The clinical, metabolic and endocrine features and the quality of life in adults with childhood-onset craniopharyngioma compared with adult-onset craniopharyngioma

Background: Craniopharyngioma is a parasellar tumour that, although benign, tends to behave aggressively. It can occur at any age but most commonly presents in childhood or adolescence. Objectives: To investigate the frequency and severity of problems associated with craniopharyngioma, using the large international database (KIMS) for adult patients with GH deficiency (GHD), and to assess the differences between the adult onset (AO, aged 18 or above) disease and adults with childhood onset (CO) craniopharyngioma. Design: Inclusion criteria were: an established diagnosis of craniopharyngioma, severe GHD and no recent GH treatment. These criteria were fulfilled by 393 (184 female, 209 male) patients; 241 had AO (mean age 28.7±8.7 years) and 152 had CO disease (age 42.0±12.3 years). Disease history, clinical features and anthropometric data were recorded at the time of enrolment in the database, and body composition, serum IGF-I, serum lipids and quality of life (QoL) were assessed. Results: Peak age at onset of craniopharyngioma was 15–20 years. Ninety percent of patients had been treated surgically. CO patients were shorter than AO patients and had much lower IGF-I standard deviation scores (SDS). The majority had hypopituitarism and over 60% had diabetes insipidus. Body mass index (BMI) was higher in AO males (30.2±5.5) than in CO males (28.5±7.5); waist circumference was also greater. Obesity was more common in AO patients (51.8% vs 39.1%). Body composition did not differ between groups. Cholesterol and triglycerides were higher in AO than in CO patients, but high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol did not differ. Quality of life, assessed by Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA) and the Nottingham Health Profile, was markedly reduced in all groups with no significant differences between them; the QoL-AGHDA score correlated with age at onset of both craniopharyngioma and GHD, and also with BMI in AO patients. Conclusions: These data emphasise the generally poor state of health of patients treated for craniopharyngioma, with respect to endocrine and metabolic function, and also the markedly reduced quality of life. In addition to GHD, most patients have evidence of hypothalamic damage with associated obesity, diabetes insipidus and hypopituitarism. Adults with CO craniopharyngioma were shorter, had lower IGF-I, lower BMI, less obesity and slightly lower blood lipid levels than patients with AO craniopharyngioma.

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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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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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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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Seven years of growth hormone (GH) replacement improves quality of life in hypopituitary patients with adult-onset GH deficiency

Acta Endocrinologica ◽

10.1530/eje-16-0875 ◽

2017 ◽

Vol 176 (2) ◽

pp. 99-109 ◽

Cited By ~ 20

Author(s):

Mariam Elbornsson ◽

Alexandra Horvath ◽

Galina Götherström ◽

Bengt-Åke Bengtsson ◽

Gudmundur Johannsson ◽

...

Keyword(s):

Quality Of Life ◽

Growth Hormone ◽

Gh Deficiency ◽

Well Being ◽

Life Assessment ◽

Hormone Deficiency ◽

First Year ◽

Adult Onset ◽

Gh Replacement

Objective Few studies have determined the effects of long-term growth hormone (GH) replacement on quality of life (QoL). This study investigated the effects of 7 years of GH replacement on QoL. Design A prospective, single-center, open-label study of 95 adults (mean age 52.8 years; 46 men) with adult-onset GH deficiency (GHD). Methods QoL was measured using Quality of Life-Assessment for Growth Hormone Deficiency in Adults (QoL-AGHDA) and Psychological General Well-Being (PGWB) scores. Results The GH dose was gradually increased from 0.13 mg/day to 0.42 mg/day. IGF-I SD score increased from −1.49 at baseline to 0.35 at study end. The GH replacement induced sustained improvements in total QoL-AGHDA and PGWB scores. GHD women had a more marked improvement in total QoL-AGHDA score than GHD men after 5 and 7 years. Most of the improvement in QoL was seen during the first year, but there was a small further improvement also after one year as measured using QoL-AGHDA. All QoL-AGHDA dimensions improved, but the improvement in memory and concentration as well as tenseness occurred later than that of other dimensions. Correlation analysis demonstrated that the patients with the lowest baseline QoL had the greatest improvement in QoL. Conclusions Seven years of GH replacement improved QoL with the most marked improvements in GHD women and in patients with low baseline QoL. Most, but not all, of the improvement in QoL was seen during the first year. Some QoL-AGHDA dimensions (memory and concentration, tenseness) responded at a slower rate than other dimensions.

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A 34-Year-Old Male with Possible Myopathic Process

10.1093/med/9780190491901.003.0022 ◽

2016 ◽

Author(s):

Jeffrey A. Cohen ◽

Justin J. Mowchun ◽

Victoria H. Lawson ◽

Nathaniel M. Robbins

Keyword(s):

Quality Of Life ◽

Spinal Muscular Atrophy ◽

Motor Neurons ◽

Muscular Atrophy ◽

Age At Onset ◽

Homozygous Deletion ◽

Adult Onset ◽

Type Iv ◽

Electrodiagnostic Study

Adult-onset spinal muscular atrophy (SMA type IV) presents in a manner similar to a myopathy. Normal CK and a neurogenic pattern of denervated changes on electrodiagnostic study suggest the actual diagnosis. The diagnosis of SMA is confirmed by the presence of a homozygous deletion or mutation of the SMN1 gene in most patients. Both the presence of SMN1 deletion/mutation and the effectiveness of rescue from a second copy of the gene, SMN2, determines the age at onset and severity of SMA. Differential includes other genetic conditions affecting motor neurons, postpolio syndrome, monomelic amyotrophy, and motor neuropathies/poly-radiculopathies. The management of SMA is predominantly supportive, but this can significantly impact quality of life.

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Heterogeneity in responsiveness of perceived quality of life to body composition changes between adult- and childhood-onset Japanese hypopituitary adults with GH deficiency during GH replacement

Acta Endocrinologica ◽

10.1530/eje-07-0016 ◽

2007 ◽

Vol 156 (6) ◽

pp. 637-645 ◽

Cited By ~ 12

Author(s):

Hisashi Urushihara ◽

Shunichi Fukuhara ◽

Shigeru Tai ◽

Satoshi Morita ◽

Kazuo Chihara

Keyword(s):

Quality Of Life ◽

Body Composition ◽

Fat Mass ◽

Physical Functioning ◽

General Health ◽

Gh Deficiency ◽

Bodily Pain ◽

Japanese Adults ◽

Igf I

Objective: To examine the responsiveness of quality of life (QoL) associated with changes in clinical indices relevant to GH deficiency (GHD) in Japanese hypopituitary adults. Design and methods: QoL was determined using the Short Form (SF)-36 in Japanese adults with adult-(AO; n = 27) or childhood- (CO; n = 37) onset GHD in a 24-week double-blind placebo-controlled study with a fixed GH dose, and a subsequent 48-week open-label extension study with GH doses individualized using serum IGF-I levels. Results: Baseline QoL was significantly decreased from the Japanese national reference in both onset types, more so in AO patients. Throughout the study, AO patients showed a trend for an increase in physical functioning and general health (P = 0.0564 and 0.0999 respectively), whereas CO patients showed no changes in these domains. Fat mass changes negatively correlated with the changes in physical functioning and general health in AO patients (r = −0.42 and −0.64 respectively), but to a lesser degree in CO patients (r = −0.36 and −0.32 respectively). CO patients displayed significant decreases in social functioning (P = 0.0305) and mental health (P = 0.0442) and a decreasing trend in bodily pain (P = 0.0769), although no correlation between these decreases and any measured clinical index was observed, except between changes in bodily pain and IGF-I levels (r = −0.43). Conclusions: QoL impairment was evident in Japanese adults with GHD, particularly in AO patients. In AO patients, general health and physical functioning domains were responsive to fat mass changes during GH treatment; this association was not evident in CO patients. These relationships between QoL and body composition warrant verification.

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