Growth Hormone (GH) Treatment Decreases Plasma Kisspeptin Levels in GH-Deficient Adults with Prader–Willi Syndrome

Obesity and growth hormone (GH)-deficiency are consistent features of Prader–Willi syndrome (PWS). Centrally, kisspeptin is involved in regulating reproductive function and can stimulate hypothalamic hormones such as GH. Peripherally, kisspeptin signaling influences energy and metabolic status. We evaluated the effect of 12-month GH treatment on plasma kisspeptin levels in 27 GH-deficient adult PWS patients and analyzed its relationship with metabolic and anthropometric changes. Twenty-seven matched obese subjects and 22 healthy subjects were also studied. Before treatment, plasma kisspeptin concentrations in PWS and obese subjects were similar (140.20 (23.5–156.8) pg/mL vs. 141.96 (113.9–165.6) pg/mL, respectively, p = 0.979)) and higher (p = 0.019) than in healthy subjects (124.58 (107.3–139.0) pg/mL); plasma leptin concentrations were similar in PWS and obese subjects (48.15 (28.80–67.10) ng/mL vs. 33.10 (20.50–67.30) ng/mL, respectively, p = 0.152) and higher (p < 0.001) than in healthy subjects (14.80 (11.37–67.30) ng/mL). After GH therapy, lean body mass increased 2.1% (p = 0.03), total fat mass decreased 1.6% (p = 0.005), and plasma kisspeptin decreased to levels observed in normal-weight subjects (125.1(106.2–153.4) pg/mL, p = 0.027). BMI and leptin levels remained unchanged. In conclusion, 12-month GH therapy improved body composition and decreased plasma kisspeptin in GH deficient adults with PWS. All data are expressed in median (interquartile range).

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Sustained Benefits of Growth Hormone on Body Composition, Fat Utilization, Physical Strength and Agility, and Growth in Prader-Willi Syndrome are Dose-Dependent

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2001-0805 ◽

2001 ◽

Vol 14 (8) ◽

Cited By ~ 36

Author(s):

Aaron L. Carrel ◽

Susan E. Myers ◽

Barbara Y. Whitman ◽

David B. Allen

Keyword(s):

Growth Hormone ◽

Body Composition ◽

Prader Willi Syndrome ◽

Critical Question ◽

Gh Therapy ◽

Gh Treatment ◽

Physical Strength ◽

Gh Secretion ◽

Induced Changes ◽

Dose Dependent

AbstractBackground: Obesity and hypotonia in children with Prader-Willi syndrome (PWS) are accompanied by abnormal body composition resembling a growth hormone (GH) deficient state. Hypothalamic dysfunction in PWS includes decreased GH secretion, suggesting a possible therapeutic role for GH treatment. While recent studies have demonstrated short-term benefits of treatment with GH, a critical question is whether beneficial changes persist or wane with prolonged therapy, and whether these effects on body composition are dose-dependent as seen in adult GH deficiency.Objectives and Methods: After 24 months of GH theapy at a dose of 1 mg/mResults: During months 24-36 of GH therapy, further changes in body composition (decrease in fat mass, and increase in lean body mass), growth velocity, and REE occurred with standard and higher-dose GH therapy (1.5 mg/m2/day), but not with lower dose GH (0.3 mg/m2/day). Prior improvements in BMD, and strength and agility, which occurred during the initial 24 months, were sustained during the additional 12 months (to 36 months) regardless of dose.Conclusions: Salutary and sustained . GH- induced changes in growth, body composition, and physical function in children with PWS require GH doses of >0.3 mg/m

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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.

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Issues in the Transition From Childhood to Adult Growth Hormone Therapy

PEDIATRICS ◽

10.1542/peds.104.s5.1004 ◽

1999 ◽

Vol 104 (Supplement_5) ◽

pp. 1004-1010

Author(s):

David B. Allen

Keyword(s):

Growth Hormone ◽

Replacement Therapy ◽

Blood Lipid ◽

Hormone Deficiency ◽

Late Adolescent ◽

Gh Therapy ◽

Gh Treatment ◽

Beneficial Effects ◽

Gh Replacement ◽

Adult Growth

The consequences of severe growth hormone deficiency (GHD) in adults and the beneficial effects of GH replacement therapy are clear. However, the majority of children who have a diagnosis of GHD and who are treated with GH do not have permanent GHD and will not require treatment during adulthood. Several issues must be considered in selecting candidates for adult GH treatment and transitioning their care from pediatrics to adult medicine. Counseling about possible lifelong treatment should focus on children with panhypopituitarism and those with severe isolated GHD that is associated with central nervous system abnormalities. When to terminate growth-promoting GH therapy should be guided by balancing the high cost of late-adolescent treatment with the attainment of reasonable statural goals. Retesting for GH secretion is appropriate for all candidates for adult GH therapy; the GH axis can be tested within weeks after the cessation of treatment, but confirming an emerging adult GHD state with body composition, blood lipid, and quality-of-life assessments may require 1 year or more of observation. Selecting patients for lifelong adult GH replacement therapy will present diagnostic, therapeutic, and ethical problems similar to those in treating childhood GHD. The experience and expertise of pediatric endocrinologists in diagnosing and treating GHD should be offered and used in identifying and transitioning appropriate patients to adult GH therapy.

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Growth Hormone (GH) treatment in adults with Prader-Willi Syndrome (PWS) restores plasma kisspeptin to normal levels

Endocrine Abstracts ◽

10.1530/endoabs.73.aep476 ◽

2021 ◽

Author(s):

Giménez-Palop Olga ◽

Laia Casamitjana ◽

Raquel Corripio ◽

Pareja Rocío ◽

Joan Carles Oliva ◽

...

Keyword(s):

Growth Hormone ◽

Prader Willi Syndrome ◽

Gh Treatment

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Impact of Overweight on Effectiveness of Treatment with Human Growth Hormone in Growth Hormone Deficient Children: Analysis of German KIGS Data

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0031-1285913 ◽

2011 ◽

Vol 119 (09) ◽

pp. 544-548 ◽

Cited By ~ 4

Author(s):

T. Reinehr ◽

S. Bechtold-Dalla Pozza ◽

M. Bettendorf ◽

H.-G. Doerr ◽

B. Gohlke ◽

...

Keyword(s):

Growth Hormone ◽

Growth Velocity ◽

Normal Weight ◽

First Year ◽

Overweight Children ◽

Gh Treatment ◽

Prepubertal Children ◽

Significant Difference ◽

Igf I ◽

Group A

AbstractWe hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests.Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepubertal children with GHD from the German KIGS database according to BMI (underweight=group A, normal weight=group B, overweight=group C) (median age: group A, B, C: 7.3, 7.28, and 8.4 years).Maximum GH levels to tests (median: group A, B, C: 5.8, 5.8, and 4.0 µg/ml) were significantly lower in group C. IGF-I SDS levels were not different between the groups. Growth velocity in the first year of GH treatment was significantly lower in the underweight cohort (median: group A, B, C: 8.2, 8.8, and 9.0 cm/yr), while the gain in height was not different between groups. The difference between observed and predicted growth velocity expressed as Studentized residuals was not significantly different between groups. Separating the 164 overweight children into obese children (BMI>97th centile; n=71) and moderate overweight children (BMI>90th to 97th centile, n=93) demonstrated no significant difference in any parameter.Overweight prepubertal children with idiopathic GHD demonstrated similar levels of responsiveness to GH treatment compared to normal weight children. Furthermore, the IGF-I levels were low in overweight children. Therefore, a misclassification of GHD in overweight prepubertal children within the KIGS database seems unlikely. The first year growth prediction models can be applied to overweight and obese GHD children.

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Atypical depression in growth hormone deficient adults, and the beneficial effects of growth hormone treatment on depression and quality of life

Acta Endocrinologica ◽

10.1530/eje.0.1510325 ◽

2004 ◽

pp. 325-332 ◽

Cited By ~ 36

Author(s):

T Mahajan ◽

A Crown ◽

S Checkley ◽

A Farmer ◽

S Lightman

Keyword(s):

Quality Of Life ◽

Growth Hormone ◽

Rating Scales ◽

Nottingham Health Profile ◽

Psychiatric Evaluation ◽

Gh Therapy ◽

Gh Treatment ◽

Psychiatric Interview ◽

Atypical Depression

OBJECTIVE: Some growth hormone deficient adults (GHDAs) have an impaired quality of life, which may improve with growth hormone (GH) treatment. The objective of our study was to make an in-depth psychiatric evaluation of patients with adult-onset (AO) and childhood-onset (CO) GH deficiency (GHD), and to assess the time course of changes in their quality of life and symptoms of depression in response to GH treatment. DESIGN: The study design was a 4-month, double-blind, cross-over, placebo-controlled trial of GH therapy. METHODS:We used a detailed psychiatric interview to characterise 25 patients with proven GHD at baseline. They were reassessed at monthly intervals during treatment with GH or placebo, using the Nottingham Health Profile and two well-recognised depression rating scales. RESULTS: 11/18 (61%) of the patients with AO-GHD, but 0/7 of the patients with CO-GHD, were found to have atypical depression at baseline. There were significant improvements in the depression rating scale scores after 2 months of GH therapy, with significant improvements in emotional reaction and social isolation scores from 1 month, and in energy levels and sleep disturbance from 2 and 3 months respectively. CONCLUSIONS: The results of our study confirm that a large proportion of GHDAs have unequivocal psychiatric morbidity, and suggest that a response to treatment can be seen after a short trial of GH therapy. We hypothesise that this rapid improvement of symptoms of atypical depression represents a direct central effect of GH therapy.

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Changes to Thyroid Function (TF) Following Growth Hormone (GH) Therapy in Children with Prader-Willi Syndrome (PWS)

Journal of Paediatrics and Child Health ◽

10.1111/jpc.13945_2 ◽

2018 ◽

Vol 54 ◽

pp. 4-5

Keyword(s):

Growth Hormone ◽

Thyroid Function ◽

Prader Willi Syndrome ◽

Gh Therapy

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Safety and effectiveness of growth hormone therapy in infants with Prader-Willi syndrome younger than 2 years: a prospective study

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2018-0539 ◽

2019 ◽

Vol 32 (8) ◽

pp. 879-884 ◽

Cited By ~ 3

Author(s):

Raquel Corripio ◽

Carla Tubau ◽

Laura Calvo ◽

Carme Brun ◽

Núria Capdevila ◽

...

Keyword(s):

Growth Hormone ◽

Prospective Study ◽

Mixed Model ◽

Standard Deviation Score ◽

Uniparental Disomy ◽

Chromosome 15 ◽

Prader Willi Syndrome ◽

Gh Treatment ◽

Maternal Uniparental Disomy ◽

A Prospective Study

Abstract Background There is little evidence of the effects of early treatment with growth hormone (GH) in infants with Prader-Willi syndrome (PWS). A prospective study was conducted to assess the safety of GH therapy in infants younger than 2 years of age with PWS. Methods A total of 14 patients with PWS started treatment with GH under the age of 2 years and were followed over a 2-year period. A deletion of chromosome 15 was present in nine infants (64.3%) and maternal uniparental disomy 15 in five infants (35.7%). The median age at start of GH treatment was 9.6 months (interquartile range [IQR] 9.0–18.3 months). Changes in height standard deviation score (SDS), body mass index (BMI) SDS and subcapsular and tricipital skinfolds in the follow-up period were evaluated with a mixed-model regression analysis using the Package R. Results There were no fatal adverse events. A significant decrease (p < 0.001) in tricipital and subcapsular skinfold thickness, with an upward trend of height SDS and a downward trend of BMI SDS, was observed. Infants who started GH before 15 months of age started walking at a median of 18.0 [17.0–19.5] months vs. 36.6 [36.3–37.8] months for those who began treatment with GH after 15 months of age (p = 0.024). Conclusions GH treatment in infants with PWS less than 2 years of age is safe and improved body composition. Infants who received GH before the age of 15 months started to walk earlier.

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Delayed Bone Age Might Accelerate the Response to Human Growth Hormone Treatment in Small for Gestational Age Children with Short Stature

International Journal of Endocrinology ◽

10.1155/2019/8454303 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

Jung-Eun Moon ◽

Cheol Woo Ko

Keyword(s):

Growth Hormone ◽

Short Stature ◽

Gestational Age ◽

Small For Gestational Age ◽

Human Growth ◽

Bone Age ◽

Pediatric Endocrinology ◽

Gh Therapy ◽

Gh Treatment ◽

The Impact

Purpose. Growth hormone (GH) treatment is recommended to improve growth and psychosocial problems in short stature children born small for gestational age (SGA). Although GH therapy in these patients has been extensively studied, the impact of therapy according to delays in bone age (BA) is not known well. Objective. To investigate the effects of GH therapy in SGA patients with short stature according to BA delay. Methods. We retrospectively analyzed changes in height SD score (SDS) and BA/chronological age (CA) after 6 and 12 months of GH therapy in patients grouped according to BA delay. We studied 27 SGA children with short stature in the pediatric endocrinology clinic of Kyungpook National University Children’s Hospital. Results. Of the 27 patients, 9 had <2 years of BA delay, while 18 had >2 years of delay. There were no significant differences between the two groups in terms of gestational age and weight at birth, height SDS, IGF-1 SDS, and growth hormone dosage at the beginning of therapy. However, height SDS increased significantly in the group with >2 years of BA delay after 6 months of GH therapy (−2.50 ± 0.61 vs −1.87 ± 0.82; p=0.037) and 12 months (−2.27 ± 0.70 vs −1.63 ± 0.65; p=0.002). When height SDS was compared between with and without GHD, there were no significant differences. Conclusions. Delayed BA (>2 years) may impact the response to GH treatment in SGA children with short stature.

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