Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. OBJECTIVE: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). DESIGN: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). SETTING: Eight Scandinavian referral centers. PATIENTS: From 1998 to 2005, 191 patients with mild PHPT were included. INTERVENTION: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). MEASUREMENTS: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. RESULTS: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). LIMITATION: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. CONCLUSION: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. PRIMARY FUNDING SOURCE: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.

Low concentrations of serum testosterone predict acute myocardial infarction in men with type 2 diabetes mellitus.

BACKGROUND: The aim of the present study was to investigate the associations between endogenous testosterone concentrations and the incidence of acute myocardial infarction (AMI) in men and women with and without type 2 diabetes. METHODS: The study comprised 1109 subjects ≥40 years of age (mean age 62 ± 12 years) participating in a baseline survey in Sweden in 1993-94. Information about smoking habits and physical activity was obtained using validated questionnaires. Serum concentrations of testosterone and sex hormone-binding globulin (SHBG) were obtained using radioimmunoassay. Diagnosis of type 2 diabetes was based on WHO's 1985 criteria. Individual patient information on incident AMI was ascertained by record linkage with national inpatient and mortality registers from baseline through 2011. RESULTS: The prevalence of type 2 diabetes at baseline was 10.0% in men and 7.5% in women. During a mean follow-up of 14.1 years (±5.3), there were 74 events of AMI in men and 58 in women. In age-adjusted Cox models, a significant inverse association between concentrations of testosterone and AMI-morbidity was found in men with type 2 diabetes (HR = 0.86 CI (0.75-0.98)). In a final model also including waist-to-hip ratio, systolic blood pressure, total cholesterol and active smoking, the association still remained statistically significant (HR = 0.754 CI (0.61-0.92)). CONCLUSION: Low concentrations of testosterone predicted AMI in men with type 2 diabetes independent of other risk factors. Trials with testosterone investigating the effect regarding cardiovascular outcome are still lacking. Future trials in this field should take into account a modification effect of diabetes.

Ten-year mortality after severe traumatic brain injury in western Sweden: a case control study.

PRIMARY OBJECTIVE: Life expectancy may be substantially reduced for many years after severe traumatic brain injury (TBI). This study investigated the patterns of the short- and long-term all-cause mortality and the rates of primary causes of death in patients with severe TBI. SUBJECTS: This study was of 166 consecutive patients (6-82 years) with severe TBI admitted to Sahlgrenska University Hospital, Gothenburg, Sweden, from 1999-2002. The control group consisted of 809 subjects from the community, matched to the TBI cohort for age, gender and postcode area at the time of the injury. METHODS: Survival outcome and cause of death were ascertained 10 years after the injury from the Swedish National Board of Health and Welfare register. The cumulative death rates and causes of death in cases and controls were compared. RESULTS: The risk of death was increased for at least 10 years after severe TBI. The distribution of the causes of deaths differed between cases and controls in the first year of follow-up, but not between 1-year survivors and controls. CONCLUSION: Further research will be required to determine how to improve treatment so as to lower late mortality among survivors of severe TBI.

Low sex hormone-binding globulin is associated with hypertension: a cross-sectional study in a Swedish population.

BACKGROUND: The aim of this study was to investigate the association of sex hormone-binding globulin (SHBG) and hypertension in a Swedish population. METHODS: The study is based on a random sample of a Swedish population of men and women aged 30-74 years (n=2,816). Total testosterone, oestradiol and SHBG were measured in 2,782 participants. Free androgen index was then calculated according to the formula FAI=100 × (Total testosterone)/SHBG. Hypertension was diagnosed according to JNC7. RESULTS: In men, but not in women, significant association between SHBG and both diastolic (diastolic blood pressure: ß=-0.143 p<0.001) and systolic blood pressure (systolic blood pressure ß=-0.114 p<0.001) was found. The association was still significant after adjusting for age, body mass index (BMI), homeostatic model assessment insulin resistance (HOMA-IR), triglycerides, high density lipoproteins (HDL) and C-reactive protein (CRP) (diastolic blood pressure: ß=-0.113 p<0.001; systolic blood pressure ß=-0.093 p=0.001). An inverse association was observed between SHBG and hypertension in both men (B=-0.024 p<0.001) and women (B=-0.022 p<0.001). The association was still significant in women older than 50 years after adjustments for age, BMI, physical activity, CRP and alcohol consumption (B=-0.014, p=0.008). CONCLUSION: In conclusion, these results show a strong association between SHBG and blood pressure independent of major determinants of high blood pressure. This association might be addressed to direct effects of SHBG in endothelial cells through the receptor for SHBG. If this is confirmed by other observational and experimental studies, it might become a new field for the development of therapies for lowering blood pressure.

Falsely Elevated Estradiol Results in a 62-Year-Old Male Patient.

Falsely increased estradiol levels can lead to unnecessary tests and therapeutic interventions. Here, we present a case of a 62-year-old man with falsely elevated estradiol, which led to subsequent follow-up testing and prescriptions. Alternative immunoassay testing, in conjunction with Scantibodies' blocking reagents, polyethylene glycol precipitation, and liquid chromatography-tandem mass spectrometry confirmation demonstrated that the falsely elevated estradiol was due to the presence of macro-estradiol. This report emphasizes the importance of recognizing analytical interferences in immunoassays to appropriately manage subsequent testing and patient care.

Reninom ­ en ovanlig men botbar orsak till sekundär hypertoni.

Reninoma - rare juxtaglomerular tumor associated with hypertension We present a case study of two female patients, aged 20-30 years, who were diagnosed with reninoma, a rare juxtaglomerular tumor associated with hypertension, high plasma renin and hypokalemia. Both patients were referred to the Department of Internal Medicine at Sahlgrenska University Hospital, but their cases were ten years apart. In both instances, the renin-secreting tumor was surgically removed, resulting in the normalization of blood pressure without the need for antihypertensive medication. Based on our findings, we recommend physicians interested in hypertension to analyze plasma renin levels before starting antihypertensive treatment in young patients. Additionally, we suggest performing an MRI of the kidneys followed by renal vein catheterization, which can confirm but not exclude the presence of a reninoma. It is important to note that treatment with RAAS (renin-angiotensin-aldosterone system) blockers may mask the effects of reninoma on blood pressure and potassium levels. Since RAAS blockers are contraindicated during pregnancy, it is of particular importance to diagnose reninoma in young women of childbearing age.

Positive Effect of Parathyroidectomy Compared to Observation on BMD in a Randomized Controlled Trial of Mild Primary Hyperparathyroidism.

Mild or asymptomatic disease is now the dominating presentation of primary hyperparathyroidism (PHPT). However, bone involvement with decreased bone mineral density (BMD) and an increased risk of fractures has been demonstrated. Indications for parathyroidectomy (PTX) in mild PHPT have been debated for years. There is a need of long-term randomized studies comparing PTX with observation without intervention (OBS). Here, we present bone health data from the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH), a randomized controlled trial, comparing PTX to OBS. This study included 191 patients (96 OBS/95 PTX), and 129 patients (64 OBS/65 PTX) were followed for 10 years to the end of study (EOS). BMD was measured with dual-energy X-ray absorptiometry (DXA), peripheral fractures were noted, and spine radiographs were obtained for vertebral fracture assessment. There was a significant treatment effect of PTX on BMD compared with OBS for all analyzed compartments, most explicit for the lumbar spine (LS) and femoral neck (FN) (p < 0.001). The mean changes in T-score from baseline to 10 years were from 0.41 for radius 33% (Rad33) to 0.58 for LS greater in the PTX group than in the OBS group. There was a significant decrease in BMD for all compartments in the OBS group, most pronounced for FN, Rad33, and ultradistal radius (UDR) (p < 0.001). Even though there was a significant treatment effect of PTX compared with OBS, there was only a significant increase in BMD over time for LS (p < 0.001). We found no difference between groups in fracture frequency in the 10-year cohort, neither with modified intention-to-treat (mITT) analysis nor per protocol analysis. Because BMD is only a surrogate endpoint of bone health and PTX did not reduce fracture risk, observation could be considered a safe option for many patients with mild PHPT regarding bone health in a 10-year perspective. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Effect of surgery on cardiac structure and function in mild primary hyperparathyroidism.

CONTEXT: The cardiovascular (CV) risk profile is worsened in primary hyperparathyroidism (PHPT), and CV mortality is related to serum calcium levels. It is unknown whether CV mortality is increased in the most common form of PHPT and whether the increased CV risk is reversible after surgery. OBJECTIVE: To investigate reversibility of echocardiographic variables in patients with mild PHPT who were randomized to observation without surgery or operation, and followed for 2 years. DESIGN/SETTING/PATIENTS: Forty-nine patients (mean age 63 ± 7 years, 8 men) who had performed the 2-year visit in a randomized study on mild PHPT (serum calcium at baseline 2·65 ± 0·09 mm) (observation) vs 2·67 ± 0·06 mm (surgery) and where echocardiography had been performed, participated in the study. RESULTS: Calcium and parathyroid hormone (PTH) levels were normalized following surgery and were stable in the observation group. PTH levels at baseline were highly correlated with ventricular mass. Detailed echocardiography revealed a minor and borderline significant treatment effect of surgery on left ventricular mass index (LVMI) compared to observation (P = 0·066) and a significant 11% reduction in diastolic dimension of the interventricular septum (IVSd-mean) in the surgery group (P<0·01), with no alterations in the observation group. CONCLUSIONS: Based on detailed echocardiographic measures over a 2-year observation period, we found only minor differences between the two groups. However, the potential treatment effect on LVMI and the within-group differences in IVSd-mean suggest that longer follow-up may yield larger and clinically important differences.

Effects of Parathyroidectomy on Quality of Life: 10 Years of Data From a Prospective Randomized Controlled Trial on Primary Hyperparathyroidism (the SIPH-Study).

Primary hyperparathyroidism (PHPT) was previously considered a disease presenting with multiorgan involvement and a wide range of symptoms. Today, the disease presents with no symptoms or mild symptomatology in most patients. Data regarding nonspecific symptoms such as pain, fatigue, memory loss, depression, and other neuropsychiatric signs have been ambiguous, and results from prospective long-term randomized control trials are lacking. The Scandinavian Investigation on Primary Hyperparathyroidism (SIPH) is a prospective randomized controlled trial (RCT) with 10-year follow up, comparing parathyroidectomy (PTX) to observation without any treatment (OBS). From 1998 to 2005, 191 patients with mild PHPT were included from Sweden, Norway, and Denmark. A total of 95 patients were randomized to PTX and 96 to OBS. The generic Short Form-36 survey (SF-36) and the Comprehensive Psychopathological Rating Scale (CPRS) were studied at baseline, 2, 5, and 10 years after randomization. After 10 years, the PTX group scored significantly better on vitality (PTX 65.1 ± 20.2 versus OBS 57.4 ± 22.7; p = .017) compared to the OBS group in SF-36. We found no differences between the groups in the physical subscales. The OBS group had no significant change in any of the SF-36 scores throughout the study. The CPRS showed an improvement of symptoms in both groups for single items and sum scores after 10 years compared to baseline. There were, however, no significant differences between the two groups in the CPRS data. The results of this large and long-term RCT indicate improvement in some of the mental domains of SF-36 following PTX. However, the treatment effects between the groups were subtle with uncertain clinical significance. The observation group had stable SF-36 values and improvement in CPRS symptom-scores. Thus, in considering only quality of life (QoL) and in the absence of declines in renal and skeletal parameters, it may be safe to observe patients with mild PHPT for a decade. © 2020 American Society for Bone and Mineral Research (ASBMR).

Physiological and pharmacological basis for the ergogenic effects of growth hormone in elite sports.

Growth Hormone (GH) is an important and powerful metabolic hormone that is secreted in a pulsatile pattern from cells in the anterior pituitary, influenced by several normal and pathophysiological conditions. Human GH was first isolated in the 1950s and human derived cadaveric GH was initially used to treat patients with GH deficiency. However, synthetic recombinant GH has been widely available since the mid-1980s and the advent of this recombinant GH boosted the abuse of GH as a doping agent. Doping with GH is a well-known problem among elite athletes and among people training at gyms, but is forbidden for both medical and ethical reasons. It is mainly the anabolic and, to some extent, the lipolytic effects of GH that is valued by its users. Even though GH's rumour as an effective ergogenic drug among athletes, the effectiveness of GH as a single doping agent has been questioned during the last few years. There is a lack of scientific evidence that GH in supraphysiological doses has additional effects on muscle exercise performance other than those obtained from optimised training and diet itself. However, there might be synergistic effects if GH is combined with, for example, anabolic steroids, and GH seems to have positive effect on collagen synthesis. Regardless of whether or not GH doping is effective, there is a need for a reliable test method to detect GH doping. Several issues have made the development of a method for detecting GH doping complicated but a method has been presented and used in the Olympics in Athens and Turin. A problem with the method used, is the short time span (24-36 hours) from the last GH administration during which the test effectively can reveal doping. Therefore, out-of-competition testing will be crucial.However, work with different approaches to develop an alternative, reliable test is ongoing.

The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism

Context: Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors. Objective: To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism. Design, patients, interventions, main outcome measures: 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization. Results: In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected. Conclusion: In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.

Fracture incidence in GH-deficient patients on complete hormone replacement including GH.

UNLABELLED: Fracture risk in GHD patients is not definitely established. Studying fracture incidence in 832 patients on GH therapy and 2581 matched population controls, we recorded a doubled fracture risk in CO GHD women, but a significantly lower fracture risk in AO GHD men. INTRODUCTION: The objective of this study was to evaluate fracture incidence in patients with confirmed growth hormone deficiency (GHD) on replacement therapy (including growth hormone [GH]) compared with population controls, while also taking potential confounders and effect modifiers into account. MATERIALS AND METHODS: Eight hundred thirty-two patients with GHD and 2581 matched population controls answered a questionnaire about fractures and other background information. Incidence rate ratio (IRR) and 95% CI for first fracture were estimated. The median time on GH therapy for childhood onset (CO) GHD men and women was 15 and 12 yr, respectively, and 6 and 5 yr for adult onset (AO) GHD men and women, respectively. RESULTS: A more than doubled risk (IRR, 2.29; 95% CI, 1.23-4.28) for nonosteoporotic fractures was recorded in women with CO GHD, whereas no risk increase was observed among CO GHD men (IRR, 0.61) and AO GHD women (IRR, 1.08). A significantly decreased incidence of fractures (IRR, 0.54; 95% CI, 0.34-0.86) was recorded in AO GHD men. CONCLUSIONS: Increased fracture risk in CO GHD women can most likely be explained by interaction between oral estrogen and the GH-IGF-I axis. The adequate substitution rate of testosterone (90%) and GH (94%) may have resulted in significantly lower fracture risk in AO GHD men.

Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial.

CONTEXT: The clinical presentation of primary hyperparathyroidism (pHPT) has changed during the last half century, and the diagnosis is now more often made by chance in patients with no specific symptoms. OBJECTIVE: The present study is a randomized, controlled trial that investigates the effects of parathyroidectomy or medical observation in mild asymptomatic pHPT on morbidity and quality of life (QoL). DESIGN/SETTING/PATIENTS: A total of 191 patients (26 men) with asymptomatic pHPT [mean age 64.2 +/- 7.4 (sd) yr] were recruited in the study and randomized to medical observation (serum calcium level 2.69 +/- 0.08 mmol/liter) or surgery (2.70 +/- 0.08 mmol/liter). We here report baseline and 1 (n = 119) and 2 yr data (n = 99) on those who had completed the follow-up visits by the end of the inclusion period. RESULTS: At baseline, the patients had significantly lower QoL (SF-36) and more psychological symptoms, compared with age- and sex-matched healthy subjects. The two groups were similar at baseline, and no clinically significant changes in these parameters were seen during the observation time. Calcium and PTH normalized after surgery. The areal bone mineral density increased in the group randomized to operation, whereas the bone mineral density remained stable in the medical observation group. No change in kidney function (creatinine) or blood pressure was observed longitudinally or between the groups. CONCLUSIONS: Asymptomatic patients with mild pHPT have decreased QoL and more psychological symptoms than normal controls. No benefit of operative treatment, compared with medical observation, was found on these measures so far.

Nonfatal stroke, cardiac disease, and diabetes mellitus in hypopituitary patients on hormone replacement including growth hormone.

CONTEXT: The impact of long-term GH replacement on cerebrovascular and cardiovascular diseases and diabetes mellitus in hypopituitary patients is unknown. OBJECTIVE: The incidence of nonfatal stroke and cardiac events, and prevalence of type 2 diabetes mellitus (T2D) and cardioprotective medication were compared between cohorts of GH-deficient (GHD) patients and population controls. DESIGN AND PARTICIPANTS: The incidence of nonfatal stroke and cardiac events was estimated retrospectively from questionnaires in 750 GHD patients and 2314 matched population controls. A prevalence of T2D and cardioprotective medication was recorded at the distribution of questionnaires. Time since first pituitary deficiency to start of GH therapy was 4 and 2 yr, and time on GH therapy was 6 yr for GHD women and men, respectively. RESULTS: Lifelong incidence of nonfatal stroke was tripled in GHD women and doubled in GHD men, but a decline was seen in both genders during periods after first pituitary hormone deficiency and GHD, during which most patients had GH therapy. The lifelong incidence of nonfatal cardiac events declined in GHD men during first pituitary hormone deficiency and GHD periods. GHD women had a higher prevalence of T2D and lipid-lowering medication, whereas GHD men had a higher prevalence of antihypertensive medication. CONCLUSIONS: The declined risks of nonfatal stroke in both genders and of nonfatal cardiac events in GHD men during periods on GH replacement may be caused by prescription of cardioprotective drugs and 6-yr GH replacement. GHD women had an increased prevalence of T2D, partly attributed to higher body mass index and lower physical activity.

Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month's treatment with supraphysiological doses of growth hormone.

OBJECTIVES: To study the effects on insulin-like growth factor binding proteins (IGFBP)-4 and -5 after one month's treatment with supraphysiological doses of growth hormone (GH) in healthy, active young adults with a normal GH-IGF-I axis. Furthermore, the possible use of IGFBP-4 and IGFBP-5 as markers of GH doping is discussed. DESIGN: Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25.9 years (range 18-35), participated in this randomized, double-blind, placebo-controlled, parallel study with three groups (n=10; 5 men and 5 women in each group). The groups comprised the following: placebo, GH 0.1IU/kg/day [0.033mg/kg/day] and GH 0.2IU/kg/day [0.067mg/kg/day]. RESULTS: Baseline levels of IGFBP-4 were higher (+20%), while IGFBP-5 levels were lower (-37%) in women than in men. IGFBP-5 levels were positively correlated to age, but no significant correlation was found for IGFBP-4. In the pooled group with active GH treatment (n=20), both IGFBP-4 and IGFBP-5 levels were increased vs. the placebo group from day 14 until end of treatment [day 28, IGFBP-4 (+40%, p<0.01) and IGFBP-5 (+61%, p <0.001)]. After inclusion of serum IGF-I as a covariate in the linear regression analysis, the associations between GH treatment and the IGFBP-4 and IGFBP-5 levels were not significant. CONCLUSIONS: This study shows that the levels of IGFBP-4 and IGFBP-5 are affected by supraphysiological GH treatment given to young, healthy, physically active adults of both genders. The present study, including relatively few subjects, does not support that IGFBP-4 and IGFBP-5 can be used as IGF-I independent markers in a forthcoming method for detecting GH doping, although, further studies are needed to investigate the potential use of IGFBP-4 and IGFBP-5 as markers of GH doping.

Effect of Surgery Versus Observation: Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study).

Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm2 and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p < 0.001) and CTX-1 (p < 0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm2 ) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p < 0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p < 0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm2 ) for all compartments (FN, p < 0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p < 0.001) with the exception of the LS, where BMD was stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT. © 2017 American Society for Bone and Mineral Research.

Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes.

CONTEXT: Despite the fact that the use of GH as a doping agent in sports is widespread, little is known about its short-term effects. OBJECTIVE: The objective was to study the effects of GH on exercise capacity. DESIGN: A double-blind, placebo-controlled study was used, with a treatment period of 28 d. SETTING: Subjects from general community studied ambulatory at a university hospital. PARTICIPANTS: Thirty healthy active young normal volunteers (15 women and 15 men) were recruited by local announcement, and all completed the study. INTERVENTION: All subjects were randomized to receive a low GH dose (0.033 mg/kg.d or 0.1 IU/kg.d), a high GH dose (0.067 mg/kg.d or 0.2 IU/kg.d), or placebo. MAIN OUTCOME MEASURES: Power output and oxygen uptake on bicycle exercise were the main outcome measures. RESULTS: We found no effect of the low or high dosages of GH on maximum oxygen uptake during exercise (mean +/- se for placebo, 45.2 +/- 1.6 to 45.2 +/- 2.1 ml/kg.min; GH low dose, 42.8 +/- 1.6 to 42.8 +/- 1.6 ml/kg.min; GH high dose, 44.8 +/- 3.4 to 44.8 +/- 2.2 ml/kg.min; not significant by two-way ANOVA). Neither was there any effect on maximum achieved power output during exercise or on blood pressure, heart rate, or the electrocardiographic ST level at rest or during exercise. GH significantly increased total body weight (P = 0.028), an effect predominantly ascribed to fluid retention (increased extracellular water volume), whereas muscle mass (as indicated by intracellular water volume) did not change. However, changes in the latter correlated to changes in physical performance, possibly due to different training efforts. CONCLUSION: Administration of supraphysiological recombinant human GH during a period of 4 wk does not improve power output or oxygen uptake.