bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone remodelling markers and serum cytokines in patients with hyperthyroidism
Authors: Akalin Aysen , Colak Ömer , Alatas Özkan , Efe Belgin 
Published: March 2003

Summaryobjective This study was designed in order to evaluate bone turnover with bone formation and resorption markers in hyperthyroidism and its possible relationship with serum cytokines interleukin 6 (IL‐6) and tumour necrosis‐α (TNF‐α), levels of thyroid hormones and thyroid autoantibodies.design and patients Twenty‐six hyperthyroid patients including nine with Graves’ disease, 14 with toxic multi‐nodular disease and three toxic adenoma were studied. Twenty normal subjects served as the control group.measurements Serum calcium, phosphorus, total and bone‐specific alkaline phosphatase, procollagen type 1‐C peptide (PICP), osteocalcin, IL‐6 and TNF‐α measurements were performed and deoxypyridinoline (free DPD), calcium, phosphorus and creatinine levels were measured in fasting morning urine specimens of all hyperthyroid patients and all controls. Also, serum total and free T3 and T4 and TSH were analysed and thyroid antiperoxidase and antithyroglobulin antibodies were determined in sera of hyperthyroid patients. Patients with hyperthyroidism received propylthiouracil treatment until the achivement of euthyroidism and then serum cytokine levels were remeasured.results Mean serum values of osteocalcin, total and bone‐specific alkaline phosphatase were all significantly higher in hyperthyroid patients than in normal controls. PICP levels were not significantly different between these two groups. Urinary deoxypyridinoline levels were markedly elevated in hyperthyroid patients compared to the control group. There was a significant positive correlation between urinary free DPD levels and serum free T3, free T4 and T4 levels. Serum free T4 levels also correlated with urinary calcium levels. Serum IL‐6 values were significantly higher in hyperthyroid patients compared to control group. TNF‐α levels were slightly lower in patients with hyperthyroidism. No significant correlation was found between bone remodelling markers and serum cytokines. Serum Il‐6 levels were correlated positively with age. After the treatment period both IL‐6 and TNF‐α returned to levels comparable with euthyroid controls.conclusion Bone turnover is increased in favour of resorption and the rate of resorption is associated with the levels of thyroid hormones in hyperthyroidism. The increase in the levels of serum IL‐6 in hyperthyroidism is not related directly with bone resorption seen in hyperthyroidism.
Dynamics of the plasma concentrations of TSH, FT4 and T3 following thyroxine supplementation in congenital hypothyroidism
Authors: Bakker Bert , Kempers Marlies J. E. , De Vijlder Jan J. M. , Van Tijn David A. , Wiedijk Brenda M. , Van Bruggen Michael , Vulsma Thomas 
Published: March 2003

Summaryobjective The dynamics of the plasma concentrations of various diagnostic determinants of thyroid function were analysed in children with congenital hypothyroidism (CH) after the start of T4 supplementation. The description of the biochemical dynamics of TSH and free T4 (FT4) during the first period of thyroxine treatment is important to depict the practical outlines of the initial dosage of T4 and dosage adjustments for newborns with variable forms of CH.design A retrospective analysis was performed of frequent plasma TSH, total T4 (T4), FT4 and total T3 (T3) measurements in 30 CH neonates during the first weeks of treatment, treated with initial daily T4 dosages ranging from 4·8 to 11·1 µg/kg.results A 50% reduction in the initial plasma TSH concentration was achieved after 3–4 days of treatment, independent of CH severity. At a median of 32 days after the start of T4 supplementation, plasma TSH ranged between 0·4 and 4·0 mU/l. The mean interval needed for FT4 to reach the age‐related normal values (12–29 pmol/l) was 3 days. The increase in plasma T3 concentrations levelled off within a few days, when T4 reached concentrations of around 100 nmol/l.conclusions Plasma T3 and FT4 concentrations reach the normal range a few days after thyroxine treatment is started. By contrast, normalization of plasma TSH concentration takes several weeks. At the time that plasma TSH is normalized, CH neonates show a higher range of plasma FT4 concentrations than the normal range. When TSH normalization is the goal of treatment in CH, the target range for plasma FT4 during treatment in the first months needs to be adapted. During the first month of treatment the plasma TSH concentration is not helpful in assessing the proper T4 supplementation dosage. Once plasma TSH has reached normal values, it becomes a reliable determinant in addition to plasma FT4.
Ghrelin immunoreactivity in human plasma is suppressed by somatostatin
Authors: Nørrelund Helene , Hansen Troels K. , Ørskov Hans , Hosoda Hiroshi , Kojima Masayasu , Kangawa Kenji , Weeke Jørgen , Møller Niels , Christiansen Jens S. , Jørgensen Jens Otto L. 
Published: March 2003

Summaryobjective Ghrelin was recently identified as a specific endogenous ligand for the growth hormone secretagogue receptor (GHS‐R). This new hormone was isolated from rat and human stomach and was reported to circulate in human plasma, but the regulation and physiological significance of ghrelin in humans have not been clarified. The present study was undertaken to test the following hypotheses: (1) prolonged fasting, which is known to stimulate GH secretion, is associated with changes in ghrelin immunoreactivity; (2) somatostatin in the systemic circulation regulates ghrelin secretion; and (3) GH affects ghrelin levels.design and patients The study population included normal subjects investigated on three occasions (fasting alone, fasting and somatostatin infusion ± GH); GH‐deficient adults investigated after 12 and 36 h of fasting ± GH, as well as patients with active acromegaly before and after somatostatin analogue treatment.results Somatostatin infusion lowered ghrelin levels 70–80% (P < 0·0001), whereas continued fasting ± GH did not significantly affect ghrelin levels. In active acromegaly, suppression of plasma ghrelin levels was recorded after a single subcutaneous octreotide injection as well as during prolonged administration of slow‐release octreotide.conclusions (1) Amplification of GH release during prolonged fasting is not caused by an increase in ghrelin immunoreactivity, (2) systemic somatostatin suppresses plasma ghrelin levels independently of GH status, and (3) the feasibility of measuring ghrelin in the circulation provides an opportunity for studying the interaction between hormones and nutrition.
Dehydroepiandrosterone, 17α‐hydroxyprogesterone and aldosterone responses to the low‐dose (1 µg) ACTH test in subjects with preclinical adrenal autoimmunity
Authors: Laureti Stefano , Candeloro Paola , Aglietti Maria Chiara , Giordano Roberta , Arvat Emanuela , Ghigo Ezio , Santeusanio Fausto , Falorni Alberto 
Published: March 2003

Summaryobjective The appearance of 21‐hydroxylase autoantibodies (21OHAbs) identifies subjects with preclinical adrenal insufficiency. In 21OHAb‐positive subjects, the adrenocortical function is best evaluated by peak cortisol (F) levels after the low‐dose (1 µg) ACTH stimulation test (LDT). No information is currently available on the correlation between F and other adrenocortical hormone responses to the LDT in subjects with an ongoing autoimmune adrenal process. In this study, we tested the hypothesis that the dehydroepiandrosterone (DHEA), 17α‐hydroxyprogesterone (17OHP) and aldosterone (A) responses to the LDT are consensual to that of F during the preclinical phase of autoimmune adrenal insufficiency.design and patients We studied 12 subjects positive for 21OHAb, in the absence of clinical signs of adrenal insufficiency. On the basis of peak F levels after the LDT, and according to the lower level of normal observed in 15 healthy volunteers (510·4 nmol/l), patients were subdivided into two groups: group A, n = 6 subjects with normal F response; and group B, n = 6 subjects with impaired F response. Results were expressed as absolute delta increase (Δ) between peak and basal levels.results ΔF was significantly higher in group A (314·5 ± 115·8 nmol/l) than in group B (151·7 ± 88·2 nmol/l) (P = 0·041). ΔDHEA and Δ17OHP were also significantly higher in group A (17·0 ± 13·5 nmol/l and 6·1 ± 4·4 nmol/l, respectively) than in group B (0·69 ± 2·25 nmol/l and 1·9 ± 1·7 nmol/l, respectively) (P = 0·002 and P = 0·041). The difference in ΔA between the two groups did not reach statistical significance (group A 321·8 ± 272·0 pmol/l vs. group B 157·0 ± 154·0 pmol/l). ΔDHEA, Δ17OHP and ΔA tended to correlate positively with ΔF (P = 0·039, P = 0·039 and P = 0·044, respectively), but the correlations did not reach significance after correction of the P‐value.conclusions Our study demonstrates a high concordance between F and DHEA, 17OHP and A responses to the LDT in subjects with preclinical adrenal autoimmunity, thus strengthening the concept that the LDT is an accurate test to identify early adrenal dysfunction.
Intima‐media thickness in cardiovascularly asymptomatic hypopituitary adults with growth hormone deficiency: relation to body mass index, gender, and other cardiovascular risk factors
Authors: Leonsson Maria , Hulthe Johannes , Oscarsson Jan , Johannsson Gudmundur , Wendelhag Inger , Wikstrand John , Bengtsson Bengt‐Åke 
Published: March 2003

SummaryObjective Increased cardiovascular mortality and carotid atherosclerosis have been observed in hypopituitary patients with untreated GH deficiency (GHD), but results are contradictory and relations to cardiovascular risk factors are not clear. The aim of this study was to investigate intima‐media thickness (IMT) in relation to cardiovascular risk factors in adults with GHD.Design Cross‐sectional observational study of 21 men and 13 women with GHD, but without cardiovascular disease, compared to two healthy control groups matched for age, sex and smoking habits. One control group was matched for body mass index (BMI) and the other group was nonobese.Measurements IMT of the carotid and femoral arteries, blood pressure, blood samples and anthropometric data.Results Patients had 12% thicker composite carotid IMT [(IMT of common carotid artery + IMT of bulb)/2] compared to nonobese controls (P = 0·022), but IMT was not different compared to BMI‐matched controls. Femoral IMT did not differ between patients and controls. Patients had higher waist : hip ratio (WHR), heart rate, serum triglycerides and fasting insulin concentrations in combination with lower high‐density lipoprotein (HDL) cholesterol and smaller low‐density lipoprotein (LDL) peak particle size compared to both nonobese and to BMI‐matched controls. This cardiovascular risk pattern was more pronounced in female patients than in male patients compared to their gender controls. Carotid IMT was related to age, serum cholesterol, LDL cholesterol and smoking in the patient group. Only age was independently related to carotid IMT in multivariate analysis.Conclusions These results indicate that high BMI in GH‐deficient patients contribute to their increased intima‐media thickness. However, several cardiovascular risk factors are present in this patient group independent of their increased BMI, especially in women.
Expression of pituitary tumour transforming gene (PTTG) and fibroblast growth factor‐2 (FGF‐2) in human pituitary adenomas: relationships to clinical tumour behaviour
Authors: McCabe C. J. , Khaira J. S. , Boelaert K. , Heaney A. P. , Tannahill L. A. , Hussain S. , Mitchell R. , Olliff J. , Sheppard M. C. , Franklyn J. A. , Gittoes N. J. L. 
Published: March 2003

Summaryobjective Pituitary tumour transforming gene (PTTG) encodes a multifunctional protein that is implicated in initiating and perpetuating pituitary adenoma growth. PTTG appears to have key regulatory functions in determining control of many fundamental cellular events including mitosis, cell transformation, DNA repair and gene regulation. Several of these events are mediated through interactions with PTTG binding factor (PBF) and fibroblast growth factor‐2 (FGF‐2). Given this background, we have determined the expression of PTTG, PBF, FGF‐2 and its receptor FGF‐R‐1 in a large cohort of pituitary adenomas and have sought associations between levels of gene expression and clinical markers of tumour behaviour.patients and methods We used real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) and Western blot analyses to measure PTTG, PBF, FGF‐2 and FGF‐R‐1 expression in ex vivo pituitary tumours (N = 121). Clinical data, including accurate radiological assessment of tumour characteristics, were used to determine any associations between gene expression and tumour behaviour.results PTTG was increased significantly (fivefold, P = 0·005) in adenomas compared with normal pituitaries. We also demonstrated that PBF was similarly raised in adenomas (sixfold, P = 0·0001), and was significantly correlated with PTTG expression. FGF‐2 and its receptor FGF‐R‐1 were also raised in adenomas compared with normal pituitary tissue. Moreover, significantly enhanced expression of FGF‐R‐1 was observed in invasive adenomas compared with other pituitary tumours.conclusions Our data support a fundamental role for PTTG‐mediated upregulation of FGF‐2 signalling in pituitary tumorigenesis and growth, and suggest that receptor‐mediated mechanisms of growth factor action may be critically important. Further prospective studies are required to determine whether measurement of FGF‐R‐1 mRNA will be of clinical use as a prognostic marker in patients with pituitary adenomas.
Long‐term outcome and mortality after transsphenoidal adenomectomy for acromegaly
Authors: Beauregard Catherine , Truong Uyen , Hardy Jules , Serri Omar 
Published: March 2003

Summaryobjective Acromegaly has long been associated with increased mortality but few long‐term follow‐up data are available in patients treated for this disease. We therefore studied a group of 103 patients who underwent transsphenoidal adenomectomy for acromegaly between 1970 and 1999 and were followed for one to 30 years.design and patients A retrospective chart review was performed on 103 patients living in the province of Quebec, Canada. Mortality data were obtained by hospital charts, contact with the patient's family or death certificates. Stringent biochemical criteria were used to define remission (random GH < 2·5 µg/l, or GH nadir after an oral glucose load is < 1 µg/l and IGF‐I within the normal range) and patient survival in the group in remission and the group with persistent disease were compared to survival of the population of Quebec, Canada, using the probabilities of the Poisson distribution.results There were four deaths in the perioperative period, one of which was directly related to surgery. Initial remission was obtained in 82% of microadenomas, 60% of macroadenomas and 24% of invasive adenomas. The long‐term (≥ 10 years) remission rate for surgery alone was 52%. A second transsphenoidal surgery, radiation therapy and/or octreotide were used in a subset of patients with persistent disease. Long‐term remission was obtained in 63% of patients. Five (mean age, 64 years) of the 57 patients in remission died; this rate did not differ significantly from the mortality rate expected in the general population (P = 0·18). Thirteen (mean age, 59·8 years) of the 34 patients with persistent disease died; this rate was significantly higher than that expected in the general population (P = 0·008).conclusions Our observations confirm that uncontrolled acromegaly increases mortality compared to the general population and that mortality rates similar to the general population are restored once remission is induced.
Recombinant human growth hormone treatment in elderly patients undergoing elective total hip replacement
Authors: Weissberger Andrew J. , Anastasiadis Anastasios D. , Sturgess Ian , Martin Finbarr C. , Smith Michael A. , Sönksen Peter H. 
Published: March 2003

Summaryobjective Measures to prevent postoperative catabolism may be of greatest benefit in the elderly because of their reduced lean tissue reserve. We examined the effects of recombinant human growth hormone (GH) treatment on body composition and physical performance in elderly patients undergoing elective total hip replacement.methods We recruited 33 patients (aged 60–82 years) scheduled for hip replacement. The study was double‐blind and placebo‐controlled with parallel groups. GH or placebo was administered for 14 weeks preoperatively (target GH dose 0·04 U/kg/day) and 4 weeks postoperatively (with dose doubled for first 2 weeks postoperatively). Serum IGF‐I, body composition, mid‐thigh muscle cross‐sectional area, muscle strength and 4‐min walking distance were measured at baseline, 2–3 days preoperatively and 4 weeks postoperatively.results Mean serum IGF‐I doubled during GH treatment. Lean body mass increased preoperatively by an average of 5·2% (representing 1·8 kg) with GH treatment (P < 0·05 vs. placebo), but fell postoperatively by 3% in both groups. Similar changes pre‐ and postoperatively were seen for mid‐thigh muscle cross‐sectional area, such that there was no net loss in the GH group but a fall of more than 10% in the placebo group (P < 0·005 vs. GH). There was a trend towards a favourable effect of GH on strength in the majority of muscles tested, but this was significant only for the abductors of the nonoperated hip (P < 0·02), where there was a 7% increase in strength over the whole study compared with a 25% decrease in the placebo group. Four‐minute walking distance improved postoperatively by a mean of 26·9 m in the GH group compared with a 19·5 m reduction in the placebo group (P < 0·05). Dose‐related side‐effects were seen in the majority of patients receiving GH.conclusions In elderly patients undergoing total hip replacement, preoperative GH treatment results in improvements in lean body mass and skeletal muscle mass that are sufficient to offset postoperative losses. The treatment may also preserve or improve muscle strength and postoperative walking ability.
TSH‐R expression and cytokine profile in orbital tissue of active vs. inactive Graves’ ophthalmopathy patients
Authors: Wakelkamp I. M. M. J. , Bakker O. , Baldeschi L. , Wiersinga W. M. , Prummel M. F. 
Published: March 2003

Summaryobjective From in vitro studies using cultures of orbital fibroblasts, it has become clear that cytokines play an important role in the orbital inflammation in Graves’ ophthalmopathy (GO). Orbital fibroblasts seem to be the key target cells of the autoimmune attack, and they are able to express the TSH receptor (TSH‐R). In vivo data on the presence of cytokines in orbital tissues are sparse, and mostly limited to samples obtained from patients with endstage, inactive GO; the same holds true for the presence of the TSH‐R. The aim of the present study was to determine whether the cytokine profile and TSH‐R expression differ in the active vs. the inactive stage of GO.design and measurements Orbital fat/connective tissue was obtained from six patients with active, untreated GO undergoing emergency orbital decompression, and from 11 patients with inactive GO subjected to rehabilitative decompressive surgery. The mRNA levels of various cytokines and the TSH‐R were assessed by real‐time polymerase chain reaction (PCR) using the LightCycler. Data are expressed as ratios (unknown mRNA/β‐actin mRNA).results Active GO patients had much higher TSH‐R expression than inactive patients: 4/0–24 (median value/range) vs. 0/0–9, P = 0·01. TSH‐R expression was related to the Clinical Activity Score (r = 0·595, P = 0·015). Patients with active GO compared to those with inactive GO had higher mRNA levels of the proinflammatory cytokines interleukin‐1β (IL‐1β) (445/153–877 vs. 0/0–455, P = 0·001), IL‐6 (1583/968–18825 vs. 559/0–7181, P = 0·01), IL‐8 (1422/38–7579 vs. 32/0–1081, P = 0·046) and IL‐10 (145/58–318 vs. 27/0–189, P = 0·002). In active GO there also existed a trend towards a predominance of T helper 1 (Th1)‐derived cytokines as evident from higher IL‐2 (37/0–158 vs. 0/0–68, P = 0·043), interferon‐γ (IFN‐γ) (20/0–79 vs. 0/0–16, P = 0·12) and IL‐12 (2·3/0–14·8 vs. 0/0–1·6, P = 0·10) mRNAs. IL‐1 receptor agonist (IL‐1RA), IL‐2 receptor (IL‐2R), IL‐3, IL‐4, IL‐5, IL‐13, IL‐18 and tumour necrosis factor‐α (TNF‐α) mRNAs were similar in both groups.conclusions These data show that at the mRNA level, TSH‐R expression is largely present only during the active stages of GO. The active phase is characterized by the presence of proinflammatory and Th1‐derived cytokines, whereas other cytokines, among them Th2‐derived cytokines, do not seem to be linked to a specific stage of GO.
Is inhibin B a potential marker of gonadotoxicity in prepubertal children treated for cancer?
Authors: Crofton P. M. , Thomson A. B. , Evans A. E. M. , Groome N. P. , Bath L. E. , Kelnar C. J. H. , Wallace W. H. B. 
Published: March 2003

Summarybackground and objective Chemotherapy treatment of childhood cancer may impair gonadal function, which may be manifested only in adulthood as permanent sterility. Detection of gonadal dysfunction in prepubertal children has been hampered by the absence of a sensitive marker. Inhibin B is secreted by small antral follicles and Sertoli cells in females and males, respectively, and may be a marker of gonadal function in prepubertal children. The aim of this pilot study was to evaluate inhibin B in relation to sensitive measurements of gonadotrophins as markers of the early gonadotoxic effects of chemotherapy in prepubertal children treated for cancer.study design and subjects Twenty‐five prepubertal children (9 females), median age 4·5 years (range 1·2–12·8 years) with cancer (16 solid tumours, nine acute lymphoblastic leukaemia, ALL) were studied longitudinally. Blood samples were collected before and during chemotherapy (solid tumours) or immediately following induction and first intensification (ALL). Post‐treatment (1–6 months) samples were collected in 12 of the patients (5 females).measurements Dimeric inhibin B was measured by double antibody enzyme‐linked immunosorbent assay (ELISA). FSH and LH were measured by sensitive time‐resolved immunofluorescence.results Girls: Pretreatment inhibin B was slightly high in one girl but normal for age and sex in all others: median 16·1 (range 9·4–186·2) ng/l, median SD score +0·2 (−1·3 to +2·6). Inhibin B decreased to undetectable levels (< 8 ng/l) in 8/9 girls during treatment (P = 0·03), with no accompanying rise in FSH or LH. Post‐treatment recovery of inhibin B was variable: median 16·1 (range < 8·0–44·2) ng/l, median SD score +0·1 (range < −2·4 to +1·8). Sustained undetectable inhibin B levels were observed in 2/5 girls with correspondingly elevated FSH concentrations (11·8 and 10·9 U/l). Boys: Inhibin B was normal for age and sex in all boys before treatment with no significant change during or after treatment (medians 93 ng/l, 85 ng/l and 94 ng/l, SD scores −0·3, −0·6 and −0·2, respectively). Inhibin B decreased to undetectable levels in one boy post‐treatment with no accompanying increase in FSH or LH.conclusions In prepubertal girls with cancer, chemotherapy is associated with suppression of inhibin B, usually transient, which may indicate arrest of follicle development. Sustained suppression of inhibin B following treatment may be indicative of permanent ovarian damage. In prepubertal boys, chemotherapy had little immediate effect on Sertoli cell production of inhibin B, although one boy showed a delayed effect. Inhibin B, together with sensitive measurements of FSH, may be a potential marker of the gonadotoxic effects of chemotherapy in prepubertal children with cancer.