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Adrenal Mass

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3401. Endocrinological and auxological abnormalities in young children with optic nerve hypoplasia: a prospective study. (Abstract)

months of age.The prevalence of endocrinopathies was 71.7%: 64.1% of subjects had growth hormone (GH) axis abnormalities, 48.5% hyperprolactinemia, 34.9% hypothyroidism, 17.1% adrenal insufficiency, and 4.3% diabetes insipidus (DI). Endocrinopathies were not associated with ONH laterality, absence of the septum pellucidum, or pituitary abnormalities on neuroimaging. End height standard deviation score (SDS) was similar to start length SDS independent of GH surrogate status. A significant increase (...) in end weight SDS was found for the cohort (p < .001). A body mass index (BMI) >85th percentile was noted in 44.4% of the cohort and in 52.1% of subjects with GH axis abnormalities. Initial hyperprolactinemia was positively associated with increased end BMI SDS (p = .004).These prospective findings confirm the high prevalence of pituitary endocrinopathies in children with ONH reported in previous retrospective studies. Our data reveal that some of these children maintain normal height velocity

2006 Journal of Pediatrics

3402. Endocrine abnormalities and impaired growth in human immunodeficiency virus-infected children. (Abstract)

, IGFBP-3 values and DHEA:cortisol ratios were associated with weight- and body mass index-for-age z scores ([WAZ] P = 0.019, <.001 respectively, and [BMZ] P = 0.029, 0.038). DHEA concentration was associated with height-for-age z score (P = 0.049).In these HIV-infected children compared with their uninfected counterparts, IGFBP-3 concentration was different between groups. Infected children had multiple endocrine associations with growth and body composition not found in their uninfected peers. We (...) hypothesize that in HIV-infected children, growth hormone resistance and shunting of precursors from adrenal androgen to cortisol production contributes to altered body composition and stunting.

2007 Pediatric Infectious Dsease Journal

3403. Low levels of dehydroepiandrosterone sulphate in plasma, and reduced sympathoadrenal response to hypoglycaemia in premenopausal women with rheumatoid arthritis. Full Text available with Trip Pro

Low levels of dehydroepiandrosterone sulphate in plasma, and reduced sympathoadrenal response to hypoglycaemia in premenopausal women with rheumatoid arthritis. To evaluate the function of the hypothalamic-pituitary-adrenal axis and sympathoadrenal system in premenopausal women with rheumatoid arthritis (RA).Insulin-induced hypoglycaemia (0.1 IU/kg) was produced in 15 glucocorticoid-naive patients with long term RA with low disease activity and in 14 healthy women matched for age and body mass (...) levels, without concomitant differences or changes in DHEA, ASD, 17OHP, and cortisol responses to hypoglycaemia in patients with RA, indicate an isolated decrease in adrenal androgen production. Significantly lower responses of EPI and NE to hypoglycaemia may suggest sympathoadrenal hyporeactivity in patients with RA.

2005 Annals of the Rheumatic Diseases

3404. Erlotinib response of EGFR-mutant gefitinib-resistant non-small-cell lung cancer. (Abstract)

craniotomy to remove his brain metastasis. Tumor progressed in both lung and left adrenal gland. He underwent second-line docetaxel chemotherapy. Tumor progressed again 7 months later. He was subsequently treated with gefitinib 250mg QD. Complete regression of the lung tumor and partial response of the left adrenal gland mass was achieved. Nine months later, the left lower lobe lung tumor and left adrenal gland tumor progressed. A lung biopsy from the left lower lobe disclosed an adenocarcinoma which (...) harbored an in-frame deletion in exon 19 (heterozygous delE746-A750) of EGFR without a second mutation such as T790M in exon 20. Subsequent erlotinib 150mg QD was administered. He experienced grade 1 skin rash, diarrhea and paronychia following erlotinib.This patient achieved a partial response to erlotinib treatment. He remained on erlotinib for a total of 18 months until the left adrenal gland tumor progressed.This case demonstrated that NSCLC bearing in-frame deletion in exon 19 of EGFR may respond

2007 Lung Cancer

3405. Lower adrenocortical and adrenomedullary responses to hypoglycemia in premenopausal women with systemic sclerosis. (Abstract)

Lower adrenocortical and adrenomedullary responses to hypoglycemia in premenopausal women with systemic sclerosis. To evaluate function of the hypothalamic-pituitary-adrenal (HPA) axis, adrenomedullary hormonal system (AMHS), and sympathetic noradrenergic system (SNS) in premenopausal women with systemic sclerosis (SSc).Insulin-induced hypoglycemia (0.1 IU/kg) was performed in 17 longterm, glucocorticoid-naive SSc patients with low disease activity and in 18 healthy women matched for age (...) and body mass index (BMI). Concentrations of glucose, adrenocorticotrophic hormone (ACTH), cortisol, androstenedione (ASD), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17a-hydroxyprogesterone (17OHP), epinephrine (EPI), norepinephrine (NE), interleukin 1ss (IL-1ss), IL-6, and tumor necrosis factor-a (TNF-a) were analyzed in plasma.Basal plasma levels of cortisol, ASD, 17OHP, DHEAS, IL-1ss, IL-6, and TNF-a were not significantly different in SSc compared to controls. Patients

2006 Journal of Rheumatology

3406. 17alpha-estradiol: a brain-active estrogen? Full Text available with Trip Pro

stroke and oxidative stress, and in transgenic mice with Alzheimer's disease; and influences spatial memory and hippocampal-dependent synaptic plasticity. The present study measured the endogenous content of 17alpha-estradiol in the brain and further clarified its actions and kinetics. Here we report that: 1) endogenous levels of 17alpha-estradiol and its precursor estrone are significantly elevated in the postnatal and adult mouse brain and adrenal gland of both sexes, as determined by liquid (...) chromatography/tandem mass spectrometry; 2) 17alpha-estradiol and 17beta-estradiol bind estrogen receptors with similar binding affinities; 3) 17alpha-estradiol transactivates an estrogen-responsive reporter gene; and 4) unlike 17beta-estradiol, 17alpha-estradiol does not bind alpha-fetoprotein or SHBG, the estrogen-binding plasma proteins of the developing rodent and primate, respectively. 17alpha-Estradiol was also found in the brains of gonadectomized or gonadectomized/adrenalectomized mice, supporting

2005 Endocrinology

3407. Endothelium-derived steroidogenic factor enhances angiotensin II-stimulated aldosterone release by bovine zona glomerulosa cells. Full Text available with Trip Pro

Endothelium-derived steroidogenic factor enhances angiotensin II-stimulated aldosterone release by bovine zona glomerulosa cells. Endothelium-derived steroidogenic factor (EDSF) is an endothelial peptide that stimulates aldosterone release from bovine adrenal zona glomerulosa (ZG) cells. The regulation of aldosterone release by combinations of EDSF and angiotensin II (AII) or EDSF and ACTH was investigated. Endothelial cells (ECs) and EC-conditioned media (ECCM) increased aldosterone release (...) from ZG cells, an activity attributed to EDSF. AII (10(-12) to 10(-8) M) and ACTH (10(-12) to 10(-9) M) also stimulated the release of aldosterone from ZG cells. The stimulation by AII, but not ACTH, was greatly enhanced when ZG cells were coincubated with ECs. AII was metabolized by ECs to peptides identified by mass spectrometry as angiotensin (1-7) and angiotensin IV. There was very little metabolism of AII by ZG cells. Neither of these two AII metabolites altered aldosterone release from ZG

2007 Endocrinology

3408. Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Full Text available with Trip Pro

1.69 (1.23-2.33), androstenedione 1.94 (1.40-2.69), testosterone 1.85 (1.33-2.57) and free testosterone 2.50 (1.76-3.55). For the oestrogens, relative risk estimates were: oestrone 2.07 (1.42-3.02), oestradiol 2.28 (1.61-3.23) and free oestradiol (odds ratios 2.13 (1.52-2.98)). Adjustments for body mass index or other potential confounding factors did not substantially alter any of these relative risk estimates. Our results have shown that, among postmenopausal women, not only elevated serum (...) oestrogens but also serum androgens are associated with increased breast cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.

2005 Endocrine-Related Cancer

3409. Expression of human hormone-sensitive lipase (HSL) in postmeiotic germ cells confers normal fertility to HSL-deficient mice. Full Text available with Trip Pro

Expression of human hormone-sensitive lipase (HSL) in postmeiotic germ cells confers normal fertility to HSL-deficient mice. Hormone-sensitive lipase (HSL, Lipe, E.C.3.1.1.3) is a multifunctional fatty acyl esterase that is essential for male fertility and spermatogenesis and that also plays important roles in the function of adipocytes, pancreatic beta-cells, and adrenal cortical cells. Gene-targeted HSL-deficient (HSL-/-) male mice are infertile, have a 2-fold reduction in testicular mass (...) the testicular transgene, activity was 2-fold greater than normal. HSL transgene mRNA became detectable in testes between 19 and 25 days of age, coinciding with the first wave of postmeiotic transcription in round spermatids. In contrast to nontransgenic HSL-/- mice, HSL-/- males expressing the testicular transgene were normal with respect to fertility, testicular mass, testicular esterified/free cholesterol ratio, and testicular histology. Their cauda epididymides contained abundant, normal-appearing

2004 Endocrinology

3410. Reversible changes in adrenocorticotropin (ACTH)-induced adrenocortical steroidogenesis and expression of the peripheral-type benzodiazepine receptor during the ACTH-insensitive period in young rats. Full Text available with Trip Pro

. Another group of pups received ACTH from pd 2-7, followed by saline from pd 8-14. On the final day, all pups were challenged with a test injection of ACTH or saline. Exposure to ACTH, but not saline, for 1 wk significantly increased adrenal mass, the corticosterone response to ACTH, and the expression of PBR protein and mRNA. Continued ACTH treatment for a second week maintained adrenal mass, steroidogenesis, and PBR mRNA expression. When ACTH was withdrawn after 1 wk and replaced with daily saline (...) injections, however, adrenal mass, ACTH-inducible steroidogenesis, and PBR expression returned to levels comparable to those in age-matched saline controls (i.e. animals that had not received ACTH injections during the first 2 wk). Thus, although ACTH was capable of inducing increased steroidogenic capacity of the juvenile rat adrenal, its effects were only manifest when pups were exposed regularly to high plasma ACTH levels. ACTH, therefore, has significant, but reversible, effects on the development

2004 Endocrinology

3411. Identification of the adrenocorticotropin and ginkgolide B-regulated 90-kilodalton protein (p90) in adrenocortical cells as a serotransferrin precursor protein homolog (adrenotransferrin). Full Text available with Trip Pro

of Ginkgo biloba (EGb 761) and its purified component ginkgolide B (GKB). We have now identified p90. GKB (2 mg/kg x d, i.p.) was administered to rats for 8 d. Adrenocortical cells were prepared and stimulated with ACTH for 3 h. Cells obtained from saline-treated rats responded to ACTH by producing high amounts of corticosterone, an effect that was inhibited in cells obtained from GKB-treated animals. Samples were fractionated by 2D-PAGE and matrix-assisted laser desorption ionization mass spectrometry (...) analysis of the p90 spots isolated from the gels revealed sequences sharing identity with the serotransferrin precursor protein. Further PCR screening of a rat adrenal cDNA library identified a sequence with a high degree of homology (79%) to serotransferrin precursor protein, and a lesser degree to rat transferrin (54%) and human melanotransferrin (32.8%). p90, in 2D-PAGE immunoblots, was also recognized by a monoclonal antibody raised against human 97-kDa melanotransferrin. Iron binding assays

2004 Endocrinology

3412. Cyclic adenosine 5'-monophosphate-dependent sphingosine-1-phosphate biosynthesis induces human CYP17 gene transcription by activating cleavage of sterol regulatory element binding protein 1. Full Text available with Trip Pro

Cyclic adenosine 5'-monophosphate-dependent sphingosine-1-phosphate biosynthesis induces human CYP17 gene transcription by activating cleavage of sterol regulatory element binding protein 1. In the human adrenal cortex, ACTH activates steroid hormone biosynthesis by acutely increasing cholesterol delivery to the mitochondrion and chronically increasing the transcription of steroidogenic genes (including CYP17) via a cAMP-dependent pathway. In the present study, we characterized the role (...) of sphingolipids in ACTH-dependent steroidogenesis. H295R human adrenocortical cells were treated with ACTH or dibutyryl cAMP (Bt2cAMP) and the content of several sphingolipid species quantified by mass spectrometry. Both ACTH and Bt2cAMP decreased cellular amounts of several sphingolipids, including sphingomyelin, ceramides, and sphingosine and stimulating the activity of sphingosine kinase and increasing the release of sphingosine-1-phosphate (S1P) into the media. S1P increased CYP17 mRNA expression

2006 Endocrinology

3413. Effects of gonadectomy on glucocorticoid metabolism in obese Zucker rats. Full Text available with Trip Pro

alter weight gain, glucose intolerance, or hyperinsulinemia in obese animals. Gonadectomy increased adrenal mass (P < 0.05), suppressed 11betaHSD1 activity and/or mRNA in liver and adipose, increased 5alpha-reductase 1 mRNA in liver (P < 0.05), and increased 5beta-reductase activity only in obese animals (P < 0.05). Differences in hepatic 11betaHSD1 mRNA expression and adipose activity between lean and obese animals were normalized by gonadectomy, whereas obese gonadectomized animals maintained (...) Effects of gonadectomy on glucocorticoid metabolism in obese Zucker rats. Glucocorticoids are metabolized by 11beta-hydroxysteroid dehydrogenase 1 (11betaHSD1) and the A-ring reductases (5alpha- and 5beta-reductases). Dysregulation of these enzymes has been reported in liver and adipose tissue in obese humans and animals, potentially leading to altered intracellular glucocorticoid concentrations and compensatory activation of the hypothalamic-pituitary-adrenal axis. This dysregulation

2007 Endocrinology

3414. 17alpha-hydroxylase/17,20-lyase deficiency caused by a novel homozygous mutation (Y27Stop) in the cytochrome CYP17 gene. Full Text available with Trip Pro

17alpha-hydroxylase/17,20-lyase deficiency caused by a novel homozygous mutation (Y27Stop) in the cytochrome CYP17 gene. 17alpha-Hydroxylase/17,20-lyase deficiency, a rare autosomal recessive form of congenital adrenal hyperplasia, is caused by mutations in the cytochrome P450c17 (CYP17) gene. We report on a case of complete 17alpha-hydroxylase/17,20-lyase deficiency due to a novel homozygous mutation of CYP17.A 20-yr-old female Turkish patient (46,XX) presented with primary amenorrhea, sexual (...) infantilism, and easy fatigability.The patient's steroid metabolism showed increased levels of mineralocorticoid precursors and low or undetectable plasma concentrations of 17alpha-hydroxycorticoids, androgens, and estrogens before and after ACTH stimulation. The gas chromatography-mass spectrometry urinary steroid profile was dominated by metabolites of corticosterone and its precursors, while cortisol and C(19)-steroid metabolites were lacking. ACTH, FSH, and LH levels were elevated. These hormonal

2005 Journal of Clinical Endocrinology and Metabolism

3415. [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings. Full Text available with Trip Pro

scrutinizing images. The hypothesis that MTO-PET is of value in the management of adrenal tumors, especially incidentaloma, was stated before data collection.Sensitivity was 0.89 and specificity was 0.96 for MTO-PET in proving adrenocortical origin of the lesions. Pheochromocytomas, metastases to the adrenal gland, and nonadrenal masses were all MTO negative. PET measurements using standardized uptake values (SUV) in pathological adrenocortical tissue could differentiate lesions larger than 1-1.5 cm from (...) [11C]metomidate positron emission tomography of adrenocortical tumors in correlation with histopathological findings. Adrenal incidentalomas are common findings necessitating extensive laboratory work-up and repetitive radiological examinations. Positron emission tomography (PET) using (11)C-labeled metomidate (MTO) has previously been described as a tool for specific adrenocortical imaging.We evaluated 212 MTO-PET examinations in 173 patients to identify its role in the management of adrenal

2006 Journal of Clinical Endocrinology and Metabolism

3416. Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. Full Text available with Trip Pro

Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea. Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition (...) not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls.Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed.Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving

2007 Journal of Clinical Endocrinology and Metabolism

3417. Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications. Full Text available with Trip Pro

patients. The objective of this study was to rigorously compare plasma IL-6 levels, measured over 24 h, in MDD patients and healthy controls. Given the activating role of IL-6 on the hypothalamic-pituitary-adrenal (HPA) axis, and the relevance of its dysregulation in MDD, we also analyzed the relations between IL-6 and cortisol levels.We studied nine patients and nine controls, individually matched by gender, age (+/-5 yr), body mass index (+/-2 kg/m2), and menstrual cycle phase. Diagnosis of MDD

2005 Journal of Clinical Endocrinology and Metabolism

3418. Serum profiles of free and conjugated neuroactive pregnanolone isomers in nonpregnant women of fertile age. Full Text available with Trip Pro

neuroactive pregnanolone isomers and their polar conjugates in women, serum allopregnanolone (P3alpha5alpha), isopregnanolone (P3beta5alpha), pregnanolone (P3alpha5beta), epipregnanolone (P3beta5beta), pregnenolone, estradiol (including their polar conjugates), and additional steroids were measured in 16 women in the follicular and luteal phases of the menstrual cycle using gas chromatography/mass spectrometry and RIA for the analysis. Linear models and Spearman's correlations were used for data (...) changing progesterone formation during the menstrual cycle. In the follicular phase, the positive correlation with conjugated pregnenolone, the independence of progesterone, and the negative age relationships of PI indicate their adrenal origin. The dependence on progesterone and the independence of conjugated pregnenolone suggest a gonadal source of PI in the luteal phase. The neuroactivating PI prevailed over neuroinhibiting PI.

2006 Journal of Clinical Endocrinology and Metabolism

3419. Relation of cardiovascular risk factors in women approaching menopause to menstrual cycle characteristics and reproductive hormones in the follicular and luteal phases. Full Text available with Trip Pro

risk factors and urinary LH, FSH, estrone conjugates, and pregnanediol glucuronide (Pdg) measured across one menstrual cycle or 50 d.Menstruating women (n = 500) who were free from diabetes or past stroke or heart attack enrolled in the Daily Hormone Study-Study of Women's Health across the Nation were studied.Body mass index (BMI), blood pressure, hemostatic, and metabolic factors were measured.Few differences existed in risk factors between women with evidence of luteal activity and those (...) to CVD risk factors, in large part through their common association with BMI. More favorable levels of metabolic and hemostatic factors were associated with higher levels of follicular-phase estrogen, a pattern consistent with a more competent ovary, and higher levels of follicular-phase PdG, perhaps of adrenal origin. Metabolic and hemostatic factors may be sensitive to hormonal variation during the early perimenopausal transition.

2006 Journal of Clinical Endocrinology and Metabolism

3420. Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. Full Text available with Trip Pro

Bone demineralization and vertebral fractures in endogenous cortisol excess: role of disease etiology and gonadal status. The effects of endogenous cortisol (F) excess on bone mass and vertebral fractures have still not been thoroughly investigated. The aim of this cross-sectional case-control study was to investigate factors influencing bone demineralization and vertebral fractures in different conditions of F excess, i.e. Cushing's disease and adrenal and ectopic Cushing's syndrome.Eighty (...) consecutive patients and 80 controls were prospectively enrolled: 37 patients (21 females) with pituitary ACTH-secreting adenoma, 18 (14 females) with adrenocortical adenoma, 15 (11 females) with adrenal carcinoma of mixed secretion, and 10 (three females) with ectopic ACTH secretion. The groups had similar age. At diagnosis, bone mineral density (BMD) was determined by the dual-energy x-ray absorptiometry technique at the lumbar spine (L1-L4) and femoral neck; vertebral fractures were investigated

2006 Journal of Clinical Endocrinology and Metabolism

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