bluuebunny/crossref_metadata_2025 huggingface dataset:
Cabergoline treatment rapidly improves gonadal function in hyperprolactinemic males: a comparison with bromocriptine
Authors: De Rosa M , Colao A , Di Sarno A , Ferone D , Landi ML , Zarrilli S , Paesano L , Merola B , Lombardi G
Published: January 2005

This study evaluated the effects of chronic treatment with cabergoline (CAB), a new, potent and long-lasting ergoline-derived dopamine agonist, on seminal fluid parameters and sexual and gonadal function in hyperprolactinemic males in comparison with the effect of bromocriptine (BRC) treatment. Seventeen males with macroprolactinoma were treated with CAB at a dose of 0.5-1.5 mg/week (n = 7), or BRC at a dose of 5-15 mg/day (n = 10) for 6 months. Baseline prolactin (PRL) was 925.7 +/- 522.6 microg/l in the CAB-treated group and 1059.4 +/- 297.6 microg/l in the BRC-treated group. All the patients suffered from libido impairment, ten from reduced sexual potency, and six had infertility. In five patients provocative bilateral galactorrhea was found. Seminal fluid analysis, functional seminal tests and penis rigidity and tumescence, measured by nocturnal penile tumescence (NPT) using Rigiscan equipment, were assessed before and after 1, 3 and 6 months of CAB or BRC treatment. Hormone profiles were assessed before and after 15, 30, 60, 90 and 180 days of both treatments. Before treatment, all patients had a low sperm count with oligoasthenospermia, reduced motility and rapid progression with an abnormal morphology and decreased viability, and a low number of erections. After 1 month, serum PRL levels were significantly reduced in both groups of patients (20.6 +/- 6.6 microg/l during CAB and 256.3 +/- 115.1 microg/l during BRC treatment) and were normalized after 6 months in all patients (CAB: 7.9 +/- 2.2 microg/l; BRC: 16.7 +/- 1.8 microg/l). After 6 months, a significant increase of number, total motility, rapid progression and normal morphology was recorded in patients treated with both CAB and BRC. An increase in the number of erections during the first 3 months of both treatments was noted by NPT. However, the improvements in seminal fluid parameters and sexual function were more evident and rapid in patients treated with CAB. The number of erections was normalized after 6 months of treatment in all patients submitted to CAB treatment, and in all patients but one treated by BRC. In addition, a significant increase of serum testosterone (from 3.7 +/- 0.3 to 5.3 +/- 0.2 microg/l) and dihydrotestosterone (from 0.4 +/- 0.1 to 1.1 +/- 0.1 nmol/l) was recorded. At the beginning of treatment, mild side-effects were recorded in two patients after CAB and mild-to-moderate side-effects in five patients after BRC administration. The treatment with CAB normalized PRL levels, improving gonadal and sexual function and fertility in males with prolactinoma, earlier than did BRC treatment, providing good tolerability and excellent patient compliance to medical treatment.
Stimulation of erythropoietin secretion by continuous subcutaneous infusion of recombinant human GH in anemic patients with chronic renal failure
Authors: Sohmiya M , Ishikawa K , Kato Y
Published: January 2005

We have investigated the effect of human GH on erythropoietin (EPO) secretion in eight anemic patients with chronic renal failure (CRF) (three males and five females, aged from 46 to 83 years). Recombinant human GH was infused subcutaneously at a flow rate of 2 microg/kg body weight per 0.1 ml/h for 72 h using a portable infusion pump. Blood samples were obtained immediately before and 2, 4, 6, 12, 24, 36, 48, 60, 72, 84, 96, 108, 120 and 168 h after the start of GH infusion. Storage urine samples were obtained before and 24, 48 and 72 h after the start of the infusion. The mean (+/- S.E.M.) basal plasma GH levels increased from 1.9 +/- 0.3 to 18.8 +/- 0.7 microg/l during the GH infusion. Plasma IGF-I levels increased 12 h after the start of GH treatment and the mean peak values of 403.6 +/- 38.5 microg/l were obtained at 72 h. Plasma EPO levels increased 6 h after the start of GH infusion, and the peak values of 38.4 +/- 11.6 IU/l were obtained at 96 h (P < 0.05 vs basal values 24.5 +/- 7.2 IU/l). Reticulocyte counts increased from 28.7 +/- 5.2 x 10(3)/microl to 40.3 +/- 8.0 x 10(3)/l at 108 h, 43.6 +/- 9.2 x 10(3)/microl at 120 h and 41.7 +/- 7.7 x 10(3)/microl at 160 h (P < 0.05). Serum urea nitrogen decreased at 72 h (P < 0.05), whereas there was no significant change in urinary excretion of nitrogen. Hemoglobin levels were not significantly changed throughout the experimental period. These findings indicate that human GH has a stimulating effect on EPO secretion in anemic patients with CRF.
Elevated insulin-like growth factor (IGF) binding protein (IGFBP)-2 and IGFBP-4 expression of leukemic T-cells is affected by autocrine/paracrine IGF-II action but not by IGF type I receptor expression
Authors: Elmlinger MW , Sanatani MS , Bell M , Dannecker GE , Ranke MB
Published: January 2005

We recently found evidence indicating that the source of elevated serum insulin-like growth factor binding protein (IGFBP)-2 in leukemia was the leukemic T-cells. Here we report that locally produced IGF-II affects IGFBP-2 expression and growth of leukemic cells through the IGF type I receptor. We measured IGFBP-2, -4 and IGF type I receptor (IGF-I-R) mRNA by RT-PCR, cell growth and IGFBP-2 secretion (per 10(6) cells). IGF-I-R binding sites were assessed by 125I-IGF replacement studies. Inhibition using an IGF-II antibody showed that tumor cell-derived IGF-II accounts for a significant 25% (P < 0.001) increase in IGFBP-2 secretion and enhanced growth (P < 0.01) of leukemic T-cells after 7 days in culture. IGFBP-2 secretion, but not IGFBP-2 mRNA was specifically increased by IGFs, while no specific effect of insulin was detectable. The addition of 100 ng/ml IGF-II enhanced the IGFBP-2 secretion 2.8-fold, while the use of IGF-I only enhanced IGFBP-2 secretion 1.7-fold, although IGF-I enhanced IGF-II action. Through inhibition using JB1, a peptide inhibiting the IGF signal transduction by blocking the IGF-I-R, we demonstrated the involvement of the IGF-I-R in IGFBP-2 and -4 expression and leukemic cell growth. However, only slight differences in the IGF-I-R mRNA expression were seen for T- and B-cells compared with the differences found for the IGFBP-2 and -4 mRNA or IGFBP-2 secretion. Thus, although IGF-I-R mediates the autocrine/paracrine effects of the IGFs, IGF-I-R mRNA expression is most probably not involved in the differential IGFBP-2/IGFBP-4 expression in leukemic cells.
Effect of passive smoking on thyroid function in infants
Authors: Gasparoni A , Autelli M , Ravagni-Probizer MF , Bartoli A , Regazzi-Bonora M , Chirico G , Rondini G
Published: January 2005

OBJECTIVE: To evaluate the effect of passive smoking on thyroid function in infants. DESIGN AND METHODS: Cord serum tri-iodiothyronine (T3), free T3 (fT3), thyroxine (T4), free T4 (fT4), TSH, thyroxine binding globulin (TBG), thyroglobulin (TG) and cord plasma thiocyanate were measured at birth, and serum TG and thiocyanate after 1 year of life, in 18 infants born from parents who did not smoke (group A), in 18 infants with a father who smoked (group B) and in 18 infants with parents both being smokers (group C). RESULTS: No significant differences were observed in cord serum concentrations of T3, fT3, T4, fT4, TSH and TBG among the three groups. Median (range) TG concentrations (ng/ml) were 30.2 (5.0-102.0), 56.3 (20.5-208.0) and 76.0 (26.0-199.0) at birth (P=0.009 for groups A and B compared; P=0.0002 for groups A and C compared), and 14.9 (5.4-32.0), 19.5 (10.0-57.5) and 20.0 (14.0-40.7) at 1 year (P=0.017 for groups A and C compared), in the three groups respectively, and thiocyanate concentrations (mmol/l) were 3.3 (0.0-51.4), 12.9 (0.0-122.2) and 27.8 (3.3-184.5) at birth (P=0.015 for groups A and C compared), and 3.1 (0.0-32.7), 6.0 (0.0-47.3) and 20.3 (0.0-230.8) at 1 year (P=0.01 for groups A and C compared) in the three groups respectively. CONCLUSIONS: TG and thiocyanate concentrations at birth and at 1 year of age in infants of smoking parents are greater than in infants with non-smoking parents. These results indicate that the change in thyroid function as evaluated by serum TG concentrations observed at birth can persist at least for 1 year if the exposure to passive smoking from both parents is continued. Increased TG concentrations may be due to a direct effect of thiocyanate on the thyroid gland.
Serum levels of 3alpha-androstanediol glucuronide in hirsute and non hirsute women
Authors: Falsetti L , Rosina B , De Fusco D
Published: January 2005

This study has evaluated the behaviour of 3alpha-androstanediol glucuronide (3alpha-diol G) in 170 women of whom 85 had polycystic ovary syndrome (PCOS), 35 had idiopathic hirsutism (IH) and 50 had regular cycles (control group). Of the women with PCOS, 45 were hirsute (PCOS-H) and 40 were non hirsute (PCOS-NH). Women in the control group were not hirsute. Hirsutism was assessed by the same physician using the Ferriman-Gallway score. The body mass index (BMI) was estimated in all of the women. Plasma concentrations of 3alpha-diol G were elevated only in hirsute patients, both with PCOS and with IH. Even in PCOS-NH, concentrations of 3alpha-diol G were higher compared with controls (P < 0.001), but significantly lower (P < 0.001) than those of the PCOS-H and of the IH groups. The behaviour of 3alpha-diol G was not affected by BMI.
Second trimester levels of maternal serum total activin A and placental inhibin/activin alpha and betaA subunit messenger ribonucleic acids in Down syndrome pregnancy
Authors: Lambert-Messerlian GM , Luisi S , Florio P , Mazza V , Canick JA , Petraglia F
Published: January 2005

OBJECTIVES: Previous data have shown that inhibin A (alpha/betaA) is increased about twofold in maternal serum samples from Down syndrome pregnancy. Our objectives were to determine whether activin A (betaA/betaA) was similarly increased in maternal serum from pregnancies affected with fetal Down syndrome, and to investigate whether increased expression of each inhibin/activin subunit occurred in placental tissue from cases of fetal Down syndrome. DESIGN AND METHODS: Maternal serum total activin A levels were measured in 20 cases of fetal Down syndrome and 100 unaffected pregnancy samples. In addition, analysis of inhibin/activin alpha and betaA subunit mRNA levels was performed in placental tissue extracts from six cases of fetal Down syndrome and six tissues with a normal karyotype. RESULTS: The median total activin A level in the Down syndrome cases was 0.82 MoM (multiples of the median); values did not differ significantly (P = 0.36, Mann-Whitney U analysis) from those in unaffected pregnancies. The inhibin alpha subunit/GAPDH mRNA ratio, but not that of betaA subunit/GAPDH mRNA, was significantly greater (P < 0.01, ANOVA) in placental tissue from Down syndrome than in control placental tissue. CONCLUSIONS: Unlike inhibin A, activin A is not significantly increased in Down syndrome relative to unaffected pregnancy. Furthermore, increased amounts of maternal serum inhibin A in Down syndrome pregnancy probably result from increased placental expression of inhibin alpha, but not betaA, subunit.
Expression of adrenomedullin and adrenomedullin mRNA in ectopic ACTH-secreting tumors
Authors: Murakami O , Takahashi K , Satoh F , Totsune K , Sone M , Arihara Z , Andoh N , Mouri T
Published: January 2005

OBJECTIVE: To study the expression of adrenomedullin, a potent vasodilator peptide originally isolated from a pheochromocytoma, in ectopic ACTH-secreting tumors. METHODS: Tumor tissue concentrations of adrenomedullin, calcitonin gene-related peptide, neuropeptide Y, endothelin-1, corticotropin-releasing hormone and ACTH were measured in three ectopic ACTH-secreting tumors by RIA. The expression of adrenomedullin mRNA was examined by northern blot analysis of tissue from one of the tumors. RESULTS: Immunoreactive adrenomedullin was detected in tumor tissues of three ectopic ACTH-secreting tumors (0.60-18.5 pmol/g wet weight). Calcitonin gene-related peptide, neuropeptide Y, endothelin-1 and corticotropin-releasing hormone were also detected in the tumor tissues. The tumor tissue concentrations of immunoreactive adrenomedullin were comparable to those of these four peptides, but much lower than those of ACTH. Northern blot analysis showed the expression of adrenomedullin mRNA in one tumor from which sufficient tissue was available for such study. The plasma concentration of immunoreactive adrenomedullin was increased in one patient (41.3 pmol/l, control 13.5 +/- 3.6 pmol/l, mean +/- S.D., n = 12). CONCLUSIONS: These results suggest that adrenomedullin is produced by ectopic ACTH-secreting tumors, together with other neuropeptides, and raise the possibility that adrenomedullin is related to the pathophysiology of these tumors.
Role of nitric oxide synthase in release of endothelin from cultured human endometrial cells
Authors: Lin Z , Kubota T , Masuda M , Aso T
Published: January 2005

The aim of this study was to investigate the influence of the nitric oxide/nitric oxide synthase (NO/NOS) system on the release of endothelin-1 (ET-1) in human endometrial cells. Human endometrial stromal cells in secretory phase were incubated for 72 h in serum-free RPMI 1640 medium in the absence or presence of different concentrations of interleukin-1beta (IL-1beta) and NG-monomethyl-L-arginine (LNMMA), a specific competitive inhibitor of NOS. ET-1 released from the cultured cells into the medium was determined by specific RIA. In all the experiments at various times, IL-1beta significantly increased the release of ET-1. LNMMA significantly attenuated the release of ET-1 when the cells were cultured with both IL-1beta and LNMMA, but LNMMA alone had no effect on ET-1 release. These results suggest that the NO/NOS system in human endometrium is involved in the regulation of ET-1 release via IL-1beta secretion. It can also be inferred that NO and ET-1 control the functions of endometrium in close association with IL-1beta.
Effect of growth hormone treatment on insulin action in adipocytes from children with Prader-Willi syndrome
Authors: Kamel A , Norgren S , Lindgren AC , Luthman H , Arner P , Marcus C
Published: January 2005

OBJECTIVE: To study the effect of growth hormone (GH) treatment (2-4 months) on insulin action in adipocytes isolated from children with Prader-Willi syndrome (PWS), in whom GH deficiency appears to be a primary defect. We investigated the complex effects of GH on carbohydrate metabolism, as part of a current clinical trial of GH treatment in children with PWS. METHODS: Biopsies of subcutaneous abdominal adipose tissue were obtained from 12 children with PWS before and after 2-4 months of GH treatment. Lipogenesis was determined by the incorporation of radiolabelled glucose into lipids in isolated adipocytes, and glycerol release to the incubation medium was used as an index of lipolysis. GLUT4 RNA was measured by solution hybridization. RESULTS: With low glucose concentrations, at which glucose transport is rate-limiting, maximal insulin-induced lipogenesis was increased by 120% after GH treatment (P < 0.05), but the sensitivity to insulin (half-maximum effective hormone concentration) was unchanged. This was not accompanied by a significant change in the RNA expression of GLUT4. Neither responsiveness (maximum effect) nor sensitivity of insulin-induced inhibition of lipolysis was affected by GH treatment. CONCLUSIONS: GH treatment of children with PWS results in an upregulation of insulin-induced lipogenesis in isolated adipocytes, with no effect on insulin-induced inhibition of lipolysis. The data suggest that the site of the effect of GH on lipogenesis is distal to the insulin hormone-receptor interaction, but does not involve altered GLUT4 expression.
Primary ovarian failure caused by a solvent containing 2-bromopropane
Authors: Koh JM , Kim CH , Hong SK , Lee KU , Kim YT , Kim OJ , Kim GS
Published: January 2005

Sixteen Korean female laborers who had been exposed to a cleaning solvent composed mainly of 2-bromopropane developed primary ovarian failure. Histologic findings from these patients' ovaries were similar to those observed in ovarian failure caused by radiation or chemotherapy, i.e., reduced number and developmental arrest of primary follicles, interstitial fibrosis and hyalinization of blood vessels. We followed their clinical course for 2 years and found that two patients recovered normal ovarian function spontaneously: one became pregnant and delivered a normal full-term baby, and the other resumed regular menstrual periods with normal hormonal values. Our observations support the idea that the increasing prevalence of ovarian failure in recent years might be due to an increase in presently unidentified environmental toxic agents.
Alpha- but not beta-adrenergic receptors mediate the effect of angiotensin II in the medial preoptic area on gonadotropin and prolactin secretion
Authors: Dornelles RC , Franci CR
Published: January 2005

The aim of this work was to study the participation of alpha- and beta-adrenergic receptors on the effect of microinjection of angiotensin II (A II) into the medial preoptic area (MPOA) on the secretion of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin (PRL) in estrogen-primed ovariectomized (OVX) rats. Microinjection of A II into the MPOA increased plasma LH. This effect was reduced by previous microinjection of an alpha- (phentolamine), but not a beta- (propranolol) adrenergic blocker into the MPOA. Plasma PRL decreased after microinjection of A II into the MPOA, but this effect was unchanged by phentolamine or propranolol. There was no change in plasma FSH in any condition. These results indicate that A II in the MPOA stimulates LH secretion and inhibits PRL secretion in estrogen-primed OVX rats. The effect on secretion of LH, but not of PRL, is mediated by alpha-adrenergic receptors in the MPOA.
Age-dependent changes in body composition in postmenopausal Japanese women: relationship to growth hormone secretion as well as serum levels of insulin-like growth factor (IGF)-I and IGF-binding protein-3
Authors: Sugimoto T , Nakaoka D , Nasu M , Kanzawa M , Sugishita T , Chihara K
Published: January 2005

The present study was performed to investigate the age-dependent changes in body composition and the possible role of growth hormone (GH), insulin-like growth factor (IGF)-I and IGF-binding protein-3 (IGFBP-3) in these changes in postmenopausal Japanese women. A total of 161 Japanese women aged 45-88 years (mean 62) were enrolled in the cross-sectional study. Body composition (bone mineral content (BMC), lean body mass (LBM) and fat) was measured by dual-energy X-ray absorptiometry, and the percentage of BMC, LBM and fat was calculated by dividing each absolute value of body composition by total body mass. Urinary GH concentration divided by creatinine in nocturnal urine samples collected just after waking was used as an index of endogenous GH secretion. Serum levels of IGF-I and IGFBP-3 were measured by RIA. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 declined with age. BMC, %BMC and LBM also declined with age, while fat mass and %fat did not obviously change with age. Urinary GH levels as well as serum levels of IGF-I and IGFBP-3 correlated positively with BMC, even if age was taken into account. On the other hand, urinary GH correlated negatively with fat and %fat. In contrast, serum levels of IGF-I and IGFBP-3 correlated positively with fat and %fat. LBM did not correlate with either urinary GH or serum IGFBP-3 levels but exhibited a weakly positive correlation with serum IGF-I level. The present study suggests that the GH-IGF-I-IGFBP-3 axis positively regulates bone mass, and that GH and IGF-I-IGFBP-3 inversely regulate fat mass, i.e. GH negatively and IGF-I-IGFBP-3 positively regulates it.
Increased levels but preserved diurnal variation of serum leptin in GH-deficient patients: lack of impact of different modes of GH administration
Authors: Norrelund H , Gravholt CH , Englaro P , Blum WF , Rascher W , Chistiansen JS , Jorgensen JO
Published: January 2005

The regulation of leptin production in humans is poorly understood but appears to depend on total body fat, changes in energy intake and insulin levels. Since growth hormone (GH) is an important regulator of both lipid metabolism and insulin secretion and action, we tested whether GH status directly or indirectly regulates leptin secretion. Circadian serum leptin concentrations were measured in GH-deficient patients in two different protocols involving different modes of acute and prolonged GH exposure. In study I, eight GH-deficient patients all underwent three 4 week study periods in random order: (1) evening (2000 h) s.c. GH injections (2 IU); (2) morning (0800 h) s.c. GH injections (2 IU); (3) no GH administration. At the end of each period the patients were admitted to hospital for 24-h measurements of hormones and metabolites. For comparison, 10 age- and sex-matched healthy untreated subjects were hospitalised under identical conditions. In study II, six GH-deficient patients were hospitalised for 44 h on three occasions, separated by at least 4 weeks without GH treatment. On each occasion they received 2 IU GH, administered i.v. as (1) two boluses (at 2000 and 0200 h), (2) eight boluses (at 3 h intervals starting at 2000 h) or (3) a continuous (2000-2000 h) infusion. In both studies, serum leptin levels peaked between midnight and early morning followed by low day-time levels (P < 0.01). The mode of GH treatment or previous discontinuation did not affect the leptin level (P > 0.05), but the patients had significantly higher leptin levels than the controls (P < 0.01). The diurnal variation in leptin was compared with changes in GH, insulin, non-esterified fatty acids, 3-hydroxybutyrate, insulin-like growth factor I and glucose, but no robust cross-correlations could be demonstrated. The following conclusions were made. (1) The circadian pattern of serum leptin is not influenced by either experimental or spontaneous changes in serum GH concentrations. (2) GH deficiency is associated with elevated leptin levels which most likely reflects increased fat mass in these patients.
Sensitivity of mononuclear leucocytes to glucocorticoids in elderly hip-fracture patients resistant to suppression of plasma cortisol by dexamethasone
Authors: van Rijen EA , Harvey RA , Barton RN , Rose JG , Horan MA
Published: January 2005

OBJECTIVE: Elderly women with proximal femur fracture show a prolonged increase in plasma cortisol, which could have undesirable catabolic effects. Suppression of cortisol by dexamethasone is impaired, suggesting resistance to glucocorticoid effects at feedback inhibitory sites. We therefore wished to find out whether peripheral glucocorticoid sensitivity is normal. DESIGN: Peripheral blood mononuclear leucocytes were used as a model tissue. Blood samples were taken from elderly women about 2 weeks after hip fracture and from elderly control women. Each patient was then given 1 mg dexamethasone at 2300 h followed by further sampling at 0800 and 1600 h the next day. METHODS: Glucocorticoid-receptor binding parameters were measured by incubating whole cells with [3H]dexamethasone for 2 h at 37 degrees C. Inhibition of cell proliferation by dexamethasone was assessed by addition of [3H]thymidine to cells cultured for 65 h with concanavalin A. Cortisol and dexamethasone concentrations were measured in the dexamethasone suppression test. RESULTS: As expected, the hip-fracture patients had raised morning cortisol concentrations and impaired suppression by dexamethasone. The cells of the patients had similar numbers of glucocorticoid receptors to those of the control subjects but higher values for Kd (i.e. a lower binding affinity). The cells of the patients incorporated less [3H]thymidine than the control cells in the absence of dexamethasone. The percentage inhibition by a saturating concentration of dexamethasone was unchanged but the concentration giving half-maximal inhibition was decreased (sensitivity was increased) at the higher of the two concanavalin A concentrations used. CONCLUSIONS: These experiments in mononuclear leucocytes give no evidence of peripheral resistance to glucocorticoids in hip-fracture patients with impaired suppression of cortisol by dexamethasone.
Mineralocorticoid receptor splice variants in different human tissues
Authors: Wickert L , Watzka M , Bolkenius U , Bidlingmaier F , Ludwig M
Published: January 2005

The mineralocorticoid receptor (MR), a member of the steroid receptor family, acts as a transcription factor and mediates both aldosterone and cortisol effects. Aldosterone specificity in some tissues results from the inactivation of competing cortisol into cortisone by 11beta-hydroxysteroid dehydrogenase. In other tissues MR and the glucocorticoid receptor show overlapping physiological effects or may act together by forming a heterodimer. An additional MR splice variant (MR+4) has been found in different mRNA samples from rat tissues and human white blood cells, thereby implying additional modes of MR-regulated effects. We therefore looked for the presence of these two MR-mRNA isoforms in human classical aldosterone target tissues and various other tissues. MR-mRNA was found in all samples investigated, thereby showing the expression of MR to be more abundant than has been observed thus far. In addition, the MR+4-mRNA variant was also found in all the tissues examined.
Effect of small doses of iodine on thyroid function in patients with Hashimoto's thyroiditis residing in an area of mild iodine deficiency
Authors: Reinhardt W , Luster M , Rudorff KH , Heckmann C , Petrasch S , Lederbogen S , Haase R , Saller B , Reiners C , Reinwein D , Mann K
Published: January 2005

OBJECTIVE: Several studies have suggested that iodine may influence thyroid hormone status, and perhaps antibody production, in patients with autoimmune thyroid disease. To date, studies have been carried out using large amounts of iodine. Therefore, we evaluated the effect of small doses of iodine on thyroid function and thyroid antibody levels in euthyroid patients with Hashimoto's thyroiditis who were living in an area of mild dietary iodine deficiency. METHODS: Forty patients who tested positive for anti-thyroid (TPO) antibodies or with a moderate to severe hypoechogenic pattern on ultrasound received 250 microg potassium iodide daily for 4 months (range 2-13 months). An additional 43 patients positive for TPO antibodies or with hypoechogenicity on ultrasound served as a control group. All patients were TBII negative. RESULTS: Seven patients in the iodine-treated group developed subclinical hypothyroidism and one patient became hypothyroid. Three of the seven who were subclinically hypothyroid became euthyroid again when iodine treatment was stopped. One patient developed hyperthyroidism with a concomitant increase in TBII titre to 17 U/l, but after iodine withdrawal this patient became euthyroid again. Only one patient in the control group developed subclinical hypothyroidism during the same time period. All nine patients who developed thyroid dysfunction had reduced echogenicity on ultrasound. Four of the eight patients who developed subclinical hypothyroidism had TSH concentrations greater than 3 mU/l. In 32 patients in the iodine-treated group and 42 in the control group, no significant changes in thyroid function, antibody titres or thyroid volume were observed. CONCLUSIONS: Small amounts of supplementary iodine (250 microg) cause slight but significant changes in thyroid hormone function in predisposed individuals.
Preoperative localization of suspicious parathyroid adenomas by assay of parathyroid hormone in needle aspirates
Authors: Marcocci C , Mazzeo S , Bruno-Bossio G , Picone A , Vignali E , Ciampi M , Viacava P , Naccarato AG , Miccoli P , Iacconi P , Pinchera A
Published: January 2005

OBJECTIVE: To determine the usefulness of parathyroid hormone (PTH) measurement in needle aspirates of a suspicious neck mass to confirm its parathyroid nature in patients with primary hyperparathyroidism. METHODS: Thirty-three patients with surgically proved primary hyperparathyroidism were submitted to neck ultrasound (US), parathyroid scintigraphy, and assay of PTH in the aspirate (PTHa) of the suspicious cervical mass. RESULTS: Based on the results of neck US and parathyroid scintigraphy, patients were divided into two groups. Group 1: 16 patients (seven with nodular goiter) with concordant positive US and scintigraphic results. In all but one patient, PTHa was detectable and often markedly elevated (> 1000 pg in 12 patients, between 292 pg and 803 pg in three patients and 53 pg in one patient). The patient with undetectable PTHa had a small lower left parathyroid adenoma (8x8x10 mm). Group 2: 17 patients (12 with nodular goiter) with discordant US and scintigraphic results. PTHa established the parathyroid nature of the mass in 13 cases (> 1000 pg in 8 patients, between 501 pg and 953 pg in three patients and 90 and 79 pg in two patients): 11 of these had a suspected lesion by US examination but the scintigraphy results were negative; two had a mass that gave positive scintigraphy results but was of uncertain origin according to US: in both cases an intrathyroidal parathyroid adenoma was found. PTHa was undetectable in four cases (three with nodular goiter): all of these had equivocal US results, and three had positive scans and one a negative scan. CONCLUSIONS: Assay of PTHa is a simple method and should be useful for confirming the parathyroid nature of a cervical mass in patients with discordant or non-diagnostic US and scintigraphic results.
Comparison between tryptophan methoxyindole and kynurenine metabolic pathways in normal and preterm neonates and in neonates with acute fetal distress
Authors: Munoz-Hoyos A , Molina-Carballo A , Macias M , Rodriguez-Cabezas T , Martin-Medina E , Narbona-Lopez E , Valenzuela-Ruiz A , Acuna-Castroviejo D
Published: January 2005

OBJECTIVE: To analyze the kynurenine and methoxyindole metabolic pathways of tryptophan in order to identify changes in premature neonates and in neonates suffering from fetal distress. METHODS: One hundred and twelve neonates were assigned to three groups: normal neonates (control group), preterm neonates (neonates born before the 37th gestational week) and neonates suffering from fetal distress. Each of these groups was then divided in two subgroups according to the time of birth corresponding with the time of blood sampling: a diurnal subgroup, comprising neonates whose blood was sampled between 0900 and 2100 h, and a nocturnal subgroup, comprising neonates whose blood was sampled between 2100 and 0900 h. Blood samples from the umbilical artery and vein were taken in the delivery room at birth from each neonate for measurement of melatonin, the main methoxyindole pathway metabolite. Urine samples were collected from 0900 to 2100 h (diurnal groups) and from 2100 to 0900 h (nocturnal groups), and the presence of kynurenic acid, xanturenic acid, 3-hydroxyantranilic acid, L-kynurenine and 3-hydroxykynurenine determined. RESULTS: The results show the existence of diurnal/nocturnal differences in the concentration of melatonin in cord blood and in the urinary excretion of kynurenines. In normal neonates, the production of methoxyindoles (determined as melatonin) is decreased during the day and increases at night, whereas production of kynurenines is high during the day, decreasing at night. In the fetal distress group, a significant increase in the umbilical artery concentration of melatonin was found. This group also showed a reduction in L-kynurenine concentrations in the diurnal and nocturnal groups, and an increase in xanturenic acid and 3-hydroxyantranilic acid during the day. Correlation and regression studies confirmed that the differences in the day/night pattern of the tryptophan metabolic pathways were greater in normal neonates than in the preterm and fetal distress groups. CONCLUSIONS: The results indicate the existence of an imbalance in tryptophan metabolites in preterm infants and those with fetal distress, blunting the normal diurnal/nocturnal rhythm of both melatonin and kynurenines.
Testicular seminoma in a patient with a constitutively activating mutation of the luteinizing hormone/chorionic gonadotropin receptor
Authors: Martin MM , Wu SM , Martin AL , Rennert OM , Chan WY
Published: January 2005

A white man who had been diagnosed, 35 years previously at the age of 27 months, to have precocious puberty, was later determined to have familial male-limited precocious puberty (FMPP), on the basis of his family history, increased serum testosterone, prepubertal concentrations of follicle stimulating hormone and luteinizing hormone, and Leydig cell hyperplasia. Recently, this diagnosis was confirmed by molecular genetic analysis that demonstrated the presence of a heterozygous constitutive activating mutation of the luteinizing hormone/chorionic gonadotropin receptor. This dominant gain-of-function Asp578Gly mutation has been shown constitutively to activate the receptor in the absence of the agonist, leading to enhanced synthesis of cAMP and, in turn, to increased, sustained production of testosterone. In 1994, this patient was found to have a testicular seminoma. He represents the first case of a testicular germ cell tumor described in an FMPP patient, raising the possibility of a potentially harmful effect of prolonged increased concentrations of sex hormones, with onset early in life, upon the cellular components of the testes.
Furosemide decreases the sensitivity of glucose transport to insulin in skeletal muscle in vitro
Authors: Dimitriadis G , Leighton B , Parry-Billings M , Tountas C , Raptis S , Newsholme EA
Published: January 2005

The effects of the diuretic furosemide on the sensitivity of glucose disposal to insulin were investigated in rat soleus muscle in vitro. At basal levels of insulin, the rates of 3-O-methylglucose transport, 2-deoxyglucose phosphorylation and lactate formation were not affected significantly by furosemide (0.5 mmol/l). However, furosemide significantly decreased these rates at physiological and maximal levels of insulin. The contents of 2-deoxyglucose and glucose 6-phosphate in the presence of furosemide were not significantly different from those in control muscles at all levels of insulin studied. It is concluded that furosemide decreases the sensitivity of glucose utilization to insulin in skeletal muscle by directly inhibiting the glucose transport process.
Leptin levels in women with polycystic ovary syndrome before and after treatment with diazoxide
Authors: Krassas GE , Kaltsas TT , Pontikides N , Jacobs H , Blum W , Messinis I
Published: January 2005

Leptin, a product of the ob gene, is a 16 kDa protein which is produced by adipocytes. In humans, obesity is a common finding in women with polycystic ovary syndrome (PCOS). The role, however, of leptin in PCOS is not clear. Some studies have reported increased levels of leptin in PCOS, while others report that they are normal. Also, insulin resistance is a common finding in PCOS. The aim of this study was to investigate further the role of insulin in leptin secretion in patients with PCOS by treating them for 10 days with diazoxide, an insulin-reducing compound. Eight women with PCOS, mean age 22.1 +/- 2.7 years, with mean body mass index (BMI) 28.4 +/- 5.7kg/m2, were studied. An oral glucose tolerance test (OGTT) was performed in all women and blood samples were taken before and at 30, 60, 90, 120 and 150 min after the administration of glucose. Glucose, insulin, leptin, free testosterone, delta4 androstenedione, sex hormone binding globulin (SHBG), LH, FSH, IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) were measured in the sera taken before the administration of glucose, while glucose and insulin levels were measured in all samples which were collected after the administration of glucose. Diazoxide 300 mg daily was given to all women starting after the end of the OGTT for 10 days. A second OGTT was performed the day after the discontinuation of the diazoxide treatment. The same hormonal and biochemical parameters were also measured in all patients during the second OGTT. After the administration of diazoxide a reduction in sum insulin (262 +/- 147 vs 679 +/- 341 microU/ml. P<().01), leptin (18.5 +/- 10.6 vs 24.2 +/- 10.2 ng/ml, P<0.01), free testosterone (3.0 +/- 1.9 vs 5.1 +/- 1.9 pg/ml, P<0.01), delta4 androstenedione (3.8 +/- 1.9 vs 5.7 +/- 2.0 ng/ml, P<0.01) and IGF-I (219.5 +/- 69.2 vs 314.5 +/- 82.3 ng/ml, P<0.01) levels was observed. Serum SHBG (38.8 +/- 16.8 vs 27.8 +/- 12.1 nmol/l, P<0.01) and sum glucose levels (994.1 +/- 252.7 vs 711.1 +/- 166.1 mg/dl, P<0.05) were increased while IGFBP-3 (3.96 +/- 2.49 vs 3.75 +/- 2.24mg/l), FSH (6.2 +/- 1.8 vs 6.0 +/- 2.5 mU/l) and LH (18.9 +/- 6.7 vs 21.4 +/- 6.7 mU/l) concentrations did not change significantly. A significant positive correlation was found between serum leptin and BMI values before and after administration of diazoxide as well as between leptin, insulin and IGFBP-3 values. Also, sum insulin values correlated significantly with BMI. However, when multiple regression analysis was used this correlation was eliminated except that between leptin and BMI. This was most probably due to the small number of cases. The mechanism of the reduction of leptin levels is unclear. However, it is suggested that the concomitant decrease of insulin levels may play a role.
No relationship between identified variants in the uncoupling protein 2 gene and energy expenditure
Authors: Klannemark M , Orho M , Groop L
Published: January 2005

OBJECTIVE: The uncoupling protein 2 (UCP2) uncouples respiration from the oxidative phosphorylation in most cell types, predominantly in white fat and skeletal muscle. Since a decreased basal metabolic rate (BMR) would increase the susceptibility to weight gain, genetic alterations in the UCP2 gene could contribute to the pathogenesis of obesity and the metabolic syndrome (MSDR). DESIGN AND METHODS: To test this hypothesis, we PCR amplified the introns of the UCP2 gene and sequenced the exon/intron boundaries. This information was used to construct intronic primers and to screen obese patients with low BMR for mutations in the coding regions of the UCP2 gene, using the single-strand conformational polymorphism technique. Furthermore, we examined whether there is an association between a biallelic marker in the UCP2 gene and BMR or MSDR. RESULTS: The UCP2 gene is composed of six coding exons, covering 5 kb of chromosome 11q13. One polymorphism, but no mutations, were identified in the coding regions of the UCP2 gene. There were no significant differences in the allele or genotype frequencies of the Ala55Val polymorphism between 55 patients with MSDR and 46 healthy controls. No association was found between the UCP2 gene and BMR in patients with MSDR or in healthy controls. CONCLUSIONS: Mutation screening and association studies suggest that mutations in the coding regions of the UCP2 gene do not affect BMR and do not contribute to increased susceptibility to obesity or MSDR. The results cannot, however, exclude the possibility that variants in regulatory elements of the gene could contribute to the development of obesity or MSDR.
Endothelin receptor subtypes in the microvillous trophoblastic membrane of early gestation and term human placentas
Authors: Mondon F , Anouar A , Ferre F
Published: January 2005

The 125I-labeled endothelin-1 ([125I]ET-1) binding sites in microvillous membranes from early gestation and term human placentas were investigated. The Kds for [125I]ET-1 binding to early gestation (68 +/- 15 pmol/l) and term (45 +/- 8 pmol/l) microvilli (n = 4) were not significantly different. The density of binding sites decreased significantly, from 243 +/- 80 fmol/mg protein in early gestation microvilli to 54 +/- 10 fmol/mg protein in term microvilli. The endothelin (ET) receptor (ET-R) subtype profiles were determined by competition binding studies with unlabeled ET-1, ET-3, and selective agonists and antagonists for ETA-R and ETB-R. In early gestation placental microvilli, we observed the presence of 72%) ETB-R, (mainly ETB2-R subtype), and 28%. ETA-R. Only ETB-R (mainly the ETB2-R subtype) was present in term placental microvilli. We suggest that the ETB-R on the placental microvillous membrane is involved in specific trophoblastic functions and may play a major role in ET clearance by modulating the amounts of ETs in the maternal intervillous blood space.
Insulin receptor-related receptor in rat islets of Langerhans
Authors: Ozaki K
Published: January 2005

The physiological aspects and roles of the insulin receptor-related receptor (IRR), a novel member of the insulin receptor family, are unknown. Published work shows a characteristic localization of IRR mRNA at the cellular level in the kidney, stomach and brain. In our previous study, a specific antibody against the rat IRR beta subunit was generated and used to identify the IRR-expressing cells as B-type intercalated cells in the kidney. In this study. IRR cDNA was amplified by PCR to demonstrate IRR mRNA expression in the rat pancreas. Immunohistochemical analysis with the anti-IRR antibody revealed that IRR immunoreactivity is localized in the islets of Langerhans. The IRR-immunoreactive cells were most likely to be the islet B cells which were stained with anti-insulin antibody. This is the first finding on the involvement of IRR in the physiological functions of insulin-secreting cells.
Long-term effects of growth hormone (GH) on body fluid distribution in GH deficient adults: a four months double blind placebo controlled trial
Authors: Moller J , Fisker S , Rosenfalck AM , Frandsen E , Jorgensen JO , Hilsted J , Christiansen JS
Published: January 2005

OBJECTIVE: Short-term growth hormone (GH) treatment normalises body fluid distribution in adult GH deficient patients, but the impact of long-term treatment on body fluid homeostasis has hitherto not been thoroughly examined in placebo controlled trials. To investigate if the water retaining effect of GH persists for a longer time we examined the impact of 4 months GH treatment on extracellular volume (ECV) and plasma volume (PV) in GH deficient adults. DESIGN: Twenty-four (18 male, 6 female) adult GH deficient patients aged 25-64 years were included and received either GH (n=11) or placebo (n=13) in a double blind parallel design. METHODS: Before and at the end of each 4 month period ECV and PV were assessed directly using 82Br- and 125I-albumin respectively, and blood samples were obtained. RESULTS: During GH treatment ECV increased significantly (before: 20.48+/-0.99 l, 4 months: 23.77+/-1.38 l (P<0.01)), but remained unchanged during placebo administration (before: 16.92+/-1.01 l, 4 months: 17.60+/-1.24 l (P=0.37)). The difference between the groups was significant (P<0.05). GH treatment also increased PV (before: 3.39+/-0.27 l. 4 months: 3.71+/-0.261 (P=0.01)), although an insignificant increase in the placebo treated patients (before: 2.81+/-0.18 l, 4 months: 2.89+/-0.20 l (P=0.37)) resulted in an insignificant treatment effect (P=0.07). Serum insulin-like growth factor-I increased significantly during GH treatment and was not affected by placebo treatment. Plasma renin (mIU/l) increased during GH administration (before: 14.73+/-2.16, 4 months: 26.00+/-6.22 (P=0.03)) and remained unchanged following placebo (before: 20.77+/-5.13, 4 months: 20.69+/-6.67 (P=0.99)) leaving no significant treatment effect (P=0.08). CONCLUSION: The long-term impact of GH treatment on body fluid distribution in adult GH deficient patients involves expansion of ECV and probably also PV. These data substantiate the role of GH as a regulator of fluid homeostasis in adult GH deficiency.
Neurosurgery restores late GH rise after glucose-induced suppression in cured acromegalics
Authors: Attanasio R , Oppizzi G , Lodrini S , Dallabonzana D , Barausse M , Orlandi P , DaRe N , Cozzi R
Published: January 2005

OBJECTIVE AND DESIGN: A decrease of GH levels below 2 microg/l after an oral glucose tolerance test (OGTT) is still currently accepted as the gold standard for assessing cure in surgically treated acromegaly. Whether glucose-induced suppression of GH is accompanied by a restoration of normal GH late rebound has not yet been evaluated in this disease. In order to assess the restoration of normal GH regulation after removal of a pituitary adenoma, we have evaluated GH changes after an OGTT in a series of selected acromegalic patients (transsphenoidal surgery and lack of pituitary failure). METHODS: Twenty-nine patients (13 male, 16 female, age range 27-70 years) entered the study. Their neuroradiological imaging before neurosurgery showed microadenoma in 7, intrasellar macroadenoma in 8 and macroadenoma with extrasellar extension in 14. Plasma GH levels were assayed up to 300 min after glucose administration (75 g p.o.) and IGF-I on basal samples. RESULTS: Basal GH levels were below 5 microg/l in 20 patients and below 2 microg/l in 5 of these. Normal age-adjusted IGF-I levels were observed in 12 patients. GH values were suppressed below 2 microg/l during an OGTT in 13 patients, and below 1 microg/l in 7 of these. In 9 patients out of these 13, a marked rise in GH levels occurred after nadir. Baseline and nadir GH values of these 9 patients were not different from the corresponding values of the other 4 patients without OGTT-induced late GH peaks. CONCLUSIONS: GH rebound after GH nadir occurs in acromegalic patients considered as cured on the basis of OGTT-induced GH suppression and/or IGF-I normalization. The restoration of this physiological response could be regarded as a marker of recovered/preserved integrity of the hypothalamic-pituitary axis. Even though the reason for this GH rebound has not yet been elucidated (GHRH discharge?/end of somatostatin inhibition?), the lack of late GH peak in the patients regarded as cured by the usual criteria could be due to injury to the pituitary stalk caused by the adenoma or by surgical manipulation.
Extremely low values of serum leptin in children with congenital generalized lipoatrophy
Authors: Jaquet D , Khallouf E , Levy-Marchal C , Czernichow P
Published: January 2005

Congenital generalized lipoatrophy (CGL) is a syndrome with multiple clinical manifestations and complete atrophy of adipose tissue. The exact mechanism of this disease remains unknown. One hypothesis presupposes an abnormal development of adipocytes. Leptin, the adipocyte-specific product of the ob gene, acts as a regulatory factor of body weight. In children, as in adults, leptin levels are correlated with body mass index (BMI) and body fat mass. Some authors have demonstrated that adults with congenital or acquired generalized lipoatrophy have decreased leptin concentrations. In order to study serum leptin profile during childhood in this disease, we measured serum leptin concentrations in six children aged 5.5-11 years suffering from CGL, and investigated the relationship between metabolic parameters and the variations in leptin levels. Serum leptin concentrations (1.19+/-0.32 ng/ml (+/- S.D.)) were extremely low compared with those observed in normal children. No significant correlation was found with BMI, which is known to be one of the major determinants of serum leptin. Serum leptin values were significantly correlated with fasting insulin levels (r=0.83, P=0.024). In conclusion, extremely low leptin values measured in children with CGL could be regarded as one among other diagnostic parameters. However, the detectable levels observed in all of these children support the evidence that a small amount of body fat is likely to be present in these patients, despite complete subcutaneous lipoatrophy. Our data suggest that this small amount of adipose tissue could be metabolically active and, at least in part, sensitive to insulin. Further investigations are required to uncover the pathophysiological mechanisms of this syndrome, known to be commonly associated with insulin resistance.