scholarly journals Hepatic Steatosis Index in Acromegaly: Correlation with Insulin Resistance Regardless of the Disease Control

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Alessandro Ciresi ◽  
Valentina Guarnotta ◽  
Daniela Campo ◽  
Carla Giordano
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Noninvasive Methods ◽  
Somatostatin Receptor Ligands ◽  
Hepatic Steatosis Index ◽  
Surrogate Index ◽  
Gh Excess

Objective. In acromegaly, both lipotoxicity secondary to GH excess and insulin resistance have a significant impact on the liver. Ultrasonography has shown poor sensitivity in detecting hepatic steatosis and noninvasive methods have been proposed. We evaluated the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, and we correlated it with disease activity and insulin resistance. Design. Thirty-one patients with newly diagnosed acromegaly were studied at diagnosis and after 12 months of treatment with somatostatin receptor ligands. Methods. Glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis through ultrasonography and HSI were evaluated. Results. At diagnosis, ultrasonography documented steatosis in 19 patients (61.2%) while 26 (83.8%) showed high HSI. After 12 months, both GH (p=0.033) and IGF-1 (p<0.001) significantly decreased and, overall, 58% of patients were classified as controlled. Ultrasonography documented steatosis in all the same initial 19 patients, while only 14 patients (45.1%) showed high HSI (p<0.001). A significant reduction in HOMA-IR (p=0.002) and HSI (p<0.001) and increased ISI Matsuda (p<0.001), was documented. The change of HSI from baseline to 12 months was found to be directly correlated with the change of ISI (Rho -0.611; p=0.004) while no correlation was found with the change of GH or IGF-1 levels and other parameters. Conclusions. In acromegaly, HSI is mainly related with insulin resistance and the reduction of GH and IGF-1 levels, and above all the improvement in insulin sensitivity leads to an improvement of this surrogate index of hepatic steatosis.

Diverse Peptidyl Privileged Structures as Potent Somatostatin Receptor Ligands

2004 ◽  
Vol 1 (2) ◽  
pp. 121-125 ◽  
Author(s):  
Alexander Pasternak ◽  
Yanping Pan ◽  
Ralph Mosley ◽  
Susan Rohrer ◽  
Elizabeth Birzin ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Privileged Structures

MRI follow‐up of patients with acromegaly treated after surgery with first‐generation somatostatin receptor ligands

2021 ◽  
Author(s):  
Naia Grandgeorge ◽  
Giovanni Barchetti ◽  
Solange Grunenwald ◽  
Fabrice Bonneville ◽  
Philippe Caron
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands

scholarly journals Treatment of Aggressive Pituitary Adenomas: A Case-Based Narrative Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Odelia Cooper ◽  
Vivien Bonert ◽  
Ning-Ai Liu ◽  
Adam N. Mamelak
Keyword(s):  
Radiation Therapy ◽  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Mtor Inhibitors ◽  
Disease Recurrence ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Individualized Approach ◽  
Evidence Based Guidelines

Management of aggressive pituitary adenomas is challenging due to a paucity of rigorous evidence supporting available treatment approaches. Recent guidelines emphasize the need to maximize standard therapies as well as the use of temozolomide and radiation therapy to treat disease recurrence. However, often these adenomas continue to progress over time, necessitating the use of additional targeted therapies which also impact quality of life and long-term outcomes. In this review, we present 9 cases of aggressive pituitary adenomas to illustrate the importance of a multidisciplinary, individualized approach. The timing and rationale for surgery, radiation therapy, temozolomide, somatostatin receptor ligands, and EGFR, VEGF, and mTOR inhibitors in each case are discussed within the context of evidence-based guidelines and clarify strategies for implementing an individualized approach in the management of these difficult-to-treat-adenomas.

Molecular determinants of enhanced response to somatostatin receptor ligands after debulking in large GH producing adenomas

2020 ◽  
Author(s):  
Joan Gil ◽  
Montserrat Marqués‐Pamies ◽  
Mireia Jordà ◽  
Carmen Fajardo‐Montañana ◽  
Araceli García‐Martínez ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Molecular Determinants

scholarly journals Maintenance of Acromegaly Control in Patients Switching From Injectable Somatostatin Receptor Ligands to Oral Octreotide

2020 ◽  
Vol 105 (10) ◽  
pp. e3785-e3797 ◽  
Author(s):  
Susan L Samson ◽  
Lisa B Nachtigall ◽  
Maria Fleseriu ◽  
Murray B Gordon ◽  
Marek Bolanowski ◽  
...  
Keyword(s):  
Somatostatin Receptor ◽  
Control Measures ◽  
Double Blind Study ◽  
Efficacy And Safety ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Phase 3 ◽  
Double Blind ◽  
Somatostatin Receptor Ligands ◽  
End Of Treatment

Abstract Purpose The phase 3 CHIASMA OPTIMAL trial (NCT03252353) evaluated efficacy and safety of oral octreotide capsules (OOCs) in patients with acromegaly who previously demonstrated biochemical control while receiving injectable somatostatin receptor ligands (SRLs). Methods In this double-blind study, patients (N = 56) stratified by prior SRL dose were randomly assigned 1:1 to OOC or placebo for 36 weeks. The primary end point was maintenance of biochemical control at the end of treatment (mean insulin-like growth factor 1 [IGF-1] ≤ 1.0 × upper limit of normal [ULN]; weeks 34 and 36). Time to loss of IGF-1 response and proportion requiring reversion to injectable SRLs were assessed as broader control measures. Results Mean IGF-1 measurements were 0.80 and 0.97 × ULN for OOC and 0.84 and 1.69 × ULN for placebo, at baseline and end of treatment, respectively. Mean growth hormone (GH) changed from 0.66 to 0.60 ng/mL for OOCs and 0.90 to 2.57 ng/mL for placebo. Normalization of IGF-1 levels (≤ 1.0 × ULN) was maintained in 58.2% for OOCs vs 19.4% for placebo (P = .008); GH levels were maintained (&lt; 2.5 ng/mL) in 77.7% for OOC vs 30.4% for placebo (P = .0007). Median time to loss of response (IGF-1 &gt; 1.0 or ≥ 1.3 × ULN definitions) for patients receiving placebo was 16 weeks; for patients receiving OOCs, it was not reached for both definitions during the 36-week trial (P &lt; .0001). Of the patients in the OOC group, 75% completed the trial on oral therapy. The OOC safety profile was consistent with previous SRL experience. Conclusions OOCs may be an effective therapy for patients with acromegaly who previously were treated with injectable SRLs.

scholarly journals Role of Cannabinoid Receptor Type 1 in Insulin Resistance and Its Biological Implications

2019 ◽  
Vol 20 (9) ◽  
pp. 2109 ◽  
Author(s):  
Arulkumar Nagappan ◽  
Jooyeon Shin ◽  
Myeong Ho Jung
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Hepatic Steatosis ◽  
Cannabinoid Receptor ◽  
Inflammatory Responses ◽  
Hepatic Insulin Resistance ◽  
Leptin Resistance ◽  
Peripheral Tissues

Endogenous cannabinoids (ECs) are lipid-signaling molecules that specifically bind to cannabinoid receptor types 1 and 2 (CB1R and CB2R) and are highly expressed in central and many peripheral tissues under pathological conditions. Activation of hepatic CB1R is associated with obesity, insulin resistance, and impaired metabolic function, owing to increased energy intake and storage, impaired glucose and lipid metabolism, and enhanced oxidative stress and inflammatory responses. Additionally, blocking peripheral CB1R improves insulin sensitivity and glucose metabolism and also reduces hepatic steatosis and body weight in obese mice. Thus, targeting EC receptors, especially CB1R, may provide a potential therapeutic strategy against obesity and insulin resistance. There are many CB1R antagonists, including inverse agonists and natural compounds that target CB1R and can reduce body weight, adiposity, and hepatic steatosis, and those that improve insulin sensitivity and reverse leptin resistance. Recently, the use of CB1R antagonists was suspended due to adverse central effects, and this caused a major setback in the development of CB1R antagonists. Recent studies, however, have focused on development of antagonists lacking adverse effects. In this review, we detail the important role of CB1R in hepatic insulin resistance and the possible underlying mechanisms, and the therapeutic potential of CB1R targeting is also discussed.

scholarly journals Medical Therapy of Acromegaly

2012 ◽  
Vol 2012 ◽  
pp. 1-22 ◽  
Author(s):  
U. Plöckinger
Keyword(s):  
Medical Therapy ◽  
Mechanism Of Action ◽  
Present Status ◽  
Therapeutic Efficacy ◽  
Dopamine Agonists ◽  
Somatostatin Receptor ◽  
Postoperative Treatment ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Remission Criteria

This paper outlines the present status of medical therapy of acromegaly. Indications for permanent postoperative treatment, postirradiation treamtent to bridge the interval until remission as well as primary medical therapy are elaborated. Therapeutic efficacy of the different available drugs—somatostatin receptor ligands (SRLs), dopamine agonists, and the GH antagonist Pegvisomant—is discussed, as are the indications for and efficacy of their respective combinations. Information on their mechanism of action, and some pharmakokinetic data are included. Special emphasis is given to the difficulties to define remission criteria of acromegaly due to technical assay problems. An algorithm for medical therapy in acromegaly is provided.

scholarly journals Preoperative treatment of growth hormone (GH) producing macroadenomas with somatostatin receptor ligands (SRLs) to improve surgical outcome: a critical analysis

2018 ◽  
Vol 12 (1) ◽  
pp. 7-18
Author(s):  
Ariel Barkan
Keyword(s):  
Growth Hormone ◽  
Surgical Outcome ◽  
Somatostatin Receptor ◽  
Preoperative Treatment ◽  
Receptor Ligands ◽  
Tumor Removal ◽  
Post Surgery ◽  
Randomized Studies ◽  
Somatostatin Receptor Ligands ◽  
Complete Tumor

Thirty years ago, a hypothesis stating that preoperative shrinkage of growth hormone (GH) producing macroadenomas with somatostatin receptor ligands (SRLs) may improve surgical outcome was put forward. Since then, multiple retrospective, non-randomized studies as well as four contemporary prospective, randomized studies have been performed to evaluate the validity of that hypothesis and are critically reviewed in this manuscript. With the exception of an occasional retrospective study the great preponderance of evidence could not confirm this hypothesis. Similarly, while all prospective studies suggested better surgical outcome for SRL-pretreated tumors 3 months post surgery, the differences in outcomes between pretreated and untreated control patients disappeared after 6–12 months. Thus, preoperative treatment of macrosomatotropinomas with SRLs should not be relied upon as a means to achieve complete tumor removal and cannot be recommended.

Sign in / Sign up

Export Citation Format

Share Document