KACC 11279), that is a new Metabacillus species isolated from ...cotton-waste composts. The genome sequence from Metabacillus niabensis strain 4T19T was assembled into 462 contigs for a total size of 4,987,608 bp with a G + C content of 35.5%.
Obestatin is a 23 amino acid peptide encoded by the ghrelin gene, which, like ghrelin, is mainly produced by the stomach, as well as by a wide range of other tissues. Obestatin remains a ...controversial peptide, as the initial finding of its binding to the orphan receptor GPR39 and the inhibitory effect on food intake has been questioned. In fact, to date, its biological effects are still largely unknown, although it is becoming clear that obestatin is a pleiotropic hormone, exerting a variety of effects in different cell types and tissues. Indeed, besides regulating cell proliferation and survival, obestatin has been shown to regulate glucose and lipid metabolism, both in vitro, in pancreatic β-cells and adipocytes, and in vivo in rodents. Furthermore, its positive effects on glucose homeostasis, combined with the anti-inflammatory actions, make this peptide appealing as a candidate for treating metabolic disorders such as insulin resistance and diabetes.
ACROSTUDY: the Italian experience Grottoli, S.; Maffei, P.; Bogazzi, F. ...
Endocrine,
02/2015, Letnik:
48, Številka:
1
Journal Article
Recenzirano
Odprti dostop
ACROSTUDY is a world-wide non-interventional, post marketing surveillance study performed to monitor the safety and outcomes of pegvisomant (PEG) in clinical practice. We report data from acromegaly ...patients who have been included in the Italian ACROSTUDY registry. The data of 341 acromegaly patients (171 males) were available for analysis using data freeze (12/9/2012). Patients were enrolled in 25 Italian endocrine centres. Before and during PEG treatment IGF-I, liver enzymes, metabolic parameters, and pituitary MRI were assessed. Before PEG, 54.3 % patients had been treated with medical therapy and surgery, 22.9 % medical therapy only, and 15.8 % medical plus radiation and surgical therapy. 199 adverse events were reported in 98 patients (28.7 %). Serious adverse events were documented in 29 patients (8.5 %). 71.1 % of patients had no significant change in tumor volume. Central MRI reading was performed in 34 patients; in 7 patients, an increase in tumor volume was found. Hormonal efficacy progressively increased since the start of PEG. After 6 years, normal IGF-I levels were found in 70.9 % of patients (mean daily dose 18.1 mg). 87.1 % of patients were treated with daily PEG although in 8.8 % of patients, it was administered 2–6 times per week and in 3.8 % with weekly injections. 74.8 % received a PEG dose 10–15 mg/daily. PEG is a drug with a favorable safety profile which is efficacious also considering that in Italy it is currently available as third-line therapy.
Purpose
Pegvisomant (PEGV) treatment in acromegaly patients resistant to somatostatin analogues is less effective in the real life than in clinical trials. This is a multicenter, observational, ...retrospective, longitudinal study. The aim was to detect characteristics which improve long-term PEGV effectiveness.
Methods
87 acromegalic patients treated with PEGV have been enrolled in seven referral Italian centres. PEGV was administered for up to 4 years, at doses up titrated until IGF-1 normalization or to ≥ 30 mg/day. The rate of patients who reached IGF-1 normalization at last visit has been calculated.
Results
IGF-1 was normalized in 75.9% of patients after 1 year and in 89.6% at last visit. Disease control was associated with lower baseline GH, IGF-1 and IGF-1 xULN and was more frequent when baseline IGF-1 was < 2.7 × ULN (
p
< 0.02). PEGV dose was dependent on baseline IGF-1 > 2.7 × ULN (
p
< 0.05) and doses > 1.0 mg/BMI/day were administered more frequently when baseline IGF-1 was > 2.0 × ULN (
p
= 0.03). PEGV resistance was associated with higher BMI (
p
= 0.006) and was more frequent when BMI was > 30 kg/m
2
(
p
= 0.07). There were no significant differences between patients treated with monotherapy or combined treatment. IGF-1 normalization, PEGV dose and rate of associated treatment were similar between males and females. PEGV effectiveness was independent from previous management. Diabetic patients needed higher doses of PEGV than non-diabetic ones.
Conclusions
PEGV effectiveness improves when up titration is appropriate. Higher PEGV doses at start and a more rapid up-titration are necessary in patients with obesity and/or IGF-1 > 2.7 × ULN.
Ghrelin, a natural growth hormone secretagogue (GHS), has been identified in prostate carcinoma cell lines.
To investigate the presence of ghrelin and its receptors in human prostate tumours and in ...DU-145, PC-3 and LNCaP prostate carcinoma cell lines, and to assess the effects of ghrelin and its more abundant circulating form, des-octanoyl ghrelin, on cell proliferation.
Ghrelin and types 1a and 1b GHS receptor (GHS-R) were determined at the mRNA and protein levels by RT-PCR, in situ hybridization, immunohistochemistry and enzyme immunoassay in tissues, cell lines and culture medium. Ghrelin binding was determined by radioreceptor assay. The effects on cell proliferation were evaluated by growth curves.
Ghrelin mRNA was found in prostatic carcinomas and benign hyperplasias, but immunohistochemistry was negative. GHS-R1a and 1b mRNAs were absent from carcinomas, but GHS-R1b mRNA was present in 50% of hyperplasias. Ghrelin peptide and mRNA were present in PC-3 cells exclusively, whereas GHS-R1a and 1b mRNAs were expressed in DU-145 cells only. Specific 125ITyr4-ghrelin binding was detected in prostate tumour, DU-145 and PC-3 cell membranes and the binding was displaced by ghrelin, synthetic GHS and des-octanoyl ghrelin, which is devoid of GHS-R1a binding affinity and GH-releasing activity. Ghrelin and des-acyl ghrelin inhibited DU-145 cell proliferation, displayed a biphasic effect in PC-3 cells and were ineffective in LNCaP cells.
Specific GHS binding sites, other than GHS-R1a and 1b, are present in human prostatic neoplasms. Ghrelin, in addition to des-acyl ghrelin, exerts different effects on cell proliferation in prostate carcinoma cell lines.
Background:
Type 2 diabetes mellitus has been associated with an increased cancer risk, which can be modified by specific hypoglycemic drugs. In particular, metformin, the most frequently prescribed ...biguanide, is now considered a protective agent against cancer incidence and mortality in Type 2 diabetic patients.
Aims:
To review the potential associations between metformin use and cancer incidence and mortality and the possible biological links implicated in these associations.
Materials and methods:
We searched English-language original investigations published through September 2011.
Results:
Metformin could block the mitogenic effects of insulin, but this effect does not entirely explain the reduction in cancer incidence. Metformin also plays a direct inhibition of cancer cell growth
via
the inhibitory effects of AMP-activated protein kinase on the mTOR pathway, which regulates cell growth and proliferation. Accordingly, many epidemiological studies have shown that metformin use is associated with a lower cancer incidence and mortality through a dose-response relationship, with greater exposure being associated with stronger risk reduction. Randomized clinical trials testing the effects of metformin on both recurrence and survival in early-stage breast cancer are on-going; these trials are based on pilot studies demonstrating an adjuvant effect of this drug in breast cancer.
Conclusions:
Metformin is an inexpensive and safe drug, that may modify the increased cancer risk of Type 2 diabetic patients. On-going clinical trials will show whether this drug can enhance the effect of chemotherapy in the treatment of cancer.
Ghrelin is a novel growth hormone (GH) releaser acylated peptide that has recently been purified from stomach, and which potently binds to the GH secretagogue receptor. Ghrelin releases GH in vitro ...and in vivo in animal models, however its actions, potency and specificity in humans are unknown. In the present study, 12 healthy subjects were studied: 6 underwent four tests with ghrelin administered i.v. at the dose of 0 (placebo), 0.25, 0.5 and 1 microg/kg which corresponds to 0, 18, 37 and 75 microg total dose. A further 6 volunteers underwent two tests on different days with ghrelin at the dose of 3.3 or 6.6 microg/kg which corresponds to 250 microg and 500 microg total dose. Ghrelin-mediated GH secretion showed a dose-response curve, in which 1 microg/kg was the minimally effective dose in some individuals, but not as a group. On the contrary, the total doses of 250 microg and 500 microg elicited a powerful GH secretion, with a mean peak of 69.8+/-9.2 microg/l and 90.9+/-16.9 microg/l respectively, and areas under the curve of 4435+/-608 and 6125+/-1008 microg/l per 120 min respectively. All of them statistically significant vs placebo and vs the 1 microg/kg dose. Ghrelin administration also elicited a relevant dose-response mediated prolactin secretion suggesting no specificity of its actions. No relevant side effects were observed with ghrelin apart from a hyperhydrosis episode in two individuals tested with the higher ghrelin doses. In conclusion, ghrelin is a potent releaser of GH in normal individuals, with a dose-response pattern of operation. No saturating dose was observed.
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