bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gonadotrophin and prolactin secretory dynamics in girls with normal puberty, idiopathic precocious puberty and precocious puberty due to hypothalamic hamartoma
Authors: Uriarte M. Mercedes , Oerter Klein Karen , Barnes Kevin M. , Pescovitz Ora H. , Loriaux D. Lynn , Cutler, Jr. Gordon B. 
Published: March 2003

OBJECTIVEThis study was designed to test the hypothesis that hypothalamic hamartoma causes precocious puberty through a different neuroendocrine mechanism than that of normal puberty or of idiopathic precocious puberty.DESIGN AND PATIENTSWe compared the pattern of gonadotrophin secretion among 4 girls with precocious puberty due to hypothalamic hamartoma, 27 girls with idiopathic precocious puberty, and 14 girls with normal puberty. All subjects were breast stage 3 or 4. Blood samples were obtained every 20 min for 4 h during the day (1.000 hours to 1400 h) and night (22.00 hours to 0200 h).MEASUREMENTSLH, FSH, and prolactin were measured in each blood sample. Girls also underwent LHRH‐stimulation with measurement of LH and FSH before and after stimulation.RESULTSThere were no significant differences in mean LH level, LH peak amplitude, or LH or FSH peak frequency during either the day or the night among the three diagnostic groups. However, the mean ± SD LHRH‐stimulated peak LH levels were greater in girls with hypothalamic hamartoma than in girls with normal puberty or with idiopathic precocious puberty (194 ± 142 vs 85 ± 60 or 66 ± 54 IU/l, respectively, P < 0.05). The LHRH‐stimulated peak FSH level in girls with hypothalamic hamartoma exceeded the level for the normal pubertal girls (31 ± 19 vs 17 ± 7 IU/l, P < 0.05), but not the level for the girls with idiopathic precocious puberty (25 + 12 IU/l). The peak LH to peak FSH ratio in the girls with hypothalamic hamartoma exceeded the ratio for the girls with idiopathic precocious puberty (7.3 ± 3.9 vs 2.6 ± 3.0 IU/l, P < 0.05), but not the ratio for the normal pubertal girls (5.0 + 2.9). There were no significant differences in mean prolactin level, peak amplitude or frequency, or in the ratio of mean night to mean day prolactin, among the 3 diagnostic groups.CONCLUSIONSWe conclude that spontaneous gonadotrophin and prolactin secretion are similar among girls with hypothalamic hamartoma, idiopathic precocious puberty, or normal puberty. However, the increased LHRH‐stimulated peak LH in the girls with hypothalamic hamartoma suggests subtle differences in neuroendocrine regulation that may underlie their more rapid pubertal maturation.
The relationship between the serum leptin concentrations of thyrotoxic patients during treatment and their total fat mass is different from that of normal subjects
Authors: Zimmermann‐Belsing Tina , Dreyer Marianne , Juul Holst Jens , Feldt‐Rasmussen Ulla 
Published: March 2003

OBJECTIVEPrevious studies of leptin in thyrotoxic human subjects have been short‐term and cross‐sectional. We have measured serum leptin concentrations in thyrotoxic patients in order to study the influence of endogenous thyroid hormones on the relationship between serum leptin and fat mass.DESIGNpatients, measurements: In 10 fasting thyrotoxic patients (8 females, 2 males, mean age: 51 years) we measured serum leptin (μg/l), total thyroxine (TT4), total triiodothyronine (TT3), thyrotropin (TSH) and by Dual Energy X‐ray Absorptiometry (DEXA) total fat mass (TFM, kg) at time of diagnosis (0 months, baseline) and during 12 months treatment with thiamazole. For comparison 16 fasting thiamazole‐treated euthyroid patients (14 females, 2 males, mean age: 38 years) were studied after one year follow‐up (26 month (15–48)) and 18 normal controls (12 females, 6 males, mean age: 39 years).RESULTSThe serum leptin concentration was 9.1 (1.3 μg/l (mean (SEM) in the thyrotoxic patients and increased significantly to 16.0 (1.3 μg/l (P < 0.0005) after 12 months treatment compared to both normal subjects and their own baseline. There was a significant correlation between serum leptin concentration and TFM in the normal control group (r = 0.79, P < 0.00009), in the thiamazole‐treated euthyroid group (r = 0.85, P < 0.00003) and in the baseline thyrotoxic group (r = 0.84, P < 0.002) but the serum leptin/TFM ratio increased significantly during 12 months of antithyroid drug treatment from 0.34 (1.2 μg/l/kg to 0.53 (1.2 μg/l/kg (P < 0.03).CONCLUSIONThe thiamazole‐treated thyrotoxic patients increased their serum leptin concentrations during 12 months antithyroid drug treatment without a significant corresponding degree of changes in TFM as expected from normal controls. It is suggested that the metabolic state in thyrotoxic patients can influence the regulation of serum leptin concentrations without any associated changes in TFM.
The effects of interleukin‐2 treatment on endothelin and the activation of the hypothalamic–pituitary–adrenal axis
Authors: Raab Claudia , Weidmann Eckhart , Schmidt Alexander , Bergmann Lothar , Badenhoop Klaus , Henning Usadel Klaus , Haak Thomas 
Published: March 2003

OBJECTIVERecent reports suggest that complex interactions exist between the neuroendocrine and immune systems. It has been shown for example that cytokines are able to stimulate the hypothalamo‐pituitary‐adrenal axis. In addition, some studies present evidence that endothelin is able to modulate the activity of several hypothalamic‐pituitary axes, e.g. by inducing the ACTH production.DESIGNWe investigated the effects of interleukin‐2 on endothelin levels and the hypothalamo‐pituitary‐adrenal axis. We determined the interleukin‐6, big‐endothelin, endothelin‐1, ACTH, cortisol and AVP responses to intravenously and subcutaneously administered interleukin‐2 in 8 cancer patients in a randomized placebo controlled trial.PATIENTS8 Patients (2 female and 6 male), age 44 ± 4.8 years, were enrolled. All patients had a World Health Organization performance status of 1 or less and a Karnofsky Index of at least 80%.MEASURMENTSBlood‐samples were taken before and 15, 30, 45, 60, 120, 180, 240, 300 and 360 min after interleukin‐2 injection. Cytokine serum levels and the plasma levels of big‐endothelin, endothelin, ACTH and AVP were analysed using radioimmunoassays. Cortisol was assayed by an enzyme‐linked immunosorbent assay.RESULTSInterleukin‐2 treatment significantly increased plasma big‐endothelin levels (P < 0.01 vs basal) and endothelin‐1 levels (P < 0.05 vs basal) within two hours and this was followed by an increase in ACTH (P < 0.01 vs basal) and cortisol (P < 0.05 vs basal) within three hours. Interleukin‐6 levels increased two hours after interleukin‐2 administration (P < 0.01 vs basal). Interleukin‐2 had no detectable effect on AVP, blood pressure or heart rate.CONCLUSIONSOur data demonstrate that cytokines are able to activate the human hypothalamo‐pituitary‐adrenal axis in vivo. On the basis of the observed time kinetics and in connection with previous findings from in vitro and animal models, we conclude that endothelin may be a link between cytokines and corticotrophin‐releasing hormone, most probably functioning as a cytokine‐induced neuromodulator controlling pituitary functions.
Experience with transdermal testosterone replacement therapy for hypogonadal men
Authors: Parker Susan , Armitage Mary 
Published: March 2003

BACKGROUNDNone of the existing options for long‐term testosterone replacement therapy (TRT) for hypogonadal men are ideal. Depot replacement at frequent intervals and implants are effective but invasive and inconvenient for the patient. Oral therapy results in poor hormone levels. Both are associated with undesirable metabolic changes. A transdermal formulation therefore represents a potential therapeutic advance for testosterone replacement.OBJECTIVETo carry out a clinical audit of the acceptability and efficacy as a treatment for hypogonadism of the first transdermal testosterone therapy available in the UK (Andropatch, SmithKline Beecham) compared with existing androgen replacement options.PATIENTS AND MEASUREMENTSSerum testosterone and questionnaire data on treatment efficacy, side‐effects, therapy preference, sexual dysfunction and partner's attitudes to therapy were obtained from 50 hypogonadal men prescribed long‐term testosterone replacement.RESULTSEighty per cent of the men returned analysable questionnaires. Eighty‐four per cent experienced adverse effects with transdermal therapy, most commonly dermatological problems; 22% of the sample elected to continue with transdermal therapy, 72% returned to depot and 5% returned to oral therapy. The reservoir patches were judged to be too large, uncomfortable, visually obtrusive and noisy. Testosterone levels were comparable to those obtained with depot replacement with the added advantage of a more physiological pharmacokinetic profile. Men taking oral preparations were consistently under‐replaced.CONCLUSIONSAdverse events were substantially higher than reported from clinical trials but in keeping with the spectrum of yellow card reports received by the Committee on Safety of Medicines. The pharmacokinetic advantages are thus largely outweighed by low patient acceptability. In its present form transdermal therapy remains an expensive option for those who cannot tolerate depot testosterone replacement.
Novel DAX1 mutations in X‐linked adrenal hypoplasia congenita and hypogonadotrophic hypogonadism
Authors: Bassett J. H. D. , O'Halloran D. J. , Williams G. R. , Beardwell C. G. , Shalet S. M. , Thakker R. V. 
Published: March 2003

OBJECTIVEMutations of the DAX1 gene (Dosage‐sensitive sex reversal‐Adrenal hypoplasia congenita critical region on the X chromosome gene 1), which encodes a novel orphan nuclear receptor, have been identified in patients with X‐linked adrenal hypoplasia congenita (AHC) and hypogonadotrophic hypogonadism (HHG). We have investigated two kindreds with AHC and HHG for DAX1 mutations.METHODSTwo kindreds with five affected males, four carrier females and four unaffected males were investigated. The gonadotrophin deficiency in three of the boys was observed to be partial until mid‐puberty. DAX1 mutations in the entire 1413 bp coding region were sought by DNA sequence analysisRESULTSTwo DAX1 mutations, situated within exon 1, were detected. These consisted of an insertional mutation at codon 183 that led to a frameshift and a premature Stop at codon 184, and a missense mutation Leu278Pro that involved a highly conserved leucine residue within the proposed ligand binding domain. Co‐segregation of these mutations with the disease in each family, and their absence from 107 alleles in 73 (39 males and 34 females) unrelated control individuals, was demonstrated by allele specific oligonucleotide hybridization (ASO) analysis for the insertional mutation, and by Ban I restriction endonuclease analysis for the missense mutation.CONCLUSIONSTwo novel DAX1 mutations have been detected in two families with adrenal hypoplasia and hypogonadotrophic hypogonadism. The finding of partial gonadotrophin deficiency in the affected males from these families is notable and an early recognition of such a possibility in a patient, which may be facilitated by DAX1 mutational analysis, may help to prevent the sequelae of delayed androgen replacement therapy.
High precursor level in maternal blood results from the alternate mode of proopiomelanocortin processing in human placenta
Authors: Raffin‐Sanson Marie‐Laure , Massias Jean Francis , Ankotche Amos , Coste Joël , De Keyzer Yves , Oliver Charles , Dumont Chantal , Cabrol Dominique , Ferré Francoise , Bertagna Xavier 
Published: March 2003

OBJECTIVEACTH‐producing non‐pituitary tumours are often associated with altered precursor processing, particularly in the most aggressive ones. Since placental tissue is characterized by its ability to express the proopiomelanocortin (POMC) gene and rapid cellular proliferation, we examined whether intact POMC could be released physiologically during human gestation.SUBJECTSOne hundred and fifty six normal pregnant women, 12 with multiple pregnancies, and 23 non‐pregnant controls. Twenty‐eight women were studied in the immediate postpartum period.MEASUREMENTSWe measured plasma POMC levels with a specific immunoradiometric assay (IRMA) using a combination of antibodies directed against ACTH and β endorphin. Results obtained with this first IRMA were confirmed in 22 subjects with a second assay using the same β endorphin antibody and a more distal antibody directed against the N‐terminal fragment of POMC. Reverse transcription‐PCR detected full length, pituitary‐like, POMC mRNA in human placenta.RESULTSPlasma POMC was undetectable (<60 U/ml) in 23 normal subjects. In normal monofetal pregnancies, POMC became detectable in most women by the third month and then increased steadily until mid‐gestation: 168 ± 108 (U/ml; mean ± SD) between 12 and 15 weeks, 190 ± 103 between 16 and 19 weeks, 324 ± 180 between 20 and 23 weeks, 276 ± 171 between 24 and 27 weeks, 292 ± 177 between 28 and 31 weeks, 290 ± 235 between 32 and 35 weeks and 308 ± 210 between 36 weeks and parturition. Plasma POMC was significantly higher in multiple pregnancies with very high levels in three triplet‐bearing mothers: 671, 941, and 1731 U/ml at 31, 33 and 32 weeks, respectively. POMC levels felt quickly in post partum, becoming undetectable in five of 13 women on day 1, seven of eight on day 2 and five of six on day 3. Plasma POMC displayed no diurnal variation, was not suppressed by glucocorticoid administration and did not correlate with plasma ACTH or cortisol. In contrast, plasma POMC positively correlated with plasma CRH.CONCLUSIONSPregnancy is the only condition in which POMC is produced and released physiologically, similar in some respects to the ectopic ACTH syndrome. POMC is derived solely from the placenta, with no interference from maternal pituitary secretion, and is thus a new and specific placental marker.
Recombinant interferon α (rIFN‐α) does not potentiate the effect of iodine excess on the development of thyroid abnormalities in patients with HCV chronic active hepatitis
Authors: Minelli Roberta , Braverman Lewis E. , Valli Maria Antonietta , Schianchi Claudia , Pedrazzoni Mario , Fiaccadori Franco , Salvi Mario , Magotti Maria Grazia , Roti Elio 
Published: March 2003

OBJECTIVETo determine whether the administration of pharmacological quantities of iodine during interferon‐alpha (rIFN‐α) treatment of chronic viral hepatitis B and C (HCV) would exacerbate the potential adverse effects of rIFNα on thyroid function.DESIGNThyroid function tests were carried out in 48 euthyroid patients before and during rIFN‐α therapy of HCV. Twenty‐one of these patients were also treated with 10 drops saturated solution of potassium iodine (SSKI, ∼350 mg iodine daily). Eight patients with HCV but not treated with rIFN‐α received 10 drops SSKI.PATIENTSAll patients were enthyroid prior to rIFN‐α therapy for HCV or iodine and thyroid function tests were similar in the three groups.MEASUREMENTSSerum free T4, free T3, and TSH concentrations were measured prior to and at 30 and 60 days of rIFN‐α therapy in the three groups of patients. The serum TSH response to TRH was assessed before rIFN‐α therapy and on day 60. Thyroid peroxidase antibodies were measured before and during therapy.RESULTSDuring the 2‐month study period, similar small but significant decreases in serum FT4 and FT3 and compensatory small significant increases in TSH concentrations were observed in the patients treated with rIFN‐α + iodine and iodine alone but not in the patients receiving rIFN‐α alone. Abnormal thyroid function tests were observed more frequently in patients receiving rIFN‐α + iodine and iodine alone compared to those receiving rIFN‐α alone.CONCLUSIONSExcess iodine administered to patients treated with rIFN‐α induced small changes in thyroid function similar to those observed in patients treated with iodine alone. Thus, rIFN‐α and iodine do not appear to be synergistic in the development of abnormal thyroid function tests over a 2‐month treatment period.
Evaluation of bone metabolism after the use of an inhaled glucocorticoid (flunisolide) in patients with moderate asthma
Authors: Hauache  , Amarante  , Vieira  , Faresin  , Fernandes  , Jardim  , Lazaretti‐Castro  
Published: March 2003

OBJECTIVEWe have investigated the effects of the inhaled corticosteroid flunisolide on bone metabolism and adrenal function in patients with moderate asthma.SUBJECTS AND DESIGNTwenty ambulatory patients (13 females, 7 males, mean age ± SD of 36.4 ± 12.4 years) with moderate asthma were recruited. None had taken corticosteroids for at least 1 month. Flunisolide 500 μg was given twice a day for 10 weeks, without any other medication. Blood and urine were collected before and at the end of treatment course. Cortisol (basal and 1 h after ACTH 250 μg i.v.) was measured to evaluate adrenal function. A peak cortisol response of 496 nmol/l was considered an adequate response. Serum ionized calcium, intact PTH, plasma osteocalcin (OC) and urinary pyridinoline (Pyr) and deoxy‐pyridinoline (D‐Pyr) were measured to evaluate bone metabolism. Wilcoxon paired test was performed for statistical analysis. Results are expressed as mean ± SD.RESULTSIn most patients (85%), there was no difference after treatment with flunisolide on basal and stimulated cortisol levels. We found a significant decrease of OC (3.55 ± 1.42 to 2.97 ± 1.05 nmol/l) and Pyr (66.4 ± 20.0 to 59.5 ± 24.9 pmol/μmol creatinine) levels after treatment (P < 0.05). We also observed a positive correlation between the variations seen in pre and post treatment values of OC and Pyr/D‐Pyr.CONCLUSIONSThe use of inhaled flunisolide 1000 μg/day for 10 weeks had no suppressive effect on adrenal function in the majority of asthmatic patients studied. However, the effects seen on bone and mineral metabolism, evidenced by the significant fall in osteocalcin and pyridinoline levels, may indicate a possible systemic effect of this drug. Clinical consequences of long‐term treatment with flunisolide need to be further evaluated.
Circadian variation of plasma cortisol in prepubertal children with normal stature, short stature and growth hormone deficiency
Authors: Hermida Ramón C. , García Leopoldo , Ayala Diana E. , Fernández José R. 
Published: March 2003

OBJECTIVESWhen studying the relationship between spontaneous secretion of growth hormone (GH) and cortisol in children, most studies show no correlation in mean levels of these two hormones, while others found positive or even strongly negative correlations. These contradictory results could be partly due to the inability to properly compare hormones that are characterized by circadian and ultradian variations in their secretory profiles. We aim here to study possible differences in rhythm characteristics of plasma cortisol with stature and to compare the circadian secretory patterns of cortisol and GH.PATIENTSWe analysed data from 135 prepubertal children: (1) 14 GH‐deficient children; (2) 36 children with short stature (2–3 SD below their peer group mean); (3) 57 children with very short stature (3–4 SD below their peer group mean); and (4) a reference group of 28 children with normal stature (± 2 SD). Subjects were living in a hospital setting on a diurnal waking (07.30–22.30 h), nocturnal resting routine during sampling, consuming the usual hospital diet at fixed times.MEASUREMENTSCortisol and GH concentrations were determined by radioimmunoassay in plasma obtained at about 2–3 h intervals during most of the day and at half‐hour intervals between 22.00 and 02.00 h. Circadian rhythm characteristics obtained by least‐squares estimation were compared between groups divided according to gender and stature with a parameter test.RESULTSshow a statistically significant circadian rhythm in cortisol secretion for all groups studied (P < 0.001 in all cases). A comparison of circadian parameters indicated similar characteristics between subjects of short, very short and normal stature. Despite a borderline statistically significant difference in rhythm‐adjusted mean and amplitude of GH between nondeficient and GH‐deficient children, there was no difference in the circadian pattern of cortisol secretion between these two groups. No correlation was found in circadian mean, amplitude, average, standard deviation, standard error, minimum or maximum between GH and cortisol for any of the groups of children.CONCLUSIONSAny possible relation between GH and cortisol remains unclear. Moreover, GH‐deficient children are not necessarily characterized by either hyper‐ or hypocortisolaemia.
Evaluation of free insulin‐like growth factor‐I measurement on the diagnosis and follow‐up treatment of growth hormone‐deficient adult patients
Authors: Musolino Nina Rosa C. , Da Cunha Neto Malebranche B. , Marino Raul , Giannella‐Neto Daniel , Bronstein Marcello D. 
Published: March 2003

OBJECTIVEInsulin‐like growth factor I (IGF‐I) and IGF binding protein‐3 (IGFBP‐3) are GH‐dependent and their concentrations have been used in the diagnosis of GH deficiency. Recently, the free fraction of IGF‐I has received more attention. The aim of the study was to assess the role of free IGF‐I in the diagnosis of GH deficiency in adults, and in follow‐up during treatment with recombinant human GH (rhGH).DESIGN AND PATIENTSWe studied 24 adult patients with pituitary disease and GH deficiency and 25 matched controls. Nine patients were re‐evaluated after 6 months of treatment with rhGH (0.25 U/kg/week).MEASUREMENTSSerum levels of IGF‐I, free IGF‐I, IGFBP‐3 and IGFBP‐1 were measured by immunoradiometric assay.RESULTSSerum free IGF‐I levels were significantly lower in the GH deficient group than in the normal group (mean: 0.84 and 1.32 μg/l respectively, P = 0.0009). Furthermore, serum IGF‐I levels were also lower (mean: 92.24 and 230.47 μg/l respectively, P < 0.0001). 63% of patients had serum IGF‐I concentration below the normal range. For free IGF‐I, 52% of the GH deficient patients showed levels below the lowest value obtained for the normal group. Seventy‐five percent of the patients showed at least one of the two determinations below the normal range. The free‐total IGF‐I ratio was significantly higher (P = 0.025) in GH deficient group (range: 0.19–21.29, mean: 2.53) than in normal controls (range: 0.2–2.15, mean: 0.6). Regarding IGFBP‐3 and IGFBP‐1 no differences were observed between the two groups. During rhGH treatment the increase in serum total and free IGF‐I and IGFBP‐3 paralleled the beneficial effects on body composition.CONCLUSIONSFree IGF‐I may be another useful method for the diagnosis of GH deficiency, particularly if related to total IGF‐I concentration.