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

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.

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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.

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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.

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

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2012-2901 ◽

2013 ◽

Vol 98 (2) ◽

pp. 761-768 ◽

Cited By ~ 6

Author(s):

Aimee J. Varewijck ◽

Steven W. J. Lamberts ◽

Sebastian J. C. M. M. Neggers ◽

Leo J. Hofland ◽

Joseph A. M. J. L. Janssen

Keyword(s):

Quality Of Life ◽

Gh Treatment ◽

Igf I

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Discontinuation of Growth Hormone (GH) Treatment during the Transition Phase Is an Important Factor Determining the Phenotype of Young Adults with Nonidiopathic Childhood-Onset GH Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2009-2013 ◽

2010 ◽

Vol 95 (6) ◽

pp. 2646-2654 ◽

Cited By ~ 16

Author(s):

Maria Kołtowska-Häggström ◽

Mitchell E. Geffner ◽

Peter Jönsson ◽

John P. Monson ◽

Roger Abs ◽

...

Keyword(s):

Quality Of Life ◽

Gh Deficiency ◽

Transition Phase ◽

Childhood Onset ◽

Future Health ◽

Gh Treatment ◽

Total Cohort ◽

Igf I ◽

The Impact

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.

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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.

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The ‘bio-assay’ quality of life might be a better marker of disease activity in acromegalic patients than serum total IGF-I concentrations

Acta Endocrinologica ◽

10.1530/eje.1.01838 ◽

2005 ◽

Vol 152 (2) ◽

pp. 217-224 ◽

Cited By ~ 23

Author(s):

Ingrid E Bonapart ◽

Ron van Domburg ◽

Saskia M T H ten Have ◽

Wouter W de Herder ◽

Ruud A M Erdman ◽

...

Keyword(s):

Quality Of Life ◽

Biochemical Parameter ◽

Term Treatment ◽

Normal Serum ◽

Open Label ◽

Mortality And Morbidity ◽

Long Term Treatment ◽

Igf I

Objectives: To investigate the quality of life (QoL) in acromegalic patients in relation to biochemical parameters. Design and methods: Single-center, open label study in 14 acromegalic patients (eight woman and six men, age 33–77 years), with normal serum IGF-I levels during long-term treatment with monthly injections of 20 mg of long-acting octreotide. We investigated which biochemical parameter might reflect optimal QoL, using the SF-36 questionnaire. Results: We observed that six patients had a low QoL score at baseline in the same range as observed in cancer patients. The other eight patients had a normal QoL. GH, IGF-I nor free IGF-I could discriminate these two subgroups at baseline. After skipping one monthly injection, all six subjects with the low QoL escaped in their free IGF-I concentrations. Also total IGF-I concentrations escaped in four of these six. In the subjects with normal QoL, free IGF-I levels remained normal in all, while total IGF-I levels only escaped in one. Conclusions: This study tells us that the currently used biochemical criteria for disease control in acromegaly might be sufficient in assessing long-term mortality and morbidity, but they are insufficient in addressing the most important parameter from the patient’s perspective – QoL.

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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.

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Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults

Acta Endocrinologica ◽

10.1530/eje.1.02017 ◽

2005 ◽

Vol 153 (5) ◽

pp. 661-668 ◽

Cited By ~ 6

Author(s):

Annice Mukherjee ◽

Judith E Adams ◽

Linda Smethurst ◽

Stephen M Shalet

Keyword(s):

Quality Of Life ◽

Body Composition ◽

Lean Body Mass ◽

Body Mass ◽

Total Body Water ◽

Body Water ◽

Gh Replacement ◽

Igf I ◽

Total Body

Lean body mass (LBM) and total body water (TBW) are reduced in GH-deficient (GHD) adults and alter with GH replacement. Whether these parameters are interdependent and whether alterations in their homeostasis contribute to the perceived quality of life (QOL) deficit in GHD remains unclear. In this study, IGF-I, body composition by whole-body dual-energy X-ray absorptiometry, TBW by deuterium dilution (D2O) and two validated QOL instruments - psychological general well-being schedule (PGWB, generic, 6 domains; lower score worse QOL) and assessment of GH deficiency in adults (AGHDA, disease orientated; higher score worse QOL) were studied at baseline and after 3 and 6 months of GH replacement in thirty GHD adults. Patients with diabetes insipidus, and cardiac and renal failure were excluded. Median age-adjusted IGF-I standard deviation score increased from −3.40 (−6.40 to −1.60) to −0.2 (−1.88 to 0.78) (P < 0.0001) at a median daily GH dose of 0.4 mg. During treatment, LBM increased from 47.4 ± 10.7 kg at baseline to 49.5 ± 10.8 kg at 6 months (P = 0.0008), and fat mass decreased from 28.0 ± 12.1 kg at baseline to 27.2 ± 12.6 kg at 6 months (P = 0.0004). A non-significant trend towards an increase in TBW was observed (mean 1.7 kg, P = 0.08). The PGWB score increased from 62.9 ± 20.6 to 73.7 ± 21.7 (P = 0.0006). The AGHDA score decreased from 13.7 ± 7.3 to 8.75 ± 7.75 (P = 0.0002). At each time point, a linear correlation between LBM and TBW was demonstrated, defined by TBW = (0.972 × LBM)–10.6. However, only a weakly positive correlation existed between the percentage changes in these variables (R = 0.40, P = 0.04). No correlations were demonstrated between QOL measures and body composition. The change in LBM with physiological GH replacement correlates weakly with change in TBW, therefore factors other than TBW may also contribute to the LBM changes. Improved QOL with GH replacement is not explained by favourable changes in body composition.

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