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A Klibanski

Publications and source records attributed to A Klibanski.

At least 19 recordsLinked to original sources
PubMed2001

Hypothalamic/pituitary function following high-dose conformal radiotherapy to the base of skull: demonstration of a dose-effect relationship using dose-volume histogram analysis.

PURPOSE: To evaluate the incidence and pattern of hypopituitarism from hypothalamic (HT) and pituitary gland (PG) damage following high-dose conformal fractionated proton-photon beam radiotherapy (PPRT) to the base of skull (BOS) region in adults. The relationship between dose, volume, and PG function is explored. METHODS AND MATERIALS: Between May 1982 to October 1997, 107 adults with non-PG and non-HT neoplasms (predominantly chordoma and chondrosarcomas) of the BOS were treated with PPRT after subtotal resection(s). The median age was 41.2 years (range, 17-75) with 58 males and 49 females. Median prescribed target dose was 68.4 cobalt gray equivalent (CGE) (range, 55.8-79 CGE) at 1.80-1.92 CGE per fraction per day (where CGE = proton Gy x 1.1). The HT and PG were outlined on planning CT scans to allow dose-volume histograms (DVH) analysis. All patients had baseline and follow-up clinical testing of anterior and posterior pituitary function including biochemical assessment of thyroid, adrenal, and gonadal function, and prolactin secretion. RESULTS: The 10-year actuarial overall survival rate was 87%, with median endocrine follow-up time of 5.5 years, thus the majority of patients were available for long-term follow-up. Five-year actuarial rates of endocrinopathy were as follows: 72% for hyperprolactinemia, 30% for hypothyroidism, 29% for hypogonadism, and 19% for hypoadrenalism. The respective 10-year endocrinopathy rates were 84%, 63%, 36%, and 28%. No patient developed diabetes insipidus (vasopressin deficiency). Growth hormone deficiency was not routinely followed in this study. Minimum target dose (Dmin) to the PG was found to be predictive of endocrinopathy: patients receiving 50 CGE or greater at Dmin to the PG experiencing a higher incidence and severity (defined as the number of endocrinopathies occurring per patient) of endocrine dysfunction. Dmax of 70 CGE or greater to the PG and Dmax of 50 CGE or greater to the HT were also predictive of higher rates of endocrine dysfunction. CONCLUSION: Radiation-induced damage to the HT & PG occurs frequently after high-dose PPRT to the BOS and is manifested by anterior pituitary gland dysfunction. Hyperprolactinemia was detected in the majority of patients. Posterior pituitary dysfunction, represented by vasopressin activity with diabetes insipidus, was not observed in this dose range. Limiting the dose to the HT and PG when feasible should reduce the risk of developing clinical hypopituitarism.

Adolescent↗
PubMed2001

Hypogonadism in patients with acromegaly: data from the multi-centre acromegaly registry pilot study.

OBJECTIVE: Because acromegaly is an uncommon disorder, epidemiological data regarding the demographics of the disease such as the prevalence of hypogonadism have been limited. In order to derive clinical and epidemiological information, including underlying hormonal factors, regarding hypogonadism in patients with acromegaly, we performed a pilot study designed to develop a multi-centre acromegaly patient registry. DESIGN AND MEASUREMENTS: Medical records of patients with acromegaly seen between 1976 and 1996 at three Institutions were reviewed, and data were entered into a database using a secure internet website. Hypogonadism was defined as amenorrhoea in women and testosterone deficiency in men. Subanalysis was performed in patients with microadenomas and women less than 50 years of age, to include women of reproductive age. RESULTS: Information was available on 363 patients, of whom 54% were women. The mean age at diagnosis was 41 +/- 13 years. In subjects less than 50 years of age, hypogonadism was present in 59%. Hyperprolactinaemia was present in 45% and 21% of hypogonadal and eugonadal patients of reproductive age, respectively (P = 0.0003). GH levels were higher in patients with hypogonadism (P = 0.03). In patients < 50 years of age with microadenomas, hypogonadism was present in nine of the 22 (41%) patients, including 55% of the women and 27% of the men (P = ns). Hyperprolactinaemia was present in three of the 10 and four of the 14 of microadenoma patients with hypogonadism and eugonadism, respectively. CONCLUSION: We developed a web-based acromegaly patient registry and used it to show that hypogonadism is a frequent consequence of acromegaly, even in patients with microadenomas, who are not at risk from hypopituitarism due to local mass effects. We also demonstrated that prolactin and GH hypersecretion contribute to the pathogenesis of hypogonadism in acromegaly, and that hypogonadism may occur in microadenoma patients even in the absence of hyperprolactinaemia.

Acromegaly↗
PubMed2001

Changes in regional fat redistribution and the effects of estrogen during spontaneous weight gain in women with anorexia nervosa.

BACKGROUND: Anorexia nervosa is a disease of severe acquired undernutrition with a high and increasing prevalence among young women in the United States. OBJECTIVE: The objective was to investigate the effects of spontaneous outpatient weight recovery and estrogen administration on fat distribution in patients with anorexia nervosa. DESIGN: Twenty-seven amenorrheic women aged 26.6 +/- 1.2 y with anorexia nervosa were identified through an outpatient study of bone loss and were randomly assigned to receive or not receive estrogen without any dietary intervention other than calcium and multivitamin supplements. Body composition was measured at baseline and at 6 and 9 mo and was compared with cross-sectional values obtained in 20 healthy, eumenorrheic, age-matched (25.4 +/- 0.5 y) control subjects. RESULTS: Twenty of the 27 patients with anorexia aged 27.0 +/- 1.3 y spontaneously gained weight (4.1 +/- 0.9 kg); body mass index (in kg/m(2)) increased from 16.1 +/- 0.3 to 17.5 +/- 0.4. Fat mass and lean mass accounted for 68% and 32% of the gain in total body mass, respectively. With spontaneous weight gain, there was a significant increase in the percentage of trunk fat from 32.4 +/- 1.3% at baseline to 36.5 +/- 1.0% at 9 mo (P = 0.03), which correlated with urinary free cortisol (r = 0.66, P = 0.003). Estrogen treatment was not protective against the gain in trunk fat with spontaneous weight gain. CONCLUSIONS: In women with anorexia nervosa, spontaneous weight gain is associated with a significant increase in trunk adiposity, and estrogen administration may not protect against the accumulation of central fat with weight gain.

Adipose Tissue↗
PubMed2001

Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting.

Loss of lean body and muscle mass characterizes the acquired immunodeficiency syndrome (AIDS) wasting syndrome (AWS). Testosterone and exercise increase muscle mass in men with AWS, with unclear effects on muscle composition. We examined muscle composition in 54 eugonadal men with AWS who were randomized to 1) testosterone (200 mg im weekly) or placebo and simultaneously to 2) resistance training or no training in a 2 x 2 factorial design. At baseline and after 12 wk, we performed assessments of whole body composition by dual-energy X-ray absorptiometry and single-slice computed tomography for midthigh cross-sectional area and muscle composition. Leaner muscle has greater attenuation. Baseline muscle attenuation correlated inversely with whole body fat mass (r = -0.52, P = 0.0001). This relationship persisted in a model including age, body mass index, testosterone level, viral load, lean body mass, and thigh muscle cross-sectional area (P = 0.02). Testosterone (P = 0.03) and training (P = 0.03) increased muscle attenuation. These data demonstrate that thigh muscle attenuation by computed tomography varies inversely with whole body fat and increases with testosterone and training. Anabolic therapy in these patients increases muscle leanness.

Adult↗
PubMed2001

Androgen deficiency in women with hypopituitarism.

Androgen deficiency in men is associated with severe osteopenia, alterations in body composition including an increase in fat mass, and decreased libido. Little is known about the pathophysiology, metabolic consequences, or gender-specific effects of androgen deficiency in women. Acquired hypopituitarism in women is characterized by central hypogonadism and/or hypoadrenalism and therefore may affect critical sources of androgen production in women. We hypothesized that serum androgen levels would be decreased in women with hypopituitarism. We therefore determined serum androgen levels in 55 women with hypopituitarism and 92 controls. This included 4 subsets of hypopituitary women: 1) women less than 50 yr old not receiving estrogen, 2) women less than 50 yr old receiving estrogen, 3) women more than 50 yr old not receiving estrogen, and 4) women more than 50 yr old receiving estrogen. Premenopausal controls with regular menstrual cycles were studied in the early follicular phase, midcycle, and luteal phase during one cycle. All other subjects were studied 3 times during the month at comparable intervals to mimic these 3 time points of the normal menstrual cycle. Serum testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulfate levels were markedly reduced in all 4 groups of women with hypopituitarism compared with controls (P < 0.0001). Moreover, serum testosterone, free testosterone, and androstenedione levels were lower in women with central hypoadrenalism and hypogonadism than in subjects with hypoadrenalism or hypogonadism alone (P < 0.025). Mean DHEAS levels were decreased in hypopituitary women with both hypogonadism and hypoadrenalism compared with those in women with hypogonadism alone (P < 0.0001). These data demonstrate hypoandrogenemia in women with hypopituitarism. The physiological consequences of low androgen levels in this population remain to be determined.

Adenoma↗
PubMed2001

Effects of growth hormone (GH) administration on homocyst(e)ine levels in men with GH deficiency: a randomized controlled trial.

GH deficiency is associated with increased cardiovascular mortality and early manifestations of atherosclerosis. Elevated serum homocyst(e)ine levels have been found to be associated with increased cardiovascular risk. The effect of GH replacement on homocyst(e)ine has not been investigated to date. We evaluated the effect of GH replacement on fasting homocyst(e)inemia in a group of men with adult-onset GH deficiency in a randomized, single blind, placebo-controlled trial. Forty men with adult-onset GH deficiency were randomized to GH or placebo for 18 months, with dose adjustments made according to serum insulin-like growth factor I (IGF-I) levels. Fasting serum homocyst(e)ine, folate, vitamin B12, and total T(3) levels were determined at baseline and 6 and 18 months. Anthropometry, IGF-I levels, insulin, and glucose were measured at 1, 3, 6, 12, and 18 months. Nutritional assessment, body composition, total T(4), thyroid hormone binding index, and free T(4) index were assessed every 6 months. Homocyst(e)ine decreased in the GH-treated group compared with that in the placebo group (net difference, -1.2 +/- 0.6 micromol/L; confidence interval, -2.4, -0.02 micromol/L; P = 0.047). Homocyst(e)ine at baseline was negatively correlated with plasma levels of folate (r = -0.41; P = 0.0087). Total T(3) increased in the GH-treated group vs. that in the placebo group (net difference, 0.17 +/- 0.046 ng/dL; confidence interval, 0.071, 0.26 nmol/L; P = 0.0012). Folate and vitamin B12 levels did not significantly change between groups. Changes in homocyst(e)ine were negatively correlated with changes in IGF-I. For each 1 nmol/L increase in IGF-I, homocyst(e)ine decreased by 0.04 +/- 0.02 micromol/L (P = 0.029). In contrast, changes in homocyst(e)ine did not correlate with changes in folate, vitamin B12, total T(3), C-reactive protein, interleukin-6, or insulin levels. This study shows that GH replacement decreases fasting homocyst(e)ine levels compared with placebo. This may be one of the mechanisms involved in the putative modulation of atherosclerosis and cardiovascular risk by GH replacement.

Adult↗
PubMed2001

Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome.

Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.

Bone Density↗
PubMed2001

Somatostatin receptor-specific analogs: effects on cell proliferation and growth hormone secretion in human somatotroph tumors.

Somatostatin (SST) acts through a family of seven transmembrane domain G protein-coupled receptors to inhibit hormone secretion and cell proliferation in a variety of neuroendocrine tissues. In normal and neoplastic human pituitary somatotroph cells, SST-specific receptor types (SSTR) 1, 2, 3, and 5 are prevalently expressed, and SST and its analogs have been shown to inhibit GH secretion. However, in somatotroph adenomas, little is known regarding: 1) effects of SST and its analogs on pituitary tumor proliferation; 2) the relationship between the effects of SST analogs on GH secretion and tumor cell proliferation; and 3) whether SSTR expression predicts the antiproliferative effects of SST analogs in human somatotroph tumors. We investigated the effects of SST-14, lanreotide, and SSTR 2 (BIM-23190) and SSTR 5 (BIM-23268) specific analogs in 18 somatotroph pituitary adenomas in primary culture. Our results showed that cell proliferation was significantly inhibited by SST-14, lanreotide, BIM-23190, and BIM-23268 in 4, 7, 3, and 4 tumors, respectively (range of proliferation suppression 5-60%; median, 16%). Tumors that were responsive to SSTR 2- and 5-specific analogs were also responsive to lanreotide. SST-14 inhibited GH secretion in 8 of 13 tumors; lanreotide, BIM-23190, and BIM-23268 inhibited GH secretion in six tumors each (range of GH secretion inhibition 23-43%; median 33%). SSTR 2 and 5 messenger RNA was expressed in all tumors investigated, whereas SSTR 1 and 3 messenger RNA was expressed in 11 and 12 tumors, respectively. We observed a dissociation between the in vitro effects of SST-14 or lanreotide on tumor cell proliferation and the effects on GH secretion in human somatotroph tumors. Although differences in receptor concentration and the presence of other SST receptor subtypes may play a role, the presence of SSTR 2 and/or 5 did not have a predictive value. These data suggest that inhibition of cell proliferation occurs independently of effects on GH secretory pathways. Further studies are needed to clarify the mechanism of SST induced antiproliferative effects.

Acromegaly↗
PubMed2000

Prevalence and predictive factors for regional osteopenia in women with anorexia nervosa.

BACKGROUND: Anorexia nervosa is highly prevalent among young women. OBJECTIVE: To determine prevalence and predictive factors for regional bone loss. DESIGN: Prospective cohort analysis. SETTING: University hospital. PATIENTS: 130 women with anorexia nervosa. MEASUREMENTS: Dual-energy x-ray absorptiometry. RESULTS: The prevalence of osteopenia (-1.0 SD >/= T-score > -2.5 SD) and osteoporosis (T-score </= -2.5 SD) was 50% and 13% for the anterior-posterior spine, 57% and 24% for the lateral spine, and 47% and 16% for the total hip, respectively. Bone mineral density (BMD) was reduced by at least 1.0 SD at one or more skeletal sites in 92% of patients and by at least 2.5 SD in 38% of patients. Weight was the most consistent predictor of BMD at all skeletal sites. Twenty-three percent of patients were current estrogen users, and 58% were previous estrogen users. Bone mineral density did not differ by history of estrogen use at any site. CONCLUSIONS: Bone mineral density is reduced at several skeletal sites in most women with anorexia nervosa. Weight, but not estrogen use, is a significant predictor of BMD in this population at all skeletal sites.

Absorptiometry, Photon↗
PubMed2000

Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy.

Previous studies have indicated that there is a significant prevalence (50%) of hypogonadism among men with acquired immunodeficiency syndrome (AIDS)-associated wasting, and for these patients testosterone administration has been shown to increase lean body mass and improve quality of life. However, the prevalence of hypogonadism is not known among men with weight loss related to human immunodeficiency virus (HIV) infection who are receiving highly active antiretroviral therapy (HAART). From 1997 through 1999, we investigated total and free testosterone levels in 90 men who were <90% of ideal body weight or had weight loss of >10% from preillness weight; 71% of these subjects were receiving HAART. Twenty-one percent of the subjects receiving HAART had low free testosterone levels. No correlation was seen between weight, CD4 cell count, medication status, and other clinical factors. These data suggest that hypogonadism remains relatively common in men with AIDS wasting, despite treatment with HAART. HIV-infected men with wasting syndrome should be screened for hypogonadism and receive physiological androgen replacement therapy if they are hypogonadal.

Adult↗
PubMed2000

Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial.

BACKGROUND: Substantial loss of muscle mass occurs among men with AIDS wasting. OBJECTIVE: To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting. DESIGN: Randomized, controlled trial. SETTING: University hospital. PATIENTS: 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%). INTERVENTION: In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks. MEASUREMENTS: Cross-sectional muscle area and other indices of muscle mass. RESULTS: Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052). CONCLUSIONS: In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting.

Arm↗
PubMed2000

Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial.

BACKGROUND: Growth hormone-deficient adults have increased cardiovascular mortality. Growth hormone replacement may affect cardiovascular risk. Inflammation plays an important role in atherosclerosis, and inflammatory markers are predictive of cardiovascular events. OBJECTIVE: To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors. DESIGN: Randomized, single-blind, placebo-controlled trial. PATIENTS: 40 men with adult-onset growth hormone deficiency. INTERVENTION: Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level. MEASUREMENTS: Anthropometric, hemoglobin A1c, and central fat values were assessed every 6 months. Levels of glucose, insulin, insulin-like growth factor I, and lipids were measured at 1, 3, 6, 12, and 18 months. C-reactive protein, serum amyloid polypeptide A, inteleukin-6, and lipoprotein(a) levels were determined at baseline and 6 and 18 months. RESULTS: C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients (differences between groups, -1.9 +/- 0.6 mg/L [P = 0.0027] and -1.3 +/- 0.5 ng/L [P = 0.013], respectively). Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance (difference between groups, -2.4 +/- 1.2 mg/L; P = 0.056). Serum cholesterol levels, low-density lipoprotein cholesterol levels, and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients (differences between groups, -0.86 +/- 0.17 mmol/L [-33.2 +/- 6.6 mg/dL] [P < 0.001], -0.63 +/- 0.20 mmol/L [-24.5 +/- 5.9 mg/dL] [P < 0.001], and -0.56 +/- 0.26 [P = 0.040], respectively), but the decrease was not maintained from month 6 to month 18. Lipoprotein(a) levels increased (difference between groups, 22.0 +/- 8.0 mg/L; P = 0.0096). Short-term increases occurred in glucose levels, insulin levels, and insulin-to-glucose ratios (differences between groups, 0.54 +/- 0.16 mmol/L [9.6 +/- 2.8 mg/dL] [P = 0.0018], 37.9 +/- 9.6 pmol/L [P < 0.001], and 6.0 +/- 1.8 [P = 0.0025], respectively), but only the increase in glucose level was maintained over the long term (difference between groups, 0.56 +/- 0.17 mmol/L [10.0 +/- 3.1 mg/dL]; P = 0.0026). Hemoglobin A1c values did not change. Truncal fat-to-total fat ratios decreased (difference between groups, -0.018 +/- 0.007; P = 0.0087). CONCLUSIONS: Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers, decreases central fat, and increases lipoprotein(a) and glucose levels without affecting lipid levels.

Adipose Tissue↗
PubMed2000

Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.

BACKGROUND: Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone. METHODS: We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. RESULTS: The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups. CONCLUSIONS: On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.

Acromegaly↗
PubMed2000

Assessment of macronutrient and micronutrient intake in women with anorexia nervosa.

OBJECTIVE: The purpose of this study is to evaluate the accuracy of diet history compared to observed food intake in the nutritional assessment of women with anorexia nervosa (AN) and healthy age-matched controls. METHOD: One-month diet history was compared to 1-day observed food intake in 30 women with AN and 28 control subjects. RESULTS: Reported intake by diet history was similar to observed intake for macronutrient composition and fat intake for patients with AN. Reported energy intake was higher than observed intake (1,602 +/- 200 kcal vs. 1,289 +/- 150 kcal, p <.05), but was in agreement with predicted energy expenditure by the Harris-Benedict equation (1,594 +/- 18 kcal, p =.97) in patients with AN. Micronutrient intake by diet history was highly correlated with observed intake in patients with AN. More than one half of the patients with AN failed to meet the recommended dietary allowance (RDA) for vitamin D, calcium, folate, vitamin B12, zinc, magnesium, and copper when assessed by diet history. In contrast to patients with AN, diet history did not correlate with observed intake of energy, macronutrients, or most micronutrients among the controls. DISCUSSION: Diet history is an accurate tool to assess fat intake and macronutrient composition in patients with AN and demonstrates significant micronutrient deficiencies in this population. The agreement between total energy intake and predicted energy expenditure supports the overall utility of the diet history in the nutritional assessment of patients with AN.

Adolescent↗
PubMed2000

Cardiovascular risk markers in hypothalamic amenorrhoea.

OBJECTIVE: To determine whether women with oestrogen deficiency due to hypothalamic amenorrhoea (HA) would demonstrate a lipid and lipoprotein pattern similar to that seen in menopause with higher total cholesterol (TC), LDL, triglyceride and Lp(a) and lower HDL levels than women with regular menstrual cycles. DESIGN: Cross-sectional. PATIENTS: Fifty subjects: 21 women with HA and 30 eumenorrhoeic controls (NL) matched for age, BMI and fat-free mass. MEASUREMENTS: Lipid and lipoprotein levels. RESULTS: There was a significant difference in Lp(a) levels in the HA group between women with >19% fat intake and those <19% fat intake (352+/-231 vs. 116+/-62 mg/l, P = 0.006). Percent fat intake was the most significant determinant of Lp(a) levels in HA, accounting for 51% of the variation in Lp(a) levels. Mean HDL levels were higher in the women with HA compared with the controls (1.3+/- 0.3 vs. 1.1+/-0.2 mmol/l, P = 0.002). There was no significant difference between the groups in TC [4.4+/-0.9 (HA) vs. 4.1+/-0.8 mmol/l (NL), P>0.05], LDL [2.8+/-0.6 (HA) vs. 2.7+/-0.7 mmol/l (NL), P>0.05], triglycerides [1.8+/-0.5 (HA) vs. 1.7+/-0.5 mmol/l (NL), P>0.05] or Lp(a) [234+/-199 (HA) vs. 247+/-222 (NL) mg/l, P>0.05] levels. CONCLUSION: Reduced Lp(a) levels were associated with low dietary fat in women with HA. Moreover, in contrast to menopausal oestrogen deficiency, young women with HA and oestrogen deficiency have increased levels of HDL and no increases in TC, LDL and triglycerides. These data suggest that the negative effects of oestrogen deficiency on cardiovascular risk factors may be modified in women with hypothalamic amenorrhoea.

Adult↗
PubMed2000

Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men.

Hypogonadism is prevalent among human immunodeficiency virus-infected men, in whom significantly reduced quality of life and mood disturbances have been reported. Previous studies have not investigated the relationship between depression score and gonadal function among such patients. We first compared depression scores in hypogonadal (n = 52) and eugonadal (n = 10) patients with acquired immunodeficiency syndrome (AIDS) wasting, matched for weight and disease status, and then investigated the effects of testosterone administration on depression score in a randomized, double-blind, placebo-controlled study among the group of hypogonadal men with AIDS wasting. The primary end point in all comparisons was the Beck Depression Inventory. Hypogonadal patients demonstrated significantly increased scores on the Beck inventory compared with eugonadal-, age-, weight-, and disease status-matched subjects (15.5+/-1.1 vs. 10.6+/-1.4 mean +/- SEM, P = 0.02). Among the combined hypogonadal and eugonadal subjects, a significant inverse correlation was seen between the Beck score and both free (r = 0.41, P<0.01) and total serum testosterone levels (r = -0.43, P<0.001). The relationship between the Beck score and testosterone levels remained highly significant, controlling for weight, viral load, CD4 count, and antidepressant use (P<0.01 for free testosterone, P<0.001 for total testosterone). Furthermore, when subjects were divided into two groups, based on a Beck score greater than 18 or less than or equal to 18, serum total and free testosterone levels were significantly lower in the subjects with a Beck score greater than 18, whereas there were no differences in weight, viral load, CD4 count, or Karnofsky status. End of study data were available in 39 patients who completed the randomized, placebo-controlled study. Beck score decreased significantly only in the subjects receiving testosterone (-5.8+/-1.3, P< 0.001), but not in subjects randomized to placebo (-2.7+/-1.3, P> 0.05). In a regression analysis, the change in Beck score was related significantly to change in weight (P<0.01). These data demonstrate increased depression score in association with hypogonadism in men with AIDS wasting, independent of weight, virologic status, and other disease factors. In such patients, administration of testosterone results in a significant improvement in depression inventory score. This effect may be a direct effect of testosterone or related to positive effects of testosterone on weight and/or other anthropometric indices. Additional studies are needed to assess the effects of testosterone on clinical depression indices in human immunodeficiency virus-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Fasting hyperinsulinemia in human immunodeficiency virus-infected men: relationship to body composition, gonadal function, and protease inhibitor use.

Fat redistribution in the setting of protease inhibitor use is increasingly common and is associated with insulin resistance in human immunodeficiency virus (HIV)-infected patients. However, little is known regarding the factors that may contribute to abnormal insulin regulation in this population. We assessed fasting insulin levels in HIV-infected men and determined the relationship among insulin, body composition, endogenous gonadal steroid concentrations, and antiviral therapy in this population. We also determined the effects of exogenous testosterone administration using the homeostatic model for insulin resistance (HOMA IR) in hypogonadal HIV-infected men with the acquired immunodeficiency syndrome wasting syndrome. Fifty HIV-infected men with acquired immunodeficiency syndrome wasting were compared with 20 age- and body mass index (BMI)-matched healthy control subjects. Insulin concentrations were significantly increased in HIV-infected patients compared to those in control patients (16.6+/-1.8 vs. 10.4+/-0.8 microU/mL; P<0.05) and were increased in nucleoside reverse transcriptase (NRTI)-treated patients who did not receive a protease inhibitor (PI; 21.7+/-4.3 vs. 10.4+/-0.8 microU/mL; P<0.05). Insulin concentrations and HOMA IR were inversely correlated with the serum free testosterone concentration (r = -0.36; P = 0.01 for insulin level; r = -0.30; P = 0.03 for HOMA), but not to body composition parameters, age, or BMI. In a multivariate regression analysis, free testosterone (P = 0.05), BMI (P<0.01), and lean body mass (P = 0.04) were significant. Lower lean body mass and higher BMI predicted increased insulin resistance. The HIV-infected patients demonstrated an increased trunk fat to total fat ratio (0.49+/-0.02 vs. 0.45+/-0.02; P<0.05) and an increased trunk fat to extremity fat ratio (1.27+/-0.09 vs. 0.95+/-0.06, P = 0.01), but a reduced extremity fat to total fat ratio (0.44+/-0.01 vs. 0.49 + 0.01; P = 0.02) and reduced overall total body fat (13.8+/-0.7 vs. 17.2+/-0.9 kg; P<0.01) compared to the control subjects. Increased truncal fat and reduced extremity fat were seen among NRTI-treated patients, but this pattern was most severe among patients receiving combined NRTI and PI therapy [trunk fat to extremity ratio, 1.47+/-0.15 vs. 0.95+/-0.06 (P<0.01); extremity fat to total fat ratio, 0.40+/-0.02 vs. 0.49+/-0.01 (P<0.05)]. Insulin responses to testosterone administration were investigated among 52 HIV-infected men with hypogonadism and wasting (weight <90% ideal body weight and/or weight loss >10%) randomized to either testosterone (300 mg, im, every 3 weeks) or placebo for 6 months. Testosterone administration reduced HOMA IR in the HIV-infected men (-0.6+/-0.7 vs. +1.41+/-0.8, testosterone vs. placebo, P = 0.05) in association with increased lean body mass (P = 0.02). These data demonstrate significant hyperinsulinemia in HIV-infected patients, which can occur in the absence of PI use. In NRTI-treated patients not receiving PI, a precursor phenotype is apparent, with increased truncal fat, reduced extremity fat, and increased insulin concentrations. This phenotype is exaggerated in patients receiving PI therapy, with further increased truncal fat and reduced extremity fat, although hyperinsulinemia per se is not worse. Endogenous gonadal steroid levels are inversely related to hyperinsulinemia in HIV-infected men, but reduced lean body mass and increased weight are the primary independent predictors of hyperinsulinemia. Indexes of insulin sensitivity improve in response to physiological androgen administration among hypogonadal HIV-infected patients, and this change is again related primarily to increased lean body mass in response to testosterone administration.

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