Years Of Growth Hormone Replacement Research Articles

The metabolic consequences of thyroxine replacement in adult hypopituitary patients

The metabolic consequences of thyroxine replacement in patients with central hypothyroidism (CH) need to be evaluated. The aim was to examine the outcome of thyroxine replacement in CH. Adult hypopituitary patients (n = 1595) with and without CH from KIMS (Pfizer International Metabolic Database) were studied before and after 2 years of GH replacement. CH patients (CH, n = 1080) were compared with TSH sufficient patients (TSHsuff n = 515) as one group and divided by thyroxine dose/kg/day into tertiles (CHlow-mid-high). Anthropometry, fasting glucose, glycosylated haemoglobin (HbA1c), blood pressure, lipids, IGF-I SDS, quality of life and morbidity were studied. Analyses were standardized for gender, age, number and types of pituitary insufficiencies, stimulated GH peak, age at GH deficiency onset, aetiologies and, when appropriate, for weight and GH dose. At baseline, TSHsuff patients did not differ from CH or CHmid in any outcome. CHlow (≤ 1.18 μg thyroxine/kg/day) had increased weight, BMI and larger waist circumference (WC), CHhigh (≥ 1.58 μg thyroxine/kg/day) had lower weight, BMI, WC and IGF-I than TSHsuff and compared to their predicted weights, BMIs and WCs. For every 0.1 μg/kg/day increase of thyroxine dose, body weight decreased 1.0 kg, BMI 0.3 kg/m(2), and WC 0.65 cm. The GH sensitivity of the CH group was higher (0.76 ± 0.56 SDS/mg GH) than that of TSHsuff patients (0.58 ± 0.64 SDS/mg GH), P < 0.001. The middle thyroxine dose (1.19-1.57 μg/kg/day) seems to be the most physiological. This is equivalent to 70, 100, 125 μg thyroxine/day for hypopituitary patients of 50, 70 or 90 kg weight, respectively.

Effect of Growth Hormone Replacement Therapy on Cognition after Traumatic Brain Injury

Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III-Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.

Cardiac function in growth hormone deficient patients before and after 1 year with replacement therapy: a magnetic resonance imaging study

Assessed by conventional echocardiography the influence of growth hormone deficiency (GHD) and effects of replacement therapy on left ventricle (LV) function and mass (LVM) have shown inconsistent results. We aimed to evaluate cardiac function before and during replacement therapy employing the gold standard method cardiac magnetic resonance imaging (CMRI) and measurements of circulating levels of B-type natriuretic peptides. Sixteen patients (8 males and 8 females, mean age 49 years (range 18-75)) with severe GHD and 16 matched control subjects were included. CMRI was performed at baseline and after 1 year of GH replacement therapy. IGF-I, B-type natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) were measured after 0, 1, 2, 3, 6 and 12 months of treatment. IGF-I Z-score increased from (median (IQR)) -2.3 (-3.8 to -1.4) to 0.5 (-0.3 to 1.7). LVM index (LVMI), ejection fraction (range 63-80%), cardiac output index and levels of BNP and NT-proBNP were similar at baseline in patients compared to controls (P-values from 0.09 to 0.37). The patients had significantly smaller LV end-diastolic volume index (P = 0.032) and end-systolic volume index (P = 0.038). No significant change in LV systolic function or LVM occurred during 1 year of GH treatment. BNP levels were unchanged (P = 0.88), whereas NT-proBNP tended to decrease (P = 0.052). Assessed by the highly sensitive and precise CMRI method, untreated GHD was not associated with impaired systolic function or reduced LVMI and 1 year of GH replacement using physiological doses did not influence cardiac mass or function.

Muscle strength in elderly adults with GH deficiency after 10 years of GH replacement

Only few studies have investigated the effects of GH replacement on muscle strength in elderly patients with GH deficiency (GHD). OBJECTIVE, DESIGN, AND PATIENTS: In this prospective open-labeled study, the effects of 10 years of GH replacement on muscle strength and neuromuscular function were followed in 24 elderly GHD adults (mean age of 65.2 years; range 61-74 years). Muscle strength was compared with reference values obtained from the background population. The mean initial GH dose of 0.72 mg/day was lowered to 0.37 mg/day. The mean IGF1 SDS increased from -1.10 at baseline to 1.17 at study end. GH replacement induced a sustained increase in lean body mass and a transient increase in isometric knee flexor strength. Isometric knee extensor strength was reduced after 10 years. However, after correction for age and gender, using observed/predicted value ratios, there was sustained and even progressive increase in most variables reflecting muscle strength. Measurements of neuromuscular function showed unchanged voluntary motor unit activation after 10 years. Ten years of GH replacement therapy in elderly GHD adults resulted in a transient increase in isometric knee flexor strength, and provided protection from most of the normal age-related decline in muscle performance and neuromuscular function.

Clinical features of GH deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

Patients in remission from Cushing's disease (CD) have many clinical features that are difficult to distinguish from those of concomitant GH deficiency (GHD). In this study, we evaluated the features of GHD in a large cohort of controlled CD patients, and assessed the effect of GH treatment. Data were obtained from KIMS, the Pfizer International Metabolic Database. A retrospective cross-sectional comparison of background characteristics in unmatched cohorts of patients with CD (n=684, 74% women) and nonfunctioning pituitary adenoma (NFPA; n=2990, 39% women) was conducted. In addition, a longitudinal evaluation of 3 years of GH replacement in a subset of patients with controlled CD (n=322) and NFPA (n=748) matched for age and gender was performed. The cross-sectional study showed a significant delay in GHD diagnosis in the CD group, who had a higher prevalence of hypertension, fractures, and diabetes mellitus. In the longitudinal, matched study, the CD group had a better metabolic profile but a poorer quality of life (QoL) at baseline, which was assessed with the disease-specific questionnaire QoL-assessment of GHD in adults. After 3 years of GH treatment (mean dose at 3 years 0.39 mg/day in CD and 0.37 mg/day in NFPA), total and low-density lipoprotein cholesterol decreased, while glucose and HbAlc increased. Improvement in QoL was observed, which was greater in the CD group (-6 CD group versus -5 NFPA group, P<0.01). In untreated GHD, co-morbidities, including impairment of QoL, were more prevalent in controlled CD. Overall, both the groups responded similarly to GH replacement, suggesting that patients with GHD due to CD benefit from GH to the same extent as those with GHD due to NFPA.

Clinical features of growth hormone (GH) deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

Clinical features of growth hormone (GH) deficiency and effects of 3 years of GH replacement in adults with controlled Cushing's disease

P23 Effects of 3-year growth hormone (GH) replacement therapy on bone mineral density in younger and elderly adults with adult onset GH deficiency

Objective: Little is known of the effects of long-term GH replacement on bone mineral content (BMC) and bone mineral density (BMD) in elderly GH deficient (GHD) adults. Design/Patients/Methods: In this prospective, single-centre, open-label study, the effects of 3-year GH replacement were determined in 45 GHD patients above 65 years of age and in 45 younger control GHD patients with a mean age of 39.5 (SEM 1.1) years. All patients had adult onset disease and both groups were comparable in terms of number of anterior pituitary hormonal deficiencies, gender, body mass index (BMI), and waist:hip ratio. Results: The mean maintenance dose of GH was 0.24 (0.02) mg/day in the elderly patients and 0.33 (0.02) mg/day in the younger GHD patients (p<0.01). The three years of GH replacement induced a marginal effect on total body BMC and BMD whereas femur neck and lumbar (L2-L4) spine BMC and BMD increased in both the elderly and the younger patients. The treatment response in femur neck BMC was less marked in the elderly patients (p<0.05 vs. younger group). However, this difference disappeared after correction for the lower dose of GH in the elderly patients using an analysis of covariance. There were no between-group differences in responsiveness in BMC or BMD at other skeletal locations. Conclusions: This study shows that GH replacement increases lumbar (L2-L4) spine and femur neck BMD and BMC in younger as well as elderly GHD patients. This supports that long-term GH replacement is useful also in elderly GHD patients. Page 2 of 29

From isolated GH deficiency to multiple pituitary hormone deficiency: an evolving continuum – a KIMS analysis

To describe baseline clinical presentation, treatment effects and evolution of isolated GH deficiency (IGHD) to multiple pituitary hormone deficiency (MPHD) in adult-onset (AO) GHD. Observational prospective study. Baseline characteristics were recorded in 4110 patients with organic AO-GHD, who were GH naïve prior to entry into the Pfizer International Metabolic Database (KIMS; 283 (7%) IGHD, 3827 MPHD). The effect of GH replacement after 2 years was assessed in those with available follow-up data (133 IGHD, 2207 MPHD), and development of new deficiencies in those with available data on concomitant medication (165 IGHD, 3006 MPHD). IGHD and MPHD patients had similar baseline clinical presentation, and both groups responded similarly to 2 years of GH therapy, with favourable changes in lipid profile and improved quality of life. New deficiencies were observed in 35% of IGHD patients, which was similar to MPHD patients with one additional deficit other than GH. New deficiencies most often presented within the first year but were observed up to 6 years after GH commencement. Conversion of IGHD into MPHD was not predicted by aetiology, baseline characteristics, surgery or radiotherapy, whereas in MPHD additional deficits were predicted by age (P<0.001) and pituitary disease duration (P<0.01). Both AO-IGHD and -MPHD patients have similar baseline clinical presentation and respond equally well to 2 years of GH replacement. Hypopituitarism in adults seems to be a dynamic condition where new deficiencies can appear years after the initial diagnosis, and careful endocrine follow-up of all hypopituitary patients, including those with IGHD, is warranted.

Effects of 5 years of growth hormone (GH) replacement therapy on cardiac parameters and physical performance in adults with GH deficiency

The purpose of this study was to evaluate the effects of 5 years of GH substitution on cardiac structure and function, physical work capacity and blood pressure levels in adults with GH deficiency (GHD). Fourteen patients were clinically assessed every 3 months for 5 years. Transthoracic echocardiography and exercise test were performed at baseline, 24, 48 and 60 months. Blood pressure (BP) was measured by means of ambulatory monitoring of blood pressure at baseline, 6, 12, 24 and 60 months. Left ventricular mass and its index increased progressively during the 5 years of GH substitution (P = 0.008 and 0.007, respectively). There were no significant changes in all others cardiac parameters evaluated. It was observed a significant improve in functional capacity (P < 0.001) and maximal oxygen uptake (P = 0.006) during the treatment. Diurnal systolic BP increased by 15 mmHg (P = 0.024) and diurnal diastolic BP by 4.5 mmHg (P = 0.037). There was no change in dirnal systolic pressure load but a considerable but non-statistically significant reduction in diurnal diastolic pressure load was observed during the study. During the night diastolic BP increased by 4 mmHg (P = 0.012) despite a substantial but non-statistically significant reduction in diastolic pressure load. We observed an increase in the proportion of persons with a non-physiological nocturnal fall (non-dippers) throughout the study (from 36.4% at baseline to 54.6% after 60 months of therapy). We concluded that 5 years of GH replacement promoted positive effects on exercise capacity and maximum oxygen uptake in spite of a modest increase in BP levels and left ventricular mass. Continuous monitoring is mandatory to arrive at further conclusions concerning the effects of GH substitution in adults on cardiovascular parameters with respect to possible unfavorable long term effects.

GH replacement in hypopituitarism improves lipid profile and quality of life independently of changes in obesity variables

GH deficiency (GHD) in adults is characterized by elevated body mass index (BMI), increased waist girth (WG) and increased fat mass (FM). Information about how these indicators of obesity affect the lipid profile and quality of life (QoL) of GHD subjects is scarce. It is also unclear how changes in these indicators brought about by GH replacement influence lipids and QoL. Adult GHD subjects from the Pfizer International Metabolic Database were grouped according to BMI (n=291 with BMI <25 kg/m(2), n=372 with BMI 25-30 kg/m(2), n=279 with BMI >30 kg/m(2)), WG (n=508 with normal WG, n=434 with increased WG) and FM (n=357) and according to changes in these variables after 1 year of GH replacement. Serum IGF-I concentrations, lipid concentrations and QoL using the QoL Assessment of GHD in Adults questionnaire were assessed at baseline and after 1 year of treatment. At baseline, total and low-density lipoprotein (LDL) cholesterol were similarly elevated in the BMI and WG groups, but high-density lipoprotein (HDL) cholesterol decreased and triglycerides increased with increasing BMI and WG. QoL was progressively poorer with increasing BMI and WG. After 1 year of GH replacement, total and LDL cholesterol and QoL improved in all BMI, WG and FM groups. Variables of obesity adversely affect the already unfavourable lipid profile in GHD subjects by decreasing HDL cholesterol, but do not counteract the positive effect of GH replacement on LDL cholesterol. Similarly, QoL is influenced by obesity, but responds equally well to GH treatment independent of BMI, WG and FM.

Impact of the primary aetiology upon the clinical outcome of adults with childhood-onset GH deficiency

The impact of the aetiology of childhood-onset GH deficiency (CO-GHD) on the clinical presentation during adulthood and the response to GH replacement has been poorly defined. Our study aims to characterize CO-GHD in adults due to different aetiologies and evaluate the effect of 2 years of GH replacement therapy. Data from 353 adults with CO-GHD from Pfizer International Metabolic Database KIMS were retrospectively grouped according to GHD aetiology: non-organic disorder (n=147), organic pituitary disease (n=159), and brain tumour (n=47). Extent of pituitary dysfunction, IGF-I concentration, lipid concentrations and quality-of-life (QoL) were assessed at baseline and after 2 years of GH replacement. GHD was diagnosed at a later age in the organic pituitary group than in the other groups, resulting in a shorter duration of GH treatment during childhood. However, the final height was greater in the organic pituitary group. Panhypopituitarism was most common in the non-organic disorder and in the organic pituitary groups, while isolated GHD was more prominent in the brain tumour group. Serum IGF-I levels were the lowest in the non-organic group. QoL was the poorest in the brain tumour group. Lipid profile and QoL improved significantly during GH replacement. The adverse consequences of CO-GHD in adulthood vary between aetiologies, but improve similarly with GH treatment. It is, therefore, important to consider retesting all patients with CO-GHD in early adulthood and, if persistent severe GHD is confirmed, recommence GH replacement.

Growth Hormone Treatment in Prepubertal Children With Celiac Disease and Growth Hormone Deficiency

To evaluate the growth response to growth hormone (GH) replacement therapy during a gluten-free diet in patients with celiac disease (CD) associated with GH deficiency (GHD). A total of 14 prepubertal children affected by CD and GHD with no catch-up growth after >/=12 months of gluten-free diet and a reversion to seronegativity for antiendomysium antibodies and 10 age-matched prepubertal children with idiopathic GHD (IGHD) entered the study. All of the patients were treated with the same GH dosage (0.25 mg/kg subcutaneously each week). Height, growth rate, and body mass index were measured at the time of diagnosis of CD, at the time of endocrinological evaluation, and after the first, second, and third year of GH replacement therapy. Growth rate strikingly increased (P < 0.005) during the first year of therapy in a similar way in subjects with CD/GHD and IGHD (from a median standard deviation score [SDS] of -2.34 to an SDS of 3.25 and from an SDS of -1.29 to an SDS of 2.79, respectively). During the second and third years of GH treatment, the growth rate tended to decrease but the values at the third year were always positive (CD/GHD, median SDS, 1.10; IGHD, median SDS, 0.11), indicating continued catch-up growth. In patients with CD with GH deficiency confirmed after >/=12 months of gluten-free diet, GH replacement therapy should be started to allow complete catch-up growth in children. In addition, the effect of GH treatment in patients who comply with a gluten-free diet seems to be comparable to that observed in children with IGHD.

Ten-year GH replacement increases bone mineral density in hypopituitary patients with adult onset GH deficiency

There are few studies that have determined the effects of long-term GH replacement on bone mineral density (BMD) in GH-deficient (GHD) adults. In this study, the effects of 10 years of GH replacement on BMD were assessed in 87 GHD adults using dual energy X-ray absorptiometry (DEXA). The results show that GH replacement induced a sustained increase in BMD at all the skeletal sites measured. Little is known of the effect of more than 5 years of GH replacement therapy on bone metabolism in GHD adults. In this prospective, open-label, single-center study, which included 87 consecutive adults (52 men and 35 women; mean age of 44.1 (range 22-74) years) with adulthood onset GHD, the effect of 10 years of GH replacement on BMD was determined. The mean initial dose of GH was 0.98 mg/day. The dose was gradually lowered and after 10 years the mean dose was 0.47 mg/day. The mean insulin-like growth factor-I (IGF-I) SDS increased from 1.81 at baseline to 1.29 at study end. The GH replacement induced a sustained increase in total, lumbar (L2-L4) and femur neck BMD, and bone mineral content (BMC) as measured by DEXA. The treatment response in IGF-I SDS was more marked in men, whereas women had a more marked increase in the total body BMC and the total body z-score. There was a tendency for women on estrogen treatment to have a larger increase in bone mass and density compared with women without estrogen replacement. Ten years of GH replacement in hypopituitary adults induced a sustained, and in some variables even a progressive, increase in bone mass and bone density. The study results also suggest that adequate estrogen replacement is needed in order to have an optimal response in BMD in GHD women.

Baseline characteristics and response to GH replacement of hypopituitary patients previously irradiated for pituitary adenoma or craniopharyngioma: data from the Pfizer International Metabolic Database

To test the hypothesis whether the effects of GH replacement therapy in adults could be affected by prior pituitary irradiation, the baseline characteristics and response to GH were evaluated in adults with severe GH deficiency (GHD), who had received or not irradiation for the treatment of pituitary adenoma or craniopharyngioma. Data from 447 patients, who had received radiotherapy (427 in addition to surgery), and 630 patients, who were operated on but not irradiated for their tumour, were retrieved from Pfizer International Metabolic Database (KIMS) and compared at baseline and 1 and 2 years following the onset of GH replacement. Irradiated and non-irradiated patients exhibited the expected phenotype of GHD at baseline. However, irradiated patients had a greater impairment in the quality of life (QoL), a higher fat mass, lower high-density lipoprotein cholesterol levels and a lower bone mineral content (BMC) than non-irradiated patients. Treatment with GH induced similar changes in both groups. After 1 year of GH replacement, there was an increase in serum IGF-I and fat-free mass, a reduction in fat mass and an improvement in QoL, all changes being equivalent in irradiated and non-irradiated patients. The lipid profile also improved with the irradiated patients showing a better response. These beneficial effects were maintained and the BMC also increased in both groups by the second year of treatment. This analysis shows that prior irradiation for pituitary adenoma or craniopharyngioma does not compromise the beneficial effects of GH replacement therapy.

Healthcare utilization, quality of life and patient-reported outcomes during two years of GH replacement therapy in GH-deficient adults – comparison between Sweden, The Netherlands and Germany

This study set out to determine the change in quality of life (QoL) and healthcare utilization during 2 years of growth hormone (GH) replacement therapy in adults with GH deficiency. Data were compared from three European countries. Analysis was made from KIMS, the Pfizer International Metabolic Database on adult GH deficiency. QoL and healthcare utilization were measured at baseline and after 1 and 2 years of GH replacement in patient cohorts from Sweden (n = 302), The Netherlands (n = 103) and Germany (n = 98). QoL was assessed by the QoL-Assessment in Growth Hormone Deficient Adults (QoL-AGHDA) questionnaire, and the KIMS Patient Life Situation Form was used to evaluate healthcare utilization. QoL improved significantly (P < 0.0001) and comparably in all three cohorts. The improvement was seen during the first year of treatment and QoL remained improved during the second year. The number of days in hospital was reduced by 83% (P < 0.0001) during GH replacement. There were no country-specific differences either at baseline or during follow-up. The same was true for the number of days of sick leave (reduction of 63%; P = 0.0004). Significant reductions were recorded in the number of doctor visits in each of the three cohorts after 2 years of GH replacement (P < 0.05). This study provides a detailed comparative analysis of GH replacement therapy in GHD patients in three European countries. Despite some differences in treatment strategies, the beneficial effects on QoL, patient-reported outcomes and healthcare utilization are essentially similar in the healthcare environment of Western European countries.

Improvement of Cardiac Performance and Cardiovascular Risk Factors in Children with GH Deficiency after Two Years of GH Replacement Therapy: An Observational, Open, Prospective, Case-Control Study

GH deficiency (GHD) in adults is associated with a cluster of cardiovascular risk factors that may contribute to an increased mortality for cardiovascular disease. The aim of this study was to evaluate the effect of GHD and GH replacement therapy on cardiac performance, lipid profile, and insulin resistance in children. This was a 2-yr case-control prospective study. Thirty children with GHD aged 9.3 +/- 0.5 yr and 30 healthy matched controls were studied. Children were studied before and after 1 and 2 yr of GH replacement (GHD children) or no treatment (controls). Lipid profile, serum insulin levels, homeostasis model of assessment (HOMA) index, and left ventricular (LV) mass and function by echocardiography were the main outcome measures. At study entry, the LV mass index was significantly lower in GHD children (50.2 +/- 1.7) than in controls (60.3 +/- 2.5 g/m(2); P < 0.002), whereas LV systolic and diastolic function, lipid profile, insulin levels, and HOMA index were similar. In GHD children LV mass index significantly increased (66.3 +/- 2.4 g/m(2); P < 0.0001) after 1 yr of GH replacement and remained stable thereafter. LV systolic and diastolic function did not change during treatment. After 2 yr of GH replacement, total cholesterol (P < 0.007) and the atherogenic index (P < 0.0001) significantly decreased, whereas fasting insulin levels (P < 0.001) and HOMA index (P < 0.0001) significantly increased compared with both pretreatment and control values. GHD in children is associated with a reduced cardiac size but with a normal cardiac function, lipid profile, and insulin sensitivity. Two years of GH replacement normalizes cardiac morphology, improves lipid profile, and slightly impairs insulin sensitivity.

Glucose Metabolism and Visceral Fat in GH Deficient Adults: Two Years of GH-Replacement

Glucose Metabolism and Visceral Fat in GH Deficient Adults: Two Years of GH-Replacement

Sheehan’s syndrome: baseline characteristics and effect of 2 years of growth hormone replacement therapy in 91 patients in KIMS – Pfizer International Metabolic Database

Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. It is one of the most important causes of hypopituitarism, and hence growth hormone deficiency (GHD), in developing countries. However, little is known about the effects of growth hormone (GH) replacement therapy in patients with Sheehan's syndrome. The demographic background characteristics of 91 GH-deficient patients with Sheehan's syndrome (mean age +/- s.d., 46.3 +/- 9.4 years) were compared with those of a group of 156 GH-deficient women (mean age +/- s.d., 51.5 +/- 13.1 years) with a non-functional pituitary adenoma (NFPA). The baseline characteristics and the effects of 2 years of GH replacement therapy were also studied in the 91 patients with Sheehan's syndrome and an age-matched group of 100 women with NFPA (mean age +/- s.d. 44.5 +/- 10.2 years). All patients were enrolled in KIMS (Pfizer International Metabolic Database). Patients with Sheehan's syndrome were significantly younger at pituitary disorder onset, diagnosis of GHD and at entry into KIMS than patients with NFPA (P < 0.01), and had significantly lower insulin-like growth factor I levels (P < 0.001). At baseline, quality of life (QoL) was significantly (P < 0.05) reduced in patients with Sheehan's syndrome compared with those with NFPA (P < 0.001). With regard to treatment effects, lean body mass increased significantly (P < 0.05), QoL improved significantly (P < 0.05) and total and low-density lipoprotein-cholesterol decreased significantly (P < 0.05) in patients with Sheehan's syndrome after 1 year of GH replacement therapy. Similar significant changes in QoL and lipid profiles occurred in patients with NFPA after 2 years of GH replacement. Blood pressure remained unchanged in patients with Sheehan's syndrome, but decreased significantly (P < 0.01) in the group with NFPA after 1 year, before returning to pretreatment levels at 2 years. In conclusion, patients with Sheehan's syndrome have more severe GHD compared with individuals with NFPA. GH replacement therapy in patients with Sheehan's syndrome may have beneficial effects on QoL, body composition and lipid profile.

Glucose Metabolism and Visceral Fat in GH Deficient Adults: Two Years of GH-Replacement

The aim of this study was to evaluate the effect of 24 months of growth hormone (GH) replacement on glucose metabolism and visceral fat in 17 adults with GH deficiency: 9 men and 8 women; age 40 +/- 1.8 yr. [range 20-61] and body mass index 25 +/- 0.8 Kg/m2. Glucose metabolism was evaluated by a standard oral glucose tolerance test (OGTT), by the homeostatic model assessment (HOMA) insulin resistance index and by the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan.Twenty-four months of GH replacement induced an increase in the prevalence of abnormal glucose tolerance, with significant progressive increment in 2h-OGTT insulin levels at 3, 12 and 24 months (p = 0.005). Plasma glucose levels and ISI-composite did not alter during the study. HOMA-IR index increased only in the group of patients (n = 8) who had abnormal OGTT at 24 months (p = 0.012). Visceral fat reduced at month 12 and remained decreased until the end of the study (p = 0.009). In conclusion, the present study suggests that adults with GH deficiency after twenty-four months of GH replacement developed abnormal glucose tolerance, probably due to an increase in insulin resistance, associated with higher insulin levels, despite favorable alterations in body composition.

Three-years of growth hormone (GH) replacement therapy in GH-deficient adults: effects on quality of life, patient-reported outcomes and healthcare consumption.

The objective was to investigate the effects of 3 years of growth hormone (GH) replacement therapy in GH deficient (GHD) patients in Sweden. An open label study in 237 adults with GHD (116 men and 121 women), consecutively enrolled in KIMS (Pfizer's international metabolic database) in Sweden. QoL and healthcare consumption were determined using questionnaires [QoL-assessment of GHD in Adults (QoL-AGHDA), the psychological general well-being (PGWB) index and the patient life situation form (PLSF)]. The mean starting dose of GH was 0.13 mg/day and the mean maintenance dose was 0.37 mg/day. The mean insulin-like growth factor I (IGF-I) SD score increased from -1.92 at baseline to 0.38 after 3 years. There was a sustained increase in QoL as measured by the QoL-AGHDA and PGWB questionnaires. The number of doctor visits and the number of days in hospital were reduced after 3 years of GH replacement. The number of days of sickleave decreased during the first 2 years of treatment, but returned towards baseline values after 3 years. Leisure-time physical activity and satisfaction with physical activity increased. Three years of GH replacement therapy induced a sustained improvement in QoL. Healthcare consumption was reduced, although the reduction in the number of days of sickleave was not statistically significant after 3 years of treatment.