Essential Role of the RIα Subunit of cAMP-Dependent Protein Kinase in Regulating Cardiac Contractility and Heart Failure Development.

Background: The heart expresses 2 main subtypes of cAMP-dependent protein kinase (PKA; type I and II) that differ in their regulatory subunits, RIα and RIIα. Embryonic lethality of RIα knockout mice limits the current understanding of type I PKA function in the myocardium. The objective of this study was to test the role of RIα in adult heart contractility and pathological remodeling.

The phenotype of the pediatric patient with Cushing syndrome but without obesity.

Objective: Cushing syndrome (CS) often presents with obesity that is not as severe in children as it is in adults. The role of obesity in the severity of metabolic syndrome in children with CS has not been studied. This study evaluates whether pediatric patients with CS have obesity-specific differences in their demographic, biochemical, and presenting findings.

Diagnostic and management challenges in paediatric Cushing's syndrome.

Objective: Cushing syndrome (CS) is the result of chronic exposure to glucocorticoid excess. CS in children is most often caused by the administration of exogenous steroids. Endogenous CS is rare in the paediatric population and is caused mainly by tumours of the pituitary and adrenal glands, with ectopic sources being extraordinarily rare before the age of 18 years.

The spectrum of growth hormone excess in Carney complex and genotype-phenotype correlations.

Context: Carney complex (CNC) is a familial neoplasia syndrome associated with growth hormone (GH) excess (GHE).

Objective: To describe the frequency of GHE in a large cohort of patients with CNC, and to identify genotype-phenotype correlations.

Methods: Patients with CNC with at least one biochemical evaluation of GH secretion at our center from 1995-2021 (n=140) were included in the study.

EndoBridge 2023: highlights and pearls.

EndoBridge 2023 took place on October 20-22, 2023, in Antalya, Turkey. Accredited by the European Council, the 3-day scientific program of the 11 Annual Meeting of EndoBridge included state-of-the-art lectures and interactive small group discussion sessions incorporating interesting and challenging clinical cases led by globally recognized leaders in the field and was well attended by a highly diverse audience. Following its established format over the years, the program provided a comprehensive update across all aspects of endocrinology and metabolism, including topics in pituitary, thyroid, bone, and adrenal disorders, neuroendocrine tumors, diabetes mellitus, obesity, nutrition, and lipid disorders.

Lipodystrophy in methylmalonic acidemia associated with elevated FGF21 and abnormal methylmalonylation.

A distinct adipose tissue distribution pattern was observed in patients with methylmalonyl-CoA mutase deficiency, an inborn error of branched-chain amino acid (BCAA) metabolism, characterized by centripetal obesity with proximal upper and lower extremity fat deposition and paucity of visceral fat, that resembles familial multiple lipomatosis syndrome. To explore brown and white fat physiology in methylmalonic acidemia (MMA), body composition, adipokines, and inflammatory markers were assessed in 46 patients with MMA and 99 matched controls. Fibroblast growth factor 21 levels were associated with acyl-CoA accretion, aberrant methylmalonylation in adipose tissue, and an attenuated inflammatory cytokine profile.

Paediatric Cushing syndrome: a prospective, multisite, observational cohort study.

Background: Paediatric endogenous Cushing syndrome is a rare condition with variable signs and symptoms of presentation. We studied a large cohort of paediatric patients with endogenous Cushing syndrome with the aim of describing anthropometric, clinical, and biochemical characteristics as well as associated complications and outcomes to aid diagnosis, treatment, and management.

Methods: In this prospective, multisite cohort study, we studied children and adolescents (≤18 years at time of presentation) with a diagnosis of Cushing syndrome.

False Negative Inferior Petrosal Sinus Sampling in Young-Onset Cushing Disease: What Happens Next.

Introduction: False negative results during inferior petrosal sinus sampling (IPSS) may complicate the diagnostic evaluation of patients with ACTH-dependent Cushing syndrome (CS). The management of these patients can be confusing for clinicians and lead to delayed management.

Methods: We studied patients with young-onset (<21yo) CD who underwent IPSS during their diagnostic evaluation.

variants in patients with thyrotrophinomas, cyclical Cushing's disease and prolactinomas.

Introduction: Germline loss-of-function variants in , encoding peptidylglycine α-amidating monooxygenase (PAM), were recently discovered to be enriched in conditions of pathological pituitary hypersecretion, specifically: somatotrophinoma, corticotrophinoma, and prolactinoma. PAM is the sole enzyme responsible for C-terminal amidation of peptides, and plays a role in the biosynthesis and regulation of multiple hormones, including proopiomelanocortin (POMC).

Methods: We performed exome sequencing of germline and tumour DNA from 29 individuals with functioning pituitary adenomas (12 prolactinomas, 10 thyrotrophinomas, 7 cyclical Cushing's disease).

FAF1 Gene Involvement in Pituitary Corticotroph Tumors.

Cushing's disease (CD) is caused by rare pituitary corticotroph tumors that lead to corticotropin (ACTH) excess. Variants in , a pro-apoptotic protein involved in FAS-induced cell death, have been implicated in malignant disorders but the involvement of in pituitary tumors has not been studied. Genetic data from patients with CD were reviewed for variants in gene.

High-frequency variants in PKA signaling-related genes within a large pediatric cohort with obesity or metabolic abnormalities.

Introduction: Pediatric obesity has steadily increased in recent decades. Large-scale genome-wide association studies (GWAS) conducted primarily in Eurocentric adult populations have identified approximately 100 loci that predispose to obesity and type II diabetes. GWAS in children and individuals of non-European descent, both disproportionately affected by obesity, are fewer.

GPR101: Modeling a constitutively active receptor linked to X-linked acrogigantism.

GPR101 is a G protein-coupled receptor (GPCR) implicated in a rare form of genetic gigantism known as X-linked acrogigantism, or X-LAG. In particular, X-LAG patients harbor microduplications in the long arm of the X-chromosome that invariably include the GPR101 gene. Duplications of the GPR101 gene lead to the formation of a new chromatin domain that causes over-expression of the receptor in the pituitary tumors of the patients.

The utility of IGF1 in the evaluation of pediatric patients with endogenous hypercortisolemia.

Background: Cushing Disease (CD) is a rare endocrine disorder associated with impaired growth hormone (GH) and short stature. Insulin-like growth factor-1 (IGF-1) is a marker of GH secretion.

Methods: Patients with young onset CD (<21 years old) and available IGF-1 levels at diagnosis and/or follow-up were studied (total = 194, diagnosis = 174, follow-up = 104).

Genes and environment: An old pair in a new era.

What is the relationship between our genes and the environment we live in with regard to health? Like the debate about nature or nurture in the determination of our personality and behavior, the issue of genes and environment has been discussed intensely in the last two centuries. Is it Darwin or Lamarck who is right about the basic determinants of our health, especially as we age in a rapidly changing environment? Evolutionary biology as proposed by Darwin with natural selection at its core may not be able to explain almost instant adjustments of phenotypic traits to the pressures of the environment. Epigenesis, a concept that dates from Aristotle, provides a mechanism for the environment to affect variation in genetic traits that may become heritable.