Efficacy of a long-acting growth hormone (GH) preparation in patients with adult GH deficiency.

CONTEXT: Treatment of adult GH deficiency (AGHD) with daily injections of GH results in decreased adipose mass, increased lean body mass (LBM), increased bone mineral density, and improved quality of life. OBJECTIVE: This study seeks to determine whether a depot preparation of GH given every 14 d would lead to comparable decreases in trunk adipose tissue as daily GH. DESIGN: This open-label, randomized study compares subjects receiving depot GH, daily GH, or no therapy. SETTING: The study was performed at 23 university or local referral endocrine centers. PATIENTS OR OTHER PARTICIPANTS: One hundred thirty-five adults with AGHD syndrome participated in the study. INTERVENTION: Subjects were randomized to receive depot GH (n = 51), daily GH (n = 53), or no treatment (n = 31) for 32 wk. The dose of GH was titrated so that IGF-I was less than or equal to +2 SD of the age-adjusted normal range. MAIN OUTCOME MEASURE: Trunk adipose tissue was the main outcome measure as measured by dual energy x-ray absorptiometry. RESULTS: The percentage of the trunk region that is fat increased by 0.4 in the no treatment group, but decreased by 3.2 (P = 0.001 vs. untreated) in the GH depot group and by 2.5 (P < 0.004 vs. untreated) in the daily GH group. Visceral adipose tissue area decreased by 9.1% in the GH depot group and by 6.8% in the daily GH group. LBM and high-density lipoprotein increased in both treatment groups. Side effect profiles were similar. Three subjects receiving GH experienced serious episodes of adrenal insufficiency. CONCLUSIONS: GH diminishes trunk and visceral adipose tissue and increases LBM in AGHD. A depot form of GH that is administered every 14 d is as safe and effective as daily GH injections.

Estrogens are essential for male pubertal periosteal bone expansion.

The skeletal response to estrogen therapy was studied in a 17-yr-old boy with congenital aromatase deficiency. As expected, estrogen therapy (1 mg estradiol valeriate/d from age 17 until 20 yr) normalized total and free testosterone and reduced the rate of bone remodeling. Dual-energy x-ray absorptiometry-assessed areal bone mineral density (BMD) of the lumbar spine and femoral neck increased significantly (by 23% and 14%, respectively), but peripheral quantitative computed tomography at the ultradistal radius revealed no gain of either trabecular or cortical volumetric BMD. The increase in areal BMD was thus driven by an increase in bone size. Indeed, longitudinal bone growth (height, +8.5%) and especially cross-sectional area of the radius (+46%) and cortical thickness (+12%), as measured by peripheral quantitative computed tomography, increased markedly during estrogen treatment. These findings demonstrate that androgens alone are insufficient, whereas estrogens are essential for the process of pubertal periosteal bone expansion typically associated with the male bone phenotype.