bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thyroid volume and urinary iodine in European schoolchildren: standardization of values for assessment of iodine deficiency
Authors: Delange F , Benker G , Caron Ph , Eber O , Ott W , Peter F , Podoba J , Simescu M , Szybinsky Z , Vertongen F , Vitti P , Wiersinga W , Zamrazil V 
Published: December 2008

Abstract
Up to 1992, most European countries used to be moderately to severely iodine deficient. The present study aimed at evaluating possible changes in the status of iodine nutrition in 12 European countries during the past few years. Thyroid volume was measured by ultrasonography in 7599 schoolchildren aged 7–15 years in one to fifteen sites in The Netherlands, Belgium, Luxemburg, France, Germany, Austria, Italy, Poland, the Czech and Slovak Republics, Hungary and Romania. The concentrations of urinary iodine were measured in 5709 of them. A mobile unit (ThyroMobil van) equipped with a sonographic device and facilities for the collection of urine samples visited all sites in the 12 countries. All ultrasounds and all urinary iodine assays were performed by the same investigators. The status of iodine nutrition in schoolchildren has markedly improved in many European countries and is presently normal in The Netherlands, France and Slovakia. It remains unchanged in other countries such as Belgium. There is an inverse relationship between urinary iodine and thyroid volume in schoolchildren in Europe. Goiter occurs as soon as the urinary iodine is below a critical threshold of 10 μg/dl. Its prevalence is up to 10 to 40% in some remote European areas. This work produced updated recommendations for the normal volume of the thyroid measured by ultrasonography as a function of age, sex and body surface area in iodine-replete schoolchildren in Europe. This study proposes a method for a standardized evaluation of iodine nutrition on a continental basis, which could be used in other continents.
European Journal of Endocrinology 136 180–187
Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height
Authors: Weintrob Naomi , Dickerman Zvi , Sprecher Elliot , Galatzer Avinoam , Pertzelan Atalia 
Published: December 2008

Abstract
Objective: To review the characteristics of children with non-classical 21-hydroxylase deficiency (NC-21-OHD) diagnosed during infancy and childhood, and to evaluate the relationship of pubertal and bone age maturation at initiation of glucocorticoid therapy with the course of puberty and final height.
Design: We retrospectively compared the course of puberty, growth pattern and final height in two groups of patients: group A (two males, six females), hydrocortisone (HC) treatment 7·5–15 mg/m2 per 24 h, initiated ≥1 year before onset of true puberty and group B (seven females), treatment started with the first signs of true puberty present.
Participants: Thirteen girls and two boys with NC-21-OHD diagnosed at age range 0·5–10·6 years were followed-up for 9·0 ± 3·8 years (mean±s.d.). Therapy with HC was initiated because of signs of hyperandrogenism, accelerated growth and bone maturation, or true precocious puberty. The HC dose was adjusted according to linear growth and basal plasma androgen levels.
Results: Puberty and peak height velocity developed significantly earlier in the girls of group B: gonadarche at 7·9 ± 1·4 years and peak height velocity at 9·2 ± 1·4 years vs 10·2 ± 0·4 years (P = 0·002) and 11·5 ± 0·7 years (P = 0·006) in group A. Menarche, however, occurred only slightly earlier in group B (12·0 ± 1·1 vs 12·8 ±0·5 years, P = 0·068). All eight children in group A achieved a final height within the range of their mean parental height standard deviation scores (SDS) in comparison with only 1/7 in group B (P = 0·0014). Seven of eight patients who started therapy before a bone age of 9 years achieved a final height within the parental height SDS range, compared with 2/7 who started therapy later (P = 0·041). The final height SDS was significantly better for group A (0·05 ± 0·19, mean ± s.e.m.) than group B (−1·63 ± 0·23, P = 0·0007), even when adjusted for a significant effect of the mean parental height SDS (A, −0·63 ± 0·28; B, −0·89 ± 0·31, P = 0·0245, ANCOVA).
Conclusion: Every child with signs of excess androgen activity or early puberty should be studied for the possibility of NC-21-OHD. Screening programs for populations with a high frequency of the gene for NC-21-OHD would facilitate early diagnosis and treatment. Pubertal stage and bone age at the introduction of therapy dictate height prognosis. Initiation of therapy before puberty with careful follow-up and HC dose adjustment can assure the achievement of genetic adult height.
European Journal of Endocrinology 136 188–195
Impairment of 11β-hydroxylase but not 21-hydroxylase in adrenal 'incidentalomas'
Authors: Reincke Martin , Peter Michael , Sippell Wolfgang G , Allolio Bruno 
Published: December 2008

Abstract
Recent reports have shown an exaggerated response of 17-hydroxyprogesterone in up to 70% of patients with incidentally detected adrenal adenomas ('incidentalomas'). This has been explained by pre-existing 21-hydroxylase deficiency which may be a pathogenetic factor in the development of adrenal tumours. However, other defects in steroidogenesis, such as mild 11β-hydroxylase deficiency, could also result in increased 17-hydroxyprogesterone secretion. We therefore studied the glucocorticoid and mineralocorticoid pathways in patients with adrenal 'incidentalomas' by measuring multiple adrenal steroids before and after 1–24 ACTH stimulation. Twenty patients with adrenal 'incidentalomas' (14 females, 6 males) and 27 healthy controls (14 females, 13 males) were studied. All subjects underwent a 1–24 ACTH stimulation test (250 μg i.v.) with determination of progesterone, 11-deoxycorticosterone, corticosterone, 17-hydroxyprogesterone, 11-deoxycortisol and cortisol at O and 60 min. All steroids were measured by RIA after extraction and HPLC. Patients with 'incidentalomas' had higher stimulated concentrations of 17-hydroxyprogesterone (21·6 ± 8·4 vs 4·2 ± 0·3 nmol/l; P ≤ 0·001), 11-deoxycortisol (8·1 ± 1·2 vs 3·6 ± 0·3 nmol/l; P ≤ 0·001), progesterone (8·28 ± 2·82 vs 1·08 ± 0·15 nmol/l; P ≤ 0·001), and 11-deoxycorticosterone (2·1 ± 0·39 vs 0·78 ± 0·12 nmol/l; P = 0·002) compared with controls. In contrast, cortisol and corticosterone concentrations were not different. There was evidence for impairment of 11β-hydroxylase activity by an increased 11-deoxycortisol/cortisol ratio (0·012 ± 0·003 vs 0·005 ± 0·001 in controls; P = 0·002) and 11-deoxycorticosterone/corticosterone ratio (0·04 ± 0·003 vs 0·015 ± 0·003; P = 0·003). The conclusions reached were that patients with adrenal 'incidentalomas' have increased responses of precursors of the mineralocorticoid and glucocorticoid pathway including 17-hydroxyprogesterone after stimulation with ACTH. This seems to be caused by impairment of 11β-hydroxylase activity rather than by impaired 21-hydroxylase activity in these tumours.
European Journal of Endocrinology 136 196–200
Effect of a high-fat diet on energy balance and thermic effect of food in hypothyroid rats
Authors: Iossa Susanna , Mollica Maria Pina , Lionetti Lillà , Barletta Antonio , Liverini Giovanna 
Published: December 2008

Abstract
We have carried out measurements of energy balance in hypothyroid rats fed a low-fat or a high-fat diet for eighteen days. We have also measured cephalic and processing thermic effect of food (TEF) after a low-fat or a high-fat meal.
Body lipid gain, carcass lipid content and gross efficiency were significantly (P < 0·05) higher in hypothyroid rats fed a high-fat diet compared with hypothyroid rats fed a low-fat diet, while metabolizable energy intake and energy expenditure remained unchanged. Cephalic TEF after a low-fat meal was significantly (P < 005) lower in hypothyroid rats fed a high-fat diet compared with hypothyroid rats fed a low-fat diet, while it was significantly (P <0·05) higher after a high-fat meal than after a low-fat meal in hypothyroid rats fed a high-fat diet. No significant variation was found in processing TEF after a low-fat or a high-fat meal.
Our results indicate that hypothyroid rats are unable to develop increased energy expenditure and increased TEF in response to a high-fat diet.
European Journal of Endocrinology 136 309–315
Effects of selenium and iodine deficiency on thyroid hormone concentrations in the central nervous system of the rat
Authors: Campos-Barros Angel , Meinhold Harald , Walzog Barbara , Behne Dietrich 
Published: December 2008

Abstract
Objective: The effects of single and combined nutritional selenium and iodine deficiency on intracellular thyroid hormone concentrations and type II 5′-iodothyronine deiodinase (5′D-II) activity were examined in different regions of the adult rat brain.
Design: Four groups (n=6) of weanling female Wistar rats proceeding from a breeding line fed a selenium-deficient or a selenium-replete diet for 3 generations, were fed selenium-deficient, iodine-deficient, combined selenium- and iodine-deficient or selenium- and iodine-replete diets for 2 months before they were killed.
Methods: Tissue thyroxine (T4) and tri-iodothyronine (T3) concentrations were determined by highly sensitive RIAs after extraction of the iodothyronines from the tissue samples. The measurement of 5′D-II was based on the release of radioiodide from the 125I-labelled substrate.
Results: Selenium deficiency significantly decreased tissue T3 concentrations in the hippocampus, hypothalamus and striatum to 70–80% of controls, whereas no significant changes were found in the cerebellum, cerebral cortex and brain stem. Tissue T4 concentrations were only marginally affected with the exception of a 35% increase in the cerebral cortex. Iodine deficiency dramatically diminished serum T4 levels as well as intracellular T4 concentrations in all regions examined up to 10–30% of control. In spite of a threefold enhancement of 5′D-II, the iodine-deficient animals still had a significant reduction of tissue T3 concentrations (50–65% of controls) in all regions excepting the cerebellum. The combination of selenium and iodine deficiency did not significantly alter this pattern of changes.
Conclusions: These findings suggest that prolonged selenium deficiency as well as iodine deficiency may compromise thyroid hormone homeostasis in the adult brain leading to tissue hypothyroidism and therefore to impaired brain function.
European Journal of Endocrinology 136 316–323
Effects of 5,5′-diphenylhydantoin on the metabolic pathway of thyroid hormone in rats
Authors: Schröder-van der Elst Janny P , van der Heide Daan , DiStefano Joe J , van der Bent Chris , Kaptein Ellen , Visser Theo J 
Published: December 2008

Abstract
Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels and interferes with the metabolic pathway of TH. To test the hypothesis that DPH affects the enterohepatic cycle of TH and, thus, the kinetics of TH turnover, we performed a kinetic experiment (three-compartment analysis) and a steady-state, double-isotope equilibrium experiment in rats treated for 3 weeks with DPH (50 mg/kg body weight per day) and in untreated controls. This included measurements of TH and TH metabolite levels, as well as the activities of enzymes involved in the TH metabolic pathway.
DPH treatment resulted in a decrease in the production of thyroxine (T4) (by 25%) and triiodothyronine (T3) (by 37%), a decrease in the T3 concentration in all three pools, and a redistribution of T4 from the fast to the slow pool. The amount of T4 increased in intestinal contents and feces by 66% and 71% respectively. Expressed as a fraction of daily TH disposal, fecal loss of T4 was enhanced from 10 to 23% and that of T3 from 16 to 21%. An increase in T4 and T3 UDP-glucuronyltransferase activities was observed, suggesting that the increased fecal loss of T4 and T3 is secondary to an increased biliary output of their glucuronides. The reduced secretion of TH and increased fecal clearance during DPH treatment can lead in the long run to depletion of TH stores.
European Journal of Endocrinology 136 324–329
Growth hormone increases and insulin-like growth factor-I decreases circulating lipoprotein(a)
Authors: Laron Z , Wang X L , Klinger B , Silbergeld A , Wilcken D E L 
Published: December 2008

Abstract
Background: elevated serum lipoprotein(a) (Lp(a)) is a strong risk factor for coronary artery disease (CAD). Genetic factors appear to account for the major variance in Lp(a) levels but the contribution hormones make in modulating Lp(a) levels is not yet clear. In the present investigation we determined the effects of human growth hormone (hGH) and insulin-like growth factor-I (IGF-I) on circulating Lp(a).
Methods: four groups of patients were studied. Group a: adults with GH deficiency (n=7) treated with hGH (0·05 U/kg/day, s.c.); group b: girls with Turner syndrome (n=7) treated with hGH (0·1 U/kg/day, s.c.); group c: prepubertal boys with idiopathic short stature (n=6) treated with the GH secretagogue (GHRP) hexarelin (60 μg t.i.d. intranasally); group d: Laron syndrome patients (n=10) treated with IGF-I (100–200 μg/kg/day, s.c.). Following overnight fasting, serum was sampled before the initiation of treatment and during 6–9 months treatment.
Results: serum IGF-I rose significantly in all the subjects in all four groups. In the first three groups in which IGF-I was elevated by exogenous or endogenous GH stimulation, serum Lp(a) increased significantly (119±35%, P<0·01; 126±44%, P<0·05; 102±29% P<0·01 for groups a, b, and c respectively). By contrast, serum Lp(a) levels decreased in group d to whom exogenous IGF-I was administered (–66±5%, P<0·001). The differential effect of endogenous vs exogenous IGF-I on serum Lp(a) paralleled the behaviour of serum insulin. Insulin was significantly increased in all the subjects receiving hGH or GHRP (65·2±31%, P=0·109; 93·7±53%, P=0·062; 3536·8±52·7%, P<0·01 for groups a, b, and c respectively) whereas insulin levels were reduced following exogenous administration of IGF-I (—34·1±9·1%, P<0·01).
Conclusions: we conclude that long-term GH treatment increases and IGF-I decreases circulating levels of Lp(a). These findings may have clinical relevance in view of the increasing use of hGH in children and adults and the role of Lp(a) as a CAD risk factor.
European Journal of Endocrinology 136 377–381
Greater disorderliness of ACTH and cortisol release accompanies pituitary-dependent Cushing's disease
Authors: van den Berg Gerrit , Pincus Steven M , Veldhuis Johannes D , Frölich Marijke , Roelfsema Ferdinand 
Published: December 2008

Abstract
We investigated the episodicity of 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 25 healthy matched controls, with a recently introduced scale- and modelindependent regularity statistic, approximate entropy (ApEn). The mean (± s.e.m.) ApEn value for plasma ACTH concentrations in Cushing's disease was 1·3817 ± 0·033, and in controls 0·8394 ± 0·049 (P< 10−10); for plasma cortisol concentrations the values were 1·4575 ± 0·052 and 0·8637 ± 0·020 respectively (P<10−10), implying greater irregularity of release for both hormones in Cushing's subjects. The calculated sensitivity and specificity of ApEn for ACTH profiles were 94% and 100% respectively. For cortisol the sensitivity and specificity were both 100%. ApEn was not correlated with sex, age, or the total 24-h secretion rate of ACTH and cortisol in patients and controls. The increased ApEn in patients with Cushing's disease points to an increased disorderliness of ACTH and cortisol secretion compared with healthy controls. In conjunction with the available literature, we hypothesize more generally that autonomous endocrine tumors may be typified by reduced regularity, orderliness, or synchrony of the time structure of hormone release.
European Journal of Endocrinology 136 394–400
Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment
Authors: Juul Anders , Müller Jørn , Skakkebæk Niels E 
Published: December 2008

Abstract
In healthy boys, the pituitary–gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with GnRH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys.
Methods: PSA was measured by an ultrasensitive immunofluorometric assay with a detection limit of 003 μg/l. Testosterone was measured by an RIA with a sensitivity of 0·23 nmol/l, and sex hormone binding globulin was measured by a time-resolved immunofluoresence assay (sensitivity 0·23 nmol/l). Five boys with central precocious puberty (CPP) were studied before and after 12 months of GnRH agonist treatment. Sixty healthy boys (12 in each Tanner stage of puberty) and 37 healthy young males served as controls.
Results: PSA levels were immeasurable in all prepubertal boys, whereas PSA levels increased with increasing stage of pubertal maturation. There was a significant correlation between PSA and testosterone and free androgen indices (r = 0·61 and r = 0·65 respectively, both P< 0001). All 5 boys with CPP had significantly elevated PSA levels which decreased to very low or immeasurable levels after GnRH agonist treatment.
Conclusion: PSA may be a useful marker of testosterone activity in boys with normal or precocious puberty.
European Journal of Endocrinology 136 401–405
Lanreotide in the treatment of patients with thyroid eye disease
Authors: Krassas G E , Kaltsas Th , Dumas A , Pontikides N , Tolis G 
Published: December 2008

Abstract
Octreotide, a potent synthetic somatostatin (SM) analogue, was recently evaluated and found to have a beneficial effect in thyroid eye disease (TED), mostly in those patients with a positive Octreoscan-111. Lanreotide (LRT; Somatuline-Ipsen), a new SM long-acting analogue, is more active than natural SM and shows a much longer duration of action. The aim of the present preliminary study was to evaluate the therapeutic effect of LRT in the treatment of TED. Five patients, three males and two females, mean age 50·6±7·6 s.d. (45–64) years, all with severe symptoms of TED were studied. A similar number of patients, matched for age, sex and severity of ophthalmopathy served as controls. All the patients and controls were investigated with orbital scintigraphy using 111In DTPA-d-Phe1-octreotide (Octreoscan111) and selected on the basis of positive octreoscan. The NOSPECS system, as adapted by Donaldson et al. (Journal of Clinical Endocrinology and Metabolism 1973 37 276–-285) and a disease activity score, as proposed recently by an International Workshop, have been followed in this study in order to evaluate the response to treatment. The five patients who comprised the treatment group received 0·04 g LRT i.m. once every 2 weeks over a period of 3 months, after which the Octreoscan-111 was repeated. The control patients were given an injection of water i.m., also once every 2 weeks for 3 months, after which they were evaluated clinically. No Octreoscan-111 was performed in the controls. All patients and controls were evaluated by the same physician, who was unaware of the type of treatment used. A decrease in the NOSPECS score and the clinical activity score was regarded as a positive response, while no change or an increase in the NOSPECS score along with no clinical improvement was regarded as a-negative response. After 3 months of treatment with LRT, four patients showed a statistically significant improvement in ophthalmopathy in both eyes and one in one eye. Three of the control patients with TED did not show any change, one showed a minor improvement in one eye and no change in the other and one showed deterioration in both eyes. An interesting finding was that orbital Octreoscan-111 activity was absent in all the patients after LRT treatment. In conclusion, these preliminary results show that LRT has a beneficial effect on patients with TED, and that since it has to be given only once every 2 weeks, it is probably superior to any other form of SM treatment. However, as the number of patients was small, further studies are needed to confirm our results.
European Journal of Endocrinology 136 416–422
Parathyroid hormone-related protein in neonatal and reproductive goats determined by a sensitive time-resolved immunofluorometric assay
Authors: Rong Haiqin , Hydbring Eva , Olsson Kerstin , Burtis William J , Rankin Wayne , Grill Vivian , Bucht Elisabet 
Published: December 2008

Abstract
Objective: High concentrations of parathyroid hormone-related protein (PTHrP) have been found in goat milk but it is not known whether it can enter the circulation of the neonate. In this study we have developed a sensitive two-site lanthanide immunofluorometric assay (IFMA) using dissociation and enhancement time-resolved fluorometry to address this question.
Method: Affinity-purified anti-PTHrP 38–67 raised in rabbit was biotinylated and immobilized in streptavidin-coated microtitration wells as a 'capture' antibody. As a signal, affinity-purified anti-PTHrP 1–34, raised in sheep, was labeled with an europium chelate. A sensitivity of 0·3 pmol/l was achieved. PTHrP levels were determined in the plasma of eleven neonatal, seven parturient and six non-pregnant, non-lactating goats as well as in goat milk.
Results: The circulating PTHrP levels (mean±s.d.) were significantly increased at day 1 (6·1± 1·7 pmol/l; P< 0·01) and day 3 (3·5±0·6 pmol/l; P< 0·05) after birth in the male kids (n = 8) bottle-fed with milk from the dams, compared with before (2·2±0·7 pmol/l)and 30 min after (2·0±0·6 pmol/l) the first feeding and 14 days (2·4±0·8 pmol/l) later. In the female kids (n = 3) fed with formula there was no such increase and the concentrations remained between 1·6–1·9 pmol/l. In the parturient goats the mean±s.d. PTHrP levels before, during and after parturition were 2·9±1·7. 4·2±2·4 and 3·7±2·2 pmol/l respectively (n = 7) which demonstrated that plasma PTHrP was higher during and after parturition in comparison with before (P < 0·05). The levels in non-pregnant, non-lactating goats were 3·3±1·5 pmol/l (n = 6). PTHrP levels in goat milk were in the nanomolar range and were highest in the colostrum.
Conclusions: A significant increase of plasma PTHrP was observed in goat kids fed with milk from their dams and this increase was not found in kids fed with formula. Plasma PTHrP was also increased during parturition.
European Journal of Endocrinology 136 546–551