bluuebunny/crossref_metadata_2025_split huggingface dataset:
RECOVERY FROM GLUCOCORTICOID INHIBITION OF THE RESPONSES TO CORTICOTROPHIN‐RELEASING HORMONE
Authors: WATSON A. C. , ROSENFIELD R. L. , FANG V. S. 
Published: March 2008

SUMMARYWe have characterized the recovery of the hypothalamic‐pituitary‐adrenal (HPA) axis from inhibition by short‐term prednisolone administration. Predni‐solone was given in a dosage averaging 25 mg at 12 h intervals orally for up to 2 weeks to adult volunteers. Human corticotrophin releasing hormone (hCRH) tests were performed at 0901 h using a bolus injection of 1 μg/kg before and 24–48 h after discontinuing the prednisolone. In the initial control study, hCRH stimulated a two‐fold rise in plasma ACTH and a 30% rise in plasma cortisol within 30 min (ACTH rose from 18.5 ± 4.5, SEM, pg/ml to 36.5 ± 12.6 pg/ml and cortisol from 415 ± 58 to 531 ± 69 nmol/l in response to hCRH. One dose of prednisolone had no effect on the ACTH or cortisol response to hCRH administered 24 h later. Twenty‐four hours after discontinuing a 1 week course of prednisolone, baseline plasma ACTH (3.9 ± 0.6 pg/ml) and cortisol (146 ± 17 nmol/l) were markedly suppressed, as was the cortisol response to hCRH (peak 198 ± 22). However, the plasma ACTH response to hCRH was not significantly suppressed. Forty‐eight hours after discontinuing prednisolone, the recovery of ACTH secretion was complete (baseline 10.9 ± 4.2, peak 36.4 ± 14.8 pg/ml), but the cortisol response to hCRH was still depressed (peak 294±66 nmol/l). Recovery from a 2 week course of prednisolone had similar characteristics except plasma cortisol was depressed more profoundly. Plasma dehydroepian‐drosterone (DHA) during hCRH tests and dehydroepiandrosterone sulphate (DHAS) paralleled plasma cortisol. We interpret these data to suggest that the sequence of recovery from 1 to 2 weeks of glucocorticoid inhibition is characterized first by return to normal of ACTH secretion, followed by sequential returns to normal of CRH and adrenal steroid secretion. During recovery from this relatively short course of glucocorticoids, the events reported to be characteristic of withdrawal from chronic glucocorticoid therapy appear to occur in foreshortened sequence.
OUTCOME FOLLOWING STANDARDIZED 185 MBq DOSE 131I THERAPY FOR GRAVES' DISEASE
Authors: WATSON A. B. , BROWNLIE B. E. W. , FRAMPTON C. M. , TURNER J. G. , ROGERS T. G. H. 
Published: March 2008

SUMMARYThe clinical outcome of 199 patients with Graves' disease treated with standardized 185MBq 131I therapy doses has been analysed. Most patients were controlled with antithyroid drugs prior to the 131I therapy, and also received antithyroid drugs for several months following 131I. The median follow‐up period was 5.5 years. The single 185MBq 131I dose successfully treated 72.4% of patients. The 1,2 and 5 year hypothyroid figures were 15.5%, 19.3% and 27.3%, respectively. Previous thyroidectomy was associated with an increased hypothyroid rate. Retreatment was required by 25.6%, with 3.5% requiring more than two 131I doses. Discriminant analysis of pretreatment variables suggests that patients with large goitres or severe disease (serum T3 > 10nmol/l) should be treated with higher doses of 131I.
EFFECTS OF THYROID HORMONES (T4, T3), BROMOCRIPTINE AND TRIAC ON INAPPROPRIATE TSH HYPERSECRETION
Authors: SALMELA P. I. , WIDE L. , JUUSTILA H. , RUOKONEN A. 
Published: March 2008

SUMMARYInappropriate TSH hypersecretion was diagnosed in a 38‐year‐old woman (case 1) and in a 38‐year‐old man (case 2). Both of them had earlier been treated by ablative therapy for hyperthyroidism. The present diagnosis was based on elevated basal serum TSH levels despite elevated serum free thyroid hormone levels. Both of them had exaggerated TSH responses to TRH (peak value 240 mU/l in case I and 408 mU/l in case 2). Their albumin and prealbumin levels were normal. The serum TBG level was normal in case 1 but was elevated in case 2. Serum levels of alpha‐subunits of TSH, and pituitary CT scans were normal. Despite mild clinical hyperthyroidism, peripheral indices of thyroid hormone action were normal. They had also relatives with apparent resistance to thyroid hormones. In view of the possibility that prolonged pituitary thyrotrophic stimulation is detrimental, various therapeutic approaches to suppress TSH levels were tried. Both T3 and T4 treatments lowered serum TSH levels, but were poorly tolerated. Acute administration of L‐dopa or bromocriptine reduced serum TSH levels, but this was not seen during long‐term therapy. TRIAC treatment lowered serum TSH levels, and the drug was well tolerated. Serum TSH responses to TRH were not blunted during T3, T4 or TRIAC treatments. Somatostatin also reduced serum TSH levels, but did not potentiate the effect of low dose T3 therapy. Our results suggest that the patients had unbalanced pituitary and peripheral thyroid hormone resistance, predominantly at the pituitary level. Of the drugs studied, TRIAC seemed to be the most suitable therapy.
CONTINUOUS SUBCUTANEOUS GROWTH HORMONE RELEASING FACTOR ANALOGUE AUGMENTS GROWTH HORMONE SECRETION IN NORMAL MALE SUBJECTS WITH NO DESENSITIZATION OF THE SOMATOTROPH
Authors: BRAIN C. , HINDMARSH P. C. , BROOK C. G. D. , MATTHEWS D. R. 
Published: March 2008

SUMMARYThe effects of 8 day continuous subcutaneous (s.c.) infusions of growth hormone releasing hormone analogue (NLE27GRF(1–29)NH2 (GHRH.A)) on growth hormone (GH) secretion were studied in 14 normal adult male volunteers. GHRH.A was administered in doses which ranged from 7.5 to 120 ng/kg/min in doubling steps. Baseline GH profiles obtained during a 24 h infusion of normal saline in each subject were compared with profiles performed on days 1 and 8 of the infusion. Doses above 30 ng/kg/min augmented GH pulse amplitude and frequency. Doses of 60 ng/kg/min and 120 ng/kg/min appeared more satisfactory as these represented doses on the upwards slope of the dose response curve. However, at a dose of 120 ng/kg/min the GH secretion did not return to baseline for 12 of the 24 h. There was no evidence of desensitization or of depletion of the releasable GH pool with any dose. The possibility of treatment of short children with depot preparations of GHRH.A appears promising.
GROWTH HORMONE (GH) RESPONSES TO ARGININE AND L‐DOPA ALONE AND AFTER GHRH PRETREATMENT
Authors: PAGE M. D. , DIEGUEZ C. , VALCAVI R. , EDWARDS C. , HALL R. , SCANLON M. F. 
Published: March 2008

SUMMARYIn order to investigate the mechanisms by which arginine and L‐dopa cause GH release in humans we measured the GH response to GHRH 1–44 (200 μg i.v.), arginine (30 g i.v. over 30 min) and L‐dopa (500 mg orally) administered alone and 120 minutes following pretreatment with GHRH 1–44 (200 μg i.v.) in normal male subjects. Prior GHRH administration abolished the GH response to subsequent GHRH. Arginine infusion induced a rise in GH levels maximal at 45 min. Following GHRH pretreatment the GH response to arginine was enhanced, with peak values of 19.3 ± 6.4 vs 53.3 ± 16.5 mU/l (mean + SEM) respectively (P < 0.02). L‐dopa alone induced a rise in GH levels maximal at 90 min (17.6 ± 7.4 mU/l, mean ± SEM) but this rise was abolished by pretreatment with GHRH.
THE RELATIONSHIP BETWEEN THE RESPONSE TO GROWTH HORMONE THERAPY AND PRE‐TREATMENT GROWTH HORMONE SECRETORY STATUS
Authors: HINDMARSH P. C. , SMITH P. J. , PRINGLE P. J. , BROOK C. G. D. 
Published: March 2008

SUMMARYIn 35 children (22 M, 13 F) aged between 5.3 years and 10.3 years who received Somatrem therapy for 1 year there was a curvi‐linear relationship between pre‐treatment GH secretory status (x) and response (y) (change in height velocity standard deviation score (SDS)) to therapy described by the equation y= A + B (e−Cx). A, B and C are constants. Dose of GH administered was found to be an important additional factor in determining respone to therapy. This was confirmed by stepwise multiple regression which resulted in a correlation coefficient of 0.74. These data suggest that in the assessment of response to GH therapy, pretreatment height velocity and/or GH secretory status as well as dose and frequency of GH administration need to be taken into account.
BLOCKAGE OF THE POSITIVE FEEDBACK EFFECT OF OESTRADIOL DURING PROLONGED ADMINISTRATION OF CLOMIPHENE CITRATE TO NORMAL WOMEN
Authors: MESSINIS IOANNIS E. , TEMPLETON ALLAN 
Published: March 2008

SUMMARYThe effect of clomiphene citrate on the occurrence and timing of the endogenous LH surge in superovulated cycles is unclear. To study further this event, five normally ovulating women were treated with clomiphene citrate 100 mg per day in two different cycles, that is, for 5 days in one cycle (days 2 to 6, CC‐5) and for 15 days in another cycle (days 2 to 16, CC‐15). During the CC‐5 cycle, the normal pattern of LH levels seen in spontaneous cycles was observed with an endogenous LH surge in all women followed by ovulation and normal luteal function. In contrast, during the CC‐15 cycle, a continuous and progressive increase of basal LH levels was seen with no surge, resulting in follicular luteinization but no ovulation. The results suggest that in normal women treated with clomiphene the occurrence of an endogenous LH surge is dependent on a significant decrease in the circulatory concentration of clomiphene at mid‐cycle.
THE EFFECT OF CALCITONIN ON GROWTH HORMONE SECRETION IN MAN
Authors: LOOIJ B. J. , ROELFSEMA F. , VAN DER HEIDE D. , FROLICH M. , SOUVERIJN J. H. M. , KRUSEMAN A. C. NIEUWENHUIJZEN 
Published: March 2008

SUMMARYTo determine whether human calcitonin inhibits GH secretion in man, as has been described for salmon calcitonin, the effect of an i.v. bolus of human calcitonin or saline on GH release after either insulin‐induced hypoglycaemia or the administration of GH‐releasing hormone (GHRH) or saline was studied. After the injection of calcitonin, no spontaneous GH surges were seen; the GH response to hypoglycaemia was diminished and the response to GHRH almost completely suppressed. Administration of calcitonin also caused a small and transient rise in plasma PRL and TSH but not LH levels, and no change in the integrated PRL or TSH response. Calcium and magnesium levels did not change. It is concluded that human calcitonin suppresses GH secretion in man, but not by suppressing GHRH and probably not by increasing somatostatin release. In addition, calcitonin has limited PRL and TSH‐releasing activity.
HLA CLASS II DNA GENOTYPES IN GRAVES' DISEASE: CLUES TO INHERITANCE OF THE HLA‐LINKED COMPONENT OF SUSCEPTIBILITY
Authors: FLETCHER J. , FRANKLYN J. A. , McLACHLAN S. M. , YOUNG E. , SHEPPARD M. C. 
Published: March 2008

SUMMARYRestriction fragment length polymorphism analysis using DQα, DQβ and DRβ cDNA probes was performed in Graves' disease patients and control subjects. The following restriction fragment patterns were increased in frequency in patients compared with control subjects: 10 + 70 + 4.0kb DRβ/Taq1 fragments (66%vs32%; P < 0.01;corrected P< 0.06),7.0+4.0 kbDQβ/BamHI fragments (55%vs 15%; P< 0.001; corrected P<0006), and a DQα/TaqI 4.6kb fragment (75%vs 36%; P< 0.005; corrected P < 0.02). These associations could be accounted for by the known association of the B8‐DR3 haplotype with the disorder. No non‐DR3‐related restriction fragment pattern was associated with the disease using any of the probes with restriction enzymes TaqI and BamHI.The 10+7‐0 + 4‐0kb DRβ/TaqI restriction pattern was identified in 23 of 35 Graves' disease patients. All 23 subjects were heterozygous for this pattern. This was inconsistent with simple recessive inheritance of the DR3‐associated component of disease susceptibility (P=001).The implications of these findings are discussed with reference to models for the inheritance of the HLA‐linked component of Graves' disease susceptibility.
NORMAL NEONATAL SURGE OF GONADOTROPHINS AND SEX STEROIDS IN INFANTS OF MEN WITH ISOLATED HYPOGONADOTROPHIC HYPOGONADISM
Authors: ROSE SUSAN R. , CASSORLA FERNANDO , SHERINS RICHARD J. 
Published: March 2008

SUMMARYThe inheritance of isolated hypogonadotrophic hypogonadism (IHH) is not fully determined. Although men with this diagnosis can be treated to induce fertility, it is not known whether their offspring will inherit the hormonal deficiency. We evaluated the hypothalamic‐pituitary‐gonadal axis in nine children (born to men with IHH) during the first few months of life. This axis normally shows activation in infancy similar to that which occurs at puberty. Luteinizing hormone (LH) releasing hormone stimulated a peak LH response in excess of prepubertal levels (39.0 ± 11 mIU/ml [mean ± SD]). Testosterone in males (6.2 ± 2.8 nmol/1 and oestradiol in two of the females (320 and 100 pmol/1) were also in excess of prepubertal levels. These infants of men with IHH showed no evidence of inheriting hypogonadotrophic hypogonadism. While further studies will be conducted at the usual age of puberty to confirm spontaneous activation of the hypothalamic‐pituitary‐gonadal axis, our studies suggest that it may be possible to assess the integrity of this axis at a much younger age.
SPECTRUM OF THYROID FUNCTION ABNORMALITIES IN GESTATIONAL TROPHOBLASTIC NEOPLASIA
Authors: DESAI R. K. , NORMAN R. J. , JIALAL I. , JOUBERT S. M. 
Published: March 2008

SUMMARYThe relative influences of the putative thyroid stimulator, pregnancy state and non‐thyroidal illnesses, were assessed in 52 patients with gestational trophoblastic neoplasia (GTN). In this study biochemical thyroid status was assessed with the aid of thyrotrophin (TSH) measurements by a sensitive immunoradiometric assay and measurement of total and free thyroid hormone concentrations. The reference group consisted of 63 patients with normal pregnancy. Thyroid function in the GTN patients was also compared with that in 36 female patients with Graves' disease and 34 female patients with non‐thyroidal illnesses. We found the major influence on thyroid functions in Group I (‘Hyperthyroid’) patients with GTN to be the presence of the thyroid stimulator, while non‐thyroidal illnesses played an important role in Group II (‘High T4 syndrome’) and III (‘euthyroid’) patients with GTN. Thyroid function was also stimulated in Group II patients. The influence of pregnancy was seen in all three groups of patients with GTN, who had higher TBG concentrations than non‐pregnant patients. We conclude that there is a spectrum of thyroid function abnormalities in GTN, and that thyroid function in an individual patient is determined by the relative influence of the thyroid stimulator, non‐thyroidal illnesses and the pregnancy.
FAMILIAL POLYCYSTIC OVARIES: A GENETIC DISEASE?
Authors: HAGUE WILLIAM M. , ADAMS JUDITH , REEDERS STEPHEN T. , PETO TIMOTHY E. A. , JACOBS HOWARD S. 
Published: March 2008

SUMMARYHigh resolution ultrasonography was used to establish the presence of polycystic ovaries (PCO) in 50 women with symptoms of polycystic ovary syndrome and in 17 women with congenital adrenal hyperplasia. One hundred and thirty‐seven post‐menarcheal, premenopausal female members of the families of these patients were scanned to assess the heredity of the condition. Familial PCO was found in 56 of the 61 pedigrees (92%) in which sufficient members were available for study. The frequency of PCO in the relatives of the patients with congenital adrenal hyperplasia was no different from that found in the main group. Twenty‐four out of thirty‐six (67%) mothers of probands and 45 out of 52 (87%) sisters of probands were affected. The segregation ratio (fraction of females affected) for all sibships was 107 out of 133 (80.5%). The volumes of the polycystic ovaries (mean 9.97 ml, 95% confidence limits (CL) ±0.75) were significantly different from those of the normal ovaries (mean 5.38 ml, 95% CL ±0.26) (P<00001), although there was no significant difference between the volumes of the ovaries of the probands and those of their affected relatives. Even after allowing for a high frequency of PCO in the general population (22%), the observed segregation ratios were significantly different from those predicted for autosomal dominant (P < 10−4) and X‐linked dominant (P=0.0002) modes of inheritance. A number of mechanisms which might account for the observed segregation ratio are considered. These include meiotic drive due to a genetic segregation distorter, vertical transmission of an infective agent, and environmental factors, such as the effect of maternal androgen on gonadal develpment.
BIOACTIVE LH IN WOMEN WITH POLYCYSTIC OVARIES AND THE EFFECT OF GONADOTROPHIN SUPPRESSION
Authors: MAVROUDIS K. , EVANS A. , MAMTORA H. , ANDERSON D. C. , ROBERTSON W. R. 
Published: March 2008

SUMMARYDiscrepancies between levels of bioactive LH (B‐LH) and immunoreactive LH (5‐LH) in polycystic ovarian syndrome (PCO) have been reported previously. Serum levels of I‐LH, B‐LH (by dispersed Leydig cell assay), FSH, oestradiol (E2) and progesterone (Prog) were measured once to three times weekly over 4 weeks in 13 women with classical clinical, ultrasound and endocrine features of PCO. Eleven women attending for infertility but whose profiles when studied three times weekly by combined endocrine and ultrasound assessment were normal and ovulatory served as controls. Seven of the women with PCO were evaluated during and after 3 weeks suppression with ethinyloestradiol (30 μg) plus 150 μg either of desogestrel or levonorgestrel; two were given both treatments. Both I‐LH and B‐LH levels were higher in PCO patients (20 ± SD 5 U/l and 46 ± 9 U/l respectively, P< 0.0001), compared with all phases of the normal cycles except the mid‐cycle peak. The B‐LH to I‐LH (B: I LH) ratio in PCO patients (2.5 ± 0.7) was higher than in all the control cycle phases (P < 0.05). I‐LH, B‐LH, B: I LH ratio, FSH and E2 were all suppressed from the second week of oestrogen‐progestogen treatment (P<001) and returned gradually to pretreatment levels by the third or fourth week after suppression. The LH and FSH levels and B:I LH ratio in PCO patients during suppression were comparable with levels in the early and mid‐follicular phases of control cycles but the LH/FSH ratio remained significantly raised (P < 001) at 2.3 ± 0.7. Significant correlations were found between I‐LH and B‐LH (P<0.02) and between E2 levels and B:I LH ratio (P<005). We conclude that the abnormal B: I LH ratio in PCO is reversed by suppression with sex steroids, suggesting that qualitatively abnormal LH circulating in this condition is a secondary rather than a primary abnormality.
ORCADIAN VARIATION OF GH‐INDEPENDENT IGF‐BINDING PROTEIN IN DIABETES MELLITUS AND ITS RELATIONSHIP TO INSULIN. A NEW ROLE FOR INSULIN?
Authors: HOLLY J. M. P. , BIDDLECOMBE R. A. , DUNGER D. B. , EDGE J. A. , AMIEL S. A. , HOWELL R. , CHARD T. , REES L. H. , WASS J. A. H. 
Published: March 2008

SUMMARYEvidence is accumulating that a non‐GH dependent insulin‐like growth factor‐binding protein (IGF‐BP) is not only a carrier protein but also has an active role in the growth process.We have measured levels of this IGF‐BP, using a specific RIA, over 12 or 24‐h periods in 11 adolescents with diabetes mellitus and five normal adults. In each of the normals the IGF‐BP was undetectable for most of the day but with a broad nocturnal peak observed, with levels up to 50 μU/l. The levels of IGF‐BP were unrelated to the secretory pattern for GH but correlated inversely with the concentration of circulating insulin. In the diabetics a very similar pattern was observed, but with detectable levels throughout the day and much higher peak levels seen at night. Peak levels were up to 120 μg/1 if a long‐acting insulin preparation was administered in the evening but were 400–500 μg/1 if the long‐acting preparation was administered in the morning. The IGF‐BP was strongly correlated with plasma glucose in this latter group.In a further group of diabetics overnight profiles were obtained on two separate nights, a normal night and a night with euglycaemia maintained with a glucose clamp technique. Euglycaemia failed to affect peak levels of the binding protein, although the shape of the nocturnal peak was altered consistent with the altered pattern of circulating free insulin. In this group a strong inverse correlation was obtained between the IGF‐BP and free insulin levels.
SELLA SIZE AND CONTENTS IN SHEEHAN'S SYNDROME
Authors: SHERIF IBRAHIM H. , VANDERLEY CHRISTINE M. , BESHYAH SALEM , BOSAIRI SOAD 
Published: March 2008

SUMMARYHigh‐resolution computerized tomography was used to assess the size and contents of the pituitary fossa in 57 patients with Sheehan's syndrome and 17 female control subjects. No correlation was found either in the patients or the control group, between sella volume and age, weight, height, parity or time interval from postpartum haemorrhage to scan. The sella volume showed wide variation. The mean sella volume for all patients was 565 mm3 (SD 292) in contrast to a mean volume for the controls of 922 mm3 (SD 155). The difference was statistically significant (P> 0.001) using the Mann‐Whitney test. The stalk was visualized in 46 patients (81 %) (20 of these showed other pituitary tissue in addition). The remaining 11 patients showed no pituitary tissue, and only pure CSF density was observed.
THE CARDIOVASCULAR EFFECTS OF OCTREOTIDE TREATMENT IN ACROMEGALY: AN ECHOCARDIOGRAPHIC STUDY
Authors: THUESEN LEIF , CHRISTENSEN STIG E. , WEEKE JØRGEN , ØRSKOV HANS , HENNINGSEN PER 
Published: March 2008

SUMMARYNine acromegalic patients were treated by the somatostatin analogue SMS 201–995 octreotide (Sandostatin (octreotide), Sandoz, Basle, Switzerland)) 250 μg/ day in 4 divided s.c. injections (50 + 50 + 50 +100 μg) for 1 month, 250 μg/24 h as continuous s.c. infusions for another month and thereafter 200 μg three times daily as s.c. injections. Echocardiography was performed before the treatment, following 1 month of octreotide s.c. infusion/injection and after 6 and after 12 months of octreotide treatment. No differences in serum growth hormone, heart rate, blood pressure, cardiac contractility or left ventricular wall mass or wall thickness were found between the infusion and the injection periods. As compared to the pretreatment levels serum growth hormone decreased by 62 and 66%, respectively following 6 and 12 months octreotide treatment. The heart rate per minute (± SD) decreased from the pretreatment level of 75 ± 12 to 63·13 (P> 0.007) at month 12. The systolic and the diastolic blood pressure decreased from the pretreatment level of 121 ± 8 and 79 ± 5 mmHg respectively to 108 ± 7 (P> 0.0007) and 71 ± 7 mmHg (P> 0.0001) respectively at month 12. The left ventricular wall thickness was reduced from 26 ± 3 mm before treatment to 24 ± 3 mm (P> 0.05) at month 6 and to 24 ± 4 mm (P> 0.04) at month 12. The left ventricular wall mass was 168 ± 48 g/m2 before octreotide treatment, 156 ± 46 g/m2 (NS) after 6 months and 157 ± 52 g/m2 after 12 months (P> 0.08) of octreotide treatment. In age and sex‐matched normal control subjects the left ventricular wall thickness was 20 ± 2 mm, and the left ventricular wall mass was 122 ± 26 g/m2. The wall thickness and the wall mass were increased in the acromegalic patients as compared to the controls before and following the octreotide treatment periods. We suggest that reduction of serum growth hormone levels by octreotide in acromegalic patients is associated with a decrease of the left ventricular wall thickness, but the wall thickness is not reduced to levels of normal control subjects.