Adult Growth Hormone Deficiency Assessment Research Articles

Growth hormone secretion, fatigue and quality of life after childhood traumatic brain injury.

Traumatic brain injury (TBI) is a recognised cause of hypopituitarism in adults but the prevalence after childhood TBI remains controversial. To investigate long-term endocrine outcomes and quality of life (PedsQL and QoL-AGHDA (Quality of Life in Adult Growth Hormone Deficiency Assessment)) following childhood TBI. Prospective study. Participants with moderate/severe TBI (n = 31) and controls (n = 17). Mean (range) age: 19.8 ± 4.2 (11-26), time post TBI: 9 (7-11) years. Detailed endocrine evaluation of stimulated (insulin tolerance test (ITT)) and spontaneous GH secretion (overnight profile) was undertaken in the TBI group; QoL and neuroimaging in both groups. No participant had seizures, short stature, precocious puberty or hypothyroidism. In 6/25 the ITT GH response was below age-defined cut-offs and cortisol <500 nmol/L in 2/25. Mean spontaneous GH secretion was <3.1 µg/L in 16/22 but peak GH was low only in 1/22 profiles. One patient had abnormal spontaneous and stimulated GH secretion and hypogonadism. Fatigue and depression scores were higher in TBI patients (P = .011 and P = .020). Fatigue correlated with measures of spontaneous but not stimulated GH secretion. Overall QoL (PedsQL) did not differ between groups but specific attributes of health state (cognition, memory) were impaired in TBI patients. Pituitary neuroimaging was normal in all participants. Fatigue and depression were common 8-10 years post childhood TBI. One individual had GHD (1/22) using rigorous diagnostic criteria. A single ITT potentially over-diagnosed GHD in 25% (6/25) without clear correlation with symptoms underlying the importance of using two diagnostic tests in TBI survivors.

What Is the Best Way of Assessing Neurocognitive Dysfunction in Patients With Primary Hyperparathyroidism?

The patient attending with asymptomatic primary hyperparathyroidism (PHPT) is a common occurrence in the outpatient endocrine setting. Indeed, more than 80% of contemporary PHPT patients are considered asymptomatic at diagnosis. A frequent question in clinical practice is at what stage may the patient be offered curative surgery. This may well relate to the duration and the degree of hypercalcemia, evidence of end-organ effects, and whether clear symptoms may or may not be attributable to the underlying condition. There are well-recognized psychological and cognitive changes that can occur in the context of PHPT. A challenge for the clinician is to discern to what extent these symptoms may be present (often very close questioning is required) and how to measure and categorize them. Assessment can be difficult because patients who have PHPT tend to be more elderly, and they often have other overlapping comorbidities that may cloud the diagnosis. A decision then has to made as to whether such symptoms are likely to be a result of prolonged hypercalcemia, to what extent they can be attributed to the underlying disease, and whether they constitute sufficient weight to warrant surgical intervention in an otherwise "asymptomatic" patient. Practice tends to vary, and some clinicians may undertake watchful waiting or conservative management, whereas others may more readily push for surgical parathyroidectomy as a definitive treatment. We reviewed the literature on the subject of neuropsychological testing in the management of PHPT. POSITIONS: A controversy in clinical endocrinology is how to assess the cognitive, quality of life, and psychological effects of hypercalcemia. Multiple tools are being used, and significant changes have often been demonstrated in such parameters after parathyroidectomy. We reviewed the latest studies on this subject and assessed the usefulness and validity of such tools in clinical practice, identifying several scores and measures that have been validated in clinical practice; comparisons are made with similar assessments such as the Adult Growth Hormone Deficiency Assessment questionnaire.

Adaptation of the QoL-AGHDA scale for adults with growth hormone deficiency in four Slavic languages

PurposeThe Quality of Life in Adult Growth Hormone Deficiency Assessment (QoL-AGHDA) is a disease-specific quality of life measure specific to individuals who are growth hormone deficient. The present study describes the adaptation of the QoL-AGHDA for use in the following four Slavic languages; Czech, Polish, Serbian and Slovakian.MethodsThe study involved three stages in each language; translation, cognitive debriefing and validation. The validation stage assessed internal consistency (Cronbach's alpha), reproducibility (test-retest reliability using Spearman's rank correlations), convergent and divergent validity (Correlations with the NHP) and known group validity.ResultsThe QoL-AGHDA was successfully translated into the target languages with minimal problems. Cognitive debriefing interviewees (n = 15-18) found the measures easy to complete and identified few problems with the content. Internal consistency (Czech Republic = 0.91, Poland = 0.91, Serbia = 0.91 and Slovakia = 0.89) and reproducibility (Czech Republic = 0.91, Poland = 0.91, Serbia = 0.88 and Slovakia = 0.93) were good in all adaptations. Convergent and divergent validity and known group validity data were not available for Slovakia. The QoL-AGHDA correlated as expected with the NHP scales most relevant to GHD. The QoL-AGHDA was able to distinguish between participants based on a range of variables.ConclusionsThe QoL-AGHDA was successfully adapted for use in the Czech Republic, Poland, Serbia and Slovakia. Further validation of the Slovakian version would be beneficial. The addition of these new lanaguage versions will prove valuable to multinational clinical trials and to clinical practice in the respective countries.

Growth hormone deficient patients after traumatic brain injury – Baseline characteristics and benefits after growth hormone replacement – An analysis of the German KIMS database

Objective In recent years, traumatic brain injury (TBI) has been identified as a significant cause of growth hormone deficiency (GHD). The aim of the present study was to characterize adult TBI patients with GHD to elucidate the effect of human growth hormone (hGH) replacement in TBI patients as documented in the German Pfizer International Metabolic (KIMS) database. Design As of October 2006, 84 TBI patients had been included in the German KIMS database ( n = 28 childhood-onset and 54 adult-onset GHD). All 84 TBI patients were matched with 84 patients with GHD due to non-functioning pituitary adenoma (NFPA) also included in this database. Analysis of clinical and outcome variables was performed, with comparisons of childhood vs. adult TBI, and TBI vs. NFPA patients, at baseline and one-year follow-up. Results TBI patients with GHD were significantly younger at the onset of pituitary disease and exhibited a significantly longer time span between GHD diagnosis and KIMS entry than NFPA patients. Those KIMS patients who had sustained their TBI in childhood were of significantly shorter stature than adult-onset TBI patients. At 1-year follow-up, insulin-like growth factor I (IGF-I) standard deviation score levels had returned to the normal range and quality of life (QoL), as measured by QoL- Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire, improved significantly in TBI as in NFPA patients. Conclusion This analysis provides preliminary data that TBI patients with GHD benefit from hGH replacement in terms of improved QoL in a similar fashion as do NFPA patients. Moreover, it suggests that belated diagnosis and treatment in childhood-onset GHD due to TBI might be related to a shorter final height in these children.

The Characteristics of Quality of Life Impairment in Adult Growth Hormone (GH)-Deficient Survivors of Cancer and Their Response to GH Replacement Therapy

We studied 50 (27 women and 23 men) GH-deficient (GHD) cancer survivors and 47 (24 women and 23 men) GHD patients with pituitary pathologies. All GHD patients were considered for GH replacement on the basis of subjectively poor quality of life (QOL). Primary outcome measures were scores of QOL instruments psychological general well-being schedule (PGWB) and assessment of GH deficiency in adults (AGHDA) at baseline and early (6-13 months) and long-term (24-77 months) treatment follow-up. Of secondary interest were six PGWB domains. Linear mixed effect regression was used to model each QOL outcome. The groups differed with respect to three covariates: age, gender, and body mass index. These variables were included in all fitted models. Baseline scores for PGWB and AGHDA were not different between groups. Ranking of PGWB domains were similar between groups at baseline (lowest domain, vitality). The pattern of change in mean scores for all outcome measures from baseline did not differ between groups (P = 0.86). All QOL variables improved significantly with treatment [estimated mean change +/- se: PGWB, 16.2 +/- 1.7; AGHDA, -6.2 +/- 0.6; PGWB domains (transformed percentage scales): anxiety, 12.4 +/- 1.7; depression, 14.1 +/- 2.1; health, 12.4 +/- 1.7; self-control, 11.3 +/- 2.0; well-being, 15.2 +/- 1.7; vitality, 22.5 +/- 2.0 (vitality, greatest change)]. There was no evidence of group difference in early follow-up or long-term follow-up means for any outcome variable. The QOL in adult GHD cancer survivors was comparable to that in GHD adults with pituitary pathologies and improved with GH replacement in a similar manner. We conclude that QOL impairment in adult GHD cancer survivors appears mainly related to GHD rather than cancer diagnosis and treatment.

Aspects of growth hormone deficiency and replacement in elderly hypopituitary adults

Normal ageing is associated with a decline in spontaneous growth hormone (GH) secretion, and although elderly hypopituitary adults demonstrate an increase in total and central fat compared with age-matched controls and are distinguishable from control subjects in terms of GH responsiveness on dynamic testing, there are few data available on the response to GH replacement in older subjects. We have studied the baseline characteristics of 295 patients (173 males and 122 females) aged >65 years of age who began GH replacement therapy at the time of entry into the KIMS program (Pfizer International Metabolic Database) and the effects of GH replacement in 125 patients who completed at least 12 months of GH replacement therapy. Data were compared with those of 2469 (1249 males and 1220 females) patients aged <65 years with adult-onset GH deficiency (GHD). The patients were selected using strict criteria in accordance with the recommendations from the Growth Hormone Research Society. There was a higher proportion of pituitary adenoma relative to craniopharyngioma in the older age group (P<0.001), but there was no difference between groups in the degree of hypopituitarism (number of additional hormone deficiencies). Blood pressure, cholesterol and low-density lipoprotein (LDL) cholesterol levels were positively correlated with age, and older patients had a predictably higher prevalence of diabetes mellitus, coronary heart disease, stroke and history of hypertension. Quality of life (Assessment of Growth Hormone Deficiency in Adults (AGHDA) score) was impaired in both groups before the start of GH therapy. GH replacement doses were lower in older patients with GHD as compared with patients <65 years old. After 12 months of GH replacement, significant improvements were evident in waist circumference, waist/hip ratio, lean body mass, diastolic blood pressure, total and LDL cholesterol levels and AGHDA scores in patients aged <65 years. Similar significant reductions were evidenced in patients >65 years old compared with those observed in younger patients. The total number of adverse events was similar in younger and older patients with GHD. However, younger patients had more fluid retention-related adverse events such as headache, oedema and arthralgia; whereas, older patients with GHD had more adverse events related to glucose metabolism, cardiovascular events and neoplasms. These data indicate a positive benefit from GH replacement in older patients with hypopituitarism - particularly in relation to quality of life - using a lower dose of GH for replacement and with appropriate age-related safety controls.

Assessment of quality of life in adults receiving long-term growth hormone replacement compared to control subjects.

There are few studies of quality of life (QOL) in adults with growth hormone deficiency (GHD) compared to matched control populations without GHD. These have shown impairments in a variety of QOL measures, which improve but do not normalize after short-term replacement with GH. There is little information on QOL in long-term treated GHD patients compared with controls without GHD. A total of 120 adults with GHD who had received GH replacement for at least 1 year were identified from the neuroendocrine clinic. Patients were asked to complete eight QOL questionnaires and an Energy Visual Analogue Scale (VAS). Results were compared with 83 control subjects without GHD from the local population who agreed to complete seven of the QOL questionnaires (excluding Disease Impact scale) and the energy VAS. The eight questionnaires were a combination of generic and disease-specific questionnaires used to assess health related QOL, namely: Short Form-36 (SF-36), Nottingham Health Profile (NHP), Disease Impact, Life Fulfilment and Satisfaction scales, Mental Fatigue Questionnaire (MFQ) and Self Esteem scale, Hospital Anxiety Depression (HAD) scale and QOL-AGHDA (assessment of GHD in adults). Eighty-nine patients returned questionnaires and 85 (71%) had complete data for analysis. The mean (SD) duration of GH replacement was 36.0 +/- 26.4 (range 13-159) months. Mean age was 43.9 +/- 15.8 years (37 males) in treated GHD patients compared to a mean age 41.7 +/- 10.5 years (32 males) in the controls. Mean IGF-1 levels were 22.5 +/- 13.6 nmol/l in the GHD patients and the mean dose of GH replacement was 1.2 +/- 0.4 IU daily. Analysis of the QOL questionnaires from the GH treated patients revealed highly significant impairments in all measures (most P </= 0.0001, except life fulfilment-material, P = 0.33) compared to the control population. This large population with treated GH deficiency have significant impairments in multiple aspects of QOL despite replacement with GH and other pituitary hormones for at least 1 year (mean 3 years). It is likely therefore that other factors in addition to GH deficiency must influence QOL in these patients. Further strategies to improve QOL in these individuals should therefore be considered, e.g. psychological support and treatments and physical treatments (such as exercise programmes).

Influences on quality of life in GH deficient adults and their effect on response to treatment.

Studies of the effect of GH on quality of life (QOL) in growth hormone deficient (GHD) adults have reported conflicting results. Recently, however, we have demonstrated that by selecting only those patients with impaired QOL the efficacy of GH replacement on QOL can be greatly improved. The improvement in QOL was observed to correlate significantly with that recorded before commencing GH therapy. This study aims to assess if demographic variables affect QOL in untreated GHD adults or the improvement in QOL following GH therapy. An open study of GH replacement, initiating treatment with a dose of 0.8 IU/day and titrating the dose by 0.4 IU increments to normalize the IGF-I SDS between - 2.0 and + 2.0 SD of the age related normal range. 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. Blood was taken for insulin-like growth factor 1 (IGF-I). The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires were used to assess quality of life at baseline, three and eight months after commencing GH. The patients were subgrouped on the basis of gender, age of onset of GHD, pathology and presence of additional pituitary hormone deficits. The cohort consisted of 40 females and 25 males, 45 of adult-onset (AO) and 20 of childhood-onset (CO). GH deficiency resulted from a hypothalamo-pituitary pathology, or treatment thereof, in 36 patients and as a result of cranial irradiation for a primary brain tumour or prophylaxis in acute lymphoblastic leukaemia in 29 patients. Isolated GH deficiency (IGHD) was present in 25 patients, and 32 patients were demonstrated to have at least two additional pituitary hormone deficits (MPHD). No significant difference was detected between baseline PGWB scores of the subgroups. Multiple linear regression analysis revealed the age of onset of GHD to be a significant determinant of both the baseline PGWB (P = 0.05) and AGHDA (P = 0.025) scores, AO patients perceiving the greater distress. A significant improvement, from baseline, in both QOL scores was observed in all subgroups at three months, and in all subgroups at eight months except IGHD, where a trend towards improvement in the AGHDA score was observed but failed to reach significance. The mean improvement in the PGWB following GH therapy was not significantly different between subgroups. Multiple linear regression analysis confirmed baseline PGWB and AGHDA scores to be the most important variable in prediction of the level of improvement in respective scores following GH therapy. Age of onset was also observed to be a significant determinant of the PGWB scores following GH therapy (P = 0.02), the CO cohort experiencing the greater improvement. A similar relationship between age of onset and AGHDA scores was not observed (P = 0.22). Baseline QOL as assessed by self-rating questionnaires is influenced by the age of onset of the GH deficiency, adult onset patients expressing the greater distress. Improvements in QOL scores are influenced by both baseline score and to a lesser extent the age of onset of GHD, the greater improvement being observed in childhood onset patients. The degree of improvement was observed to be independent of gender, pathology and number of pituitary hormone deficits. In a cohort selected by subjectively impaired QOL, we have demonstrated childhood onset GHD patients perceive themselves to have less impairment of QOL pretreatment. In contrast to previous data in unselected cohorts, however, we have shown that those childhood onset GHD patients in whom QOL is significantly reduced, show a capacity for improvement that is equal to, if not greater, than that seen in adult onset-GHD patients.

One-year follow-up of quality of life in adults with untreated growth hormone deficiency

OBJECTIVE The aim of the study was to evaluate the impact on health-related quality of life (HRQoL) in untreated GHD patients using the disease-specific Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire. DESIGN AND PATIENTS A cohort of 356 consecutive adult GHD patients, diagnosed after the age of 18 years, from the endocrinology units of 37 Spanish hospitals were included over a 6-month period in a longitudinal observational quality-of-life study. In addition, patients' HRQoL scores were compared to those obtained from a random sample of 963 subjects from the general population recruited by trained interviewers in a 6-month period and matched by age and sex to figures of the 1991 Spanish census. MEASUREMENTS Patients were evaluated at baseline and after 12-months. Socio-demographic and health variables such as age,sex, level of education, income level, number of chronic diseases and self-reported health status were recorded at baseline and follow-up visits. Patients underwent physical and analytical examination and completed the AGHDA questionnaire. A survey including socio-demographic, self-reported health status and the AGHDA questionnaire was administered at the individuals' homes. RESULTS Mean score for patients at baseline was 9.4 (CI = 8.4–10.4) and at 12 months 10 (CI = 8.8–11). HRQoL was worse in the case of older patients with a low level of education, lower income levels, reporting having an associated chronic disease and poor self-reported health status (P < 0.01). Untreated GHD patients maintain or slightly worsen their HRQoL after 12 months of follow-up, with high individual variability. Although AGHDA scores worsened during the observation period, differences were not statistically significant. AGHDA mean score in controls was 5.49 (CI = 5.27–5.71). Comparison of the mean AGHDA scores between patients and controls previously standardized by level of education and age were statistically different (P < 0.01), indicating that patients declared a worse HRQoL than the general population except for those aged 60–69 years. GHD patients presented a deterioration in HRQoL almost double that of the general population. CONCLUSIONS These results permit comparison of patients' scores against reference scores with regard to the desirable effect of treatment. Future use of the AGHDA questionnaire in clinical trials should try to establish a relationship between biological and HRQoL changes.

One-year follow-up of quality of life in adults with untreated growth hormone deficiency.

The aim of the study was to evaluate the impact on health-related quality of life (HRQoL) in untreated GHD patients using the disease-specific Assessment of Growth Hormone Deficiency in Adults (AGHDA) questionnaire. A cohort of 356 consecutive adult GHD patients, diagnosed after the age of 18 years, from the endocrinology units of 37 Spanish hospitals were included over a 6-month period in a longitudinal observational quality-of-life study. In addition, patients' HRQoL scores were compared to those obtained from a random sample of 963 subjects from the general population recruited by trained interviewers in a 6-month period and matched by age and sex to figures of the 1991 Spanish census. Patients were evaluated at baseline and after 12-months. Socio-demographic and health variables such as age, sex, level of education, income level, number of chronic diseases and self-reported health status were recorded at baseline and follow-up visits. Patients underwent physical and analytical examination and completed the AGHDA questionnaire. A survey including socio-demographic, self-reported health status and the AGHDA questionnaire was administered at the individuals' homes. Mean score for patients at baseline was 9.4 (CI = 8.4-10.4) and at 12 months 10 (CI = 8.8-11). HRQoL was worse in the case of older patients with a low level of education, lower income levels, reporting having an associated chronic disease and poor self-reported health status (P < 0.01). Untreated GHD patients maintain or slightly worsen their HRQoL after 12 months of follow-up, with high individual variability. Although AGHDA scores worsened during the observation period, differences were not statistically significant. AGHDA mean score in controls was 5.49 (CI = 5.27-5.71). Comparison of the mean AGHDA scores between patients and controls previously standardized by level of education and age were statistically different (P < 0.01), indicating that patients declared a worse HRQoL than the general population except for those aged 60-69 years. GHD patients presented a deterioration in HRQoL almost double that of the general population. These results permit comparison of patients' scores against reference scores with regard to the desirable effect of treatment. Future use of the AGHDA questionnaire in clinical trials should try to establish a relationship between biological and HRQoL changes.