Ghrelin is a peptide predominantly produced by the stomach. Ghrelin displays strong GH-releasing activity. This activity is mediated by the activation of the so-called GH secretagogue receptor type 1a. This receptor had been shown to be specific for a family of synthetic, peptidyl and nonpeptidyl GH secretagogues. Apart from a potent GH-releasing action, ghrelin has other activities including stimulation of lactotroph and corticotroph function, influence on the pituitary gonadal axis, stimulation of appetite, control of energy balance, influence on sleep and behavior, control of gastric motility and acid secretion, and influence on pancreatic exocrine and endocrine function as well as on glucose metabolism. Cardiovascular actions and modulation of proliferation of neoplastic cells, as well as of the immune system, are other actions of ghrelin. Therefore, we consider ghrelin a gastrointestinal peptide contributing to the regulation of diverse functions of the gut-brain axis. So, there is indeed a possibility that ghrelin analogs, acting as either agonists or antagonists, might have clinical impact.

Context: Pegvisomant is a GH receptor antagonist. The ACROSTUDY is a global safety surveillance study of long-term treatment of acromegaly with pegvisomant. Objective: The objective of the study was to monitor long-term safety and treatment outcomes. Design: ACROSTUDY is open to all patients with acromegaly who are treated with pegvisomant. We report an interim analysis of data captured from 1288 subjects enrolled before a database freeze of December 31, 2009. Setting: This was a global noninterventional surveillance study. Main Outcome Measure(s): Long-term monitoring of safety, including central magnetic resonance imaging (MRI) reading and treatment outcomes, was measured. Results: Subjects (n = 1288) were treated with pegvisomant for a mean of 3.7 yr and followed up in ACROSTUDY for a mean of 2.1 yr. A total of 1147 adverse events (AE) were recorded in 477 subjects (37%), among which 192 AE in 124 subjects (9.6%) were considered to be related to pegvisomant. Serious AE were recorded in 159 subjects (12.3%), whereas pegvisomant-related Serious AE were recorded in 26 subjects (2%). No deaths (15 subjects; 1.2%) were attributed to pegvisomant use. The incidence of increase in pituitary tumor size in the subset with confirmed MRI increases on central reading represented 3.2% of the overall cohort with at least two available MRI (n = 936). Injection-site reactions were reported in 28 cases (2.2%). In 30 patients (2.5%), an elevated aspartate aminotransferase or alanine aminotransferase of more than 3 times the upper level of normality was reported. There were no reports of liver failure. After 5 yr of pegvisomant treatment, 63.2% of subjects had normal IGF-I levels at a mean dose of 18 mg/d. Conclusions: Data entered and evaluated in ACROSTUDY indicate that pegvisomant is an effective and safe medical treatment in patients with acromegaly. The reported low incidence of pituitary tumor size increase, liver enzyme elevations, and lipodystrophy at the injection site are reassuring.

Objective: To evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120 mg/month) and pegvisomant (40–120 mg/week) in acromegaly.Design: This is a 28-week, multicenter, open-label, single-arm sequential study.Methods: Patients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120 mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120 mg/month plus pegvisomant (60 mg once weekly, adapted every 8 weeks based on IGF1 levels to 40–80 mg once weekly or 40 or 60 mg twice weekly).Results: In total, 33 (57.9%) patients had normalized IGF1 following coadministration (P<0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60 mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P5×upper limit of normal with normalization after withdrawal).Conclusions: In patients partially controlled by SSAs, LA (120 mg/month) plus pegvisomant normalized IGF1 in 57.9% of patients after 7 months, at a median effective pegvisomant dose of 60 mg/week, and 78.9% at any time. In these patients, results suggest a pegvisomant-sparing effect versus daily pegvisomant monotherapy.

This review intends to provide the reader with a practical overview of several (patho)physiological conditions in which knowledge of the interplay between growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin is important. This might help treating physicians in making the right decisions on how to intervene and improve metabolism for the benefit of patients, and to understand why and how metabolism responds in their specific cases. We will specifically address the interplay between GH, IGF-1, and insulin in type 1 and 2 diabetes mellitus, liver cirrhosis, and acromegaly as examples in which this knowledge is truly necessary.

Purpose: The Pituitary Society established the concept and mostly qualitative parameters for defining uniform criteria for Pituitary Tumor Centers of Excellence (PTCOEs) based on expert consensus. Aim of the study was to validate those previously proposed criteria through collection and evaluation of self-reported activity of several internationally-recognized tertiary pituitary centers, thereby transforming the qualitative 2017 definition into a validated quantitative one, which could serve as the basis for future objective PTCOE accreditation. Methods: An ad hoc prepared database was distributed to nine Pituitary Centers chosen by the Project Scientific Committee and comprising Centers of worldwide repute, which agreed to provide activity information derived from registries related to the years 2018–2020 and completing the database within 60 days. The database, provided by each center and composed of Excel® spreadsheets with requested specific information on leading and supporting teams, was reviewed by two blinded referees and all 9 candidate centers satisfied the overall PTCOE definition, according to referees’ evaluations. To obtain objective numerical criteria, median values for each activity/parameter were considered as the preferred PTCOE definition target, whereas the low limit of the range was selected as the acceptable target for each respective parameter. Results: Three dedicated pituitary neurosurgeons are preferred, whereas one dedicated surgeon is acceptable. Moreover, 100 surgical procedures per center per year are preferred, while the results indicated that 50 surgeries per year are acceptable. Acute post-surgery complications, including mortality and readmission rates, should preferably be negligible or nonexistent, but acceptable criterion is a rate lower than 10% of patients with complications requiring readmission within 30 days after surgery. Four endocrinologists devoted to pituitary diseases are requested in a PTCOE and the total population of patients followed in a PTCOE should not be less than 850. It appears acceptable that at least one dedicated/expert in pituitary diseases is present in neuroradiology, pathology, and ophthalmology groups, whereas at least two expert radiation oncologists are needed. Conclusion: This is, to our knowledge, the first study to survey and evaluate the activity of a relevant number of high-volume centers in the pituitary field. This effort, internally validated by ad hoc reviewers, allowed for transformation of previously formulated theoretical criteria for the definition of a PTCOE to precise numerical definitions based on real-life evidence. The application of a derived synopsis of criteria could be used by independent bodies for accreditation of pituitary centers as PTCOEs.