bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of chronic GnRH analogue administration on gonadotrophin and α‐subunit secretion in post‐menopausal women
Authors: Oppenheim Daniel S. , Bikkal Helen , Crowley William F. , Klibanskl Anne 
Published: March 2008

OBJECTIVE To investigate in detail the regulation of LH, FSH, and α‐subunit secretion by a GnRH agonist analogue under physiological conditions of gonadotrophin elevation.SUBJECTS Six normal healthy post‐menopausal women.DESIGN Subjects were given D‐Trp6‐Pro9‐Net‐GnRH (GnRHa), 32 μg/kg, subcutaneously, dally for 24 days. On days 1, 2, 3, 4, 7, 11, 14, 17, 21, and 24, blood samples before and after GnRHa injection were taken. Sampling was continued off GnRHa twice a week for 4 weeks and then on days 66, 76, and 98. GnRH tests (100 μg l. v.) were performed on days 0, 24, and 98.MEASUREMENTS All serum samples were analysed for LH, FSH, and α‐subunit levels.RESULTS LH and FSH levels reached a maximum on day 2 after which there was a steady decline to day 24. LH did not begin to rise again until day 44 (20 days off GnRHa), then rose steadily. FSH began to rise earlier, on day 34 (10 days off GnRHa). α‐Subunit levels also showed maximum elevation on day 2 but remained equally elevated throughout the period of GnRHa administration and then fell rapidly to baseline by day 34. LH, FSH, and α‐subunit responses to i. v. GnRH were absent on day 24 and were equivalent to baseline on day 98.CONCLUSIONS We conclude that there is a striking dissociation in the regulation of gonadotrophin and α‐subunit secretion in response to GnRHa in normal post‐menopausal women. Gonadotrophin secretion is profoundly suppressed during GnRHa administration and recovers only after a long delay post‐treatment, while α‐subunit is markedly stimulated and recovers rapidly. The difference between this pattern and that seen in patients with pituitary tumours could be useful for diagnosis.
The effect of iodide on serum thyroid hormone levels in normal persons, in hyperthyroid patients, and in hypothyroid patients on thyroxine replacement*
Authors: Phillppou George , Koutras Demetrios A. , Plperlngos Gregory , Souvatzoglou Athanasslos , Moulopoulos Spyrldon D. 
Published: March 2008

OBJECTIVE To clarify the duration and the extent of the antithyroid effect of lodides In hyperthyroldlsm, and to Investigate whether Iodides have an additional perlpheral effect on the metabollsm of thyrold hormones, as has been reported for some organic IodIne compounds.DESIGN The effect on the perIpheral thyroId hormone levels of 150 mg of potassIum Iodide dally (equIvalent to 114 mg of IodIde) foro 3–7 weeks was compared In 21 hyperthyroId patients and 12 healthy controls. A possible effect of IodIde on the perIpheral metabollsm of thyroId hormones was Investigated by assessing the serum levels of thyroid hormone In 12 hypothyroid patients on thyroxine replacement for 2 weeks.PATIENTS There were 21 thyrotoxic patients, 12 healthy hospital controls, and 12 patients with complete or near‐complete hypothyroldlsm, on thyroxine replacement.MEASUREMENTS The following were measured before and at weekly intervals after Iodide administration: (1) pulse rate, (2) serum T4, (3) serum T3, (4) serum TSH, (5) serum thyroxlne‐binding capacity (TBC), (6) serum rT3, (7) serum thyroxine‐binding globulln (TBG), (8) the free‐T4 Index, calculated as T4/TBC.RESULTS In the hyperthyroid patients serum T4, T3 and rT3 decreased, whereas serum thyroxlne‐binding globulin and thyroxine binding capacity Increased. Serum T3, however, did not become completely normal In all cases. After 21 days, serum T4 and T3 started Increasing again in some cases, but other patients remained outhyrold even after 6 weeks. In the normal controls there was a small but significant and consistent decrease In serum T4, T3 and rT3 and an Increase In serum TSH. Finally, In the T4‐treated hypothyroid patients there was no consistent change, except for an Increase of serum T4 at 1 and 14 days and a decrease of serum TSH the first day.CONCLUSION Iodides in hyperthyroldlsm have a variable and unpredictable Intensity and duration of antlthyrold effect. Their antithyroid effect Is smaller In normal controls. They have no Important effect on the peripheral metabolism of thyroid hormones.
Expression of the neuroendocrine cell marker 7B2 in human ACTH secreting tumours
Authors: Vieau D. , Linard C. G. , Mbikay M. , Lenne F. , Chretien M. , Luton J. P. , Bertagna X. 
Published: March 2008

OBJECTIVE AND DESIGN Pro‐opiomelanocortin gene expression is a ubiquitous phenomenon which takes place not only in the pituitary but also in many normal and tumoral non‐pituitary tissues. However, the clinical features of the ectopic ACTH syndrome are rarely encountered. To further investigate this problem we examined series of normal human pltuitaries and endocrine tumours evaluating the tissue content of pro‐oplomelanocortin peptides, and the state of neuroendocrine differentiation as Indicated by the biochemical marker 7B2.PATIENTS AND MEASUREMENTS Tissue concentration of 7B2, pro‐opiomelanocortin products (joining peptide and β‐endorphin) were measured in 13 pituitary corticotrophic adenomas and 13 non‐pituitary tumours associated with the ectopic ACTH syndrome (five out of 20 bronchial carcinold tumours, two out of 19 phaeochromocytomas, one out of 11 medullary thyroid carcinomas, three pancreatic and two thymic carcinold tumours). Molecular weight forms of immunoreactive 7B2 and 7B2 RNA messenger were determined using Western and Northern biot analysis respectively.RESULTS In all tissues examined, concentrations of Immunoreactive β‐endorphin (fmol/mg tissue wet weight) showed widely distributed values from <0.7 to 1340000, which were correlated (r= 0.975, P <0.01) with that of immunoreactive joining peptide, another pro‐oplomelanocortin fragment. In the 13 non‐pituitary tumours associated with the ectopic ACTH syndrome, immunoreactive β‐endorphin concentrations ranged from 8.6 to 548000, whereas in normal and tumoral pituitaries they varied from 16600 to 364800, and 5000 to 1340000, respectively.Immunoreactive 7B2 was detected In 67 of 68 neuroendocrine tumours. Tissue concentrations (fmol/mg tissue wet weight) of immunoreactive 7B2 varied from 135 to 1787 in pituitary tumours; from <0.5 to 555 In bronchial carclnolds; from 21.7 to 793 In phaeochromocytomas; from < 1.6 to 948 In medullary thyroid carcinomas. Western blot analysis showed a predominant molecular weight form of immunoreactive 7B2 at 22 kDa. Northern blot analysis of RNA extracted from ACTH secreting pituitary and non‐pituitary tumours showed a predominant signal hybridizing at 1.5 kb with a 7B2 probe.CONCLUSION These results show that all ACTH secreting tumours have biochemical markers for neuroendocrine differentiation. Tissue concentrations of pro‐opiomelanocortin peptides are variable, being extremely high in the most benign tumours and low in those with an aggressive growing pattern, and are not correlated with the biochemical neuroendocrine markers.
Regulation by glucocorticoids of interferon gamma‐induced HLA‐DR antigen expression in cultured human orbital fibroblasts
Authors: Heufelder Armin E. , Bahn Rebecca S. , Smith Terry J. 
Published: March 2008

OBJECTIVE The purpose of this study was to determine whether glucocorticoids can block the induction of HLA‐DR antigen expression by interferon gamma in human fibroblasts in culture.DESIGN AND PATIENTS Confluent cultures of fibroblasts derived from the orbit or the skin of patients with Graves' ophthalmopathy or from normal subjects were treated with interferon gamma (100 U/ml) without or with graded concentrations of steroids.MEASUREMENTS Cultures were analysed for HLA‐DR expression using quantitative immunoblotting and indirect immunofluorescence.RESULTS Glucocorticoids could block HLA‐DR induction in a dose‐dependent manner. At 10‐8 mol/1, the steroids dexamethasone and RU 28362 inhibited expression by 70% (P <0.004) and 56% (P <0.002) respectively. RU 38486, a glucocorticoid antagonist, could reverse the effect of both glucocorticoids, an action that was also dose dependent. At 10‐5 mol/1, RU 38486 blocked virtually the entire glucocorticoid effect.CONCLUSIONS These results suggest that glucocorticoids can regulate HLA‐DR induction by interferon gamma at physiological concentrations, an action which is stereospecific and mediated through the glucocorticoid receptor.
Luteinizing hormone response to clomiphene citrate in central precocious puberty
Authors: Morelra Ayrton C. , Castro Margaret , Maclel Lea M. Z. , Hiltner Angela N. 
Published: March 2008

OBJECTIVE The aim of the present study was to determine the LH response to clomiphene citrate administration in children with central precocious puberty and different bone ages to gain insight into the hypothalamic maturation mechanism.PATIENTS AND METHODS Twelve children with untreated central precocious puberty were studied. Five had central nervous system lesions and seven had idiopathic central precocious puberty. Their chronological and bone ages ranged from 1·7 to 8·8 years and 3·5 to 13·5 years, respectively. Clomiphene citrate (3 mg/kg/day) was administered orally for 7 days. Blood samples were collected on days 0, 6 and 8. LH and FSH were determined by RIA. The results were compared with GnRH responses or with bone age.RESULTS No Increase over basal LH levels was detected in four patients, but increased LH levels were detected in the remaining eight during clomiphene administration. The shift from negative to positive responses was around 8–9 years bone age. The sum of LH responses (days 6 and 8) to clomiphene citrate, and particularly the 8th‐day LH levels, were significantly correlated with their respective bone age (r= 0·83). However, the LH responses to GnRH were not significantly correlated with bone age or with LH responses to clomiphene.CONCLUSIONS This study shows that the LH responsiveness to clomiphene citrate In central precocious puberty increases with skeletal maturation, indicating that the activation of the hypothalamic pubertal mechanism in central precocious puberty may progress in a gradual sequence. These changes in LH response to clomiphene in central precocious puberty mimic those observed with the development of normal puberty, but occur at a much earlier age.
The use of the polymerase chain reaction in prenatal diagnosis of growth hormone gene deletions
Authors: Mullis P. E. , Brickell P. M. 
Published: March 2008

OBJECTIVE Familial isolated growth hormone deficiency (IGHD) type IA is characterized by a complete absence of human growth hormone (hGH) resulting in most cases from either a 6·7 or 7·7 kb deletion of DNA containing the hGH‐1 gene. These patients have a strong initial anabolic response to exogenous recombinant hGH (r‐hGH) therapy, frequently associated with the development of immune intolerance to r‐hGH which causes an arrest of response to r‐hGH replacement. This disorder is inherited as an autosomal recessive trait.PATIENTS AND DESIGN In two pregnancies at risk, the polymerase chain reaction (PCR) was applied as a method for identifying hGH‐1 gene deletions in DNA obtained by chorionic villus sampling (CVS) in the first trimester.RESULTS Homozygotes for the 6·7kb deletion of DNA containing the hGH‐1 gene were easily and conclusively detected by the absence of 1900, 761 and 712bp fragments after Smal digestion of the polymerase chain reaction products. In contrast, the pattern found in heterozygotes for the hGH‐1 gene deletion was difficult to distinguish from the pattern found in normal homozygotes.CONCLUSIONS We conclude that the polymerase chain reaction method is valuable for diagnosing individuals who are homozygous for hGH‐1 gene deletions, while heterozygotes and normal individuals may be difficult to distinguish from each other. We suggest that, in these cases, Southern blotting remains the analysis to perform.
Endocrine dysfunction in Kearns‐Sayre syndrome
Authors: Harvey J. N. , Barnett D. 
Published: March 2008

Kearns‐Sayre syndrome (KSS) is a form of mitochondrial myopathy in which specific clinical features, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and cardiac conduction defects, occur. KSS has also been associated with a variety of endocrine and metabolic disorders, in particular short stature, gonadal failure, diabetes mellitus, thyroid disease, hyperaldosteronism, hypomagnesaemia, and bone, tooth and calcification abnormalities. A case is described exhibiting all of these features. A survey of the literature was conducted to determine the prevalence of these conditions among reported cases. Cases with hypoparathyroidism were considered separately to see if they constituted a distinct subgroup with multiple endocrine dysfunction.Short stature was common, being documented in 38% of cases. Gonadal dysfunction before or after puberty was also common (20% of cases) and affected both sexes equally. Diabetes mellitus was recorded in 13% of cases, half of which required insulin. Thyroid disease, hyperal‐dosteronism and hypomagnesaemia were uncommon but were probably not looked for in many cases. Bone or tooth abnormalities and calcification of the basal ganglia were found both in those with and without hypoparathyroldism. While endocrine and metabolic dysfunction was found more commonly in those with hypoparathyroldism this is likely to be due to increased recognition rather than increased prevalence. No evidence of an autoimmune polyendocrine syndrome including hypoparathyroldism was found.
Insulin secretion, insulin sensitivity and hepatic insulin extraction in primary hyperparathyroidism before and after surgery
Authors: Kautzky‐Willer A. , Pacinl G. , Niederle B. , Schernthaner G. , Prager R. 
Published: March 2008

OBJECTIVE Primary hyperparathyroidism (pHPT) is associated with hypertension, hyperinsulinaemia, and insulin resistance. The present study investigated the causes of these metabolic disturbances by quantifying insulin sensitivity and glucose effectiveness, and by assessing the time course of β‐cell insulin secretion and hepatic insulin extraction, during a dynamic condition such as after an intravenous glucose load. In addition, we evaluated the possible link between metabolic disorders and high blood pressure.SUBJECTS We studied 16 patients with pHPT, before and 12 weeks after parathyroldectomy; eight of these patients were re‐evaluated one year after surgery. The control group consisted of 18 healthy volunteers.DESIGN AND MEASUREMENTS All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. The data from the intravenous glucose tolerance test were analysed by means of the minimal model technique which yields relevant parameters to comprehend the metabolic status of the single individual.RESULTS The glucose intolerance condition was characterized by a severely impaired insulin sensitivity in pHPT (3.2 ± 0.5 vs 9.5 ± 1.5 x 104/min/(μU/ml) of control subjects; P < 0.001), as well as by a reduced glucose effectiveness, (0.02 ± 0.002 vs 0.03 ± 0.003/min of control subjects; P < 0.04). Total insulin secretion during the 4 hours of the test was almost twofold elevated in comparison to the control subjects (32795 ± 4769 vs 16864 ± 1850 pM, P < 0.004) and its basal component significantly correlated with the high blood pressure. Hepatic extraction of insulin was significantly increased in pHPT (85.2 vs 76.2%,
P < 0.03), possibly as a compensatory mechanism of hypersecretion, which however did not prevent peripheral hyperinsulinaemia in pHPT. Patients with pHPT were divided into two subgroups with normal and impaired glucose tolerance. The patients with impaired glucose tolerance had a significant reduction of first phase insulin response, although their basal and stimulated insulin levels were higher. Tissue insulin sensitivity and glucose effectiveness did not significantly differ between the two subgroups. After surgery, all the biochemical parameters (former hypercalcaemia, hypophosphataemia, elevated parathormone levels) were normalized, insulin sensitivity significantly improved (6.1 x 104/min/(μU/ml), P < 0.001), whereas glucose effectiveness remained completely unchanged. Basal and stimulated insulin responses were insignificantly lowered after surgery, and hepatic extraction did not change either.CONCLUSIONS Patients with pHPT exhibited decreased insulin sensitivity and insulin hypersecretion. The latter is only partially amellorated by increased hepatic insulin extraction. After surgery, although the biochemical abnormalities were fully reversible, the metabolic changes improved only partially.
The sensitivity of growth hormone secretion to medical treatment in acromegalic patients: influence of age and sex
Authors: van der Lely A. J. , Harrls A. G. , Lamberts S. W. J. 
Published: March 2008

OBJECTIVE We investigated the relationship between age, sex, pituitary tumour volume, serum GH, PRL and IGF‐I levels with the responsiveness of GH to TRH, bromocriptine and octreotide in patients with acromegaly.DESIGN We performed a retrospective study. Correlations were determined between all variables using univariate regression analysis.PATIENTS One hundred previously untreated acromegalic patients were studied (60 males (age 23–76; mean 49 years) and 40 females (age 25–83; mean 51 years)).MEASUREMENTS We studied tumour volume, fasting morning circulating levels of GH, PRL and IGF‐I, mean 24‐hour circulating GH levels and the acute GH responses to TRH, bromocriptine and octreotide.RESULTS Tumour size was related to serum and mean 24‐hour GH levels, but not to IGF‐I. Circulating IGF‐I and GH levels were related only for the group of patients whose fasting and unsuppressed GH level was 80 mU/l (40 μg/l) or less. Older patients tended to have lower circulating GH and IGF‐I levels. There was a close similarity in the responsiveness of tumorous GH secretion to TRH, bromocriptine and octreotide. An elevated serum PRL level predicted a stronger inhibitory response of bromocriptine on GH. The sensitivity of GH release to octreotide was highest in elderly (especially male) acromegalics, as well as in patients with lower IGF‐I levels.CONCLUSIONS Hormone secretion by GH secreting pituitary tumours, as well as circulating IGF‐I levels, tend to be lower in elderly patients. These tumours are more sensitive to octreotide, especially in elderly male patients. This suggests that octreotide might be used especially successfully as a primary medical therapy in elderly, male acromegalics.
High serum sex hormone‐binding globulin (SHBG) in premature thelarche
Authors: Belgorosky A. , Chaler E. , Rivarola M. A. 
Published: March 2008

OBJECTIVE We determined serum sex hormone‐binding globulin (SHBG), serum dehydroepiandrosterone sulphate, serum oestradiol and serum testosterone and its fractions in girls with premature thelarche.DESIGN Blood was drawn from girls with recently diagnosed (3–12 weeks) premature thelarche. Serum was kept frozen for at least one year before hormonal determination to exclude precocious puberty by clinical evaluation. PATIENTS Seventeen girls with premature thelarche aged 0.83–7.16 years were studied, and compared with a group of 22 normal prepubertal girls.MEASUREMENTS SHBG was measured by saturation analysis and serum dehydroepiandrosterone sulphate, serum total oestradiol and serum total testosterone were determined by radioimmunoassay. Non‐SHBG‐bound testosterone and free testosterone were calculated from an equation derived from the law of mass action.RESULTS Median serum SHBG in premature thelarche was 137 nmol/l (range 64–221), significantly higher than in normal controls, 93.7 (32–172) (P < 0.05) non‐parametric test of medians. Serum SHBG decreased significantly with age in controls but not in premature thelarche. No difference was found in serum dehydroepiandrosterone sulphate. Median serum total testosterone (0.34 nmol/l, 0.17–0.97), median serum non‐SHBG‐bound testosterone (0.04 nmol/l, 0.02–0.10) and median free testosterone (2.2 pmol/l, 1.0–4.5) were significantly lower in premature thelarche than in control (P < 0.001).CONCLUSIONS Serum SHBG is high and bioavailable T is low in girls with premature thelarche. This might alter the oestrogen/androgen ratio in the breast.
Point mutations detected in the androgen receptor gene of three men with partial androgen insensitivity syndrome
Authors: Saunders P. T. K. , Padayachi T. , Tincello D. G. , Shalet S. M. , Wu F. C. W. 
Published: March 2008

OBJECTIVE Determine the sequence of the androgen receptor gene in men with impaired responsiveness to androgens in order to identify the molecular basis of their under‐virilization.DESIGN Blood samples were used as the source of genomic DNA. Portions of the androgen receptor gene were amplified by polymerase chain reaction and sequenced.PATIENTS Samples were obtained from three patients and five normal fertile controls. Patients were all 46 XY and were undervirilized with ambiguous external genitalia, gynaecomastla and infertility.MEASUREMENTS Total cellular DNA was purified from peripheral blood leucocytes. Pairs of ollgonucleotide primers designed to flank the individual exons of the androgen receptor gene were synthesized. The specific regions of the androgen receptor were amplified from the samples of cellular DNA by polymerase chain reaction. Amplified DNA was purified, sequenced and compared to the published sequence.RESULTS In all three patients point mutations in the androgen receptor gene were detected but no defects were detected in samples from normal controls. In two of the patients, an identical single nucleotide change from G to T was detected. This nucleotide was within the codon for amino acid 866 and would change it from valine to leucine. Amino acid 866 is found within an area of the steroid binding domain thought to be involved in receptor dimerization. Within the repetitive sequence of exon I patient 1 had 21 glutamine residues and patient 2 had 25. In the third patient a single change of G to A would result in incorporation of lysine in place of a conserved arginine residue at position 607 within the second zinc finger of the DNA binding domain. The sequence of the androgen receptor gene of the mother of the third patient revealed her to be heterozygous for the same defect.CONCLUSION Patients 1 and 2 are unrelated although they have an identical point mutation in their androgen receptor gene. A patient with complete androgen insensitivity syndrome has been reported to have a defect at the same position causing the amino acid substitution of methlonine for valine. Therefore we confirm that the nature of the amino acid change in the peptide sequence of the androgen receptor as well as its location within the protein, can have a profound effect on the phenotypic severity of androgen resistance. Studies on mutated receptors from individuals with a wide range of degrees of androgen resistance may enable us to construct a map of the key amino acids in the different domains of the protein.