Treatment of acromegaly with the nonpeptide, highly selective somatostatin receptor type 2 agonist paltusotine.

Injectable first-generation somatostatin receptor ligands (fg-SRLs) are the standard of care of medical treatment for acromegaly. While fg-SRLs control acromegaly in up to 50 % of patients, they may lead to bothersome injection pain and site reactions. Paltusotine is an investigational, highly selective somatostatin receptor subtype 2 agonist, which is administered orally once a day.

Epigenetic Control of Adamantinomatous Craniopharyngiomas.

Introduction: Studies addressing the methylation pattern in adamantinomatous craniopharyngioma (ACP) are lacking.

Objective: To identify methylation signatures in ACPs regarding clinical presentation and outcome.

Methods: Clinical and pathology data were collected from 35 patients with ACP (54% male; 18.

Evaluation of bone mineral density, microarchitecture, and detection of fractures on young patients living with human immunodeficiency virus: when and how to screen?

Purpose: People living with the human immunodeficiency virus (PLWH) developed higher life expectancy along with chronic bone disease over the past years. Our purpose is to evaluate bone mineral density, bone microarchitecture and fractures in young PLWH and understand the disease's contribution to bone derangements and fracture risk.

Methods: Eighty-one HIV-infected and 54 control young (20-50 years) male and female subjects were enrolled in this study.

Long-term Efficacy and Safety of Pasireotide in Patients With Acromegaly: 14 Years of Single-Center Real-World Experience.

Context: Acromegaly is a rare, chronic, debilitating disorder caused by prolonged hypersecretion of growth hormone (GH) and overproduction of insulin-like growth factor I (IGF-I). Medical therapies, including the somatostatin receptor ligand (SRL) pasireotide, are frequently used to restore biochemical control.

Objective: As patients often receive therapy over prolonged periods, long-term data from real-life settings are needed.

miR-383-5p, miR-181a-5p, and miR-181b-5p as Predictors of Response to First-Generation Somatostatin Receptor Ligands in Acromegaly.

Acromegaly is a chronic systemic disease caused in the vast majority of cases by growth hormone (GH)-secreting adenoma, with surgery being the first-line treatment. When a cure is not attained with surgery, first-generation somatostatin receptor ligands (fg-SRLs) are the most common medication prescribed. Predictors of response to fg-SRLs have been studied; however, they cannot fully predict the response to fg-SRL.

Pituitary acting drugs: cabergoline and pasireotide.

First-line treatment for Cushing´s disease is transsphenoidal surgery. But in cases of persistent or recurrent disease after surgery, contraindications to surgery, severe hypercortisolism control before surgery, or for patients waiting for radiotherapy effects, medical therapy may be indicated. Pituitary-directed agents include cabergoline and pasireotide.

Telomere length and Wnt/β-catenin pathway in adamantinomatous craniopharyngiomas.

Objectives: To evaluate how telomere length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations.

Design: Retrospective cross-sectional study enrolling 42 aCP patients from 2 tertiary institutions.

Methods: Clinicopathological features were retrieved from the patient's charts.

Approach to the Patient: Differential Diagnosis of Cystic Sellar Lesions.

Cystic lesions arising in the sellar region are not uncommon and encompass cystic pituitary adenomas, Rathke cleft cysts, craniopharyngiomas, and arachnoid cysts. Their clinical presentation may be similar, including headache, visual field defects, and anterior pituitary hormone deficits, which makes differential diagnosis challenging. On the other hand, imaging features may indicate certain pathologies.

Pituitary MRI Standard and Advanced Sequences: Role in the Diagnosis and Characterization of Pituitary Adenomas.

Pituitary adenomas (PAs) represent the most frequently found lesions in the sellar region; however, several other lesions may be encountered in this region, such as meningiomas, craniopharyngiomas, and aneurysms. High-quality imaging is fundamental for diagnosis, characterization, and guidance of treatment planning of PAs. Sellar magnetic resonance imaging (MRI) is considered the imaging modality of choice for the evaluation of lesions in the sella turcica.

Prolactinomas.

Hyperprolactinemia, defined by a level of serum prolactin above the standard upper limit of normal range, is a common finding in clinical practice and prolactinomas are the main pathological cause. Prolactinomas lead to signs and symptoms of hormone oversecretion, such as galactorrhea and hypogonadism, as well as symptoms of mass effect, including visual impairment, headaches and intracranial hypertension. Diagnosis involves prolactin measurement and sellar imaging, but several pitfalls are involved in this evaluation, which may difficult the proper management.

Current opinion on the diagnosis and management of non-functioning pituitary adenomas.

Introduction: Non-functioning pituitary adenomas (NFPAs) are clinically silent tumors and the second most common pituitary adenoma. Surgery is the mainstay of treatment as there is, as yet, no effective medical treatment.

Areas Covered: We present current knowledge on the clinical diagnosis, histopathological classification, molecular data, and management strategies in NFPA.

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

Background: It is still controversial if activating mutations in the stimulatory G-protein α subunit ( mutation) are a biomarker of response to first generation somatostatin receptor ligands (fg-SRL) treatment in acromegaly. Thus, we aimed to evaluate whether mutation predicts long-term response to fg-SRL treatment and to characterize the phenotype of patients harboring mutations.

Methods: sequencing was performed by Sanger.

The Future of Somatostatin Receptor Ligands in Acromegaly.

Currently, the first-generation somatostatin receptor ligands (fg-SRLs), octreotide LAR and lanreotide autogel, are the mainstays of acromegaly treatment and achieve biochemical control in approximately 40% of patients and tumor shrinkage in over 60% of patients. Pasireotide, a second-generation SRL, shows higher efficacy with respect to both biochemical control and tumor shrinkage but has a worse safety profile. In this review, we discuss the future perspectives of currently available SRLs, focusing on the use of biomarkers of response and precision medicine, new formulations of these SRLs and new drugs, which are under development.

Machine Learning-based Prediction Model for Treatment of Acromegaly With First-generation Somatostatin Receptor Ligands.

Context: Artificial intelligence (AI), in particular machine learning (ML), may be used to deeply analyze biomarkers of response to first-generation somatostatin receptor ligands (fg-SRLs) in the treatment of acromegaly.

Objective: To develop a prediction model of therapeutic response of acromegaly to fg-SRL.

Methods: Patients with acromegaly not cured by primary surgical treatment and who had adjuvant therapy with fg-SRL for at least 6 months after surgery were included.

Clinical significance of filamin A in patients with acromegaly and its association with somatostatin and dopamine receptor profiles.

Filamin-A (FLNA) plays a crucial role in somatostatin receptor (sst) subtype-2 signaling in somatotropinomas. Our objective was to investigate the in vivo association between FLNA and sst2 expression, sst5 expression, dopamine receptor subtype-2 (D2) expression, somatostatin receptor ligand (SRL) responsiveness and tumor invasiveness in somatotropinomas. Quantitative real-time PCR was used to evaluate the absolute mRNA copy numbers of FLNA/sst2/sst5/D2 in 96 somatotropinomas.

Predictors of surgical outcome and early criteria of remission in acromegaly.

Background: Transsphenoidal surgery (TSS) is the cornerstone of acromegaly treatment, however there are no robust predictors of surgical outcome and remission can only be defined three months after surgery.

Purpose: To analyze if biochemical, demographical, radiological, and immunohistochemical characteristics are predictors of surgical remission and investigate if immediate postoperative GH and IGF-I levels can help defining remission earlier.

Methods: Consecutive acromegaly patients submitted to TSS between 2013-2016 were evaluated.

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

Background: Few studies evaluated the use of cabergoline (CAB) for acromegaly treatment in monotherapy or in combination with first-generation somatostatin receptor ligands (SRLs).

Aim: To evaluate the efficacy, predictors of response and safety of CAB treatment in acromegaly both in monotherapy and in combination with SRLs.

Methods: We retrospectively collected demographic, biochemical, tumour and treatment data.

Apoplexy in nonfunctioning pituitary adenomas.

Pituitary apoplexy is an uncommon event, occurring due to the infarction and/or haemorrhage usually of a previously unknown pituitary adenoma. It can occur in all adenoma subtypes but is more common in nonfunctioning pituitary adenomas. The physiopathology is not completely clear, and precipitating factors, such as major surgeries, anticoagulant use or pituitary dynamic tests, can be found in up to 40% of patients.

Molecular evidence and clinical importance of β-arrestins expression in patients with acromegaly.

β-arrestins seem to have a role in endocytosis and desensitization of somatostatin receptor subtype 2 (sst2) and could be associated with the responsiveness to somatostatin receptor ligands (SRL) in patients with acromegaly. To investigate the in vivo correlation between β-arrestins 1 and 2 with sst2, sst5 and dopamine receptor subtype 2 (D2) expressions, and the association of β-arrestins with response to first-generation SRL and invasiveness in somatotropinomas. β-arrestins 1 and 2, sst2, sst5 and D2 mRNA expressions were evaluated by quantitative real-time RT-PCR on tumoral tissue of 96 patients.