Faculty Bibliography

CONTEXT/BACKGROUND:Visceral adiposity is associated with increased cardiometabolic risk and decreased GH secretion. OBJECTIVE:Our objective was to determine the effects of GH administration in abdominally obese young men on body composition, including liver fat, mitochondrial function, and cardiovascular (CV) risk markers. DESIGN AND PARTICIPANTS/METHODS:This was a 6-month, randomized, double-blind, placebo-controlled study with 62 abdominally obese men (IGF-1 below the mean, no exclusion based on GH level), 21 to 45 years of age. MAIN OUTCOME MEASURES/METHODS:We evaluated abdominal fat depots, thigh muscle and fat (computed tomography), fat and lean mass (dual-energy x-ray absorptiometry), intramyocellular and intrahepatic lipids (proton magnetic resonance spectroscopy), mitochondrial function (dynamic phosphorous magnetic resonance spectroscopy), CV risk markers, carotid intimal-medial thickness, and endothelial function. RESULTS:GH administration resulted in a mean IGF-1 SD score increase from -1.9 ± 0.08 to -0.2 ± 0.3 in the GH group and a decrease in visceral adipose tissue (VAT), VAT/sc adipose tissue, trunk/extremity fat, intrahepatic lipids, high-sensitivity C-reactive protein and apolipoprotein B/low-density lipoprotein vs placebo after controlling for the increase in weight observed in both groups. There were inverse associations between change in IGF-1 levels and change in VAT, VAT/sc adipose tissue, trunk fat, trunk/extremity fat, high-sensitivity C-reactive protein, and apolipoprotein B. Mitochondrial function improved in the GH group compared with placebo after controlling for change in glucose. There was no change in thigh fat, muscle mass, intramyocellular lipids, cholesterol, fibrinogen, intimal-medial thickness, or endothelial function. There was no increase in fasting glucose or hemoglobin A1c in the GH vs placebo group, although glucose during the 2-hour oral glucose tolerance test increased slightly. CONCLUSION/CONCLUSIONS:GH replacement in abdominally obese men improves body composition, including liver fat, mitochondrial function, and markers of CV risk. Although fasting glucose was unchanged, a slight increase in 2-hour glucose during an oral glucose tolerance test was noted.

OBJECTIVE:Hyperinsulinaemia is an important determinant of the polycystic ovarian syndrome (PCOS). In addition to lifestyle measures, therapeutic strategies include the use of oestrogen-progesterone combination pills (EP), and insulin sensitizers such as metformin, either alone or in combination. Data are limited regarding the impact of metformin alone vs metformin with EP on cardiometabolic risk in overweight adolescents with PCOS. We hypothesized that metformin alone would lead to an improvement in HbA1C and lipid levels in overweight adolescent girls with PCOS compared with meformin with EP. STUDY DESIGN/METHODS:Retrospective clinic-based therapy. PATIENTS AND MEASUREMENTS/METHODS:We examined the effects of therapy with metformin alone (n = 14) vs metformin with EP (n = 13) on HbA1C and lipid parameters over 10-14 months in 27 overweight girls, drawn from a clinic population of adolescents with PCOS. RESULTS:The groups did not differ for age, body mass index (BMI), HbA1C or baseline lipids. After at least 10 months, the metformin only group compared with the metformin and EP group had a decrease in total cholesterol (-0·605 ± 0·100 vs 0·170 ± 0·348 mm, P = 0·02, nonparametric test) and triglycerides (-0·342 ± 0·184 vs 0·262 ± 0·133 mm, P = 0·02), despite similar changes in BMI (-1·6 ± 0·7 vs 0·6 ± 2·1 kg/m(2) , P = 0·25) and HbA1C (0·03 ± 0·06 vs 0·03 ± 0·13%, P = 0·99). Differences between groups remained significant after controlling for baseline parameters and for changes in BMI. CONCLUSION/CONCLUSIONS:Metformin alone more effectively improves lipid parameters than metformin with EP in adolescent PCOS, as indicated by a decrease in total cholesterol and triglycerides. This effect is not related to BMI changes.

OBJECTIVE:Obesity has been associated with cognitive decline in longitudinal studies of older individuals. We hypothesized that the cognitive sequelae of obesity may be detectable in the reproductive years. In addition, we explored the hypothesis that these associations may be mediated by the hormonal milieu. DESIGN AND METHODS/METHODS:Of 49 young healthy lean and overweight women aged 20-45, we investigated the association between performance on a battery of cognitive tests, body composition parameters [body mass index, total fat, abdominal (visceral, subcutaneous, and total) adipose tissue, and muscle], and hormone levels (insulin, adiponectin, leptin, insulin-like growth factor 1 (IGF-1), estrogen, testosterone, and vitamin D). RESULTS:We found a significant negative association between both visceral adiposity and muscle, and performance in the domain of verbal learning and memory, after controlling for age and education. Other body composition parameters showed similar trends (0.05 < P < 0.10). Additionally, the degree of insulin resistance was negatively associated with executive function domain. None of the associations between the other hormones examined (adipokines, IGF-1, gonadal hormones, and vitamin D) and cognitive function were significant. CONCLUSION/CONCLUSIONS:These preliminary findings suggest a possible association between obesity and cognitive function in healthy young women of reproductive age. More research is warranted into the potential modulatory effect of insulin resistance on this association.

Bone histomorphometry measurements require high spatial resolution that may not be feasible using multidetector CT (MDCT). This study evaluated the trabecular microarchitecture of lumbar spine using MDCT and C-arm CT in a series of young adult patients with anorexia nervosa (AN). 11 young females with AN underwent MDCT (anisotropic resolution with a slice thickness of ~626 μm) and C-arm CT (isotropic resolution of ~200 µm). Standard histomorphometric parameters the of L1 vertebral body, namely the apparent trabecular bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular number (TbN) and trabecular separation (TbSp), were analysed using MicroView software (GE Healthcare, Piscataway, NJ). Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Trabecular parameters derived from MDCT and C-arm CT were compared, and their association with BMD parameters was evaluated. Histomorphometric parameters derived from C-arm CT, namely TbTh, TbN and TbSp, were significantly different from the corresponding MDCT parameters. There were no significant correlations between C-arm CT-derived parameters and the corresponding MDCT-derived parameters. C-arm CT-derived parameters were significantly (p<0.001) correlated with anteroposterior L1 spine BMD and Z-scores: TbTh (r=0.723, r=0.744, respectively), TbN (r=-0.720, r=-0.712, respectively) and TbSp (r=0.656, r=0.648, respectively). BV/TV, derived from C-arm CT, was significantly associated with body mass index (r=0.636) and ideal body weight (r=0.730) (p<0.05). These associations were not present in MDCT-derived parameters. This study suggests that the spatial resolution offered by C-arm CT more accurately captures the histomorphometric parameters of trabecular morphology than MDCT in patients with AN.

The lateral aspect of the hip is composed of a complex array of osseous and soft tissue structures. Both common and uncommon clinical entities are encountered in the lateral hip. This article briefly introduces fundamental imaging anatomy and the functional roles of different osseous and soft tissue structures in the lateral aspect of the hip, followed by a discussion of relevant imaging findings of lateral hip pathology. Greater trochanteric pain syndrome is frequently encountered in patients with lateral hip pain and encompasses a spectrum of soft tissue abnormalities including trochanteric and subgluteal bursitis, and tendinopathy or tears of the gluteal tendons. In addition, different types of injuries to the gluteal myotendinous unit and injuries to the indirect head of the rectus femoris, proximal iliotibial band, and the lateral joint capsular ligaments can present with lateral hip pain. Some of the less common soft tissue abnormalities of the lateral hip include Morel-Lavallée lesion and meralgia paresthetica.

OBJECTIVE:We previously reported improved body composition and cardiovascular risk markers plus a small decrease in glucose tolerance with GH administration vs placebo for 6 months to abdominally obese premenopausal women. The objective of this study was to determine whether the effects of GH treatment on cardiovascular risk markers, body composition and glucose tolerance in obese women persist 6 months after GH withdrawal. DESIGN AND PATIENTS/METHODS:Fifty abdominally obese premenopausal women completed a trial of rhGH vs placebo for 6 months; thirty-nine women completed a subsequent 6-month withdrawal observation period. MEASUREMENTS/METHODS:IGF-I, body composition by CT, (1) H-MRS and DXA, serum cardiovascular risk markers, oral glucose tolerance test (OGTT). RESULTS:IGF-I standard deviation scores (SDS) within the GH group were -1.7 ± 0.1 (pretreatment),-0.1 ± 0.3 (after 6 months of GH) and -1.7 ± 0.1 (6 months post-GH withdrawal). Six months after GH withdrawal, total abdominal and subcutaneous adipose tissue, total fat, trunk fat, trunk/extremity fat, hsCRP, apoB, LDL, and tPA were higher than at the 6-month (GH discontinuation) timepoint (P ≤ 0.05). All body composition and cardiovascular risk markers that had improved with GH returned to baseline levels by 6 months after GH discontinuation, as did fasting and 2-h OGTT glucose levels. CONCLUSION/CONCLUSIONS:The effects of GH administration to abdominally obese premenopausal women have a short time-course. The beneficial effects on body composition and cardiovascular risk markers, and the side effect of altered glucose tolerance returned to pretreatment levels after GH withdrawal. There was no suppression of endogenous IGF-I levels, which returned to baseline after GH withdrawal.

Soft tissue abnormalities about the hip represent a common clinical problem. Although the signs and symptoms of some of these abnormalities are clinically evident, other entities are frequently overlooked. This article provides an overview and discusses the role of major imaging modalities, especially MR imaging, the primary modality for evaluation of many soft-tissue abnormalities. An introduction to fundamental imaging anatomy and functional roles of soft tissue structures about the hip is provided, recognizing their importance in making the correct diagnosis. Intra-articular and extra-articular soft tissue abnormalities reviewed systematically according to their mechanism of injury and anatomic or functional compartments.

OBJECTIVES/OBJECTIVE:Neurofibromatosis 1 (NF1), NF2, and schwannomatosis are characterized by a predisposition to develop multiple neurofibromas and schwannomas. Currently, there is no blood test to estimate tumor burden in patients with these disorders. We explored whether S100β would act as a biomarker of tumor burden in NF since S100β is a classic immunohistochemical marker of astrocytes, oligodendrocytes and Schwann cells and a small study showed S100β concentrations correlate with the volume of vestibular schwannomas. DESIGN AND METHODS/METHODS:We calculated whole-body tumor burden in subjects with NF1, NF2, and schwannomatosis using whole-body MRI (WBMRI) and measured the concentration of S100β in plasma using ELISA. We used chi-square tests and Spearman rank correlations to test the relationship between S100β levels and whole-body tumor burden. RESULTS:127 consecutive patients were enrolled in the study (69 NF1 patients, 28 NF2 patients, and 30 schwannomatosis patients). The median age was 40years, 43% were male, and median whole-body tumor volume was 26.9mL. There was no relationship between the presence of internal tumors and the presence of detectable S100β in blood for the overall group or for individual diagnoses (p>0.05 by chi-square for all comparisons). Similarly, there was no correlation between whole-body tumor volume and S100β concentration for the overall group or for individual diagnoses (p>0.05 by Spearman for all comparisons). CONCLUSIONS:Plasma S100β is not a useful biomarker for tumor burden in the neurofibromatoses. Further work is needed to identify a reliable biomarker of tumor burden in NF patients.

OBJECTIVE:To determine the prevalence of infection diagnosed by percutaneous computed tomography (CT)-guided sternoclavicular (SC) sampling in cases of suspected joint infection. MATERIALS AND METHODS/METHODS:A retrospective search was performed in reports of SC joint CT-guided biopsies in adults from July 1992 to July 2012. We reviewed medical records, radiology, microbiology, laboratory, and surgical reports. A positive result was defined as demonstration of a pathogenic organism, either by microscopy or growth in culture, confirming the diagnosis of SC joint infection. A negative result was defined as the absence of such findings. Patients in whom sampling was unsuccessful or not subjected to microbiology were excluded. In addition, CT images were reviewed by the consensus of two musculoskeletal radiologists. RESULTS:A total of 41 patients (mean age 57.1 years) underwent CT-guided SC joint sampling, 27 of whom underwent microbiology studies. Sampling was performed using core biopsy alone in 19%, fine needle aspiration alone in 44%, and aspiration combined with core biopsy in 37%. Positive results were found in 52% (14/27) of patients. Related diseases and predisposing conditions for infection were found in 79% of positive patients. Negative results were found in 48% (13/27) of patients. There were no procedure-related complications. The dominant CT findings were soft tissue swelling (negative group), and effusion and/or capsular hypertrophy/distension (positive group). CONCLUSIONS:CT-guided sampling is a safe procedure with positive microbiological cultures in slightly more than half of cases.

Recent studies have shown a positive correlation between brown adipose tissue (BAT) and bone mineral density (BMD). However, mechanisms underlying this relationship are unknown. Insulin-like growth factor 1 (IGF-1) is an important regulator of stem cell differentiation promoting bone formation. IGF binding protein 2 (IGFBP-2) binds IGF-1 in the circulation and has been reported to inhibit bone formation in humans. IGF-1 is also a crucial regulator of brown adipocyte differentiation. We hypothesized that IGFBP-2 is a negative and IGF-1 a positive regulator of BAT-mediated osteoblastogenesis. We therefore investigated a cohort of 15 women (mean age 27.7±5.7years): 5 with anorexia nervosa (AN) in whom IGF-1 levels were low due to starvation, 5 recovered AN (AN-R), and 5 women of normal weight. All subjects underwent assessment of cold-activated BAT by PET/CT, BMD of the spine, hip, femoral neck, and total body by DXA, thigh muscle area by MRI, IGF-1 and IGFBP-2. There was a positive correlation between BAT and BMD and an inverse association between IGFBP-2 and both BAT and BMD. There was no association between IGF-1 and BAT. We show for the first time that IGFBP-2 is a negative predictor of cold-induced BAT and BMD in young non-obese women, suggesting that IGFBP-2 may serve as a regulator of BAT-mediated osteoblastogenesis.