Unaltered ratio of circulating levels of growth hormone/GH isoforms in adults with Prader–Willi syndrome after GHRH plus arginine administration

Abstract Purpose Prader–Willi syndrome (PWS) is a neurodevelopmental disorder with hypothalamic dysfunction due to deficiency of imprinted genes located on the 15q11-q13 chromosome. Among them, the SNORD116 gene appears critical for the expression of the PWS phenotype. We aimed to clarify the role of SNORD116 in cellular and animal models with regard to growth hormone therapy (GHT), the main approved treatment for PWS. Methods We collected serum and induced pluripotent stem cells (iPSCs) from GH-treated PWS patients to differentiate into dopaminergic neurons, and in parallel used a Snord116 knockout mouse model. We analyzed the expression of factors potentially linked to GH responsiveness. Results We found elevated levels of circulating IGFBP7 in naive PWS patients, with IGFBP7 levels normalizing under GHT. We found elevated IGFBP7 levels in the brains of Snord116 knockout mice and in iPSC-derived neurons from a SNORD116-deleted PWS patient. High circulating levels of IGFBP7 in PWS patients may result from both increased IGFBP7 expression and decreased IGFBP7 cleavage, by downregulation of the proconvertase PC1. Conclusion SNORD116 deletion affects IGFBP7 levels, while IGFBP7 decreases under GHT in PWS patients. Modulation of the IGFBP7 level, which interacts with IGF1, has implications in the pathophysiology and management of PWS under GHT.

Download Full-text

Growth hormone use in prader-willi syndrome - Experience of a dedicated paediatric clinic

Endocrine Abstracts ◽

10.1530/endoabs.51.p048 ◽

2017 ◽

Author(s):

Mikaela Frixou ◽

Georgia Irene Neophytou ◽

M. Guftar Shaikh ◽

Andreas Kyriakou

Keyword(s):

Growth Hormone ◽

Prader Willi Syndrome ◽

Hormone Use

Download Full-text

Effects of Childhood Multidisciplinary Care and Growth Hormone Treatment on Health Problems in Adults with Prader-Willi Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm10153250 ◽

2021 ◽

Vol 10 (15) ◽

pp. 3250

Author(s):

Karlijn Pellikaan ◽

Anna G. W. Rosenberg ◽

Kirsten Davidse ◽

Anja A. Kattentidt-Mouravieva ◽

Rogier Kersseboom ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Treatment ◽

Multidisciplinary Care ◽

Hormone Treatment ◽

Health Problems ◽

Pituitary Hormone ◽

Childhood And Adolescence ◽

Prader Willi Syndrome ◽

Adult Age ◽

Beneficial Effects

Prader-Willi syndrome (PWS) is a complex hypothalamic disorder. Features of PWS include hyperphagia, hypotonia, intellectual disability, and pituitary hormone deficiencies. The combination of growth hormone treatment and multidisciplinary care (GHMDc) has greatly improved the health of children with PWS. Little is known about the effects of childhood GHMDc on health outcomes in adulthood. We retrospectively collected clinical data of 109 adults with PWS. Thirty-nine had received GHMDc during childhood and adolescence (GHMDc+ group) and sixty-three had never received growth hormone treatment (GHt) nor multidisciplinary care (GHMDc− group). Our systematic screening revealed fewer undetected health problems in the GHMDc+ group (10%) than in the GHMDc− group (84%). All health problems revealed in the GHMDc+ group had developed between the last visit to the paediatric and the first visit to the adult clinic and/or did not require treatment. Mean BMI and the prevalence of diabetes mellitus type 2 were significantly lower in the GHMDc+ group compared to the GHMDc− group. As all patients who received GHt were treated in a multidisciplinary setting, it is unknown which effects are the result of GHt and which are the result of multidisciplinary care. However, our data clearly show that the combination of both has beneficial effects. Therefore, we recommend continuing GHMDc after patients with PWS have reached adult age.

Download Full-text

Sleep‐disordered breathing in Australian children with Prader‐Willi syndrome following initiation of growth hormone therapy

Journal of Paediatrics and Child Health ◽

10.1111/jpc.15691 ◽

2021 ◽

Author(s):

Daan Caudri ◽

Gillian M Nixon ◽

Aleisha Nielsen ◽

Linda Mai ◽

Claire R Hafekost ◽

...

Keyword(s):

Growth Hormone ◽

Hormone Therapy ◽

Sleep Disordered Breathing ◽

Growth Hormone Therapy ◽

Prader Willi Syndrome ◽

Disordered Breathing

Download Full-text

Circulating levels of pegvisomant and endogenous growth hormone during prolonged pegvisomant therapy in patients with acromegaly

Clinical Endocrinology ◽

10.1111/cen.12239 ◽

2013 ◽

Vol 80 (1) ◽

pp. 92-100 ◽

Cited By ~ 7

Author(s):

Michael Madsen ◽

Sanne Fisker ◽

Ulla Feldt-Rasmussen ◽

Mikkel Andreassen ◽

Lars Østergaard Kristensen ◽

...

Keyword(s):

Growth Hormone ◽

Endogenous Growth ◽

Circulating Levels

Download Full-text

Ethical issues in emerging new treatments such as growth hormone therapy for children with Down syndrome and Prader-Willi syndrome

Current Opinion in Pediatrics ◽

10.1097/00008480-199608000-00018 ◽

1996 ◽

Vol 8 (4) ◽

pp. 401-405 ◽

Cited By ~ 8

Author(s):

Eric Kodish ◽

Leona Cuttler

Keyword(s):

Growth Hormone ◽

Down Syndrome ◽

Hormone Therapy ◽

Ethical Issues ◽

Growth Hormone Therapy ◽

Prader Willi Syndrome ◽

Children With Down Syndrome ◽

New Treatments

Download Full-text

Time for a general approval of growth hormone treatment in adults with Prader–Willi syndrome

Orphanet Journal of Rare Diseases ◽

10.1186/s13023-020-01651-x ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Charlotte Höybye ◽

◽

Anthony J. Holland ◽

Daniel J. Driscoll

Keyword(s):

Growth Hormone ◽

Body Composition ◽

Transition Period ◽

Neurodevelopmental Disorder ◽

Hormone Treatment ◽

Psychomotor Development ◽

Prader Willi Syndrome ◽

Gh Treatment ◽

Beneficial Effects ◽

Positive Effects

AbstractPrader-Willi syndrome (PWS) is a complex, multi-system, neurodevelopmental disorder characterised by neonatal muscular hypotonia, short stature, high risk of obesity, hypogonadism, intellectual disabilities, distinct behavioural/psychiatric problems and abnormal body composition with increased body fat and a deficit of lean body mass. Growth hormone (GH) deficiency and other hormone deficiencies are common due to hypothalamic dysfunction. In children with PWS GH treatment has been widely demonstrated to improve body composition, normalise height and improve psychomotor development. In adults with PWS, GH’s main effects are to maintain normal body structure and metabolism. The positive effects of GH treatment on body composition, physical fitness and beneficial effects on cardiovascular risk markers, behaviour and quality of life in adults with PWS are also well established from several studies. GH treatment is approved for treatment of children with PWS in many countries, but until recently not as a treatment in young adults in the transition period or for adults in general. In this commentary we want to draw attention to the uneven global use of GH treatment, specifically in adults with PWS, and advocate for GH treatment to be approved internationally, not just for children, but also for adults with PWS and based only on the diagnosis of genetically confirmed PWS.

Download Full-text