hrp0089s10.3 | Paediatric obesity: Mechanisms and novel treatment | ESPE2018

MC4R Agonists in the Treatment of Monogenic Disorders of Obesity

Kuhnen Peter

The leptin melanocortin signaling pathway plays a pivotal role in body weight regulation within the hypothalamus. Gene mutations within this cascade are leading to early onset obesity and severe hyperphagia in rodents and humans. For the affected patients it is extremely difficult to stabilize body weight based on the persisting hunger feeling. Traditional treatment options (increased exercise, reduced caloric intake) are not effective in most cases. Therefore, there is a need...

hrp0084p2-255 | Diabetes | ESPE2015

Significant Impact of Nocturnal Melatonin Secretion on Obesity-Related Metabolic Disorders in Children and Adolescents

Overberg Johanna , Kuhnen Peter , Ernert Andrea , Krude Heiko , Wiegand Susanna

Background: In addition to its function in circadian rhythm Melatonin plays an important role in energy metabolism and body weight regulation. In animals pinealectomy induces insulin resistance and administration of melatonin to diabetes prone rats ameliorates their glucose metabolism. Furthermore loss-of-function mutations of the melatonin receptor gene are associated with insulin resistance and DM II in humans.Objective and hypotheses: So far the effec...

hrp0084p3-1069 | Hypo | ESPE2015

Experience Based on 193 18F-DOPA PET CTs in Patients with Congenital Hyperinsulinism: Pearls and Pitfalls in Imaging Diagnostics in Patients with CHI

Kuhnen Peter , Prasad Vikas , Brenner Winfried , Mohnike Wolfgang , Blankenstein Oliver

Background: In congenital hyperinsulinism (CHI) 18F-DOPA PET CT plays an essential role in differentiating between focal and diffuse CHI forms and in the analysis of the localization of a potential focus before surgery.Objective and hypotheses: The aim of this retrospective analysis was the evaluation of the 18F-DOPA PET CT efficacy in a large cohort of CHI patients.Method: In the last few years 193 18</s...

hrp0089p2-p285 | Multisystem Endocrine Disorders P2 | ESPE2018

Bone Marrow Failure in McCune Albright Syndrome

Wechsung Katja , Lankes Erwin , Kuhnen Peter , Stackelberg Arend von , Schnabel Dirk

Background: A somatic activating GNAS mutation leads to the triad of café au lait macules, fibrous dysplasia and precocious puberty known as Mc Cune Albright Syndrome (MAS). We present a patient with bone marrow failure as a rare non-endocrine complication of MAS.Clinical case: A 2-year-old girl with neonatal giant cell hepatitis, a large right sided café au lait spot and fibrous dysplasia was diagnosed with MAS. The severe polyostotoc fibrous ...

hrp0082fc3.4 | Diabetes | ESPE2014

Genetics of Paediatric Type 2 Diabetes: ABCC8 Mutation in Obesity-Associated Insulin Secretion Defects

Wiegand Susanna , Simaite Deimante , Dannemann Almut , Kuhnen Peter , Krude Heiko , Gong Maolian , Raile Klemens

Background: Type 2 diabetes in children and adolescents is a rare disease with an estimated incidence (age 0–20 years) of below 5/100 000 in Germany.Objective and Hypotheses: We hypothesize that monogenic alterations might contribute to early-onset insulin secretion defects, if islet function was challenged by obesity-associated insulin resistance.Method: We follow more than 1500 children and adolescents with obesity. Patients...

hrp0082fc13.2 | Thyroid | ESPE2014

Thyroid Agenesis and Severe Thyroid Hypoplasia Caused by a New Inactivating TSH Receptor Mutation Ala579Val

Wessel Theda , Handke Daniela , Kleinau Gunnar , Winkler Franziska , Gruters Annette , Kuhnen Peter , Krude Heiko , Biebermann Heike

Background: Congenital thyroid dysgenesis usually occurs sporadically and may even be discordant in monozygotic twins. However, when caused by inactivating mutations in the TSH receptor (TSHR) it can be inherited recessively, typically resulting in thyroid gland hypoplasia. We present a new familial case of thyroid dysgenesis with two siblings of consanguineous parents. The daughter was identified in neonatal screening with severely elevated TSH and thyroid agenesis on ultraso...

hrp0084fc12.4 | Obesity - Clinical | ESPE2015

RM-493, a Melanocortin-4 Receptor (MC4R) Agonist, is Being Therapeutically Evaluated in Patients with Deficiencies in the Leptin – Proopiomelanocortin (POMC) – MC4R Hypothalamic Pathway, Including Prader–Willi Syndrome (PWS)

Kuhnen Peter , Krude Heiko , Wiegand Susanna , van der Ploeg Lex , Fiedorek Fred , Hylan Michelle , Gottesdiener Keith

Background: The hypothalamic leptin–melanocortin signalling pathway is a critical regulator of human appetite and weight regulation. Monogenetic defects in the POMC gene, the MSH ligand generating PC1 gene and the MSH receptor gene MC4R lead to severe early onset and leptin-resistant obesity. In PWS, where the function of genes such as MAGEL2 are impaired, the Magel2-/- mouse model revealed decreased POMC neuronal functioning as one c...

hrp0086fc13.6 | Management of Obesity | ESPE2016

Treatment for Early Onset and Extreme Obesity in Two POMC Deficient Patients: Successful Weight Loss with the Melanocortin-4 Receptor Agonist Setmelanotide

Kuhnen Peter , Clement Karine , Gottesdiener Keith , Fiedorek Fred , van der Ploeg Lex , Wiegand Susanna , Blankenstein Oliver , Gruters Annette , Krude Heiko

Background: POMC deficiency is an extremely rare monogenetic obesity syndrome generally characterized by early onset hyperphagia, red hair and adrenal insufficiency. So far treatment of obesity and hyperphagia with MSH substitution failed, either due to ineffectiveness or side effects of available MC4R agonists.Objective and hypotheses: We hypothesized that the new MC-4R agonist setmelanotide might be a treatment option in POMC deficient patients.<p ...

hrp0084p2-391 | Fat | ESPE2015

POMC DNA Hypermethylation Variant is Highly Associated with Obesity in Adults

Kuhnen Peter , Handke Daniela , Spranger Jochen , Fischer-Rosinsky Antje , Hinney Anke , Hebebrand Johannes , Gruters Annette , Krude Heiko

Background: POMC plays a major role in central body weight regulation. Recently we have shown that a POMC hypermethylation variant is significantly associated with obesity in children and adolescents (Kuehnen et al. PLoS Genetics 2012).Objective and hypotheses: Here we report about our extended studies to elucidate the mechanism behind the occurrence of the POMC hypermethylation variant in obese individuals.<p clas...

hrp0082fc9.3 | Beta cells | ESPE2014

In Search for New Monogenic Diabetes Genes: PCBD1

Simaite Deimante , Kofent Julia , Gong Maolian , Ruschendorf Franz , Jia Shiqi , Arn Pamela , Bentler Kristi , Ellaway Carolyn , Kuhnen Peter , Hoffmann Georg , Blau Nenad , Spagnoli Francesca , Hubner Norbert , Raile Klemens

Background: Mutations in more than 20 genes are described to cause monogenic diabetes. Nevertheless, numerous families with diabetes of unknown ethology and suspected genetic defect have no molecular diagnosis. This not only impedes our understanding of disease mechanisms but also prevents from predicting the clinical course of the patients and applying the pathogenesis-oriented treatment.Objective: To identify novel gene(s), causing monogenic adolescent...