IGF-I Bioactivity Might Reflect Different Aspects of Quality of Life Than Total IGF-I in GH-Deficient Patients During GH Treatment

Abstract Context: Little is known about the impact of childhood-onset GH deficiency (GHD), in particular the duration of GH cessation during the transition phase, on adult phenotype. Objective: We investigated the association between the manifestations and management of GHD during childhood/adolescence and the clinical features of GHD in adulthood. Design/Setting/Patients/Intervention: Patients with reconfirmed childhood-onset GHD who resumed GH treatment as adults were identified from two sequential databases (n = 313). The cohort was followed up longitudinally from GH start in childhood to reinitiation of treatment in adulthood and 1 yr beyond. Analyses were performed in the total cohort and in subgroups of patients with idiopathic GHD (IGHD) and non-IGHD. The cohorts were stratified based on duration of GH cessation (short, ≤2 yr; long, >2 yr). Main Outcome Measures: Regimen of pediatric GH administration, duration of GH interruption, IGF-I sd score, lipid concentrations, and quality of life were measured. Results: Mean duration of GH interruption was 4.4 yr. IGF-I sd score in adulthood was related to severity of childhood GHD. In non-IGHD patients, a longer duration of GH interruption was associated with a worse lipid profile (P < 0.0001). Non-IGHD patients who gained more height during childhood GH treatment reported better quality of life than those who gained less height (P < 0.05). Conclusions: Pediatricians should tailor GH treatment, not only for its beneficial effect on growth but also for future health in adulthood. In adults with reconfirmed GHD, particularly those with non-IGHD, early recommencement of GH should be considered.

Download Full-text

Circulating IGF-I levels in monitoring and predicting efficacy during long-term GH treatment of GH-deficient adults

Acta Endocrinologica ◽

10.1530/eje.0.1490499 ◽

2003 ◽

pp. 499-509 ◽

Cited By ~ 10

Author(s):

S Ezzat ◽

S Fear ◽

RC Gaillard ◽

C Gayle ◽

S Marcovitz ◽

...

Keyword(s):

Quality Of Life ◽

Body Composition ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Long Term Effects ◽

Gh Treatment ◽

Igf I ◽

Total Fat

OBJECTIVE: To investigate the effects of long-term GH in GH-deficient adults, as predicted by IGF-I levels. METHODS: Patients received GH, 5 microg/kg per day for 1 Month and 10 microg/kg per day for another 12-30 Months. Changes in body composition, cardiac structure/function, serum lipids and quality of life were measured. RESULTS: There was a significant increase in lean body mass (LBM) (2.21 kg; P<0.0001) after 6 Months, which was sustained throughout treatment. A larger increase occurred in males than females (2.97 vs 1.19 kg; P<0.0001). Total fat mass was reduced (2.56 kg; P<0.0001 (3.26 kg males, 1.63 kg females)). Responsiveness to GH varied greatly, but LBM changes correlated with IGF-I changes (P<0.004). Furthermore, thinner patients experienced greater and progressive LBM increases. There was an increase in ejection fraction (3.85+/-9.95%; P=0.0002) after 6 Months, sustained to 18 Months. These cardiac effects were equal for males and females, and did not correlate with IGF-I levels. Serum low-density lipoprotein/high-density lipoprotein ratios decreased within 6 Months, and were sustained thereafter. Quality of life improved significantly after 6 Months, an effect that was sustained/enhanced as treatment continued. No major adverse events were identified. CONCLUSIONS: Improved body composition is both reflected by IGF-I changes and predicted inversely by baseline adiposity. Other effects of GH replacement on cardiac function, dyslipidaemia and quality of life, however, do not correlate with circulating IGF-I concentrations. Our findings validate the importance of sustained GH therapy, but caution on the interpretation of IGF-I levels in monitoring the long-term effects of GH treatment.

Download Full-text

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.

Download Full-text

A Prospective Investigation of Quality of Life and Psychological Well-Being after the Discontinuation of GH Treatment in Adolescent Patients Who Had GH Deficiency during Childhood

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.8.7709 ◽

2001 ◽

Vol 86 (8) ◽

pp. 3494-3498 ◽

Cited By ~ 15

Author(s):

Lena Wirén ◽

Gudmundur Johannsson ◽

Bengt-Åke Bengtsson

Keyword(s):

Quality Of Life ◽

Gh Deficiency ◽

Well Being ◽

Gh Treatment ◽

Psychological Well Being ◽

Adolescent Patients ◽

Prospective Investigation

Download Full-text

Ghrelin Prevents Cisplatin-Induced Mechanical Hyperalgesia and Cachexia

Endocrinology ◽

10.1210/en.2007-0828 ◽

2007 ◽

Vol 149 (2) ◽

pp. 455-460 ◽

Cited By ~ 80

Author(s):

José M. Garcia ◽

Juan P. Cata ◽

Patrick M. Dougherty ◽

Roy G. Smith

Keyword(s):

Quality Of Life ◽

Chemotherapeutic Agent ◽

Thermal Sensitivity ◽

Mechanical Hyperalgesia ◽

Behavioral Tests ◽

Sprague Dawley ◽

Sprague Dawley Rats ◽

Unique Model ◽

Igf I

Complications induced by the chemotherapeutic agent cisplatin, such as neuropathy and cachexia, occur frequently, are often dose limiting, and have an impact on quality of life and survival in cancer patients. The recently discovered hormone ghrelin is a potent GH secretagogue with orexigenic and neuroprotective properties that may prevent or ameliorate these complications. The objective of this study was to determine the effects of ghrelin administration on mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Adult male Sprague-Dawley rats were given cisplatin, ghrelin, ghrelin-cisplatin, or vehicle ip. Food intake and body weight were measured daily. Behavioral tests to assess the development of hyperalgesia were conducted by measuring mechanical and thermal sensitivity. Plasma ghrelin and IGF-I levels were also measured. Our results indicate that ghrelin coadministration inhibited the development of cisplatin-induced mechanical hyperalgesia, anorexia, and cachexia induced by cisplatin. Although ghrelin treatment had no effect on plasma IGF-I levels in control rats, it prevented the decrease in IGF-I levels induced by cisplatin. The attenuation of cisplatin-induced mechanical hyperalgesia induced by ghrelin was correlated with the prevention of cisplatin-induced lowering of IGF-I. In conclusion, ghrelin administration may be useful in the treatment or prevention of chemotherapy induced neuropathy and cachexia. Attenuation of mechanical hyperalgesia in the rat by the hormone ghrelin provides a unique model for elucidating the mechanisms involved, which are essential toward our understanding of these complications.

Download Full-text

Quality of Life (QOL) in Patients with Acromegaly Is Severely Impaired: Use of a Novel Measure of QOL: Acromegaly Quality of Life Questionnaire

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1565 ◽

2005 ◽

Vol 90 (6) ◽

pp. 3337-3341 ◽

Cited By ~ 77

Author(s):

Susannah V. Rowles ◽

L. Prieto ◽

X. Badia ◽

Steven M. Shalet ◽

Susan M. Webb ◽

...

Keyword(s):

Quality Of Life ◽

Signs And Symptoms ◽

Well Being ◽

Cross Sectional Study ◽

Life Questionnaire ◽

Cross Sectional ◽

Quality Of Life Questionnaire ◽

Utility Index ◽

Igf I

Acromegaly Quality of Life Questionnaire (AcroQoL) is a new disease-generated quality of life (QOL) questionnaire comprising 22 questions covering physical and psychological aspects of acromegaly and subdivided into “appearance” and “personal relations” categories. We have performed a cross-sectional study of QOL in 80 patients [43 male (mean age, 54.2 yr; range, 20–84); median GH, 0.93ng/ml (range, <0.3 to 23.7); IGF-I, 333.1 ng/ml (range, 47.7–899)] with acromegaly. In addition to AcroQoL, patients completed three generic QOL questionnaires: Psychological General Well-Being Schedule (PGWBS), EuroQol, and a signs and symptoms score (SSS). All three generic questionnaires confirmed impairment in QOL [mean scores: PGWBS, 69.6; EuroQol, visual analog scale, 66.4 (range, 20–100) and utility index, 0.7 (range, −0.07 to 0.92); and SSS, 12 (range, 0–27)]. There was no correlation between biochemical control and any measure of QOL. AcroQoL (57.3%; range, 18.2–93.2) correlated with PGWBS (r = 0.73; P < 0.0001); and in patients with active disease, AcroQoL-physical dimension correlated with SSS (r = −0.67; P < 0.0003). In all questionnaires, prior radiotherapy was associated with impaired QOL. In conclusion, these data underline the marked impact that acromegaly has on patients’ QOL and provide the first evidence validating AcroQoL against well-authenticated measures of QOL. This indicates the potential of AcroQoL as a patient-friendly measure of disease activity.

Download Full-text

Impaired quality of life of patients with acromegaly: control of GH/IGF-I excess improves psychological subscale appearance

Acta Endocrinologica ◽

10.1530/eje-07-0697 ◽

2008 ◽

Vol 158 (3) ◽

pp. 305-310 ◽

Cited By ~ 62

Author(s):

Maria P Matta ◽

Elisabeth Couture ◽

Laurent Cazals ◽

Delphine Vezzosi ◽

Antoine Bennet ◽

...

Keyword(s):

Quality Of Life ◽

Medical Treatment ◽

Positive Impact ◽

Group I ◽

Igf I ◽

Group Ii ◽

Psychological Scales ◽

Control Criteria ◽

Design And Methods

IntroductionAcromegaly, a chronic disease caused by GH/IGF-I excess, has a major impact on quality of life (QoL).ObjectiveTo evaluate QoL of acromegalic patients in relation to control status of the disease.Design and methodsSingle center observational study including 93 patients with acromegaly recruited to complete QoL questionnaire (AcroQol). QoL was evaluated at least 3 months after surgery and/or medical treatment. Patients were divided into two groups: controlled (I) and uncontrolled (II) according to the latest consensus acromegaly ‘control’ criteria and further subdivided into four subgroups according to the previous pituitary adenoma surgery (Ib and IIb) or without surgery (Ia and IIa).ResultsMean GH (0.81±0.47 ng/ml) and IGF-I (195±71 ng/ml) values in group I were significantly lower than in group II (GH, 7.01±12.05 ng/ml and IGF-I, 513±316 ng/ml; P<0.001). There was no difference in total AcroQol score, physical, or psychological scales between groups I and II. However, when adjusted to age and disease duration since diagnosis, patients of group I (63±20%) showed an improved psychological subscale appearance than those of group II (58±17%; P=0.035). In group II, IGF-I level was lower after surgery (IIa=588±353, IIb=410±225 ng/ml; P<0.038), and psychological subscale appearance was significantly better in subgroup IIb (64.9±18.1%) than in subgroup IIa who had medical treatment (53.9±14.3%; P=0.009).ConclusionQoL is severely impaired in acromegalic patients. Control of GH/IGF-I excess by surgery or medical treatment seems to have a positive impact on psychological subscale appearance.

Download Full-text

Discontinuation of GH treatment in adolescent patients: Effects on quality of life and psychological well-being

Growth Hormone & IGF Research ◽

10.1016/s1096-6374(98)80201-3 ◽

1998 ◽

Vol 8 (4) ◽

pp. 330

Author(s):

Lena Wirén ◽

Gudmundur Johannsson ◽

Anne Rosén ◽

Bengt-Åke Bengtsson

Keyword(s):

Quality Of Life ◽

Well Being ◽

Gh Treatment ◽

Psychological Well Being ◽

Adolescent Patients

Download Full-text

Quality of Life (QoL) and IGF-I Status in Adults with Severe GHD

Endocrine Abstracts ◽

10.1530/endoabs.41.ep700 ◽

2016 ◽

Author(s):

Stephen Shalet ◽

Peter Jonsson ◽

Andreas Pleil ◽

Cecilia Camacho-Hubner ◽

Roger Abs

Keyword(s):

Quality Of Life ◽

Igf I

Download Full-text

Early versus late initiation of GH replacement in adult-onset hypopituitarism

Endocrine Connections ◽

10.1530/ec-20-0098 ◽

2020 ◽

Vol 9 (7) ◽

pp. 687-695

Author(s):

Mark R Postma ◽

Pia Burman ◽

André P van Beek

Keyword(s):

Quality Of Life ◽

Pituitary Hormones ◽

Hormone Deficiency ◽

Adult Onset ◽

Anthropometric Measures ◽

Beneficial Effects ◽

Gh Replacement ◽

Late Initiation ◽

Igf I

Introduction: Adult-onset growth hormone deficiency (AGHD) is usually the last deficiency to be substituted in hypopituitarism. In children with documented GH deficiency, treatment without delay is crucial for achieving optimal effects on growth and development. In adults, it is not known whether a delay in treatment initiation influences biochemical response and the favourable physiological effects resulting from GH replacement therapy (GHRT). Methods: A total of 1085 GH-deficient adults from KIMS (Pfizer International Metabolic Database) were included, adequately replaced with all pituitary hormones except for GH at baseline. Patients were stratified by sex and age (20–50 years and ≥50 years) and subsequently divided into two groups below and above the median duration of unsubstituted AGHD for that subgroup. The median time of unsubstituted GHD for the total cohort was 2.53 years (P5 = 0.35, P95 = 24.42). Results: Beneficial effects of 4 years of GHRT were observed on lipids and quality of life in all subgroups. A decrease in waist circumference was observed only in older (>50 years) patients. There was no difference in IGF-I SDS and in GH dose required to normalize IGF-I in patients with a duration of unsubstituted AGHD above or below the median. No relevant differences were found between the groups for anthropometric measures, cardiovascular risk factors and quality of life scores. Conclusion: In contrast to GHD in children and adolescents, no difference could be established in treatment response between early or late initiation of GHRT in AGHD in terms of required GH dose, IGF-I, metabolic health and quality of life.

Download Full-text