Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 2, specific diseases.

Pituitary adenomas are rare in children and young people under the age of 19 (hereafter referred to as CYP) but they pose some different diagnostic and management challenges in this age group than in adults. These rare neoplasms can disrupt maturational, visual, intellectual and developmental processes and, in CYP, they tend to have more occult presentation, aggressive behaviour and are more likely to have a genetic basis than in adults. Through standardized AGREE II methodology, literature review and Delphi consensus, a multidisciplinary expert group developed 74 pragmatic management recommendations aimed at optimizing care for CYP in the first-ever comprehensive consensus guideline to cover the care of CYP with pituitary adenoma.

Consensus guideline for the diagnosis and management of pituitary adenomas in childhood and adolescence: Part 1, general recommendations.

Tumours of the anterior part of the pituitary gland represent just 1% of all childhood (aged <15 years) intracranial neoplasms, yet they can confer high morbidity and little evidence and guidance is in place for their management. Between 2014 and 2022, a multidisciplinary expert group systematically developed the first comprehensive clinical practice consensus guideline for children and young people under the age 19 years (hereafter referred to as CYP) presenting with a suspected pituitary adenoma to inform specialist care and improve health outcomes. Through robust literature searches and a Delphi consensus exercise with an international Delphi consensus panel of experts, the available scientific evidence and expert opinions were consolidated into 74 recommendations.

Outcomes of Patients with Nelson's Syndrome after Primary Treatment: A Multicenter Study from 13 UK Pituitary Centers.

Context: Long-term outcomes of patients with Nelson's syndrome (NS) have been poorly explored, especially in the modern era.

Objective: To elucidate tumor control rates, effectiveness of various treatments, and markers of prognostic relevance in patients with NS.

Patients, Design, And Setting: Retrospective cohort study of 68 patients from 13 UK pituitary centers with median imaging follow-up of 13 years (range 1-45) since NS diagnosis.

Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma: results from a large patient cohort.

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence.

Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.

Uncertainties in endocrine substitution therapy for central hypocortisolism.

Central hypocortisolism is common, and has multiple potential causes. However, the treatment aims remain the same whatever the cause: to maximize quality of life, while minimizing treatment-related adverse effects. The majority of patients with central hypocortisolism now receive hydrocortisone in two to three divided doses with a total daily dose of 10-20mg, or a weight-based regimen of 8.

Focal radiation therapy for patients with persistent/recurrent pituitary adenoma, despite previous radiotherapy.

With the stricter endocrine definitions of cure following conventionally planned and fractionated radiotherapy for functioning pituitary adenomas, together with the move in the profession (since the advent of high quality MRI) to postpone radiation therapy until macroscopic disease appears after surgery, it is now realised that cure rates following conventional radiotherapy approximate three out of four rather than the >90% cited for more than a decade. Patients with persistent active tumours may be successfully further treated by focal radiation therapy by one of the stereotactic focal techniques. We have experience of such re-treatment radiation therapy in 50 patients.

Constitutive activation of the human ACTH receptor resulting from a synergistic interaction between two naturally occurring missense mutations in the MC2R gene.

Two mutations in the same allele of the ACTH receptor (melanocortin 2 receptor, MC2R) associated with clinical hypersensitivity to ACTH have been described in a single case report. Using a stable Y6 cell expression system, we demonstrate that either the C21R or S247G mutations alone produce an inactive receptor with loss of ligand binding and responsiveness. However, the presence of both mutations in the same molecule leads to a receptor with a highly significant elevation in constitutive activity (basal cAMP accumulation for wild type expressing cells 199 +/- 11 pmol/mg protein; double mutant: 374 +/- 29 pmol/mg protein, P < 0.

Expression, desensitization, and internalization of the ACTH receptor (MC2R).

Research into the functions and mechanisms of action of the melanocortin 2 receptor (MC2R) has been severely hampered by difficulties in expressing this gene in heterologous cells. This probably arises because of the need for a cofactor for cell surface expression. Using either the Y1 cell line that expresses endogenous MC2R or the Y6 cell line that expresses this putative expression factor, we have explored the mechanisms of desensitization and internalization after agonist stimulation.

Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity.

A naturally occurring ACTH receptor [melanocortin 2 receptor (MC2R)] mutation (F278C) has been identified in a subject with ACTH-independent Cushing's syndrome. Functional characterization of this mutant receptor reveals that it is associated with elevated basal cAMP accumulation when compared with wild-type receptor-expressing cell lines. Dose responsiveness is similar between wild-type and mutant receptors in cell lines expressing similar numbers of binding sites.