Prospective evaluation of a week one overnight metyrapone test with subsequent dynamic assessments of hypothalamic-pituitary-adrenal axis function after pituitary surgery.

OBJECTIVE: To determine whether an overnight metyrapone test (OMT) within the first week postpituitary surgery can definitively assess the hypothalamic-pituitary-adrenal (HPA) axis, compared with subsequent dynamic tests and glucocorticoid requirement at 6 months. DESIGN: Prospective study measuring morning cortisol levels on days 3 and 4 post-operatively, OMT day 5-7 and week 6, week 6 250 µg short Synacthen test (SST) and week 7 insulin tolerance test (ITT). PATIENTS AND MEASUREMENTS: Forty participants who underwent pituitary surgery at a single centre (Cushing's disease excluded) were followed for at least 6 months. 46% had pre-operative adrenal insufficiency. PRIMARY OUTCOME: week 1 OMT compared to glucocorticoid requirement at 6 months. SECONDARY OUTCOMES: the performance of ITT as a "definitive" test and all tests compared to glucocorticoid requirement at 6 months. RESULTS: Week 1 OMT showed concordance with ITT at week 7 of 78% and glucocorticoid requirement at 6 months of 81% respectively which was not significantly different from post-operative morning cortisol levels; 37% of participants with an abnormal OMT on day 6 had a normal OMT at week 6. All HPA axis tests showed similar concordance with glucocorticoid requirement at 6 months of 80%-85%. CONCLUSIONS: Overnight metyrapone test within the first week after pituitary surgery was no better than an early morning cortisol level at predicting glucocorticoid requirement at 6 months. OMT at week 6 demonstrated recovery of HPA axis in a substantial proportion of participants who failed earlier assessments; thus, definitive testing should be delayed until 6 weeks post-operatively.

Growth hormone (GH) enhances anaerobic capacity: impact on physical function and quality of life in adults with GH deficiency.

CONTEXT: Anaerobic capacity is impaired in adults with GH deficiency (GHD), adversely affecting physical function and quality of life (QoL). OBJECTIVE: To investigate whether GH replacement improves anaerobic capacity, physical function and QoL in adults with GHD. DESIGN: One-month double-blind placebo-controlled crossover study of GH (0·5 mg/day), followed by a 6-month open phase. PATIENTS: A total of 18 adults with GHD. MEASUREMENTS: Anaerobic power (watts) was assessed by the 30-s Wingate test, and aerobic capacity by the VO2 max (l/min) test. Physical functional was assessed by the stair climb test, chair stand test, 7-day pedometry and QoL by the AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy X-ray absorptiometry. RESULTS: GH replacement normalized IGF-1 levels during both study phases. During the 1-month placebo-controlled study, improvement in stair climb and chair stand performance was observed during GH and placebo treatment; however, there were no significant GH effects observed in any outcome measure compared to placebo. Six months of GH treatment significantly increased anaerobic power (P < 0·05), chair stand repetitions (P < 0·0001), daily step count (P < 0·05) and QoL scores (P < 0·001) compared to baseline measurements. GH treatment did not significantly improve VO2 max. Improvement in anaerobic power independently predicted an improvement in energy and vitality domain of QoL (P = 0·03). CONCLUSIONS: GH replacement improves anaerobic capacity, physical function and QoL in a time-dependent manner in adults with GHD. Improvement in the anaerobic but not aerobic energy system is likely to underlie the improvement in QoL in patients with GHD during GH replacement.

Impairment of anaerobic capacity in adults with growth hormone deficiency.

CONTEXT: The anaerobic energy system underpins the initiation of all physical activities, including those of daily living. GH supplementation improves sprinting in recreational athletes, a performance measure dependent on the anaerobic energy system. The physiological and functional link between GH and the anaerobic energy system is unknown. OBJECTIVE: The objective was to investigate whether anaerobic capacity is impaired in adults with GH deficiency (GHD) and to assess its functional significance. DESIGN: This was a cross-sectional study. PARTICIPANTS: The participants were 13 adults with GHD and 13 age-, gender- and body mass index-matched normal subjects. MAIN OUTCOME MEASURES: Anaerobic power (watts) was assessed by the 30-second Wingate test, and aerobic capacity was assessed by the VO2max (L/min) test. The functional assessment comprised the stair-climb test, chair-stand test, and 7-day pedometry. Quality of life (QoL) was assessed by the QoL-AGHDA questionnaire. Lean body mass (LBM) was quantified by dual-energy x-ray absorptiometry. RESULTS: Mean anaerobic power (5.8 ± 0.4 vs 7.1 ± 0.3 W · kg LBM(-1); P < .05) and VO2max were significantly lower in adults with GHD. The duration of the stair-climb test was longer (19.4 ± 0.7 vs 16.5 ± 0.7 s; P < .01) in adults with GHD and correlated negatively (R(2) = 0.7; P < .0001) with mean anaerobic power. The mean number of chair-stand repetitions and daily step counts were lower, and the QoL-AGHDA score was higher in adults with GHD (P < .05). In a multiple regression analysis, age, gender, LBM, and GH status were significant predictors of mean anaerobic power. Mean anaerobic power significantly predicted stair-climb performance (P < .01) and QoL (P < .05). CONCLUSIONS: Anaerobic capacity is subnormal, and it independently predicts stair-climbing capacity and QoL in adults with GHD. We conclude that GH regulates anaerobic capacity, which determines QoL and selective aspects of physical function.

Long-term efficacy and safety of subcutaneous pasireotide in acromegaly: results from an open-ended, multicenter, Phase II extension study.

Pasireotide has a broader somatostatin receptor binding profile than other somatostatin analogues. A 16-week, Phase II trial showed that pasireotide may be an effective treatment for acromegaly. An extension to this trial assessed the long-term efficacy and safety of pasireotide. This study was an open-label, single-arm, open-ended extension study (primary efficacy and safety evaluated at month 6). Patients could enter the extension if they achieved biochemical control (GH ≤ 2.5 µg/L and normal IGF-1) or showed clinically relevant improvements during the core study. Thirty of the 60 patients who received pasireotide (200-900 µg bid) in the core study entered the extension. At extension month 6, of the 26 evaluable patients, six were biochemically controlled, of whom five had achieved control during the core study. Normal IGF-1 was achieved by 13/26 patients and GH ≤ 2.5 µg/L by 12/26 at month 6. Nine patients received pasireotide for ≥24 months in the extension; three who were biochemically controlled at month 24 had achieved control during the core study. Of 29 patients with MRI data, nine had significant (≥20%) tumor volume reduction during the core study; an additional eight had significant reduction during the extension. The most common adverse events were transient gastrointestinal disturbances; hyperglycemia-related events occurred in 14 patients. Twenty patients had fasting plasma glucose shifted to a higher category during the extension. However, last available glucose measurements were normal for 17 patients. Pasireotide has the potential to be an effective, long-term medical treatment for acromegaly, providing sustained biochemical control and significant reductions in tumor volume.

Estrogen and selective estrogen receptor modulators (SERMs) for the treatment of acromegaly: a meta-analysis of published observational studies.

Estrogen and selective estrogen receptor modulator (SERM) treatments for acromegaly have received limited attention since the development of newer pharmacologic therapies. There has been ongoing research evidence suggesting their utility in the biochemical control of acromegaly. Therefore, the aim of this meta-analysis was to synthesise current evidence with a view to determining to what extent and in which acromegalic patient subsets do estrogen and SERMs reduce IGF-1 levels. A literature search was conducted (finished December 2012), which included all studies pertaining to estrogen or SERM treatment and IGF-1. Seven patient subsets were identified from six published observational studies, and were pooled using meta-analytic methods. Overall, the pooled mean loss in IGF-1 was -29.09 nmol/L (95 % CI -37.23 to -20.95). A sensitivity analysis indicated that women receiving estrogen had a substantially greater reduction in IGF-1 levels compared with women receiving SERMs, with a weighted mean loss in IGF-1 of -38.12 nmol/L (95 % CI -46.78 to -29.45) compared with -22.91 nmol/L (95 % CI -32.73 to -13.09). There was a trend that did not reach statistical significance for men receiving SERM treatment at -11.41 nmol/L (95 % CI -30.14 to 7.31). It was concluded that estrogen and SERMs are a low cost and effective treatment to achieve control of IGF-1 levels in acromegalic women either as concomitant treatment for refractory disease, or where access to conventional therapy is restricted. Their use in men requires further study.

Cancer risk after medical exposure to radioactive iodine in benign thyroid diseases: a meta-analysis.

Radioiodine-131 ((131)I) is widely used for diagnosis and treatment of benign thyroid diseases. Observational studies have not been conclusive about the carcinogenic potential of (131)I and we therefore conducted a meta-analysis. We performed a literature search till September 2011 which included (131)I as a diagnostic or treatment modality ((131)I for treatment of thyroid cancer was excluded). Data on 64 different organ or organ group subsets comprising 22 029 exposed subjects in the therapeutic cohorts and 24 799 in the diagnostic cohorts in seven studies were included. Outcome was pooled as the relative risk (RR) using both standard and bias adjusted methods. Quality assessment was performed using a study-specific instrument. No increase in overall (RR 1.06, 95% CI: 0.94-1.19), main organ group or combined organ group (four groups known to concentrate (131)I; RR 1.11, 95% CI: 0.94-1.31) risks was demonstrable. Individual organs demonstrated a higher risk for kidney (RR 1.70, 95% CI: 1.15-2.51) and thyroid (RR 1.99, 95% CI: 1.22-3.26) cancers with a strong trend for stomach cancer (RR 1.11, 95% CI: 0.92-1.33). A thyroid dose effect was seen for diagnostic doses. While there is no increase in the overall burden of cancer, an increase in risk to a few organs is seen which requires substantiation. The possible increase in thyroid cancer risk following diagnostic (131)I use should no longer be of concern given that it has effectively been replaced by the use of 99mTc-pertechnetate.

The aerobic performance of trained and untrained handcyclists with spinal cord injury.

The purpose of this study was to compare the cardiorespiratory response and mechanical efficiency (ME) of highly trained spinal cord injured (SCI) handcyclists with untrained SCI men. Ten trained handcyclists (≥ 2 years training) and ten untrained but physically active SCI men completed an incremental exercise test to exhaustion and a sub-maximal test (50 and 80 W) on an electromagnetically braked arm ergometer. The trained participants completed a questionnaire on their training and race performance over the past year, including average training volume (in kilometers), number of training sessions per week and best 20-km time trial. The trained SCI men had higher VO2 peak, peak power (p ≤ 0.001) and peak heart rate (p = 0.021) compared to the untrained SCI men. The trained men had higher (p ≤ 0.001) ME at 50 W (14.1 ± 2.0%) and 80 W (17.2 ± 2.6) compared to the untrained men (50 W; 12.5 ± 1.8 and 80 W; 15.7 ± 2.1). Peak power (r = -0.87, p = 0.001), VO2 peak (r = -0.67, p = 0.033) and ME (r = -0.58, p = 0.041) were negatively correlated with the participants best 20-km time trial. Multiple linear regression indicated peak power (p < 0.001) and VO2 peak (p = 0.021) were the best predictors (87%) of 20-km time trial performance. Highly trained SCI handcyclists have a greater aerobic capacity and ME compared to untrained SCI, and are able to reach their maximum age-predicted heart rate during an incremental exercise test. The best predictor of 20 km race performance in highly trained SCI handcyclists is peak power attained during an incremental exercise test.

The hormonal response of older men to sub-maximum aerobic exercise: the effect of training and detraining.

The hormonal response of 32 older men (70-80years) to a bout of sub-maximum aerobic exercise was examined before, after 16weeks of resistance or aerobic training and again after 4weeks of detraining. Blood samples were obtained at rest and immediately post sub-maximum exercise (30min @ 70% VO(2) max) to determine the concentrations of growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone (Test), sex hormone-binding globulin (SHBG) and the calculation of free testosterone (FT). Both training groups had significant increases in leg strength and VO(2) max after 16weeks training but leg strength and VO(2) max returned to pre-training levels in the aerobic training and resistance training groups, respectively. During the 20week study there was no change in resting concentrations of any hormones among the three groups. There was no increase in GH, IGF-1 or SHBG immediately post sub-maximum exercise in any of the groups before training, after 16weeks training or after 4weeks detraining. Testosterone and FT increased immediately post sub-maximum exercise within all groups before training, after 16weeks training and after 4weeks detraining with the increase in Test and FT higher after 16weeks of resistance training compared to before training and after 4weeks detraining within the resistance training group. The increased responsiveness of Test and FT after 16weeks of resistance training was lost after 4weeks of detraining. Our results indicate that some physiological and hormonal adaptations gained after 16weeks training are lost after only 4weeks detraining.

Relationships between blood levels of fat soluble vitamins and disease etiology and severity in adults awaiting liver transplantation.

BACKGROUND AND AIMS: Although malnutrition is common in liver disease, there are limited data on fat soluble vitamins in various diseases. The aims of this study were to: (i) determine fat soluble vitamin levels in patients assessed for liver transplantation; (ii) compare levels between different disease etiologies (hepatocellular and cholestatic) and between subgroups of hepatocellular disease; and (iii) assess the multivariate contribution to vitamin levels of etiology and various indicators of disease severity. METHODS: This was a cross-sectional study of 107 inpatients awaiting liver transplantation, mean age 47 years. Biochemical parameters included plasma retinol, 25-hydroxycholecalciferol, and vitamin E. Biochemical (albumin, bilirubin and zinc) and clinical indicators (Child-Pugh and Model of End Stage Liver Disease [MELD] scores) of disease severity were determined. RESULTS: Deficiencies of retinol (< 1.0 µmol/L), 25-hydroxycholecalciferol (< 50 nmol/L) and vitamin E (< 11 µmol/L) were present in 75%, 66% and 3%, respectively, of patients. Concentrations of retinol and vitamin E were lower in hepatocellular than cholestatic disease but 25-hydroxycholecalciferol concentrations were similar. Child-Pugh score was higher in hepatocellular than cholestatic disease. Concentrations of retinol were lower in alcoholic liver disease (ALD) than hepatitis and Child-Pugh score was higher in ALD. For the whole group, levels of retinol, 25-hydroxycholecalciferol and vitamin E were negatively related to Child-Pugh score, MELD score and bilirubin, and positively related to albumin. When Child-Pugh scores were controlled for, retinol was lower in the hepatocellular group. CONCLUSIONS: There was a high prevalence of fat soluble vitamin deficiencies with vitamin levels being related to disease severity. Retinol was lower in the hepatocellular group.

The blood pressure response of older men to maximum and sub-maximum strength testing.

Strength testing is commonly used to determine the muscular strength of older individuals participating in a resistance training program. The purpose of this study was to non-invasively examine and compare the blood pressure (BP) and heart rate (HR) response of maximum and sub-maximum strength tests in older men. Twenty-four healthy men aged 70-80 yr were recruited for the study. Participants completed a 1 repetition maximum (RM) strength test and four days later a sub-maximum strength test on an incline squat. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were measured by plethysmography during and immediately after the strength tests. SBP, DBP and HR were (P<0.001) higher during the 1RM and sub-maximum strength tests compared to resting values. Twenty seconds post 1RM, SBP and HR were higher than resting values. Twenty seconds post sub-maximum strength testing SBP and DBP were lower (P<0.02) and HR (P<0.001) was higher than resting values. SBP, DBP and HR were higher (P<0.001) during sub-maximum strength testing compared to 1RM testing. Twenty seconds post testing, SBP and DBP were lower (P<0.001) and HR was higher (P<0.001) for the sub-maximum strength tests compared to the 1RM. The results of our study demonstrate that sub-maximum strength testing resulted in greater changes in BP and HR compared to 1RM strength testing. The lower cardiovascular stress experienced during the 1RM shows that this may be a safer method of testing compared to sub-maximum strength testing in men aged 70-80 yr.

Dark adaptation in vitamin A-deficient adults awaiting liver transplantation: improvement with intramuscular vitamin A treatment.

BACKGROUND/AIMS: Although vitamin A deficiency is common in chronic liver disease, limited data exist on impairment of dark adaptation and response to therapy. The aims were (1) to assess dark adaptation in patients, (2) to assess the relationship between dark adaptation and vitamin A status, zinc and Child-Pugh score, (3) to compare perceived and measured dark adaptation and (4) to assess the dark adaptation response to intramuscular vitamin A. METHODS: This was a prospective study of 20 patients (alcoholic liver disease 10, other parenchymal diseases six, cholestatic diseases four) awaiting liver transplantation. Selection was based on low serum retinol. There were 15 age-matched controls. Dark adaptation was measured with a SST-1 dark adaptometer and perception by questionnaire. Eight patients received 50, 000 IU of retinyl palmitate, and dark adaptation was repeated at 1 month. RESULTS: Forty per cent of patients had impaired dark adaptation. Patients with alcoholic liver disease were more impaired than those with other parenchymal diseases (p=0.015). No relationship was found between dark adaptation and the biochemical indicators or Child-Pugh score. Seventy-five per cent of patients with impairment did not perceive a problem. After intervention, light of half the previous intensity could be seen (p=0.05). CONCLUSIONS: Dark-adaptation impairment was common, was worse in alcoholic liver disease, was largely not appreciated by the patients and improved with vitamin A treatment.

The effect of strength training and short-term detraining on maximum force and the rate of force development of older men.

This study examined the effect of strength training (ST) and short-term detraining on maximum force and rate of force development (RFD) in previously sedentary, healthy older men. Twenty-four older men (70-80 years) were randomly assigned to a ST group (n = 12) and C group (control, n = 12). Training consisted of three sets of six to ten repetitions on an incline squat at 70-90% of one repetition maximum three times per week for 16 weeks followed by 4 weeks of detraining. Regional muscle mass was assessed before and after training by dual-energy X-ray absorptiometry. Training increased RFD, maximum bilateral isometric force, and force in 500 ms, upper leg muscle mass and strength above pre-training values (14, 25, 22, 7, 90%, respectively; P < 0.05). After 4 weeks detraining all neuromuscular variables were significantly (P < 0.05) lower than after 16 weeks training but remained significantly (P < 0.05) higher than pre-training levels except for RFD which had returned to pre-training levels. These findings demonstrate that high-intensity ST can improve maximum force and RFD of older men. However, older individuals may lose some neuromuscular performance after a period of short-term detraining and that resistance exercise should be performed on a regular basis to maintain training adaptations.

Can aerobic training improve muscle strength and power in older men?

This study examined the effect of aerobic training on leg strength, power, and muscle mass in previously sedentary, healthy older men (70-80 yr). Training consisted of 30-45 min of cycle ergometry at 50-70% maximal oxygen consumption (VO2max), 3 times weekly for 16 wk, then 4 wk detraining, or assignment to a nontraining control group (n = 12 both groups). Training increased leg strength, leg power, upper leg muscle mass, and VO2max above pretraining values (21%, 12%, 4%, and 15%, respectively; p < .05). However, all gains were lost after detraining, except for some gain in VO2max. This suggests that cycle ergometry is sufficient stimulus to improve neuromuscular function in older men, but gains are quickly lost with detraining. For the older population cycle ergometry provides the means to not only increase aerobic fitness but also increase leg strength and power and upper leg muscle mass. However, during periods of inactivity neuromuscular gains are quickly lost.

Resistance training reduces the blood pressure response of older men during submaximum aerobic exercise.

OBJECTIVE: The objective of this study was to determine whether 16 weeks of resistance training (RT) can reduce the blood pressure response and improve the cardiovascular function of men aged 70-80 years during submaximum aerobic exercise. METHODS: Twenty-four men aged between 70 and 80 years were randomly assigned to an RT group (n = 12) and control group (n = 12). Training consisted of three sets of six to 10 repetitions at 70-90% of one repetition maximum, three times per week, on an incline squat machine for 16 weeks. Blood pressure and cardiovascular function were assessed during submaximum cycle exercise at 40 W, and 50 and 70% of maximum oxygen consumption (VO2max) before training and after 16 weeks of training. Leg strength and VO2max were assessed every 4 weeks of the 16-week study. RESULTS: At 40 W, heart rate, systolic blood pressure, and rate pressure product were lower and stroke volume was significantly higher after 16 weeks of training. At 50% VO2max, heart rate and rate pressure product were lower after 16 weeks of training and at 70% VO2max, cycle ergometry power, VO2, and arterio-venous oxygen difference were higher after 16 weeks of training. Leg strength significantly increased after 16 weeks of training. CONCLUSION: Sixteen weeks of RT significantly reduces the blood pressure response and improves the cardiovascular function of older men during submaximum aerobic exercise. Therefore, RT not only increases muscular strength and hypertrophy but also provides significant cardiovascular benefits for older individuals.

Octreotide LAR vs. surgery in newly diagnosed patients with acromegaly: a randomized, open-label, multicentre study.

OBJECTIVE: This prospective randomized study evaluated the efficacy and safety of octreotide LAR vs. surgery in newly diagnosed acromegalic patients. METHODS: Totally 104 male and female patients were enrolled in a 50-week, exploratory, open-label and randomized study. Eligible patients were randomized to receive either octreotide LAR 20 mg every 28 days or to undergo surgery. Efficacy was assessed by changes in mean GH and IGF-I serum concentrations, at weeks 12, 24 and 48. Tumour volume was assessed by contrast-enhanced MRI. In both groups, treatment adjustment was performed for patients uncontrolled at week 12 or 24. Octreotide LAR patients received a dose increased to 30 mg or, if already receiving this dose, investigator and patients could decide to cross-over to surgery. Patients uncontrolled after surgery received octreotide LAR 20 mg, increased to 30 mg if acromegaly was still uncontrolled. RESULTS: Overall success rates at weeks 24 and 48 were 25% and 28% for the octreotide LAR group and 49% and 39% for the surgery group. Only the difference observed at week 24 was statistically significant (P = 0.047). Both groups had a significant (> 20%) tumour shrinkage: 73% of patients in the octreotide LAR group and 95% in the surgery group. Major differences between octreotide LAR and surgery group in the occurrence of adverse events were gastrointestinal (71%vs. 27%), hepatobiliary (41%vs. 8%) and respiratory (5%vs. 28%). CONCLUSION: This first randomized study in unselected patients indicates that the 48-week treatment outcome of octreotide LAR as first-line treatment of acromegaly does not significantly differ from surgery. As a complete response to surgery in GH-secreting macro-adenomas can be difficult, first-line therapy with octreotide LAR can be considered as a viable alternative for most patients with acromegaly, due to its low complication rate.

Strength training improves submaximum cardiovascular performance in older men.

PURPOSE: To determine if 16 weeks of strength training can improve the cardiovascular function of older men during submaximum aerobic exercise. METHODS: Twenty four men aged 70-80 yr were randomly assigned to a strength training (ST; n = 12) and control group (C; n = 12). Training consisted of 3 sets of 6 - 10 repetitions at 70% to 90% of 1RM, 3 times per week, on an incline squat machine for 16 weeks, followed by 4 weeks detraining. Leg strength and maximum oxygen consumption (VO2 max) were assessed every 4 weeks of the 20-week study. Cardiovascular function was assessed during submaximum cycle exercise at 40 Watts, 50% and 70% of VO2 max before training, after 16 weeks training, and after 4 weeks detraining. RESULTS: At 40 Watts, heart rate (HR), systolic blood pressure, and rate pressure product (RPP) were lower and stroke volume (SV) significantly higher after 16 weeks training and 4 weeks detraining: at 50% VO2 max, HR and RPP were lower after 16 weeks training and 4 weeks detraining: at 70% VO2 max, cycle ergometry power, VO2 and arterio-venous oxygen difference (a - vO2 ) were higher after 16 weeks training. Leg strength and VO2 max increased after 16 weeks training, with leg strength remaining above pre-training levels after 4-weeks detraining. CONCLUSIONS: Sixteen weeks of strength training significantly improves the cardiovascular function of older men. Therefore strength training not only increases muscular strength and hypertrophy but also provides significant cardiovascular benefits for older individuals.

The role of growth hormone replacement in a growth hormone deficient patient with underlying cardiomyopathy and severe congestive heart failure.

It has been reported that growth hormone (GH) deficiency induced cardiomyopathy responds to growth hormone replacement therapy. We describe the case of a middle-aged male with cardiomyopathic heart failure and growth hormone deficiency of the adult secondary to surgical panhypopituitarism. We demonstrate clinical and hemodynamic improvement of cardiac function with growth hormone replacement therapy despite underlying structural heart disease.

Controversies regarding the effects of growth hormone on the heart.

Growth hormone (GH) profoundly affects the developing and adult myocardium. Adult patients with GH deficiency (GHD) and GH excess (acromegaly) provide important models in which to understand the effects of GH in adult cardiac physiology. An increasing body of clinical and experimental evidence illustrates the specific physiological abnormalities that are likely associated with the excess cardiovascular mortality observed in both acromegaly and GHD. Because human GH replacement is now available to treat adults with GHD, new questions emerge about the long-term cardiovascular effects of replacement therapy. In multiple trials, GH therapy for congestive heart failure has been proved ineffective in the absence of preexisting GHD. Case reports suggest that, in the setting of GHD, GH therapy can exert a potent beneficial effect on congestive heart failure. Long-term studies addressing cardiovascular morbidity and mortality are needed to assess the role of GH therapy for GHD.