bluuebunny/crossref_metadata_2025 huggingface dataset:
Graves' ophthalmopathy and tobacco smoking
Authors: Tallstedt Leif , Lundell Göran , Taube Adam
Published: June 2009

We have studied the smoking habits in a group of patients with hyperthyroidism caused by Graves' disease. One hundred and seventy-one patients were randomized to different forms of treatment for hyperthyroidism and the outcome of this study concerning Graves' ophthalmopathy has been described previously. There were 89 smokers (52%) and 82 non-smokers (48%). Among the smokers there were 32 patients (19%) who developed ophthalmopathy or deteriorated in an already present ophthalmopathy and 57 patients who did not (33%), whereas among the non-smokers, 14 (8%) had ophthalmopathy during the study and 68 (40%) did not (p =0.006). We could not obtain statistical significance when trying to demonstrate that smoking is a risk factor for the development of ophthalmopathy after treatment for hyperthyroidism. It was noted that smokers had higher pretreatment levels of thyrotropin-receptor antibodies (p = 0.027). In conclusion, these results support the previously described association between smoking and Graves' ophthalmopathy.
Whole-body leucine turnover in adults on conventional treatment for hypopituitarism
Authors: Beshyah Salem A , Sharp Patrick S , Gelding Susan V , Halliday David , Johnston Desmond G
Published: June 2009

This study has investigated protein metabolism in adults with hypopituitarism before and after growth hormone (GH) replacement and in matched controls. Whole-body leucine turnover was measured in 16 GH-deficient adult hypopituitary patients (nine females and seven males) on standard thyroid, adrenal and sex hormone replacement and in 20 normal controls using primed continuous infusion of l-[1 – 13C]leucine. In seven of the patients, leucine turnover was restudied following 6 months' treatment with biosynthetic human GH (0.025–0.05 IU/kg body wt daily, with the final dose determined by patient tolerance). Compared with normal controls, hypopituitary patients had significantly reduced leucine flux (mean±sd: 97.8±24.9 vs 131.0±23.0 μmol·h−1·kg−1; p<0.001), reduced leucine incorporation into protein (80.4±20.9 vs 108.8±19.6 μmol·h−1·kg−1; p<0.001) and reduced leucine oxidation (17.4±4.8 vs 22.2±8.1 μmol·h−1·kg−1; p<0.05). Leucine turnover was similar in male and female patients. In the patients, leucine flux correlated positively with body weight (p = 0.51, p<0.05) and leucine incorporation in protein correlated positively with lean body mass (p = 0.55, p <0.05) and in male patients leucine flux correlated positively with serum insulin-like growth factor I (IGF-I) levels (ρ=0.71, p<0.05). No significant relationship was observed with age or duration of hypopituitarism. Growth hormone replacement therapy did not produce a uniform effect on leucine metabolism. Mean values of leucine flux, oxidation and incorporation into protein increased, although the differences were not statistically significant. The patients on higher GH doses and with a higher serum IGF-I response were those who demonstrated an increase in leucine turnover. We conclude that leucine turnover in hypopituitary adults is reduced compared with normal controls. The effect of GH treatment for 6 months at conventional doses in hypopituitary adults is not uniform and may be dose-dependent.
Effect of noradrenaline and dopamine on progesterone and estradiol secretion of human granulosa cells
Authors: Bódis József , Tinneberg Hans R , Török Attila , Cledon Philippe , Hanf Volker , Papenfuss Falko
Published: June 2009

The aim of this study was to explore the direct action of noradrenaline and dopamine on progesterone and estradiol secretion of human granulosa cells cultured in serum-free medium. Progesterone and estradiol production was measured in the presence and absence of noradrenaline, dopamine or propranolol using radioimmunoassays; statistical analysis was performed by analysis of variance and Newman-Keul's multiple range test. Twenty-six women aged 31±3 years undergoing in vitro fertilization and embryo transfer for infertility treatment at University Women's Hospital, University of Tübingen, Germany, took part in this study. Noradrenaline significantly inhibited progesterone production by human granulosa cells in a dose-related manner at a concentration of 10−4–10−6 mol/l. Dopamine significantly stimulated estradiol secretion by granulosa cells in an inverse dose-related manner. Both effects were blocked by propranolol. The results suggest that catecholaminergic actions switch over the steroid production of human granulosa cells cultured in serum-free medium from progesterone to estradiol.
Fluid production by in vitro lungs from near-term fetal guinea pigs: effects of cortisol and aldosterone
Authors: Kindler Pawel M , Chuang Deuel C , Perks Anthony M
Published: June 2009

Lungs from near-term fetal guinea pigs (62±1 days of gestation) were supported in vitro for 3 h and fluid production was determined by a dye dilution method (Blue Dextran 2000). Three groups of control preparations (N =6 for each group) showed no changes during incubation. However, cortisol or aldosterone placed in the outer saline during the middle hour caused profound reductions in fluid production. Cortisol at 10−6 or 10−8 mol/l reduced production 80.3±10.8% and 47.8±20.5%, respectively (p<0.05–0.001; N=6 for each group); at 10−10 mol/l it failed to affect production significantly. Aldosterone was effective at lower concentrations (N=12). At 10−11 mol/l it reduced production 67.1±10.0% (p<0.01–0.001); at 7× 10−10 mol/l it produced similar effects. In contrast, there were no significant changes after treatment with 10−11 mol/l aldosterone together with an aldosterone antagonist (5 × 10−8 mol/l spironolactone; N = 6). Spironolactone alone was without effect (N = 6). The highest steroid concentrations tested corresponded to plasma concentrations in the guinea pig at delivery; therefore, it is suggested that both steroids may have a role in reducing lung fluid production close to birth in this species.
Life with Turner's syndrome—a psychosocial report from 22 middle-aged women
Authors: Sylvén Lisskulla , Magnusson Chris , Hagenfeldt Kerstin , von Schoultz Bo
Published: June 2009

Twenty-two middle-aged women (median age 44.5 years) with Turner's syndrome were interviewed about family background, social identity, emotional development, relations, female identity, sexuality and reactions to the diagnosis, to evaluate how the condition has affected their lives and coping style. During the years preceding the diagnosis and hormonal replacement therapy (HRT) they had often isolated themselves as they felt different from their peers. Ovarian failure and infertility, not the body height, were the major problems for most of the women. Infertility had affected the women very deeply and many felt depressed because of this. Adolescent behaviour, a feeling of chronic inferiority or a feeling of grief were different ways of coping with the situation. Median age at sexual debut was 19.5 years. Painful intercourse related to vaginal constriction and sore membranes was commonly reported. Most of the women had stopped HRT because of side-effects. Many of the problems experienced by the women could have been avoided if proper HRT had been administered in due time and on a long-term basis. This emphasizes the importance of regular contact with a gynecologist of special training and interest.
Cardiovascular risk factors in adult patients with growth hormone deficiency
Authors: Rosén Thord , Edén Staffan , Larson Göran , Wilhelmsen Lars , Bengtsson Bengt-Åke
Published: June 2009

Patients with adult onset growth hormone deficiency have a decreased life expectancy owing to an increased mortality from cardiovascular disease. In the present study, 104 subjects (66 men and 38 women, aged 22–74 years) with growth hormone deficiency and with adequate replacement therapy with glucocorticoids, thyroid hormones and gonadal steroids were studied with respect to known risk factors for cardiovascular disease. For comparison, data from a population study, "the MONICA study", were obtained. The patients had a significantly higher body mass index compared to controls (p<0.001). Serum triglyceride concentration was higher (p<0.001) but there was no difference in serum total cholesterol concentration. Serum high-density lipoprotein cholesterol concentration was lower (p<0.001) in the patients. There was no difference in the prevalence of diabetes mellitus. The prevalence of treated hypertension was higher (p<0.05) in the patients but the prevalence of smoking was lower (p <0.001). Even after taking the increased body mass index into consideration, the changes in the prevalence of treated hypertension (p<0.05) and in the serum concentrations of triglycerides (p<0.05) and high-density lipoprotein concentrations (p<0.001) remained. These results indicate that growth hormone deficiency alters lipoprotein metabolism and increases the risk for development of hypertension, which in turn might contribute to the increased risk for cardiovascular disease.
Correlation of orbital muscle changes evaluated by magnetic resonance imaging and thyroid-stimulating antibody in patients with Graves' ophthalmopathy
Authors: Nishikawa Mitsushige , Yoshimura Masayoshi , Toyoda Nagaoki , Masaki Hiroya , Yonemoto Toshinaga , Gondou Atsushi , Kato Tsutomu , Kurokawa Hiroaki , Furumura Toshihito , Inada Mitsuo
Published: June 2009

To evaluate the relationship between eye changes and autoantibody to the thyrotropin receptor in patients with Graves' disease, we evaluated the eye changes using magnetic resonance imaging and the results were correlated with thyroid-stimulating antibody, thyrotropin binding inhibitor immunoglobulin and thyroid growth activity. Subjects were 15 patients with Graves' disease who had Graves' ophthalmopathy, including exophthalmos and other signs and symptoms, and nine patients without ophthalmopathy; all were maintained in a euthyroid state by antithyroid drugs. The thyrotropin-binding inhibitor imunoglobulin was measured by a kit, and thyroid-stimulating antibody and thyroid growth activity were evaluated by cyclic adenosine 3′,5′-monophosphate production and [3H]thymidine incorporation, respectively, by cultured functional rat thyroid lined cells. The sum of the swelling ratios (muscle thickness to the diameter of the optic nerve) of the four extraocular muscles correlated well with the degree of exophthalmos. The thyrotropin-binding inhibitor immunoglobulin was positive in nine out of 15 patients with ophthalmopathy; however, no correlation was observed between the activity and exophthalmos or muscle swelling. No significant correlation was observed between muscle changes and thyroid growth activity either. On the other hand, thyroid-stimulating antibody (642±91%) in Graves' patients with ophthalmopathy was significantly (p<0.02) higher than that (315±84%) in patients without ophthalmopathy. Moreover, the level of the stimulating activity in Graves' patients with ophthalmopathy showed a significant (p < 0.02) positive correlation with the sum of the swelling ratios of the individual eight eye muscles. These results suggest that thyroid-stimulating antibody has a close relation to Graves' ophthalmopathy.
Interleukin 8 concentrations in amniotic fluid and peripheral venous plasma during human pregnancy and parturition
Authors: Laham Nihay , Rice Gregory E , Bishop Geoffrey J , Ransome Claire , Brennecke Shaun P
Published: June 2009

To establish the gestational and labour-associated changes in interleukin 8 (IL-8) release, we have determined the concentration of this cytokine in maternal peripheral plasma and amniotic fluid from 1 5 weeks of gestation to term and in association with spontaneous-onset labour at term and preterm. No statistically significant changes in peripheral plasma IL-8 concentration were observed during pregnancy or in association with labour onset (mean concentration 56.5±14.5 ng/l, N = 64). The IL-8 concentrations in amniotic fluid were up to 50-fold greater than those observed in peripheral plasma (p<0.05) and increased significantly (p<0.05) during pregnancy. At term, but before the onset of labour, amniotic fluid concentrations of IL-8 averaged 969.2±553.5 ng/l (N= 12). In association with labour at term, IL-8 concentrations increased to 3895.8±1414.4 ng/l (N=6, p<0.03). The concentration of IL-8 in amniotic fluid obtained from women in preterm labour averaged 1854.7±1352.6 ng/l (N=6) but was not statistically different from the concentration of IL-8 in amniotic fluid obtained from gestational aged-matched non-labouring controls. Although the precise role of intrauterine IL-8 at the time of parturition awaits elucidation, these data support the concept that this cytokine may be involved in the biochemical events associated with the onset and/or propagation of normal labour in the human.
Pulsatile luteinizing hormone secretion during the first and the fourth cycle on two different oral contraceptives containing gestodene
Authors: Hemrika Douwe J , Slaats Ed H , Kennedy John C , Robles-Korsen Ted JM de Vries , Schoemaker Joop
Published: June 2009

Oral contraceptives inhibit ovarian follicular growth by suppressing the release of gonadotropins from the pituitary. We studied basal and gonadotropin-releasing hormone-stimulated gonadotropin release, as well as pulsatile luteinizing hormone (LH) secretion, in ten healthy volunteers who had not used oral contraceptives before. Subjects received either a monophasic preparation containing 30 μg of ethinylestradiol and 75 μg of gestodene (group 1) or a triphasic formulation containing 30–40 μg of ethinylestradiol and 50, 70 and 100 μg of gestodene (group 2). Blood sampling at 10-min intervals during 6-h periods was performed on days 1, 8, 15 and 21 of both the first and fourth pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. Both LH and follicle-stimulating hormone (FSH) were measured by a sensitive immunoradiometric assay. Pulsatile LH secretion was observed in all oral contraceptive users. Mean serum LH and FSH levels, number of pulses/6 h and the amplitude of LH pulses on day 1 in both the first and fourth pill cycle did not differ from early follicular phase controls in both groups. The FSH levels were suppressed rapidly in both groups, even in first cycles, while LH serum levels progressively declined in all cycles studied. In both groups, amplitudes of LH pulses decreased from day 8 onwards, with a substantial number of low-amplitude pulses (<0.75 U/l) interspersed between large-amplitude pulses. On day 1 of the fourth pill cycle a significant number of pulses were of low amplitude. These results confirm our earlier findings that pulsatile secretion of gonadotropins is maintained during oral contraceptive use but is profoundly modified by steroid feedback. There seems to be no major difference in the suppression of the hypothalamic-pituitary axis in the first cycle on an oral contraceptive as compared to subsequent cycles.
Demonstration of biological activity of a growth hormone-releasing hormone-like substance produced by a pheochromocytoma
Authors: Saito Haruhiko , Sano Toshiaki , Yamasaki Ryuichi , Mitsuhashi Shinji , Hosoi Eiji , Saito Shiro
Published: June 2009

The biological characteristics of a growth hormone-releasing hormone (GHRH)-like substance produced by a pheochromocytoma were studied. Analysis by gel filtration chromatography combined with the use of two distinct GHRH antisera that recognize the N- and C-termini of authentic GHRH(1–44)NH2 indicated molecular heterogeneity of the immunoreactive GHRH in the tumor extract, but a component corresponding to GHRH(1–44)NH2 was the predominant form. The biological activity of this immunoreactive component was assessed in vitro by measuring its ability to induce growth hormone release from dispersed rat anterior pituitary cells. At concentrations of 0.125–2.0 nmol/l, the test materials induced a dose-related increase in growth hormone release from the cells into the incubation medium (range 992±68–1872±32 ng·1.7×105 cells−1·3 h−1), similar to that observed with synthetic GHRH(1–44)NH2 (control value 640±30 ng·1.7× 105 cells−1·3 h−1). This suggests that immunoreactive GHRH in the tumor has almost the same biological activity as the synthetic product and that a combination of pheochromocytoma and acromegaly is not always fortuitous because both diseases may be caused by a single neoplasm.
Pituitary-gonadal function in neonatal and adult female rats treated with gonadotropin-releasing hormone agonist and antagonist: short- and long-term effects
Authors: Trimiño E , Pinilla L , Aguilar E
Published: June 2009

We have analyzed the mechanisms involved in ovarian failure after administration of gonadotropin hormone-releasing hormone agonists (GnRH-A) or antagonists (GnRH-ANT). Ovarian and uterine weights, serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol and pituitary FSH and LH contents were measured in Wistar female rats injected from 1–15 or 90–104 days of age with the agonist d-Ala6-d-Gly10-GnRH or the GnRH-ANT Org. 30276. Vaginal opening, first estrous presentation, vaginal smears and reproductive capacity were also analyzed. In both neonatal and adult females GnRH-A induced pituitary desensitization and reduced ovarian and uterine weights and estradiol serum concentrations. Therefore, serum gonadotropin concentrations were increased in adults and decreased in neonatal females. Puberty occurrence and reproductive function remain unaltered after neonatal treatment with GnRH-A. In neonatal females, FSH and LH pituitary content and FSH serum concentrations decreased at the end of treatment with GnRH-ANT. The effects on LH and estradiol secretion depended on the pattern of treatment. Interestingly enough, both vaginal opening and first estrous presentation were precipitated by GnRH-ANT administration. Normal reproductive function was observed in adults. We conclude that:

(i) pituitary desensitization of receptors occurred in both neonatal and adult females after chronic administration of GnRH-A;

(ii) the ovarian failure observed in adults that is accompanied by increased serum concentrations of gonadotropins was probably due to an inhibitory effect of GnRH-A directly on the ovaries;

(iii) the blockade of GnRH action shortly after birth with GnRH-ANT precipitated the onset of puberty; possibly the antagonist blocks some suppressive effects of endogenous LHRH;

(iv) the effects of neonatal administration of GnRH-A or GnRH-ANT were transitory.
Large somatostatin-insensitive thyrotrophin-secreting pituitary tumour responsive to d-thyroxine and dopamine agonists
Authors: Karlsson FA , Burman P , Kömpe O , Westlin J-E , Wide L
Published: June 2009

A unique thyrotrophin (TSH)-secreting pituitary tumour is described in a patient with a history of recurrent thyrotoxicosis. Unlike other previously reported TSHomas, the tumour is insensitive to octreotide, a somatostatin analogue. It does not accumulate [111In]octreotide but expresses functional dopamine receptors and responds to the d-isomer of thyroxine, two characteristics beneficial in the management of the patient.
Analysis of the Gs α gene in growth hormone-secreting pituitary adenomas by the polymerase chain reaction-direct sequencing method using paraffin-embedded tissues
Authors: Hosoi Emiko , Yokogoshi Yutaka , Hosoi Eiji , Horie Hidetaka , Sano Toshiaki , Yamada Shozo , Saito Shiro
Published: June 2009

We investigated the prevalence of Gs α gene mutations in growth hormone (GH) secreting pituitary adenomas from Japanese patients with acromegaly. Forty-five GH-secreting adenomas were examined for the presence of point mutations in codons 201 or 227 of the Gs α gene using the polymerase chain reaction-direct sequencing method and deoxyribonucleic acid extracted from paraffin-embedded tumor specimens. Mutation of codon 227 of the Gs α gene was not observed in any of the tumors, but a mis-sense mutation of codon 201 was identified in two tumors (4.4%). One lesion was a densely granulated GH cell adenoma in a patient with adenomatous goiter and breast cancer. The other was a mixed GH cell-prolactin cell adenoma in a patient with multiple endocrine neoplasia type 1 associated with parathyroid hyperplasia and a pancreatic islet cell tumor. The Gs α gene detected in parathyroid tissue and pancreatic tumor tissue was of the wild type in this second patient, and the mutation was specific to the pituitary tumor. These results suggest that point mutations of codons 201 or 227 of the Gs α gene may not be important mediators of oncogenesis for GH-secreting pituitary adenomas in Japan.
Concentrations, metabolic clearance rates, production rates and plasma binding of cortisol in Antarctic phocid seals
Authors: Liggins Graham C , France John T , Schneider Robert C , Knox Bruce S , Zapol Warren M
Published: June 2009

We have reported previously that plasma of the Weddell seal, a member of the phocid family, contains a very high concentration of cortisol. The present study was undertaken to determine whether high cortisol levels were common to seals in the Antarctic environment, or to other phocidae, and to determine the mechanism of the hypercortisolaemia. High levels of cortisol (0.82–2.38 μmol/l) were found in 4 phocidae (Weddell, crabeater, leopard and Southern elephant seals), whereas levels in a member of the otariid family (Antarctic fur seal) were similar to human values. Metabolic clearance rates (MCR) and production rates (PR) of cortisol were determined in the field in Weddell (N = 1), crabeater (N= 3) and leopard (N= 3) seals following bolus injections of [3H] cortisol. The MCR and PR did not differ between the three phocids, but whereas the MCR of 410–590 1/day was twice that of human values, the PR of 460–1180 μmol·m−2·d−1 was up to 40-fold greater. The binding capacity of corticosteroid-binding globulin (CBG) was equal to or greater than the plasma concentrations of cortisol, resulting in relatively low concentrations of free cortisol. We conclude that hypercortisolaemia is maintained in phocid seals mainly by a high production rate—the highest (corrected for surface area) reported in any species. The relatively low cortisol levels in otariid seals studied in the same environment suggest that the high PR in phocidae is unrelated to the harsh climatic conditions, but may be part of their adaptation for diving to extreme depths. The phocid seals and New World primates have similarly high levels of cortisol and a high PR but CBG in the primates has low binding capacity and affinity and cortisol is mainly free.
Insulin resistance caused by amylin in conscious rats is independent of induced hypocalcemia and fades during long-term exposure
Authors: Fürnsinn Clemens , Nowotny Peter , Roden Michael , Rohac Madeleine , Pieber Thomas , Parzer Sabina , Waldhäusl Werner
Published: June 2009

To compare the effect of short- vs long-term amylin infusion on insulin sensitivity, glucose tolerance and serum calcemia, euglycemic-hyperinsulinemic clamp (26 pmol·kg−1·min−1) and glucose tolerance tests (2.4 mmol/kg over 30 min) were performed in lean Zucker rats. Three infusion protocols were employed: control group: 24 h of iv saline; short-term amylin exposure: 22 h of iv saline followed by 2 h of iv amylin (20 μg/h); long-term amylin exposure: 24 h of iv amylin (20 μg/h). Insulin resistance was induced by short-term amylin infusion during euglycemic clamping, as shown by a 41% decrease in space-corrected glucose infusion rates (μmol·kg−1·min−1; control group, 106.0±15.0; short-term iv amylin, 62.7±15.0; p<0.00 5). After long-term amylin exposure, insulin sensitivity was identical to control values (109.9±6.7). This fading action of amylin was confirmed by data from the glucose tolerance test, demonstrating glucose intolerance after short- but not after long-term amylin exposure. Serum calcium concentration decreased during short-term (2 h) amylin infusion (from 2.52±0.15 to 2.09±0.12 mmol/l; p<0.01) and hypocalcemia of a similar extent also was present after 22 h and 24 h of amylin exposure (2.10±0.09 and 2.04±0.14 mmol/l, respectively). The data demonstrate that short-term amylin infusion induces insulin resistance and glucose intolerance, both of which vanish during long-term (>22 h) amylin exposure, being apparently independent of induced hypocalcemia.
Acute change in parathyroid function in primary hyperparathyroidism following ultrasonically guided ethanol injection into solitary parathyroid adenomas
Authors: Karstrup Steen , Hegedüs Laszlo , Holm Hans H
Published: June 2009

Ultrasonically guided percutaneous injection of 96% ethanol into solitary parathyroid tumours in patients with primary hyperparathyroidism may be used as an alternative to surgery in selected patients. Contrary to surgical parathyroidectomy, the acute changes in parathyroid function following ultrasound-guided chemical parathyroidectomy have never been described. Seven consecutive and highly selected patients with primary hyperparathyroidism were treated with ultrasonically guided injection of ethanol (96%) into solitary and biopsy-verified parathyroid tumours. Basic treatment included a maximum of three injections separated by intervals of 24 h. In six of the seven patients normal serum values of ionized calcium were achieved within 36–120 h (median 36 h) and normal serum values of intact parathyroid hormone within 6–78 h (median 24 h). Three patients received two injections and three patients three injections. One patient remained hypercalcaemic in spite of three injections. Subsequent surgery showed the patient to have two parathyroid adenomas, of which only one had been detected ultrasonically. The present study has demonstrated a fast normalization of parathyroid function following two to three ethanol injections into solitary parathyroid tumours in selected patients with primary hyperparathyroidism.
Effects of octreotide on insulin-like growth factor I and metabolic indices in growth hormone-treated growth hormone-deficient patients
Authors: Laursen Torben , Jorgensen Jens OL , Ørskov Hans , Møller Jens , Harris Alan G , Christiansen Jens S
Published: June 2009

Animal studies have demonstrated that in addition to inhibiting growth hormone (GH) secretion octreotide inhibits in a direct manner hepatic or peripheral insulin-like growth factor I (IGF-I) generation. To test this hypothesis in humans we studied ten GH-deficient patients with frequent blood sampling during 38 h on two occasions. Regular GH therapy was discontinued 72 h prior to each study period. At the start of each study a subcutaneous (sc) injection of GH (3 IU/m2) was given (at 18.00 h). In a single-blinded crossover design, patients received a continuous sc infusion of either octerotide (200 μg/24 h) or placebo (saline). The pharmacokinetics of GH were similar on the two occasions. The area under the curve±sem of serum GH was 142.5±53.6 μg·l−1·h−1 (octreotide) and 144.8±41.8 μg·l−1·h−1 (placebo), (p=0.73); Cmax (μg/l) was 12.5±1.47 (octreotide) and 12.8±1.42 (placebo) (p=0.83), and Tmax (h) was 6.1±0.97 (octreotide) and 5.2±0.65 (placebo) (p=0.49). Growth hormone administration was associated with an increase in serum IGF-I (μg/l), which was identical during the two studies, from 85.3±19.4 to 174.25±30.3 for octreotide and from 97.0±26.4 to 158.8±28.2 for placebo. Mean IGF-I levels (μg/l) were 138.2±25.1 (octreotide) and 134.5±28.6 (placebo) (p=0.78). Similarly, the increase in IGF binding protein 3 (IGFBP-3) levels was identical. Mean IGFBP-3 levels (μg/l) were 2303±323 (octreotide) and 2200±361 (placebo) (p=0.25). Mean insulin levels were significantly lower during octreotide treatment (39.9±17.9 mU/l) than during placebo (59.7±17.8 mU/l) (p<0.05). Mean blood glucose levels were elevated significantly during octreotide infusion (5.98±0.23 mmol/l for octreotide and 5.07±0.16 mmol/l for placebo; p=0.001). Glucagon levels decreased non-significantly (p=0.07) and IGFBP-1 levels tended to increase during infusion of octreotide although not significantly (p=0.41). Levels of the lipid intermediates were identical on the two occasions. Alanine and lactate levels were significantly increased during octreotide infusion. Mean levels of blood alanine (μmol/l) were 470.8±24.2 (octreotide) and 360.1±17.8 (placebo) (p<0.02). Mean levels of blood lactate were 1038±81.0 (octreotide) and 894.4±73.8 (placebo) (p<0.04). We conclude that short-term continuous sc infusion of octreotide has no direct effect on the generation of IGF-I or the pharmacokinetics of exogenous GH in GH-deficient man.
Somatostatin withdrawal alone is an ineffective generator of pulsatile growth hormone release in man
Authors: Ho P Jean , Kletter Gad B , Hopwood Nancy J , Friberg Roberta DeMott , Barkan Ariel L
Published: June 2009

To assess the relative roles of growth hormone-releasing hormone (GHRH) pulse and somatostatin withdrawal as potential generators of pulsatile growth hormone (GH) release in humans, we studied GH responses to iv bolus GHRH (1 μg/kg) and to termination of a 4 h iv somatostatin infusion (7.2 μg·kg−1·h−1) in five normal young men, and in five men with previously diagnosed isolated GH deficiency. The patients were diagnosed 8–15 years previously on the basis of typical auxological and hormonal criteria, were treated with exogenous GH and were off GH therapy for 1.5–8.9 years prior to this study. Growth hormone rises to a bolus GHRH were similar between the controls and the patients (maximum GH 27.3±15.3 vs 8.0±4.0 μg/l). The controls exhibited only a small GH rise to somatostatin withdrawal (maximum GH 2.9±1.2 μg/l), while the patients did not (maximum GH 0.7±0.1 μg/l; p<0.05). We conclude that somatostatin withdrawal by itself is an ineffective promoter of GH pulsatility. Periodic quiescence of somatostatinergic neurons must be associated with a concomitant GHRH pulse in order to result in a robust GH pulse.
Differences in serum insulin-like growth factor I and sex-hormone-binding globulin levels between late and early prepuberty in patients with idiopathic and organic growth hormone deficiency
Authors: Ciaccio Marta , Belgorosky Alicia , Rivarola Marco A
Published: June 2009

It has been reported that growth hormone modulates serum levels of insulin-like growth factor I (IGF-I) positively and serum levels of sex-hormone-binding globulin (SHBG) negatively. We have measured IGF-I and SHBG concentrations in 24 prepubertal patients with growth hormone deficiency. Twelve of these patients had had intracranial tumors removed (organic growth hormone deficiency) and 12 had growth hormone deficiency of unknown etiology (idiopathic). Fifty-two prepubertal control subjects, admitted for elective surgery, were also studied. All prepubertal patients were divided into two age groups: older and younger than 7 years of age. In both groups there were patients with multiple pituitary deficiencies on hydrocortisone and/or levothyroxine sodium replacement therapy. In the age group younger than 7 years, serum IGF-I was not significantly different between organic and idiopathic growth hormone deficiency (0.28±0.21 versus 0.062±0.071 mU/l) but serum SHBG levels were different (74.6±33.5 versus 173±59 nmol/l, p<0.05). These values were not significantly different from controls (0.47±0.25 mU/l and 132±47 nmol/l, respectively). In the age group older than 7 years, there was no significant difference between organic and idiopathic growth hormone deficiency in serum IGF-I (0.33±0.17 versus 0.16±0.11 mU/l) or serum SHBG (113±72 versus 108±17 nmol/l). These values were significantly different from controls (1.04±0.36 mU/l and 68.7±31.7 nmol/l, p<0.05, respectively). It is concluded that serum IGF-I and serum SHBG are regulated by growth hormone in late puberty. In early prepuberty, however, the effect of growth hormone on these two serum parameters seems to be weak. This phenomenon could be related to an increase in the sensitivity of the cellular response to the biological effects of growth hormone with age.
Acute and chronic hyperbaric oxygen exposure in humans: effects on blood polyamines, adrenocorticotropin and β-endorphin
Authors: Casti Amos , Orlandini Giancarla , Troglio Maria G , Bacciottini Franco , Michelini Massimo , Maninetti Letizia , Vezzani Giuliano , Rastelli Gianni , Vescovi Pierpaolo
Published: June 2009

Plasma β-endorphin, adrenocorticotropin (ACTH) and blood polyamine (spermidine and spermine) concentrations were evaluated in healthy adult male athletes undergoing hyperbaric oxygen exposure for 10 days (2.8 atm, 100% O2, 60 min daily). In the "acute phase", corresponding to the first day of treatment, and in the "acute in the chronic phase", corresponding to the values obtained on the 5th and 10th days after 60 min of hyperbaric O2, both ACTH and β-endorphin levels increased significantly, whereas no variations were observed for polyamine concentrations. In the "chronic phase", corresponding to the basal values of the 5th and 10th days of treatment, we found a different pattern. In fact, the concentration of polyamines showed a remarkable enhancement, while ACTH and β-endorphin levels remained unchanged. No significant variations were observed during hyperbarism with air. These results demonstrate different modifications of polyamines and β-endorphin and ACTH in subjects submitted to hyperbaric oxygen exposure.
Light deprivation increases plasma levels of melatonin during the first 72 h of life in human infants
Authors: Jaldo-Alba F , Muñóz-Hoyos A , Molina-Carballo A , Molina-Font JA , Acuña-Castroviejo D
Published: June 2009

The development of rhythmic melatonin secretion in full-term neonates seems to occur at about 12 weeks of age, but activity of the pineal gland from 1 to 12 weeks of age is not well documented. To determine whether the pineal gland actively secretes melatonin and reacts to photoperiodic information during this period, we analyzed 45 full-term infants exposed to continuous artificial light during 24, 48 and 72 h after birth for treatment of hyperbilirubinemia. During this light treatment, the eyes of the neonates were completely covered to avoid damage, thus the infants were under continuous light deprivation. Phototherapy significantly decreased plasma bilirubin during treatment. With regard to pineal gland activity, the shortest period of light deprivation tested, 24 h, significantly increased plasma melatonin levels from 152.66±11.57 to 244.86±19.49 ng/l (mean±sem; p<0.001). The other periods tested, 48 and 72 h of light deprivation, led to similar percentages of melatonin stimulation. These results suggest that the pineal gland of neonates, before displaying rhythmic metabolic activity, is sensitive to changes in environmental illumination, indicating maturity of some features of suprachiasmatic nuclei function.
Effects of 2-buten-4-olide, an endogenous feeding suppressant, on the pulsatile secretion of luteinizing hormone in ovariectomized rats
Authors: Saito Seiichiro , Shitsukawa Keiji , Irahara Minoru , Matsuzaki Toshiya , Aono Toshihiro
Published: June 2009

The effects of 2-buten-4-olide (2-B40), an endogenous feeding suppressant, on the secretion of luteinizing hormone (LH) were studied in ovariectomized rats. Intraperitoneal (ip) administration of 2-B40: adult female ovariectomized Wistar rats were given daily ip injections of solution containing 2-B40 at 0, 50 or 100 mg/kg body wt for 14 days. This ip treatment with 2-B40 significantly decreased the mean LH concentration and pulse frequency of LH. Intravenous (iv) administration of 2-B40: a solution of 2-B40 (50 or 100 mg/kg body wt) was slowly injected through an intra-atrium catheter and blood samples were taken every 6 min for 2 h. This iv treatment significantly suppressed the LH pulse frequency but had no significant effect on the LH amplitude or mean LH. Injection of 2-B40 into the third cerebroventricle: the injection of 2-B40 into the third cerebroventricle of freely moving rats decreased the mean LH concentration and the frequency and amplitude of LH pulses. Third cerebroventricle injection of a corticotropin-releasing factor (CRF) receptor antagonist before third cerebroventricle injection of 2-B40: the specific CRF receptor antagonist α-helical-CRF (9–41) was injected into the third cerebroventricle of ovariectomized rats before injection of 2-B40. Administration of 2-B40 into the third cerebroventricle significantly decreased the mean LH, concentration and pulse frequency. Third cerebroventricle injection of the CRF antagonist at 50 μg/rat and then 2-B40 also resulted in significant suppression of the mean LH concentration and pulse frequency. These findings suggest that 2-B40 may suppress gonadotropin-releasing hormone secretion in ovariectomized rats and that its effect in decreasing LH pulses may not be caused through the CRF pathway.
Stimulatory effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on insulin and glucagon release from the isolated perfused rat pancreas
Authors: Yokota Chizuko , Kawai Koichi , Ohashi Shinichi , Watanabe Yasuko , Suzuki Seiji , Yamashita Kamejiro
Published: June 2009

Rat pancreas perfusion was performed to study the effects of pituitary adenylate cyclase activating polypeptide (PACAP) on pancreatic hormone release. Under the perfusate glucose concentration of 5.5 mmol/l, 0.1 nmol/l PACAP27 significantly stimulated both insulin and glucagon release. The degree of stimulation was in a dose dependent manner. The stimulation of insulin release was clearly dependent on the perfusate glucose concentration, when compared with 2.8, 5.5 and 8.3 mmol/l. The potency of PACAP38 on the stimulation of insulin release was greater than that of PACAP27 at 5.5 mmol/l of perfusate glucose concentration, but not at 8.3 mmol/l. No differences for glucagon and cAMP release were found between the two peptides. PACAP's stimulatory effects on insulin and glucagon release were completely abolished by an equimolar and ten times lower concentration of somatostatin, respectively. The physiologic significance of these potent effects of PACAP's islet hormones release must be clarified by further studies.
Iodized salt prophylaxis of endemic goiter: an experience in Toscana (Italy)
Authors: Aghini-Lombardi F , Pinchera A , Antonangeli L , Rago T , Fenzi GF , Nanni P , Vitti P
Published: June 2009

It is well established that iodine supplementation is effective in correcting iodine deficiency and reducing goiter prevalence. In Italy, legislation has allowed the production of iodized salt since 1972, but its consumption is on a voluntary basis. In the present study, the efficacy of legislative measures that made compulsory the availability of iodized salt in foodstores has been evaluated. Urinary iodine excretion and thyroid size, scored according to Pan American Health Organization recommendations, were determined prior to (1981) and 10 years after (1991) the introduction of legislative measures in the whole schoolchildren population residing in a restricted area of the Tuscan Appennines. Moreover, in 1991, thyroid volume was determined by ultrasonography. In 1981, mean urinary iodine excretion was 47.1±22.4 mg/kg creatinine (0.412 μmol/l) and goiter prevalence was 60%, indicating a moderate iodine deficiency. Eighty of the families subsequently used iodized salt on a regular basis; as a result of this excellent compliance, in 1991 the mean urinary iodine excretion increased to 129.7±73 mg/kg creatinine (1.24 μmol/l) and goiter prevalence dropped to 8.1%. The results of this study underline the effectiveness of iodine prophylaxis in correcting iodine deficiency and abating endemic goiter in schoolchildren, and suggest that implementation of measures that make compulsory the availability of iodized salt in foodstores overcomes the fact that there is no law governing the exclusive production and trading of iodized salt.
Impairment of neuromotor and cognitive development in iodine-deficient schoolchildren with normal physical growth
Authors: Azizi F , Sarshar A , Nafarabadi M , Ghazi A , Kimiagar M , Noohi S , Rahbar N , Bahrami A , Kalantari S
Published: June 2009

In order to detect somatic and psychomotor disturbances in children and adolescents residing in areas of iodine deficiency, schoolchildren from three areas with different degrees of iodine deficiency were studied. In Randan, the prevalence of severe endemic goiter was accompanied by alteration in thyroid function, increased thyrotropin levels and retardation of both bone and psychomotor age and decreased intellectual quotient. In Tehran, where iodine deficiency is mild, visible goiter was present in 1 5% of schoolchildren but no alterations in thyroid function, serum thyrotropin, somatic or psychomotor development could be detected. In Zagoon, where the prevalence and severity of goiter was less than Randan but more than Tehran, thyroid function was normal but slightly decreased as compared to Tehran; somatic development was unaltered, but retardation in psychomotor development was evident and the mean intellectual quotient was less than that of Tehranian schoolchildren. These findings indicate the occurrence of physical and psychomotor disturbances in apparently normal schoolchildren from areas of iodine deficiency. Alteration in psychomotor development may occur in children with normal physical growth, due to iodine deficiency.
Thyroid volume and morphology and urinary iodine excretion in a Danish municipality
Authors: Nygaard Birte , Gideon Peter , Dige-Petersen Harriet , Jespersen Niels , Sølling Karsten , Veje Annegrete
Published: June 2009

In order to throw light upon the eventual need for iodine supplementation in Denmark, four age groups of women (15, 30, 45 and 60 years) from the Holbaek municipality were invited for a clinical and ultrasound study of thyroid volume, structure and function. Of the 570 women invited, 391 accepted and were divided into the following groups: group I: 15 years, N= 113; group II: 30 years, N= 100; group III: 45 years, N=98; group IV: 60 years, N=80. The results were as follows: the thyroid gland was palpable in 39% and visible in 16% of the entire group; 19% had a family history of thyroid disorders and 7.6% had a previous thyroid disorder. Thyroid volumes (median (range)) as measured by ultrasound were 12 ml (4–29 ml), 18 ml (5–47 ml), 18 ml (7–64 ml) and 18 ml (9-51 ml) in groups I– IV, respectively. The calculated 24-h iodine excretion was 65 μg (19–365 μg), 88 μg (15-274 μg), 97 μg (40–737 μg) and 83 μg (50–999 μg) in groups I–IV, respectively. An abnormal echo structure was present in 3, 10, 21 and 30%, respectively. Defining a goitre as a thyroid volume above 28 ml indicated a goitre prevalence of 17% in females aged 30–60 years in the Holbaek area of Denmark. Among the 60-year-old women, 3% had a clinically significant goitre (WHO grade III). Thyroid volume did not correlate with iodine excretion. The benefit of iodine supplementation is discussed.
Growth hormone-, alpha-subunit and thyrotrophin-cosecreting pituitary adenoma in familial setting of pituitary tumour
Authors: Links Thera P , Monkelbaan Jan F , Dullaart Robin PF , van Haeften Timon W
Published: June 2009

A patient with acromegaly and hyperthyroidism due to a growth hormone-, thyrotrophin- and alpha-subunit-secreting pituitary adenoma is described. His deceased father had suffered from a pituitary tumour, and was likely to have had acromegaly as well. Plasma growth hormone and insulin-like growth factor I concentrations were elevated, with levels between 10 and 20 μg/l and 4.4 and 7.3 kU/l, respectively. In spite of hyperthyroidism (free thyroxine, 45 pmol/l; free triiodothyronine, 24 pmol/l), plasma thyrotrophin remained at 2.8 mU/l without any response to thyrotrophin-releasing hormone and could not be suppressed with exogenous administration of triiodothyronine. Plasma alpha-subunits were raised to 3.3–3.7 U/l (normal 0.4–1.1 U/l). Pathological examination of the surgically removed tumour showed a pituitary adenoma with the immunohistochemical presence of growth hormone, thyrotrophin, prolactin and alpha-subunit. This is the first report of a growth hormone-, thyrotrophin- and alpha-subunit-producing pituitary adenoma, which occurred in a familial setting.
Possible compensatory role of parathyroid hormone-related peptide on maintenance of calcium homeostasis in patients with non-insulin-dependent diabetes mellitus
Authors: Ishida Hitoshi , Suzuki Kiyoshi , Someya Yoshimichi , Nishimura Masayoshi , Sugimoto Chieko , Goto Masahisa , Taguchi Yoshitaka , Kasahara Hiroyuki , Kadowaki Seizo , Imura Hiroo , Seino Yutaka
Published: June 2009

Recent studies have revealed that altered mineral and vitamin D metabolism is observed in diabetic patients with the complication of osteopenia. In order to elucidate the role of parathyroid hormone-related peptide (PTHrP) on calcium homeostasis in diabetes, we have measured the serum level and urinary excretion of PTHrP as well as other serum calcium-regulating hormones in 106 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 43 control subjects. The serum concentration of intact PTH was 2.34±0.13 (mean±sem) pmol/l in NIDDM patients, which is significantly lower than the value of 3.11±0.14 pmol/l in the controls (p< <0.01). Both serum calcium and calcitonin. however, were not statistically different from controls. On the other hand, circulating PTHrP in NIDDM was 40.1±1.4 pmol/l, which is significantly elevated when compared to 27.3±1.3 pmol/l in the controls (p<0.01). Moreover, urinary excretion of PTHrP also was significantly higher in NIDDM (p<0.01). In the present study, the circulating calcium level was well preserved in NIDDM patients, although the PTH levels were shown to be decreased. The elevated serum PTHrP might, therefore, have a physiologically compensatory role on the calcium regulatory systems in NIDDM. Furthermore, this elevation is most likely due to the excess production of this peptide and not to the decrease in urinary excretion.
Expression of follistatin messenger ribonucleic acid in Sertoli cell-enriched cultures: regulation by epidermal growth factor and protein kinase C-dependent pathway but not by follicle-stimulating hormone and protein kinase A-dependent pathway
Authors: Michel U , Esselmann J , Nieschlag E
Published: June 2009

In this study the localization and regulation of steady-state follistatin messenger ribonucleic acid (mRNA) levels in testicular cell cultures were examined with a solution-hybridization assay using a specific 32P-labelled cytosolic RNA antisense probe for follistatin and a 35S-labelled cytosolic RNA antisense probe for cyclophilin as internal standard. Testes from immature rats were dispersed with collagenase and fractionated in Sertoli and Leydig cell-enriched cultures. Follistatin mRNA was mainly localized to the Sertoli cell-enriched fraction and the expression of follistatin mRNA could be stimulated in vitro with fetal calf serum, epidermal growth factor or phorbol-12-myristate-1 3-acetate (an activator of protein kinase C), whereas follicle-stimulating hormone and forskolin (an activator of protein kinase A) had no effect. Neither prostaglandin E2, the synthetic glucocorticoid RU 28362 or all-trans-retinoic acid, which all regulate follistatin mRNA levels in non-testicular cell types, nor extracellur adenosine triphosphate (a purinergic receptor agonist) or testosterone had any obvious influence on follistatin mRNA levels in Sertoli cell-enriched cuitures. From this study it is concluded that Sertoli cells are likely to be the source of follistatin expression in the rat testis, that follistatin mRNA levels in Sertoli cell-enriched cultures are subjected to regulation by epidermal growth factor and the protein kinase C-dependent pathway but are not regulated by extracellular adenosine triphosphate, follicle-stimulating hormone, all-trans-retinoic acid, prostaglandin E2, forskolin, testosterone or the glucocorticoid RU 28362 and that the regulation of follistatin mRNA is sex- and tissue-specific.