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Biomedical subjects

S Grinspoon

Publications and source records attributed to S Grinspoon.

45 records · Page 3Linked to original sources
PubMed1997

Body composition and endocrine function in women with acquired immunodeficiency syndrome wasting.

The acquired immunodeficiency syndrome (AIDS) wasting syndrome is a devastating complication of human immunodeficiency virus (HIV) infection characterized by progressive weight loss and severe inanition. In men, the wasting syndrome is characterized by a disproportionate decrease in lean body mass and relative fat sparing. In contrast, relatively little is known about the gender-specific changes in body composition that characterize AIDS wasting in women. Three groups of women were studied to determine body composition and hormonal changes with respect to stage of wasting [nonwasting (NW; weight >90% ideal body weight; weight loss <10% of preillness maximum; n = 12), early wasting (EW; weight >90% ideal body weight; weight loss >10% of preillness maximum; n = 10), and late wasting (LW; weight <90%; n = 9)] and compared with a control group of 12, healthy, age-matched women. Weight loss averaged 6 +/- 6% (NW), 15 +/- 6% (EW), and 20 +/- 8% (LW) in the three groups. Lean, fat, and muscle masses were determined by dual energy x-ray absorptiometry and urinary creatinine excretion. Subjects were 36 +/- 5 yr of age (mean +/- SD) with a CD4 cell count of 379 +/- 239 cells/mm3. The body mass index was 24.4 +/- 2.6 kg/m2 (NW), 22.2 +/- 1.2 kg/m2 (EW), 18.2 +/- 2.0 kg/m2 (LW), and 24.3 +/- 2.6 kg/m2 (controls; P < 0.01, NW vs. EW; P < 0.0001, NW vs. LW). Lean body mass indexed for height was 15.7 +/- 2.4 kg/m2 (NW), 14.8 +/- 2.0 kg/m2 (EW), and 13.7 +/- 1.2 kg/m2 (LW) and was decreased significantly only in the LW group (P < 0.05 vs. NW). Muscle mass was 96% (NW), 94% (EW), and 78% (LW) of that predicted for height (P < 0.05, NW vs. LW). In contrast, fat mass indexed for height was decreased significantly among patients in both the EW and LW groups [8.7 +/- 1.9 kg/m2 (NW), 6.5 +/- 1.9 kg/m2 (EW), and 3.7 +/- 1.4 kg/m2 (LW); P < 0.05, NW vs. EW; P < 0.001, NW vs. LW). Expressed as a percentage of the value in nonwasting HIV-positive controls (NW), the relative loss of fat was greater than the loss of lean mass with progressive degrees of wasting [EW, 25% vs. 6% (fat vs. lean); LW, 58% vs. 13%]. The prevalence of amenorrhea was 20% among study subjects [17% (NW), 10% (EW), and 38% (LW)]. The percent predicted muscle mass was significantly lower in subjects with amenorrhea (74 +/- 8%) compared to that in eumenorrheic HIV-positive subjects (94 +/- 4%; P < 0.05). Estradiol levels were lower among subjects with amenorrhea (17.6 +/- 21.8 pg/mL) compared to eumenorrheic HIV-positive (48.9 +/- 33.6 pg/mL) and control (68.3 +/- 47.6 pg/mL) subjects and did not correlate with body composition. Mean free testosterone, but not total testosterone, levels were decreased in subjects with EW and LW compared to those in age-matched healthy controls, but not compared with those in NW [0.9 +/- 0.6 ng/dL (NW), 0.7 +/- 0.4 ng/dL (EW), 0.6 +/- 0.3 ng/dL (LW), and 2.0 +/- 2.4 ng/dL (controls); P < 0.05, EW vs. controls and LW vs. controls] and correlated with muscle mass (r = 0.37; P < 0.05). The percentages of women with free testosterone levels below the age-adjusted normal range were 33% (NW), 50% (EW), and 66% (LW). Dehydroepiandrosterone sulfate levels were also low in the subjects with LW compared to those in the control group [98 +/- 85 microg/dL (NW), 102 +/- 53 microg/dL (EW), 55 +/- 46 microg/dL (LW), and 132 +/- 68 microg/dL (controls); P < 0.05 LW vs. controls] and were correlated highly with free testosterone levels (r = 0.73; P < 0.00001) and also with muscle mass (r = 0.48; P < 0.01). These data demonstrate that women lose significant lean body and muscle mass in the late stages of wasting. However, in contrast to men, women exhibit a progressive and disproportionate decrease in body fat relative to lean body mass at all stages of wasting, consistent with gender-specific effects in body composition in AIDS wasting. (ABSTRACT TRUNCATED)

Absorptiometry, Photon↗
PubMed1997

Mechanisms and treatment options for bone loss in anorexia nervosa.

Osteoporosis is present in over half of all patients with anorexia nervosa. Bone loss often occurs at a young age and may persist even after recovery, predisposing patients to debilitating spinal crush fractures. The pathogenesis of bone loss in anorexia nervosa is not completely understood and may result from a number of mechanisms, including estrogen deficiency, inadequate vitamin and calcium intake, and nutritional effects on bone formation. Recent studies demonstrate that estrogen itself is inadequate to increase bone density in a majority of patients with anorexia nervosa and suggest that nutritionally dependent factors such as insulin-like growth factor-I (IGF-I), a potent bone trophic hormone, may be important in maintaining bone mass. IT is hoped that new anabolic strategies to increase osteoblast function will become available in the future. In the interim, weight gain, restoration of gonadal function, and calcium supplementation remain the cornerstones of treatment in this disease.

Anorexia Nervosa↗
PubMed1996

Serum leptin levels in women with anorexia nervosa.

Leptin is a protein encoded by the ob gene that is expressed in adipocytes and regulates eating behavior via central neuroendocrine mechanisms. Serum leptin levels have been shown to correlate with weight and percent body fat in normal and obese individuals; however, it is not known whether the regulation of leptin is normal below a critical threshold of body fat in chronic undernutrition. We investigated serum leptin levels in 22 women, aged 23 +/- 4 yr, with anorexia nervosa. Duration of disease, weight, BMI, percent body fat, and serum leptin levels were determined for each patient. Nutritional status was assessed further by caloric intake and measurement of insulin and insulin-like growth factor I (IGF-I) levels. Twenty-three healthy women, aged 23 +/- 4 yr, taking no medications, with normal menstrual function and body mass index (BMI) between 20-26 kg/m2 (mean, 23.7 +/- 1.7 kg/m2), served as a control population for comparison of leptin levels. Subjects with anorexia nervosa were low weight (BMI, 16.3 +/- 1.6 kg/m2; normal, 20-26 kg/m2) and exhibited a striking reduction in percent body fat (7 +/- 2%; normal, 20-30%). The mean serum leptin level was significantly decreased in subjects with anorexia nervosa compared with that in age- and sex-matched controls of normal body weight (5.6 +/- 3.7 vs. 19.1 +/- 8.1 ng/mL; P < 0.0001). Serum leptin levels were correlated highly with weight, as expressed either BMI (r = 0.66; P = 0.002) or percent ideal body weight (r = 0.68; P = 0.0005), body fat (r = 0.70; P = 0.0003), and IGF-I (r = 0.64; P = 0.001), but not with caloric intake or serum levels of estradiol or insulin in subjects with anorexia nervosa. The correlation between leptin and body fat was linear, with progressively lower, but detectable, leptin levels measured even in patients with less than 5% body fat, but was not significant when the effects of weight were taken into account. In contrast, the correlation between leptin and IGF-I remained significant when the effects of weight, body fat, and caloric intake were taken into account. In normal controls, leptin correlated with BMI (r = 0.55; P = 0.007) and IGF-I (r = 0.44; P < 0.05), but not with fat mass. These data demonstrate that serum leptin levels are reduced in association with low weight and percent body fat in subjects with anorexia nervosa compared to normal controls. Leptin levels correlate highly with weight, percent body fat, and IGF-I in subjects with anorexia nervosa, suggesting that the physiological regulation of leptin is maintained in relation to nutritional status even at an extreme of low weight and body fat.

Adipose Tissue↗
PubMed1996

Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa.

Significant osteoporosis affects over half of all women with anorexia nervosa (AN). The mechanisms of bone loss in this condition are not known, and estrogen administration alone has not been shown to prevent bone loss. Insulin-like growth factor I (IGF-I), a nutritionally dependent bone trophic hormone, is know to stimulate osteoblast function and collagen synthesis in vivo and in vitro. We hypothesized that short term administration of recombinant human IGF-I (rhIGF-I) would increase bone turnover in young women with AN. We studied 23 women, aged 18-29 yr (mean +/- SD, 23 +/- 4 yr) with AN. Spinal bone density was significantly reduced compared to that in age-matched controls (0.85 +/- 0.11 vs. 1.19 +/- 0.12 g/cm2 by dual energy x-ray absorptiometry; P < 0.001) and was below the normal mean in 54% of the women. Patients were randomized to receive rhIGF-I (100 or 30 micrograms/kg) or placebo sc twice a day for 6 days. Bone turnover was assessed at baseline and after 3 and 6 days of treatment using two markers of bone formation [osteocalcin (OC) and type I procollagen carboxyl-terminal propeptide (PICP)] and three specific markers of bone resorption [pyridinoline (PYRX), deoxypyridinoline (DPYRX), and N-telopeptide (NTX)]. Serum OC was reduced significantly (P < 0.001) in women with AN compared to normal premenopausal women (5.4 +/- 3.8 vs. 8.6 +/- 4.5 ng/mL) and correlated with percent fat mass (r = 0.60;P < 0.01) and body mass index (r = 0.50;P < 0.05). Markers of bone resorption were elevated significantly compared to normal levels [DPYRX, 18.2 +/- 7.0 vs. 11.4 +/- 5.2 nmol/mmol creatinine, (P < 0.001); NTX, 53.5 +/- 22.5 vs. 36.5 +/- 14.6 nmol BCE/mmol creatinine (P < 0.01)]. IGF-I levels were relatively low at baseline compared to those in age-matched controls (203 +/- 93 vs. 262 +/- 84 ng/mL;P < 0.01) and increased to 673 +/- 268 ng/mL [P < 0.05; 100 micrograms/kg twice daily (BID)] and 545 +/- 255 ng/mL (P < 0.05; 30 micrograms/kg BID). During short term administration of rhIGF-I at a dose of 100 micrograms/kg BID, there was a significant (P < 0.05) increase in markers of bone formation, as assessed by both PICP (147 +/- 33 to 303 +/- 187 ng/mL) and OC (5.3 +/- 3.8 to 10.9 +/- 7.4 ng/mL). There was also a significant (P < 0.05) increase in markers of bone resorption as assessed by PYRX (51.0 +/- 16.6 to 87.1 +/- 8.2 nmol/mmol creatinine) and DPYRX (17.3 +/- 4.5 to 26.3 +/- 3.7 nmol/mmol creatinine). The group randomized to receive short term administration of rhIGF-I at a dose of 30 micrograms/kg BID demonstrated a significant (P < 0.05) increase in PICP (110.9 +/- 47.0 to 134.8 +/- 43.2 ng/mL) and an insignificant increase in OC levels (4.5 +/- 3.2 to 6.8 +/- 5.9 ng/mL). However, markers of bone resorption were unchanged during rhIGF-I administration at this dose. Serum PTH and serum and urinary calcium were unchanged in both treatment groups compared to placebo levels. These data demonstrate that young women with anorexia nervosa have decreased markers of bone formation and increased bone resorption. This is the first demonstration that short term rhIGF-I administration increases markers of bone turnover in severely osteopenic women with AN. The effects of short term rhIGF-I on bone turnover are dose dependent. At a dose of 100 micrograms BID, rhIGF-I administration significantly stimulated both markers of bone formation and bone resorption. At a dose of rhIGF-I of 30 micrograms BID, there was an increase in one marker of bone formation, PICP, without a change in markers of bone resorption. Further studies are required to determine whether chronic administration of rhIGF-I can affect bone mass in young women with profound osteopenia due to anorexia nervosa.

Adolescent↗
PubMed1996

Loss of lean body and muscle mass correlates with androgen levels in hypogonadal men with acquired immunodeficiency syndrome and wasting.

The acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS) is a devastating complication of human immunodeficiency virus infection characterized by a disproportionate decrease in lean body mass. The pathogenesis of the AWS is unknown, but recent data suggest that endogenous secretion of the potent anabolic hormone, testosterone; is decreased in 30-50% of men with AIDS. However, it is unknown whether decreased androgen levels are associated with decreased lean body mass and/or functional decreases in muscle strength and aerobic capacity in hypogonadal men with the AWS. In addition, testosterone is known to have stimulatory effects on GH secretion, and the loss of these effects on the GH-insulin-like growth factor I (IGF-I) axis may be an additional mechanism of decreased lean body mass in this population. Twenty hypogonadal subjects (free-testosterone < 12 pg/mL) with weight loss > 10% of preillness weight or absolute weight < 90% ideal body weight (IBW) were enrolled in the study. None of the subjects were receiving Megace. Lean body mass and fat-free mass were determined by potassium-40 isotope analysis (40K) and dual-energy x-ray absorptiometry, respectively, and analyzed with respect to gonadal function by linear regression analysis. Muscle mass was determined by urinary creatinine excretion, and exercise functional capacity was assessed by a 6-min walk test, a sit-to-stand test, and a timed get-up-and-go test. Results also were compared with gonadal function by regression analysis. IGF-I and mean overnight GH levels, determined from frequent sampling (q20 min from 2000-0800 h), were compared with results obtained from age- and sex-matched normal controls. Subjects were 26-58 yr of age (39 +/- 7 yr, mean +/- SD) with a CD4 cell count of 150 +/- 186 cells/mm3. Serum levels of FSH were elevated in 30% of the subjects. Muscle mass was significantly reduced, compared with expected mass for height (23.3 +/- 5.5 vs. 29.3 +/- 1.7 kg, P = 0.0001) and was decreased disproportionately to weight (77% of expected value for muscle mass vs. 93% of expected value for weight). Free-testosterone levels were correlated with total body potassium (R = 0.45, P < 0.05) and muscle mass (R = 0.45, P < 0.05). Total-testosterone levels were correlated with exercise functional capacity (R = 0.64, P = 0.01 for the sit-to-stand test and R = 0.53, P < 0.05 for the 6-min walk test). Mean GH levels were significantly increased (3.03 +/- 1.76 vs. 0.90 +/- 0.37 ng/mL, P < 0.001) and IGF-I levels decreased (167 +/- 66 vs. 225 +/- 69 ng/mL, P < 0.01), compared with age- and sex-matched eugonadal controls. GH levels were inversely correlated with caloric intake (R = -0.60, P = 0.02) and percent fat mass by dual-energy x-ray absorptiometry (R = 0.58, P = 0.02). Six additional hypogonadal subjects receiving Megace for AIDS wasting were analyzed separately. Nutritional status and parameters of body composition were compared in the Megace and non-Megace-treated subjects. No significant differences in caloric intake, lean body mass, fat mass, or muscle mass were demonstrated. These data demonstrate that changes in body composition, including loss of lean body and muscle mass, and deterioration in exercise functional capacity are highly correlated with androgen levels in hypogonadal men with the AWS. Furthermore, our data demonstrate significantly increased GH levels and decreased IGF-I in association with low weight in this population. These data suggest that androgen deficiency combined with classical GH resistance may contribute to the critical loss of lean body and muscle mass in hypogonadal men with the AWS. These data are the first to link muscle and lean body wasting with progressive gonadal dysfunction among the large percentage of men with AIDS wasting who are hypogonadal. This demonstrates the need for additional studies to determine the efficacy of gonadal steroid replacement to increase lean body mass in this population.

Adult↗
PubMed1995

Serum insulin-like growth factor-binding protein-3 levels in the diagnosis of acromegaly.

Insulin-like growth factor-binding protein-3 (IGFBP-3) is a GH-dependent protein that binds insulin-like growth factor-I (IGF-I) in the circulation and modulates its action at the tissue level. Because IGFBP-3 is a stable and specific marker of somatotroph function, we hypothesized that it would be a useful biochemical marker in the diagnosis of patients with acromegaly and the assessment of surgical cure. We, therefore, investigated the sensitivity of serum IGFBP-3 levels to detect GH excess in 44 patients with clinical acromegaly and pathologically confirmed somatotroph adenomas, including a cohort of 18 patients with untreated disease evaluated before transsphenoidal surgery and medical therapy. IGFBP-3 levels were compared to IGF-I and random GH levels before and after transsphenoidal surgery. Concordance among IGFBP-3, IGF-I, and GH suppressibility by glucose was also determined. In addition, the response of IGFBP-3 to glucose suppression was investigated. All 18 patients with untreated acromegaly had elevated serum IGFBP-3 levels, ranging from 4,186-10,026 micrograms/L (mean +/- SD, 6566 [plusm] 1800 micrograms/L). There was no overlap with the age-adjusted normative ranges (P = 0.0001 in patients 18-55 yr old and P = 0.0176 in patients > 55 yr old) or with the levels obtained in age-comparable controls (P = 0.0001). In 11% of untreated patients with clinical findings of acromegaly and a pathologically confirmed adenoma, IG-FBP-3 levels were elevated, although GH was suppressed to less than 2 micrograms/L with glucose. In these patients, IGF-I levels were either normal or minimally elevated and considered nondiagnostic. IGFBP-3 and IGF-I levels were correlated in patients with untreated acromegaly (r = 0.650; P = 0.0162) and after transsphenoidal surgery (r = 0.644; P = 0.0001). Neither IGF-I nor IGFBP-3 correlated with random GH levels before surgery. However, both IGF-I (r = 0.471; P = 0.0001) and IGFBP-3 (r = 0.259; P = 0.041) correlated with random GH levels in patients studied more than 1 month after transsphenoidal surgery. IGFBP-3 and IGF-I levels were concordant with GH suppressibility by glucose (P = 0.0039) and IGFBP-3 decreased with glucose suppression in 7 of 10 patients. These data indicate that IGFBP-3 is a sensitive physiological marker of somatotroph function and is concordant with glucose suppression and IGF-I levels before and after transsphenoidal surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗