Effects Of Growth Hormone Replacement Research Articles

Metabolic and quality of life effects of growth hormone replacement in patients with TBI and AGHD: A pilot study

ObjectiveTraumatic brain injury (TBI), a common cause of adult growth hormone deficiency (AGHD), affects 20% of Veterans returning from Iraq and Afghanistan (OEF/OIF/OND). Growth hormone replacement therapy (GHRT) improves quality of life (QoL) in AGHD but remains unexplored in this population. This pilot, observational study investigates the feasibility and efficacy of GHRT in AGHD following TBI. DesignIn this 6-month study of combat Veterans with AGHD and TBI starting GHRT (N = 7), feasibility (completion rate and rhGH adherence) and efficacy (improvements in self-reported QoL) of GHRT were measured (primary outcomes). Secondary outcomes included body composition, physical and cognitive function, psychological and somatic symptoms, physical activity, IGF-1 levels and safety parameters. It was hypothesized that participants would adhere to GHRT and that QoL would significantly improve after six months. ResultsFive subjects (71%) completed all study visits. All patients administered daily rhGH injections, 6 (86%) of whom consistently administered the clinically-prescribed dose. While QoL demonstrated numeric improvement, this change did not reach statistical significance (p = 0.17). Significant improvements were observed in total lean mass (p = 0.02), latissimus dorsi strength (p = 0.05), verbal learning (Trial 1, p = 0.02; Trial 5, p = 0.03), attention (p = 0.02), short-term memory (p = 0.04), and post-traumatic stress disorder (PTSD) symptoms (p = 0.03). Body weight (p = 0.02) and total fat mass (p = 0.03) increased significantly. ConclusionGHRT is a feasible and well-tolerated intervention for U.S. Veterans with TBI-related AGHD. It improved key areas impacted by AGHD and symptoms of PTSD. Larger, placebo-controlled studies testing the efficacy and safety of this intervention in this population are warranted.

ODP643 Metabolic Effects of Growth Hormone Replacement in Craniopharyngioma and Pituitary Adenoma Patients: Analysis of the Hypopituitary Control and Complications Study (HypoCCS) Database

Abstract Introduction Craniopharyngioma (CP) is a rare, parasellar tumor associated with metabolic dysfunction and panhypopituitarism. We investigated the impact of growth hormone (GH) replacement on metabolic complications in patients with adult-onset CP or pituitary adenoma (PA) using data collected between 1996 and 2012 in HypoCCS, an open-label, global prospective surveillance study of GH replacement in GH deficiency. Methods GH-treated (≥6 months) vs untreated groups in CP and PA patients were compared using ANOVA or Wilcoxon rank-sum test for continuous variables and chi-square test or Fisher's exact test for categorical variables. Multivariable analysis adjusted for GH use prior to enrollment, IGF-1 level, adrenal insufficiency, androgen replacement, and BMI. Results Of 8418 GH-treated and 1268 untreated patients in HypoCCS, 592 had CP, with 544 on GH and 48 untreated. Mean (±SD) follow-up was 5.39 (±4. 07) and 3.91 (±3. 07) years, respectively. Adverse hepatic outcomes (primary endpoint) were slightly improved with GH (19% vs 27%; p=NS). Mean lean BMI increased 0.93 (±1.56) kg/m2 with GH vs decreased 1.57 (±1.4) without GH (p=0. 022). Median (IQR) waist-hip ratio decreased -0. 01 (-0. 03-0. 03) with GH and increased 0. 03 (0-0. 06) without GH, significant on univariable (p=0. 01) and multivariable analysis (parameter estimate -0. 03 [-0. 05, -0. 004]; p=0. 02). Median blood pressure (BP) was unchanged with GH (-10-10) but increased 5.5 (0-17) mmHg without GH, significant on univariable (-5.99 [-11.44, -0.54], p=0. 032). Mortality was slightly lower with GH (3.5% vs 5.9%; p=NS). Of 3972 PA patients, there were 3346 on GH and 626 untreated; mean (±SD) follow-up was 5.38 (±3.97) and 3.93 (±3.22) years, respectively. GH did not impact hepatic outcomes (17%). Median (IQR) fasting glucose increased 6 (0-13) mg/dL with GH vs 1 (-10-7) without (p=0. 04), mean HbA1C decreased -0.12% (±1.94) with GH vs -1.95% (±1.84) without (p=0. 037), and rate of lipid medication use was in 46% on GH vs 56% without (p<0. 001). BMI increased 0.23 (-0.99-1.56) kg/m2 with GH vs 0 (-1.4-1.12) without (p=0. 002), and GH was associated with increased BMI (0.32 [0. 04-0.59]; p=0. 024). Median mean arterial pressure was 94.67 (87.33-101.67) mmHg with GH vs 93.33 (86.67-100) without (p=0. 007) and median diastolic BP was 80 (70-84) mmHg with GH vs 76 (70-82) without (p<0. 001); GH was associated with higher diastolic BP (1.43 [0.43, 2.44]; p=0. 005). Mortality was lower with GH than without (2.9% vs 5.1%), significant on univariable (p=0. 017) and multivariable analysis (0.60 [0.35-1. 03]; p=0. 066). Conclusion HypoCCS data show GH replacement in adult-onset CP lowers waist-hip ratio and slightly improves hepatic outcomes and mortality while untreated patients had increased BP. In PA patients, BMI and hypertension worsened with GH and mortality decreased, while hepatic outcomes were unchanged. The results suggest a favorable impact for GH on metabolic complications and a potential benefit for GH replacement in adult-onset CP. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement.

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

Growth hormone replacement therapy: is it safe to use in children with asymptomatic pituitary lesions?

Small pituitary cysts are commonly discovered on pediatric brain magnetic resonance imagings (MRIs), particularly in patients with growth hormone deficiency (GHD). We examined the need for operative management in children with these masses as well as the effect of growth hormone replacement (GHR) on these lesions. This was a retrospective review of pituitary protocol MRIs conducted in children 0-19 at a single center between April 2010-November 2020. Sex, indication for initial MRI, volume, and whether surgery was performed was determined. Records were reviewed to determine whether GHD was present and treatment with GHR documented. For patients with subsequent MRIs, volume on most recent scan was calculated. Of the 101 children with cysts, 25 had laboratory-confirmed GHD and 76 did not. GHD patients had a higher mean age compared to no growth hormone deficiency (NGHD) cohort (11.2 and 8.4 years, respectively; p=0.02) and a larger proportion of males (p<0.001). The mean cyst volume on initial MRI was not significantly smaller in patientswith GHD (0.063±0.012cm3) vs. those without GHD (0.171±0.039cm3, p=0.11). Of the 21 GHD patients who received GHR and had follow-up MRIs, 10 had no change in pituitary cyst size, two had cysts that shrank, and seven disappeared. The remaining two cysts enlarged an average of 0.061±0.033cm3. Zero GHR recipients required surgical intervention. Small sellar cysts discovered incidentally on imaging in children are unlikely to require surgical intervention. GHR does not appear to significantly enlarge these pediatric pituitary lesions and is safe for use.

The effectiveness of growth hormone replacement on energy expenditure and body composition in patients with adult growth hormone deficiency.

Numerous studies have shown that growth hormone (GH) replacement in adult GH deficiency (AGHD) improves the body composition and metabolic rate; however, data about the relationship between body composition and energy expenditure in these patients is scarce. Our study aimed to investigate the changes in resting energy expenditure (REE) and body composition after GH replacement in patients with AGHD. We enrolled 15 patients diagnosed with AGHD and evaluated the effect of GH replacement administered once daily for 12 months on REE, body composition measured by bioelectrical impedance analysis, and serological markers. GH replacement therapy significantly increased the serum insulin growth factor-1 levels after 4, 8, and 12 months. The REE and REE/basal energy expenditure (REE/BEE) ratio significantly increased from 1278.0 ± 490.0 kcal/day and 0.87 ± 0.23 at baseline to 1505.5 ± 449.2 kcal/day and 1.11 ± 0.21 at 4 months, 1,918.7 ± 631.2 kcal/day and 1.29 ± 0.27 at 8 months, and 1,511.1 ± 271.2 kcal/day, 1.14 ± 0.29 at 12 months (p < 0.005, p < 0.005; p < 0.01, p < 0.01; p < 0.01, p < 0.005, respectively). There was no change in the body weight, while the lean body mass increased significantly from 45.8 ± 9.5 kg at baseline to 46.9 ± 9.4 kg at 4 months and 47.5 ± 10.1 kg at 8 months (p < 0.005, p < 0.01, respectively). The fat mass also decreased at 12 months. Lipid metabolism improved after 4 and 8 months. GH replacement therapy in patients with AGHD significantly improved the REE and body composition.

SUN-577 Effect of Growth Hormone Replacement on Metabolic Profile and Vascular System in Adult Patients with Congenital Hypopituitarism

Introduction: Growth Hormone (GH) stimulates two distinct processes: anabolic effect of GH on growth through IGF1, and catabolic effect of GH stimulating lipolysis. GH deficiency (GHD) in adulthood is characterized with abnormal body composition, impairment of physical capacity and lipid and glycemic metabolism, beyond increase cardiovascular risk (CVR) factors. While in acquired hypopituitarism, GHD is always associated with CVR in several studies and demonstrated human recombinant growth hormone replacement (hrGHr) improves CVR. In congenital hypopituitarism (CH), however, the consequences of GHD and hrGHr in adulthood are unclear. Objective: To evaluate daily hrGHr in metabolic profile and vascular system in adult patients with CH. Patients and Methods: Fifty-nine adults with CH were selected for the study. They were divided into 2 groups: 1- hrGHr: 15 male, 17 female with median age 35,8 yrs, hrGHr in adult life with 7.2 yrs median time in the dose of approximately 1U per day in order to keep IGF1 in the normal range for age and sex; 2- Without hrGHr: 12 male, 15 female with 38,4 yrs median age and without hrGHr in adult life of 10.6 yrs median time. Thirty-two healthy volunteers were selected as controls. Anthropometric parameters, dual-energy X-ray absorptiometry (DXA), lipid and glycemic profile, and structural and functional parameters of the arterial vessels (carotid intima media thickness, arterial stiffness and flow mediated dilation) were evaluated and compared between the groups. Results: In patients with rhGHr the abdominal waist/height (AW/H) ratio (0,49 ± 0,06), the fat percentage (30,7 ± 10,4) and fat index (7,6 ± 3,7) were lower than the group without replacement (p= <0,001, p= <0,001 and p= 0,028, respectively). The low values of the CA/H ratio, fat percentage and fat index were independent of the diagnosis ACTH deficiency with corticosteroid replacement. Higher triglycerides (111,7 ± 62,4) and lower HDLc (49,5 ± 19,1) levels in patients without hrGHr compared to controls (p= 0,020 and p= 0,005, respectively) were observed. There was no statistical difference between glycemic profile, metabolic comorbidities and structural and function parameters of the arterial vessels between groups and controls. Conclusions: GHD in CH does not lead to accelerated premature atherosclerosis and arteriosclerosis. The hrGHr in adults with CH have beneficial effects on lipid profile and body composition and hrGHr in adulthood should be individualized.

Effect of growth hormone replacement in the vascular system of adult patients with childhood onset hypopituitarism

ObjectiveTo evaluate the human recombinant growth hormone replacement (hrGHr) in the metabolic parameters and vascular system in adult patients with childhood onset hypopituitarism (COH).Patients and methodsFifty-one adult with COH were selected for the study. They were divided into 2 groups: 1- hrGHr: 13 male, 14 female with median age 33.2 yrs, rhGHr in adult life with 7.38 yrs median time; 2 - Without hrGHr: 13 male, 11 female with 36.9 yrs median age and without hrGHr in adult life of 10.4 yrs median time. Anthropometric parameters, dual-energy X-ray absorptiometry (DEXA), lipid and glycemic profile, and structural and functional parameters of the arterial vessels (carotid intima media thickness, arterial stiffness and flow mediated dilation) were evaluated.ResultsThe diagnosis of obesity and overweight was higher in patients without hrGHr. Among the anthropometric characteristics, the waist-to-height ratio and diastolic blood pressure were higher in patients without replacement (p = 0.03 and p = 0.019, respectively). In the evaluation of body composition through DEXA, the Fat Mass Index among patients under hrGHr was significantly lower than in patients without hrGHr (p = 0.029). Although no statistical difference in the vascular parameters between patients with and without hrGHr, it was observed a trend towards a higher arterial stiffness in the group without replacement (p = 0.051). In the group of patients without hrGHr, arterial stiffness had a significant and positive correlation with the time without hrGHr (p = 0.038).ConclusionsThese data suggest that the hrGHr in adults with COH may have protective effects on cardiovascular system.

Effects of Growth Hormone Replacement on Peripheral Muscle and Exercise Capacity in Severe Growth Hormone Deficiency.

The aim of this study is to evaluate the effect of growth hormone therapy (rGH) on mitochondrial function on peripheral muscle and to correlate with exercise capacity in subjects with severe adult growth hormone deficiency (GHD). Six months, double-blind, randomized, crossover, placebo-controlled trial of subcutaneous rGH in 17 patients with GHD. Quadriceps muscle biopsies were obtained at baseline, 3 months, and 6 months to measure succinate dehydrogenase (SDH) to assess mitochondrial activity. Exercise capacity was measured with cardiopulmonary exercise testing. Lipids, glycemic parameters, and body fat levels were also measured. Serum insulin-like growth factor 1 (IGF1) levels reduced fat mass by 3.2% (p < 0.05) and normalized with rGH in the active phase (p < 0.005). Patients showed an increase in SDH (p < 0.01) from base line that differed between placebo and rGH therapy treatment groups (p < 0.05): those treated by rGH followed by placebo showed a significant increase in SDH (p < 0.001) followed by a decrease, with a significant between group difference at the end of 6 months (p < 0.05). No significant improvements or correlation with exercise capacity was found. Short-term rGH for 3 months normalized IGF1 levels, reduced fat mass, and had a significant effect on mitochondrial function, but exercise capacity was unchanged. Number ISRCTN94165486.

Growth Hormone Replacement Therapy in Patients without Adult Growth Hormone Deficiency: What Answers Do We Have So Far?

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) have been suggested as “anti-aging” therapies, or for improving quality of life with aging. In this study, we focus on the actions of GH in the main organs and organ systems of the human body, like skeletal muscle, bones and brain, particularly in regard to data and research on the use of GH replacement therapy in adults without growth hormone deficiency, especially elderly patients. Several different studies have been carried out to show what the effects and side effects of GH replacement in healthy people and what would be the impact in quality of life and life span. In this review, we demonstrate what answers we have so far about the effects of GH replacement in many organs and systems in healthy people.

The effect of growth hormone replacement on the thyroid axis in patients with hypopituitarism: in vivo and ex vivo studies.

Alterations in the hypothalamic-pituitary-thyroid axis have been reported following growth hormone (GH) replacement. The aim was to examine the relationship between changes in serum concentration of thyroid hormones and deiodinase activity in subcutaneous adipose tissue, before and after GH replacement. A prospective, observational study of patients receiving GH replacement as part of routine clinical care. Twenty adult hypopituitary men. Serum TSH, thyroid hormones - free and total thyroxine (T4) and triiodothyronine (T3) and reverse T3, thyroglobulin and thyroid-binding globulin (TBG) levels were measured before and after GH substitution. Changes in serum hormone levels were compared to the activity of deiodinase isoenzymes (DIO1, DIO2 and DIO3) in subcutaneous adipose tissue. The mean daily dose of growth hormone (GH) was 0·34 ± 0·11 mg (range 0·15-0·5 mg). Following GH replacement, mean free T4 levels declined (-1·09 ± 1·99 pmol/l, P = 0·02). Reverse T3 levels also fell (-3·44 ± 1·42 ng/dl, P = 0·03) and free T3 levels increased significantly (+0·34 ± 0·15 pmol/l, P = 0·03). In subcutaneous fat, DIO2 enzyme activity declined; DIO1 and DIO3 activities remained unchanged following GH substitution. Serum TSH, thyroglobulin and TBG levels were unaltered by GH therapy. In vitro analysis of subcutaneous adipose tissue from hypopituitary human subjects demonstrates that GH replacement is associated with significant changes in deiodinase isoenzyme activity. However, the observed variation in enzyme activity does not explain the changes in the circulating concentration of thyroid hormones induced by GH replacement. It is possible that deiodinase isoenzymes are differentially regulated by GH in other tissues including liver and muscle.

The effect of growth hormone replacement in patients with hypopituitarism on pituitary tumor recurrence, secondary cancer, and stroke.

Growth hormone replacement therapy has benefits for patients with hypopituitarism. The safety profile in regard to tumor recurrence or progression, development of secondary malignancies, or cerebrovascular stroke is still an area of debate. A comprehensive search of multiple databases-MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus was conducted through August 2015. Eligible studies that evaluated long-term adverse events in adult patients with hypopituitarism treated with growth hormone replacement therapy and reported development of pituitary tumor recurrence or progression, secondary malignancies, or cerebrovascular stroke were selected following a predefined protocol. Reviewers, independently and in duplicate, extracted data and assessed the risk of bias. Random-effects meta-analysis was used to pool relative risks and 95 % confidence intervals. We included 15 studies (published 1995-2015) that reported on 46,148 patients. Compared to non-replacement, growth hormone replacement therapy in adults with hypopituitarism was not associated with statistically significant change in pituitary tumor progression or recurrence (relative risk, 0.77; 95 % confidence interval, 0.53-1.13) or development of secondary malignancy (relative risk, 0.99; 95 % confidence interval, 0.70-1.39). In two retrospective studies, there was higher risk of stroke in patients who did not receive replacement (relative risk, 2.07; 95 % confidence interval, 1.51-2.83). The quality of evidence is low due to study limitations and imprecision. This systematic review and meta-analysis supports the overall safety of growth hormone therapeutic use in adults with hypopituitarism with no clear evidence of increased risk of pituitary tumor recurrence, malignancy, or stroke.

Liver fat in adults with GH deficiency: comparison to matched controls and the effect of GH replacement.

Existing data regarding the association between growth hormone deficiency (GHD) and liver fat content are conflicting. We aimed (i) to assess intrahepatocellular lipid (IHCL) content in hypopituitary adults with GHD compared to matched controls and (ii) to evaluate the effect of growth hormone (GH) replacement on IHCL content. Cross-sectional comparison and controlled intervention study. Cross-sectional comparison: Twenty-two hypopituitary adults with GHD and 44 healthy controls matched for age, BMI, gender and ethnicity. Intervention study: nine GHD patients starting GH replacement (GH Rx group) and nine GHD patients not starting replacement therapy (non-GH Rx group). Intervention study: GH replacement for 6 months in the GH Rx group, dosage was titrated to achieve normal IGF-1 levels. HCL content determined by proton magnetic resonance spectroscopy ((1) H MRS). Cross-sectional Comparison: There was no difference in IHCL content between GHD patients and healthy controls (1·89% (0·30, 4·03) vs 1·14% (0·22, 2·32); P = 0·2), and the prevalence of patients with hepatic steatosis (IHCL of ≥ 5·56%) was similar in the two groups (22·7% vs 15·9%; chi-square probability = 0·4). Intervention study: The change in IHCL content over 6 months did not differ between the GH Rx group and the non-GH Rx group (-0·63 ± 4·53% vs + 0·11 ± 1·46%; P = 0·6). In our study, liver fat content and the prevalence of hepatic steatosis did not differ between hypopituitary adults with GHD and matched controls. In GHD patients, GH replacement had no effect on liver fat content.

Growth Hormone Replacement in Patients with PHACE Association and Hypopituitarism

Partially empty sella with growth hormone (GH) deficiency is rarely reported in association with PHACE (posterior fossa anomalies, cervicofacial infantile hemangiomas [IHs], arterial anomalies, cardiac defects, eye anomalies, and midline/ventral defects). Consequently, little is known about the effect of GH replacement on the proliferation and involution of IHs in children with PHACE. We describe two children with PHACE and partially empty sella, both of whom received GH replacement for treatment of hypopituitarism. In our first patient we observed erythema and prominence of the vasculature in the hemangioma shortly after initiation of therapy at age 20 months, although after 4 weeks of treatment the appearance of the hemangioma stabilized and little change was seen during eight additional years of therapy. In our second patient we noted enlargement of the hemangioma after starting low-dose GH at age 5 years, prompting discontinuation of GH replacement after 3 months of therapy. The hemangiomas continued to grow after discontinuation of GH treatment. GH administration in our patients was associated with erythema and prominence of IHs. Our findings suggest that GH replacement therapy may promote transient or more prolonged proliferation of IHs and should be administered with close clinical monitoring.

Cardiovascular Risk in Adult Patients With Growth Hormone (GH) Deficiency and Following Substitution With GH—An Update

GH deficiency (GHD) of the adult is a clinical condition characterized by the presence of several traditional and emerging cardiovascular risk factors that can significantly increase cardiovascular morbidity and mortality. It is still an open issue whether GH replacement is able not only to improve cardiovascular risk factors but also to decrease cardiovascular morbidity and mortality. The major source of data acquisition included PubMed research strategies. Original articles, systematic reviews and meta-analyses, and included relevant citations were screened. In untreated GHD, cardiovascular risk is increased due to abnormal lipid profile (increased total and low-density lipoprotein cholesterol, increased triglycerides, and reduced high-density lipoprotein cholesterol) and impaired glucose metabolism. Emerging cardiovascular risk factors/markers such as proinflammatory cytokines, C-reactive protein, and adipokines are also increased in GHD patients. Increased cardiovascular morbidity and mortality have also been reported in GHD. GH treatment has been shown to improve both traditional and emerging cardiovascular risk factors and markers. However, evidence on the effects of GH replacement on cardiovascular events and mortality is limited. The GHD population may be considered at high cardiovascular risk, and GH substitution may be expected to bring an added value to patients with hypopituitarism in terms of cardiovascular protection. However, there is too limited evidence (rarely coming from randomized and controlled studies) to recommend GH treatment based on the cardiovascular status of the patients.

The effects of growth hormone replacement therapy on insulin, lipid profile and calcium in children with growth hormone deficiency

Background: Growth hormone has multiple effects on the overall form and function of growing body. Aside from these growth stimulating functions, it has marked effects on energy metabolism, it acts on fat cells to reduce the amount of stored fats, promotes protein synthesis in cells and plays a role in regulating the sugar levels in the blood.&#x0D; Objective: to investigate the effect of growth hormone replacement on lipid profile, insulin level, glucose and calcium level in patients with growth hormone deficiency (GHD).&#x0D; Method: A prospective study of 49 children; 37 boys and 12girls with a mean age(13.5±3.3)years attending the Children Welfare Teaching Hospital/ department of endocrinology with short stature proved to have an isolated growth hormone deficiency (other causes of short stature were excluded), with 20 healthy children as control were studied over a period of 11 months( from Oct. 2007 to Aug 2008). . Insulin level ,serum lipid ,blood glucose and serum calcium were estimated for control group and for those with isolated( GHD) prior to and post 11 months of growth hormone replacement therapy(GHRT) .&#x0D; Result: Insulin levels were ( 8.1 µIU/L) in patients with GHD and elevated significantly to( 17.4 µIU/L) after GHRT, without any unfavorable effects on blood glucose. Pre treatment lipid profile values were higher (total cholesterol T-C 4.1 mmol/L ,triglyceride TG 1.5 mmol/L ,low density lipoprotein LDL 2.5 mmol/L, very low density lipoproteins VLDL 0.7mmol/L, than the control group ( T-C 3.9, TG 1, LDL 1.8, VLDL 0.5) .&#x0D; Significant improvement was occurred after treatment (T-C=3.6 , TG=1.2, LDL=1.6 , VLDL=0.5); while pretreatment high density lipoproteins HDL was significantly lower (1 mmol/L) than in control (1.6) which improved significantly post treatment to (1.5) mmol/L.&#x0D; Significant decrement of Post-treatment serum Ca mmol/L (2) noticed as compared to controls (2.3) and to its baseline values (2.2). Significant improvement of height= -3.7 and body mass index {BMI} =-1.1 Z score to-2.9and 0, 7 respectively were noticed post- treatment. &#x0D; Conclusion: Several metabolic derangements are associated with (GHD) which could be managed effectively with (GHRT).

Progression of Chiari I malformations while on growth hormone replacement: a report of two cases

The effect of growth hormone replacement on Chiari I malformation (CIM) associated with growth hormone deficiency is not clear. Two patients are presented, who were found to have CIM and growth hormone deficiency. While on hormone replacement therapy, both experienced disease progression with development of syringomyelia and required surgical intervention. Growth hormone replacement for CIM associated with growth hormone deficiency does not uniformly halt or reverse syrinx progression. If a trial of hormone replacement is attempted, patients should be followed closely for progression of syringomyelia or the development of symptoms.

Effects of growth hormone replacement within the KIMS survey on estimated cardiovascular risk and predictors of risk reduction in patients with growth hormone deficiency

There is growing evidence for an increased cardiovascular (CV) risk in untreated growth hormone deficiency of adults (GHD). We aimed at estimating CV risk with established algorithms before and during GH replacement in GHD and in healthy controls and at identifying predictors of risk reduction. A prospective, nested case-control study. We included 344 patients (44·7 ± 14·9 years) from the German Pfizer (formerly Kabi) International Metabolic Database (KIMS) cohort and included a healthy sex- and age-matched control group from a primary care cohort. We calculated Framingham, Prospective Cardiovascular Münster Heart Study (PROCAM) and European Society of Cardiology (ESC) Score algorithms at all time points. In multivariate analyses, we analysed potential predictors of 2-year reduction in CV risk, defined as a higher than median reduction in risk. In KIMS, the estimated 10-year risks of CV events or CV mortality calculated with Framingham, PROCAM and ESC Score algorithms at baseline were 4·6%, 6·0% and 2·3%, respectively. These dropped to 2·4%, 4·8% and 0·8%, respectively, after 2 years of GH replacement (all P < 0·001 vs baseline) and returned to baseline levels after four years of GH replacement. In controls, the Framingham risk estimates were lower than in KIMS at baseline. All risk estimates increased during follow-up and were significantly higher than in KIMS after four years (all P < 0·01). In backward-selection models, high total cholesterol, low high-density lipoprotein (HDL) cholesterol and male sex were significant predictors of response in most scores. Two years of GH replacement decreased CV risk estimates approximately by half. Male sex, high total and low HDL cholesterol levels are potential predictors of good response.

Effects of growth hormone replacement on estimated cardiovascular risk and predictors of risk reduction in patients with growth hormone deficiency: results from the German KIMS cohort

Aims: Cardiovascular risk is increased in growth hormone deficiency (GHD). Algorithms based on conventional risk factors allow estimating the 10-year risk of cardiovascular events or mortality. These algorithms were developed in the general population. In this retrospective analysis, we aimed at estimating cardiovascular risk with these algorithms before and during GH replacement in GHD and in healthy controls and at identifying predictors of risk reduction.

Effect of Growth Hormone (GH) on Fasting and Postprandial Metabolism in GH Deficiency

Hypopituitarism with adult-onset growth hormone deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to premature and progressive atherosclerosis. An underlying cause of atherosclerosis is increased insulin resistance. Elevated fasting and postprandial glucose and lipid levels may contribute to premature atherosclerosis. We studied effects of growth hormone replacement (GHRT) on fasting and postprandial metabolic parameters as well as on insulin sensitivity in patients with adult-onset GHD. Using a standardized mixed meal, we studied insulin, glucose, non-esterified free fatty acid (NEFA) and triglycerides (TG) concentrations in the fasting state and during a 4 h postprandial period in 15 patients with adult-onset GHD before and after 4 months of GHRT. Identical investigations were performed in healthy matched control subjects. GHD patients before and after GHRT: GHRT did not result in significant changes in fasting glucose, insulin, NEFA and TG concentrations. In the postprandial period GHRT resulted in a non-significant increase in glucose and a decrease in NEFA levels in the presence of unchanged postprandial insulin and TG concentrations. GHD patients vs. control subjects: GHD patients showed similar fasting glucose, insulin and NEFA concentrations, but TG were increased. In the postprandial period GHD patients exhibited similar glucose and TG, but increased insulin and NEFA concentrations. GHRT patients vs. control subjects: Patients after GHRT had similar fasting glucose, insulin and NEFA, but increased TG concentrations. In the postprandial period patients after GHRT had increased glucose and insulin levels in the presence of similar NEFA and TG concentrations. While impaired insulin action in patients with GHD translates mainly by an impaired fasting TG metabolism, GHRT induced insulin resistance additionally encompasses postprandial glucose metabolism.