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.

scholarly journals gsp Mutation Is Not a Molecular Biomarker of Long-Term Response to First-Generation Somatostatin Receptor Ligands in Acromegaly

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4857
Author(s):  
Luiz Eduardo Wildemberg ◽  
Daniel Henriques ◽  
Paula C. L. Elias ◽  
Carlos Henrique de A. Lima ◽  
Nina R. de Castro Musolino ◽  
...  
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Biochemical Control ◽  
Molecular Biomarker ◽  
Α Subunit ◽  
Cavernous Sinus Invasion ◽  
Somatostatin Receptor Ligands ◽  
Term Response

Background: It is still controversial if activating mutations in the stimulatory G-protein α subunit (gsp mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether gsp mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring gsp mutations. Methods: GNAS1 sequencing was performed by Sanger. SST2 and SST5 were analyzed by immunohistochemistry (IHC) and real-time RT-PCR. The cytokeratin granulation pattern was evaluated by IHC. Biochemical control was defined as GH < 1.0 ng/mL and normal age-adjusted IGF-I levels. Results: gsp mutation was found in 54 out of 136 patients evaluated. Biochemical control with fg-SRL treatment was similar in gsp+ and gsp- patients (37% vs. 25%, p = 0.219). Tumors harboring gsp mutation were smaller (p = 0.035) and had a lower chance of invading cavernous sinuses (p = 0.001). SST5 protein (p = 0.047) and mRNA (p = 0.013) expression levels were higher in wild-type tumors. Conclusions: In this largest series available in the literature, we concluded that gsp is not a molecular biomarker of response to fg-SRL treatment in acromegaly. However, the importance of its negative association with cavernous sinus invasion and SST5 expression needs to be further investigated.

Role of somatostatin receptor ligands in the treatment of acromegaly – review of literature

2011 ◽  
Vol 152 (18) ◽  
pp. 715-721 ◽  
Author(s):  
Orsolya Nemes ◽  
Emese Mezősi
Keyword(s):  
Medical Therapy ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Clinical Manifestations ◽  
Oral Glucose ◽  
Receptor Ligands ◽  
Long Term Outcome ◽  
Somatostatin Receptor Ligands

Acromegaly is a rare disease with typical clinical manifestations. Untreated acromegaly carries a 2-4-fold increase in mortality in long-term outcome. The goal of treatment is double, including biochemical control of the disease (normalization of serum IGF1 levels compared to age and gender matched controls, GH levels below 1 ng/ml after oral glucose load, or random GH below 2.5 ng/ml) and control of the tumor mass. The therapeutic modalities currently available for the treatment of acromegaly are: surgery, medical therapy, radiation therapy and their combinations. The cornerstones of medical therapy in acromegaly are the somatostatin receptor ligands due to their effectiveness in controlling GH excess in 60-70 % of patients and their beneficial effects on tumor volume. Somatostatin analogues have an established role as adjuvant therapy after non-curative surgery, and evidence suggests their use as primary treatment for selected patients. The long-term use of somatostatin receptor ligands is safe and they are well tolerated. Future medical therapy consists of pasireotide, a novel, universal somatostatin receptor agonist, and a new class of drugs named dopastatins. The latter so-called chimeric molecules have strong affinity for somatostatin receptors and dopamine-2 receptors, resulting in a more effective blocking of GH secretion, according to preliminary data. The authors of this paper review the current medical therapy of acromegaly, focusing on the role of somatostatin receptor ligands. Orv. Hetil., 2011, 152, 715–721.

Treatment escape reduces the effectiveness of cabergoline during long-term treatment of acromegaly in monotherapy or in association with first-generation somatostatin receptor ligands

2018 ◽  
Vol 88 (6) ◽  
pp. 889-895 ◽  
Author(s):  
Leandro Kasuki ◽  
Marilia Duarte Dalmolin ◽  
Luiz Eduardo Wildemberg ◽  
Mônica R. Gadelha
Keyword(s):  
First Generation ◽  
Somatostatin Receptor ◽  
Term Treatment ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Long Term Treatment

scholarly journals Somatostatin receptor ligands and resistance to treatment in pituitary adenomas

2014 ◽  
Vol 52 (3) ◽  
pp. R223-R240 ◽  
Author(s):  
Daniel Cuevas-Ramos ◽  
Maria Fleseriu
Keyword(s):  
Pituitary Adenomas ◽  
Somatostatin Receptor ◽  
Somatostatin Receptors ◽  
Receptor Expression ◽  
Biologically Active ◽  
Imaging Features ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Granulation Pattern ◽  
Acth Secreting

Somatostatin (SST), an inhibitory polypeptide with two biologically active forms SST14 and SST28, inhibits GH, prolactin (PRL), TSH, and ACTH secretion in the anterior pituitary gland. SST also has an antiproliferative effect inducing cell cycle arrest and apoptosis. Such actions are mediated through five G-protein-coupled somatostatin receptors (SSTR): SSTR1–SSTR5. In GH-secreting adenomas, SSTR2 expression predominates, and somatostatin receptor ligands (SRLs; octreotide and lanreotide) directed to SSTR2 are presently the mainstays of medical therapy. However, about half of patients show incomplete biochemical remission, but the definition of resistanceper seremains controversial. We summarize here the determinants of SRL resistance in acromegaly patients, including clinical, imaging features as well as molecular (mutations, SSTR variants, and polymorphisms), and histopathological (granulation pattern, and proteins and receptor expression) predictors. The role of SSTR5 may explain the partial responsiveness to SRLs in patients with adequate SSTR2 density in the cell membrane. In patients with ACTH-secreting pituitary adenomas, i.e. Cushing's disease (CD), SSTR5 is the most abundant receptor expressed and tumors show low SSTR2 density due to hypercortisolism-induced SSTR2 down-regulation. Clinical studies with pasireotide, a multireceptor-targeted SRL with increased SSTR5 activity, lead to approval of pasireotide for treatment of patients with CD. Other SRL delivery modes (oral octreotide), multireceptor-targeted SRL (somatoprim) or chimeric compounds targeting dopamine D2 receptors and SSTR2 (dopastatin), are briefly discussed.

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

Biochemical efficacy of long-acting lanreotide depot/Autogel in patients with acromegaly naïve to somatostatin-receptor ligands: analysis of three multicenter clinical trials

Pituitary ◽  
2018 ◽  
Vol 21 (3) ◽  
pp. 283-289 ◽  
Author(s):  
Hussain Alquraini ◽  
Maria del Pilar Schneider ◽  
Beloo Mirakhur ◽  
Ariel Barkan
Keyword(s):  
Clinical Trials ◽  
Somatostatin Receptor ◽  
Receptor Ligands ◽  
Somatostatin Receptor Ligands ◽  
Multicenter Clinical Trials ◽  
Long Acting

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.

Sign in / Sign up

Export Citation Format

Share Document