bluuebunny/crossref_metadata_2025_split huggingface dataset:
The thyrotrophic role of human chorionic gonadotrophin (hCG) in the early stages of twin (versus single) pregnancies
Authors: Grün Jean‐Paul , Meuris Sylvain , De Nayer Philippe , Glinoer Daniel 
Published: November 2003

OBJECTIVEHuman chorionic gonadotrophin (hCG) is known to possess thyroid‐stimulating activity. The aim of the present study was to assess the role of hCG in stimulating the maternal thyroid gland in the early stages of normal gestation.STUDY DESIGNThirty euthyroid healthy women were investigated prospectively. In each, conception had been assisted by in vitro fertilization techniques, which allowed for the precise determination of gestational age. Women were subdivided into single (n = 17) and twin (n = 13) pregnancies. Serum intact hCG and its free α and β subunits, TSH and free T4 concentrations were measured at 6, 8, 9, 10, 11, 15, 19, 22 and 32 weeks.RESULTSIn twin pregnancies compared with single pregnancies, peak hCG concentrations (9–11 weeks) were significantly higher (mean ± SE 171 000 ± 12 500 vs 65 500 ± 7600 U/l; P < 0.001), and also much more prolonged. Human CG concentrations above 75 000 U/l lasted for less than 1 week in single, compared with up to 6 weeks in twin pregnancies. Free β‐hCG subunit concentrations paralleled those of intact hCG in both groups. The ratios of free β‐hCG subunit/total hCG were similar in single and twin pregnancies, and did not vary with gestation time. Concerning thyroid function, twin pregnancy was more frequently associated with a lowering of TSH, which was also more profound than in single pregnancies. Furthermore, while free T4 levels remained normal in single pregnancies, they were transiently supranormal (up to 52 pmol/l) in four twin pregnancies.CONCLUSIONIn twin pregnancies the placenta produces larger amounts of hCG for a prolonged period of time than in single pregnancies. Both the amplitude and duration of hCG production (i.e. the global exposure of the thyroid gland to hCG) are responsible for increased thyroidal stimulation, leading more frequently to increased free T4 and suppressed TSH levels. The results emphasize the role of hCG in stimulating maternal thyroid function in the first trimester of pregnancy. Even though the production of a variant hCG molecule with potent thyrotrophic activity cannot be excluded, this hypothesis is not required to explain the data. Clinicians should be aware of the frequent occurrence of significant but transient biochemical hyperthyroidism associated with hCG stimulation in the early stages of gestation, particularly in twin pregnancies.
Growth hormone substitution in adult growth hormone‐deficient men augments androgen effects on the skin
Authors: Blok G.J. , De Boer H. , Gooren L.J.G. , Van Der Veen E.A. 
Published: November 2003

OBJECTIVETo assess whether growth hormone (GH) administration to adult GH‐deficient men leads to increased sexual hair. The sexual hair scores are subnormal in these patients, even in the presence of normal serum androgen levels.PATIENTSForty‐six adult men with childhood‐onset of GH deficiency of whom 25 were androgen deficient and received replacement.DESIGNDouble‐blind and placebo‐controlled. Of the 46 patients, 33 started immediately with GH administration; the remaining 13 received placebo for the first 6 months followed by GH for the next 6 months. Sixty‐one age‐matched healthy men with normal height and serum concentrations of IGF‐I served as a comparison group.MEASUREMENTHair scores at 13 defined body regions were assessed before, and after 6 and 12 months of the intervention. At the same time levels of IGF‐I, dehydroepiandrosterone sulphate, androstenedione, dihydrotestosterone (DHT), testosterone and sex hormone binding globulin (SHBG) were measured. From the latter two, the free androgen index (FAI) was calculated.RESULTSBefore GH administration, hair scores in the GH deficient patients were lower than in the comparison group. In the 33 men treated with GH from the beginning, there was an increase in hair scores after 6 months. The increase in hairscores was not seen during 6 months of placebo treatment. When the placebo group switched to GH administration, their hair scores had also significantly increased after 6 months of GH substitution therapy. Upon GH administration both levels of SHBG and testosterone/DHT declined while the FAI remained unchanged.CONCLUSIONGH substitution therapy to GH deficient men has an auxiliary effect on androgen action in the skin without an increase of the FAI.
Hydrocortisone replacement therapy in children and adolescents with hypopituitarism
Authors: DeVile C. J. , Stanhope R. 
Published: November 2003

OBJECTIVEAppropriate replacement doses of glucocorticoid are important to determine in primary and secondary adrenal deficiency in children, both to avoid the risks of hypoglycaemia and adrenal crisis associated with undertreatment, and to avoid growth suppression and reduced final height potential associated with steroid excess. The aim of this study was to assess how closely conventional twice daily hydrocortisone administration mimics physiological cortisol secretion in a group of ACTH‐deficient children and adolescents.PATIENTSFifty children and adolescents (aged 3–20 years) were studied who had had surgery ± radiotherapy to the hypothalamopituitary region for removal of a craniopharyngioma. The patients were subdivided into two groups: group I comprised 44 patients known to be ACTH deficient (as determined by glucagon or insulin provocation tests of anterior pituitary function performed after surgery) and maintained on twice daily oral hydrocortisone replacement; group II comprised six patients known to be ACTH sufficient at their last assessment of pituitary function and not on hydrocortisone replacement. A third group of 10 boys (aged 7–13 years) who had no known endocrinopathy were used as controls (group III).MEASUREMENTSAfter intravenous cannula insertion, blood samples were taken every 2 h for measurement of plasma cortisol and glucose over a period of 24 h. Patients in group I continued on their usual doses of hydrocortisone, prescribed at 0800 and 1800 h.RESULTSThe mean total daily replacement dose of hydrocortisone for patients in group I was 12.3 mg/m2/day (range, 5.5–18.5). On the conventional twice daily dose regimen, there was a supraphysiological medium plasma cortisol level (629 nmol/l, range 185–1600; z = − 3.76, P = 0.0002) 2 h after the morning dose relative to the control group, and a prolonged and unphysiological nadir from 1400–1800 h (median at 1600 h 42 nmol/l, range 13–1170; z = − 3.13, P < 0.002) before the second dose of hydrocortisone was administered. Cortisol values were low, and often negligible, during the early hours of the morning (median at 0600 h 15 nmol/l, range 13–277, z = − 4.87, P < 0.00001) and spontaneous hypoglycaemia was documented in one patient on a single 0800 h sample. One patient in group II was shown to be unequivocally cortisol deficient and median cortisol values for the remaining five suggested a suboptimal rise in plasma cortisol during the early hours of the morning.CONCLUSIONOur cohort of patients provides an excellent model for the study of glucocorticoid replacement in cortisol‐deficient children and adolescents and shows, as in adults, that the aim of mimicking the physiological nyctohemeral secretion of cortisol is difficult to achieve in practice and raises a number of important considerations unique to steroid substitution therapy in this age group.
Serum IGF‐I and IGF binding proteins 2 and 3 as potential markers of doping with human GH
Authors: Kicman Andrew T , Miell John P , Teale J. Derrick , Powrie Jake , Wood Peter J , Laidler Paul , Milligan Peter J , Cowan David A 
Published: November 2003

OBJECTIVEIGF‐I and IGF binding protein (IGFBP)‐3 levels in man are positively regulated by GH status; in contrast, evidence suggests an inverse relationship between GH status and IGFBP‐2. We investigated the effects of somatropin administration on the serum concentrations of these analytes, together with serum and urinary concentrations of GH, to evaluate their potential as markers in the development of a test for detecting doping with GH in sports competitors.DESIGNSomatropin was administered subcutaneously at a dose of 0.15 U/kg bodyweight/day at 1000 h for 3 days to eight healthy men (20–32 years old).MEASUREMENTSSerum concentrations of GH, IGF‐I, IGFBP‐2 and ‐3 were determined in blood samples collected at 1600 h on the days prior to (day −1), during (days 0, 1 and 2), and following administration (days 3 and 7). Urine was collected continuously from days −2 to 3 and then on day 7.RESULTSSerum and urinary concentrations of GH were only raised on the days of administration whereas, following cessation of somatropin, the increases in the serum concentrations of IGF‐I and IGFBP‐3 were sustained for at least 1 day (30 h). Serum IGFBP‐2 decreased during the period of administration and was still suppressed on day 3. The concentration ratios of IGFBP‐3 to IGFBP‐2 and IGF‐I to IGFBP‐2 increased markedly with administration and both ratios were still significantly augmented compared with basal values 30 h after the last administration.CONCLUSIONWith acute administration of somatropin to healthy men the serum concentration of IGFBP‐2 decreases and the ratios of serum IGF‐I/IGFBP‐2 and IGFBP‐3/IGFBP‐2 increase. These ratios should be considered in the development of a test for detecting somatropin administration in sport.
Insulin action and hepatic glucose cycling in Cushing's syndrome
Authors: Heaney A. P. , Harper R. , Ennis C. , Rooney D. P. , Sheridan B. , Atkinson A. B. , Bell P. M. 
Published: November 2003

OBJECTIVEAlthough it is well established that hypercortisolism causes insulin resistance, the mechanisms responsible for impaired insulin action in Cushing's syndrome are unclear. This study investigated the contribution of the glucose/glucose‐6‐phosphate substrate cycle (G/G6P).PATIENTSEight patients with Cushing's syndrome and seven control subjects were studied. All had normal fasting plasma glucose.DESIGNInsulin action was assessed using the euglycaemic glucose clamp at insulin infusion rates of 0.4 and 2.0 mU/kg/min combined with a simultaneous infusion of [23H]‐ and [63‐H]‐glucose. Glucose/ glucose‐6‐phosphate cycle activity was calculated as the difference in glucose turnover rates determined separately for [23H]‐ and [63H]‐glucose by selective enzymatic detritiation.MEASUREMENTS AND RESULTSExogenous glucose infusion rates required to maintain euglycaemia were significantly lower in Cushing's patients compared to controls, during the 0.4 mU/kg/min (7.8±1.2 vs 15.7±0.5 μmol/kg/min, P<0.001) and the 2.0 mU/kg/min insulin infusions (26.2±2.8 vs 51.5±3.5 μmol/kg/min, P<0.001). Endogenous glucose production was similar in both groups in the postabsorptive state (10.2±0.3 vs 10.8±0.4 μmol/kg/min, P=0.50) and suppressed to a similar degree during hyperinsulinaemia. G/G6P cycle activity was markedly increased in the Cushing's group in the postabsorptive state (5.4±1.1 vs 2.0±0.5 μmol/kg/min, P=0.028) and during the 0.4 mU/kg/min (3.2±0.6 vs 1.2±0.4 μmol/kg/min, P=0.014) and 2.0 mU/kg/min insulin infusions (3.3±0.8 vs 1.1±0.5 μmol/kg/min, P=0.049).CONCLUSIONSPatients with Cushing's syndrome show marked peripheral insulin resistance and enhanced hepatic G/G6P cycle activity. In the fasting state increased glucose/glucose‐6‐phosphate cycle activity may be a protective mechanism limiting hyperglycaemia. During hyperinsulinaemia G/G6P cycle activity was increased but insulin resistance was predominantly due to reduced peripheral glucose uptake.
A comparison of the insulin tolerance/glucagon test with the short ACTH stimulation test in the assessment of the hypothalamo‐pituitary‐adrenal axis in the early post‐operative period after hypophysectomy
Authors: Mukherjee J. J. , Jacome de Castro J. , Kaltsas G. , Afshar F. , Grossman A. B. , Wass J. A. H. , Besser G. M. 
Published: November 2003

OBJECTIVEThe insulin tolerance test (ITT) is the established reference test for assessing the hypothalamo‐pituitary‐adrenal (HPA) axis. Various authorities, however, have suggested that the 250 μg short ACTH stimulation test may be used to assess the HPA axis in place of the ITT in suspected hypopituitarism, although a number of other studies have suggested that the test may be unreliable in this setting. In this study, the ITT (or glucagon test) has been compared with the 250 μg short ACTH stimulation test in patients with pituitary tumours pre‐operatively and within 2 weeks of trans‐sphenoidal hypophysectomy.DESIGNAn ITT, or a glucagon test when the ITT was contraindicated, and the 250 μg short ACTH stimulation test, were performed in all the patients before (an ITT in 18 and a glucagon test in three patients) and within 2 weeks after trans‐sphenoidal hypophysectomy (an ITT in 16 and a glucagon test in five patients).PATIENTSTwenty‐one patients with pituitary disorders (15 with acromegaly, one with a prolactinoma and five with non‐functioning tumours) were studied; four had a microadenoma, two a mesoadenoma and 15 a macroadenoma.MEASUREMENTSSerum cortisol was measured by radioimmunoassay. A normal response was defined as a rise in serum cortisol to 580 nmol/l or above for all the tests.RESULTSBefore surgery, three of 18 patients (17%) had a discrepancy between the ITT and the 30 minute short ACTH stimulation test and one of three between the glucagon test and the 30 minute short ACTH stimulation test. Combined together, pre‐operatively, four of 21 patients (19%) had discrepant results. In the early post‐operative period, the discrepancy between ITT and the 30 minute short ACTH stimulation test was higher with four of 16 patients (25%) showing discordant results; one of the five patients tested had a discrepancy between the glucagon test and the 30 minute short ACTH stimulation test. On combining the tests, the post‐operative discrepancy was five of 21 patients (24%).CONCLUSIONSThe 250 μg short ACTH stimulation test produces discordant results from the ITT in a clinically significant proportion of affected patients when assessing the HPA axis, although the rate of discordance varies according to the criteria used for normality for both the tests. We suggest that the ITT should remain the preferred test for assessing ACTH secretory capacity compared with the standard 250 μg short ACTH stimulation test, both in the pre‐operative and in the early post‐trans‐sphenoidal hypophysectomy period.
Endocrine outcome in long‐term survivors of low‐grade hypothalamic/chiasmatic glioma
Authors: Collett‐Solberg Paulo F. , Sernyak Heidi , Satin‐Smith Marta , Katz Lorraine L. , Sutton Leslie , Molloy Patricia , Moshang Jr Thomas 
Published: November 2003

OBJECTIVEWe have evaluated the frequency of endocrine abnormalities in a large group of patients with hypothalamic/chiasmatic glioma (H/CG) and its correlation with the different forms of therapy.DESIGNDescriptive retrospective study using case note review analysis.PATIENTSThe records of 68 children who survived H/CG were analysed. One third had neurofibromatosis. The mean age at tumour presentation was 5 years. The median time of follow‐up was 3.6 years. Thirty‐eight children received cranial radiation, of whom 17 also had surgery. Surgery was performed in a total of 24 patients. Fifteen patients received only chemotherapy. Eight children, all with neurofibromatosis, received no specific tumour treatment.MEASUREMENTSEndocrine dysfunction was determined by clinical manifestations and biochemical evaluation of hypothalamic‐pituitary function.RESULTSEndocrine dysfunction occurred in 42% of the children. The most common disorder was GH deficiency (GHD). Of 50 children evaluated, 15 of the 19 with GHD received cranial irradiation (P < 0.05). However, 15 children treated with more than 45 Gy grew normally. Precocious puberty was diagnosed in 11 patients. Nine patients, all treated with cranial irradiation, developed hypogonadotrophic hypogonadism. Of the 14 patients with hypothyroidism, 10 had surgery (P < 0.005). Hypoadrenalism and diabetes insipidus each occurred in eight patients, and were associated with multiple endocrine deficiencies and surgery. Endocrine deficiencies occurred in children with neurofibromatosis as frequently as children without neurofibromatosis but only when comparing those treated with cranial irradiation or surgery.CONCLUSIONSNearly all studies assessing the endocrine outcome after tumour therapy evaluate patients with different tumour types. This study investigates a specific and large population of patients with H/CG and correlates the different forms of treatment with the endocrine outcome. Precocious puberty, in children with this tumour, is probably due to tumour location rather than oncological therapy. Conversely, although endocrine deficiencies can be a result of tumour location, the major causes of endocrine abnormalities were field irradiation and tumour surgery. A notable finding not previously reported is that endocrine dysfunction occurs less often in neurofibromatosis patients treated conservatively. Furthermore, this study documents that a significant number of young children grew normally despite receiving brain irradiation of greater than 45 Gy.
Bone loss in hyperthyroid patients and in former hyperthyroid patients controlled on medical therapy: influence of aetiology and menopause
Authors: Jódar Esteban , Muñoz‐Torres Manuel , Escobar‐Jiménez Fernando , Quesada‐Charneco Miguel , Castillo Juan D. Luna del 
Published: November 2003

OBJECTIVEThe effect of hyperthyroidism on osteoporosis risk and its reversal after control of hyperthyroidism remains somewhat controversial. We assessed the values of bone mineral density in hyperthyroid patients and in former hyperthyroid patients euthyroid on medical therapy, as well as the influence of aetiology and menopause upon bone mass.DESIGNThe values of bone mineral density in hyperthyroid patients (active) and former hyperthyroid patients euthyroid on medical therapy (controlled), were compared, together with data from our control group and from the Spanish reference population. We also compared the values of bone mineral density in patients with Graves' disease with those in patients with toxic nodular goitre and assessed the influence of the menopause.PATIENTSWe studied 127 consecutive hyperthyroid patients (age 41  ±  16 years; 110 females, 17 males; 102 Graves' disease and 25 toxic nodular goitre); 78 were active (group A) and 49 controlled on medical therapy (carbimazole, mean time of euthyroidism 7.5  ±  9.1 months; group B). We also studied 43 healthy subjects (age 40  ±  14 years; 41 females, two males; group C).MEASUREMENTSBone mineral density was assessed by dual X‐ray absorptiometry at lumbar spine (L2–L4), femoral neck and Ward's triangle. Data were expressed as g/cm2 and as a Z score (SD vs Spanish reference population adjusted by age and sex). Blood was obtained to measure the levels of free T4, TSH and TSH receptor antibody.RESULTSPatients with active hyperthyroidism showed a generalized reduction in axial bone mineral density in comparison with both the control group and the reference population, whereas former hyperthyroid patients showed partial recovery of bone mass in lumbar spine and Ward's triangle. Mean Z scores at lumbar spine, femoral neck and Ward's triangle were: −0.92, −0.79 and −0.89 in group A; −0.74, −0.23 and −0.44 in group B and 0.18, 0.09 and 0.36 in group C, respectively. No differences were found between bone mineral density values from patients with Graves' disease and those with toxic nodular goitre, nor between pre‐ and postmenopausal hyperthyroid women once adjusted by age and sex.CONCLUSIONSOur data suggest that hyperthyroid patients show a generalized reduction of bone mass in the axial skeleton and that only partial recovery is present in former hyperthyroid patients after a mean of 7.5 months of biochemical euthyroidism. This recovery is insufficient to normalize the bone density in lumbar spine and Ward's triangle, although femoral bone mass was not different from that of the control group. The extent and degree of hyperthyroid bone disease surpass the effects of the menopause on the bone mass. The aetiology of hyperthyroidism does not seem to play any role in the severity of hyperthyroid bone disease.
Clinical activity score as a guide in the management of patients with Graves' ophthalmopathy
Authors: Mourits Maarten Ph. , Prummel Mark F. , Wiersinga Wilmar M. , Koornneef L. 
Published: November 2003

OBJECTIVEApproximately 35% of patients with Graves' ophthalmopathy do not respond to immunosuppressive treatment. A possible explanation for this finding is that only patients with active ophthalmopathy respond to immunosuppressive treatment, whereas patients with fibrotic end stage disease do not. To distinguish between these two groups and to predict the outcome of immunosuppressive treatment, we developed a clinical activity score (CAS) based on four of the five classical signs of inflammation and tested its efficacy in a double‐blind, prospective study.DESIGN, PATIENTS AND MEASUREMENTSThe CAS was determined by an ophthalmologist before, on the day of, and after the start of either oral prednisone or retrobulbar irradiation in 43 patients with moderate to severe Graves' ophthalmopathy. The therapeutic outcome was determined by a second ophthalmologist unaware of the CAS stores given. Success of treatment was defined as an improvement in NOSPECS class or grade.RESULTSResponders (22) and non‐responders (21) did not differ in age, sex, duration or severity of their Graves' ophthalmopathy. The pretreatment CAS, however, was significantly higher in responders than in non‐responders. Twelve of 22 responders and three of 21 non‐responders had a CAS  ≥  4 (80% vs 36%; P  <  0.01). Using this CAS cut‐off point, the accuracy of CAS in predicting the therapeutic outcome was: specificity 86%, sensitivity 55%, positive predictive value 80%, negative predictive value 64%. Patients with a CAS  ≥  4 had a similar duration of Graves' ophthalmopathy as patients with a CAS  <  4.CONCLUSIONSThe clinical activity score has a high predictive value for the outcome of immunosuppressive treatment in Graves' ophthalmopathy. Disease activity, and not disease duration, is the prime determinant of therapeutic outcome.