bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short and long‐term responses to metyrapone in the medical management of 91 patients with Cushing's syndrome
Authors: Verhelst J. A. , Trainer P. J. , Howlett T. A. , Perry L. , Rees Lesley H. , Grossman A. B. , Wass J. A. H. , Sesser G. M. 
Published: March 2008

Summary. objective To analyse the clinical and biochemical effects of metyrapone in the treatment of Cushing's syndrome.design An evaluation of the standard clinical practice at one institution.patients Ninety‐one patients with Cushing's syndrome: 57 pituitary‐dependent Cushing's disease, 10 adrenocortical adenomas, six adrenocortical carcinomas and 18 ectopic ACTH syndrome.measurementsThe acute response to metyrapone was assessed by measuring cortisol, 11‐desoxycortisol and ACTH at 0, 1, 2, 3, 4 hours after a test dose of 750 mg of metyrapone. The longer‐term effect of metyrapone was judged by measuring serum cortisol at 0900, 1200, 1500, 1800, 2100 and sometimes 2400 h and calculating a mean.results A test dose of 750 mg of metyrapone decreased serum cortisol levels within 2 hours In all groups of patients and this effect was sustained at 4 hours. At the same time, serum 11‐desoxycortisol levels Increased in all patients, while plasma ACTH Increased In patients with pituitary Cushing's disease and the ectopic ACTH‐syndrome. Fifty‐three patients with Cushing's disease were followed on short‐term metyrapone therapy (1 to 16 weeks) before other more definitive therapy. Their mean cortisol levels (median 654 nmol/l, range 408–2240) dropped to the target range of < 400 nmol/l in 40 patients (75%) on a median metyrapone dose of 2250 mg/day (range 750–6000). Metyrapone was given long term In 24 patients with Cushing's disease who had been given pituitary Irradiation, for a median of 27 months (range 3–140) with adequate control of hypercortisolaemia in 20 (83%). In 10 patients with adrenocortical adenomas and six with adrenocortical carcinomas, metyrapone in a median dose of 1750 mg/day (range 750–6000) reduced their mean cortisol levels (median 847 nmol/l, range 408–2000) to < 400 nmol/l in 13 patients (81%). In 18 patients with the ectopic ACTH‐syndrome the ‘mean cortisol levels', obtained from five or six samples on the test day (median 1023 nmol/l, range 823–6354) were reduced to < 400 nmol/l In 13 patients (70%), on a median dose of 4000 mg/day (range 1000–6000). Reduction of cortisol levels was clearly associated with clinical and biochemical Improvement. The medication was well tolerated. Transient hypoadrenalism and hirsutism were unusual but were the most common side‐effects.conclusions In our experience metyrapone remains a most useful agent for controlling cortisol levels in the management of Cushing's syndrome of all types.
The effect of drinking on atrial natriuretic peptide, vasopressin and thirst appreciation in hyperosmolar man
Authors: Burrell Louise M. , Lambert Heather J. , Baylis P. H. 
Published: March 2008

Summary.objectiyesTo assess whether drinking and oropharyngeal stimuli mediate the release of plasma atrial natrluretic peptide (ANP) in man.design Hypertonic saline was infused into male volunteers to stimulate thirst. In order to avoid any effect of volume change on ANP release, the studies were performed with the subject in the seated position.subjects Seated normal male volunteers (n= 6) were Infused with hypertonic saline at a rate of 0.06 ml/kg/min for 90 min on two separate occasions. After a 15‐min equilibrium period, subjects were allowed to drink for the following 45‐min period on one occasion, but no drinking was permitted on the other occasion.measurementsAliquots of blood were withdrawn at 30‐min intervals for 90 min during hypertonic saline Infusion, and +3, 6, 9, 12, 15, 30 and 45 min during the drinking/control period for the measurement of plasma ANP, plasma vasopressin, plasma osmolality, serum sodium and haematocr< thirst was assessed at the same time points using a visual analogue scale. Blood pressure was measured at 15‐min Intervals.results Hypertonic saline infusion induces increases in plasma vasopressin, plasma osmolality, serum sodium and thirst appreciation (P < 0.005), and blood volume (P < 0.05) on both study days; there was no increase in plasma ANP during hypertonic saline infusion. During the drinking period there was the expected decrease in plasma vasopressin (P < 0.01), plasma osmolality (P < 0.05), serum sodium (P < 0.05) and thirst appreciation (P < 0.01); no significant changes occurred In plasma atrial natriuretic peptide, mean arterial blood pressure or haematocrlt during either the drinking or the control period.conclusionsThe drinking‐mediated inhibition of thirst appreciation and plasma vasopressin is not associated with any change in plasma ANP concentrations; it does not appear that oropharyngeal stimuli contribute to the release of ANP in man.
A distribution method for analysing the baseline of pulsatile endocrine signals as exemplified by 24‐hour growth hormone profiles
Authors: Matthews D. R. , Hindmarsh P. C. , Pringle P. J. , Brook C. G. D. 
Published: March 2008

Summary. objective To develop a method for quantifying the distribution of concentrations present in hormone profiles, which would allow an observer‐unbiased estimate of the time concentration attribute and to make an assessment of the baseline.design The log‐transformed concentrations (regardless of their temporal attribute) are sorted and allocated to class intervals. The number of observations in each Interval are then determined and expressed as a percent‐age of the total number of samples drawn In the study period. The data may be displayed as a frequency distribution or as a cumulative distribution. Cumulative distributions may be plotted as sigmoidal ogives or can be transformed into discrete probabilities (linear probits), which are then linear, and amenable to regression analysis. Probability analysis gives estimates of the mean (the value below which 50% of the observed concentrations lie, which we term ‘OC50’). ‘Baseline’ can be defined in terms of percentage occupancy—the ‘Observed Concentration for 5%’ (which we term ‘OCs’) which is the threshold at or below which the hormone concentrations are measured 5% of the time.patientsWe report the use of applying this method to 24–hour growth hormone (GH) profiles from 63 children, 26 adults and one giant.results We demonstrate that GH effects (growth or gigantism) In these groups are more related to the baseline OCs concentration than peak concentration (0C5± 95% confidence limits: adults 0.05 ± 0.04, peakheight‐velocity pubertal 0.39 ± 0.22, giant 8.9 mU/I).conclusionsPulsatile hormone profiles can be analysed using this method in order to assess baseline and other concentration domains.
Long‐term follow‐up of hypothalamic‐pituitary function in patients with transsphenoidal pituitary herniation and midfacial anomalies*
Authors: Ellyin Fredrick M. , Potchynok Alan , Song Chung 
Published: March 2008

Summary. objective We wished to determine whether patients with transsphenoidal pituitary herniation were at risk of developing pituitary failure.design We followed up hypothalamic‐pituitary function annually In patients with midfacial anomalies and pituitary herniation.patients Two patients who had transsphenoldal pituitary herniation and midfacial anomalies were Included and the literature was reviewed.results Both patients became gonadotrophin, TSH and growth hormone‐deficient despite neurosurgical repair.conclusion We conclude that the early diagnosis and neurosurgical repair of transsphenoidal pituitary herniation may prevent central nervous system Infection and rhinorrhoea. Surgical repair may not prevent pituitary failure as was evident in both of our cases. Periodic evaluation of the hypothalamic‐pituitary axis is essential to determine whether early hormonal replacement therapy is necessary.
Effects of sex and age on serum GH binding protein levels in normal adults
Authors: Hattori Naoki , Kurahachi Hiroyuki , Ikekubot Katsuji , Ishlhara Takashi , Morldera Kunisaburo , Hino Megumu , Saikit Yasuhiko , Imura Hiroo 
Published: March 2008

Summary. objective The effects of sex and age on serum growth hormone binding protein (GHBP) levels during adulthood were investigated.design The levels of GHBP, insulin‐like growth factor‐I (IGF‐1), and growth hormone (GH) were determined and analysed as a function of sex and age.patients We studied 101 normal adults (45 men, aged 20–77 years; 56 women, aged 20–80 years).measurements GHBP levels were determined using an Ultrogel AcA 44 minicoiumn.results During the second and third decade, GHBP levels were not different between men (22.8±1.1%) (mean ± SE) and women (23.2±0.8%). After the age of 40 years, however, GHBP levels in men were significantly decreased (19.1 ± 0.7%), and were lower than those in women (22.7±0.9%). IGF‐I levels correlated positively with GHBP levels in men (r= 0.51, P < 0.01) but not in women (r= 0.16, NS).conclusions These results indicate that both sex and age may have some effects on the GH‐GH receptor‐IGF‐I axis.
Serum and follicular fluid insulin like growth factors I and II during growth hormone co‐treatment for in‐vitro fertilization and embryo transfer
Authors: Owen E. J. , Torresani T. , West C. , Mason B. A. , Jacobs H. S. 
Published: March 2008

Summary. objective We wished to assess the changes in serum IGF‐I and IGF‐ll concentrations during gonadotrophin treatment alone or with additional GH treatment and to compare follicular fluid IGF‐I and IGF‐II concentrations in the two treatment groups.design We performed an open study of co‐treatment with GH and subsequently a randomized double blind comparison of addition of placebo or GH to clomiphene citrate and gonadotrophins.patients We studied previously poor responders to superovulation regimens for in‐vitro fertilization and embryo transfer, six women in an open study, four of whom had ultrasound diagnosed polycystic ovaries, and 17 women in a double blind study, 12 of whom had polycystic ovaries.measurementsWe measured serum IGF‐I and IGF‐II concentrations throughout treatment cycles. Follicular fluid concentrations were measured at the time of oocyte recovery.resultsNeither serum IGF‐I nor IGF‐ll concentrations were altered by gonadotrophin treatment alone. However, co‐treatment with GH led to a significant rise In serum IGFI concentrations In women with ultrasound diagnosed polycystic ovaries. Concentrations of IGF‐I and IGF‐ll In follicular fluid were lower than in serum, although follicular fluid IGF‐I concentrations were higher in women receiving GH than in those receiving placebo.conclusionsPoor responders to superovulation regimens may have an abnormality of growth factor response. GH co‐treatment leads to an increase in circulating IGF‐I concentrations in women with polycystic ovaries but our results do not support the hypothesis that GH stimulates IGF‐I production in the human ovary.
Treatment with biosynthetic growth hormone of short thalassaemic patients with impaired growth hormone secretion
Authors: Scacchi M. , Danes' L. , Martin M. De , Dubin' A. , Fornl L. , Masalat A. , Gallisait D. , Burrai C. , Terzoll S. , Boffa C. , Marzano C. , Cavagninl F. 
Published: March 2008

Summary. objective Impairment of linear growth is a common clinical feature In patients with β‐thalassaemia major. Although growth hormone secretion appears to be normal in many short thalassaemic patients, it proves to be deficient in some of them. In these cases, administration of biosynthetic growth hormone seems justified. The aim of this study was to evaluate the effect of such treatment in a group of patients with β‐thalassaemla major presenting with growth failure and impairment of growth hormone secretion.design Recombinant human growth hormone, 0.6 U/kg body weight per week, given subcutaneously In three divided doses, was administered for 12 monthspatients Eight prepubertal patients with β‐thalassaemia‐major, presenting with severe growth retardation and Impaired growth hormone secretion In response to provocative stimuli (insulin‐induced hypoglycaemia, L‐dopa and growth hormone‐releasing hormone), were Investigated.measurementsHeight and pubertal stage of the patients, as well as plasma levels of Insulin‐like growth factor I, were determined before, during and after biosynthetic growth hormone treatment.results During the first 6 months of therapy, a significant Increase of growth velocity was observed, from a mean pretreatment value of 20.1 ± 0.45 cm/year to a value of 4.8 ± 0.66 cm/year (P < 0.002). Mean growth rate at 12 months (4.1 ± 0.50 cm/year), though slightly decreased in comparison to that recorded at 6 months, was still significantly higher than basal (P < 0.001). A significant Increase In plasma levels of Insulin‐like growth factor I was recorded during treatment (2.82 ± 0.47 vs 0.96 ± 0.22 U/ml, P < 0.005). No side‐effects, adverse reactions or alterations in routine laboratory examinations ensued during or after therapy.conclusions It appears from these data that biosynthetic growth hormone administration Is worth serious consideration In patients with β‐thalassaemia major presenting growth retardation and Impaired growth hormone secretion.
Follicle stimulating hormone stimulates the production of gonadotrophin surge attenuating factor (GnSAF) in vivo
Authors: Messinis I. E. , Hirsch P. , Templeton A. A. 
Published: March 2008

Summary. objective To study the time‐course production of gonadotrophin surge attenuating factor (GnSAF) after the onset of FSH treatment in women.design Normally cycling women were treated with FSH injections (225 IU per day) starting on cycle day 2 (0800 h). The response of LH to an i.v. Injection of 10 μg GnRH (GnSAF bioactivity) was investigated 12, 24, 36 and 48 hours after the first FSH Injection, as well as during the early follicular phase of an untreated spontaneous cycle. PATIENTS Six normally ovulating women with long‐standing unexplained infertility were studied. The women were used as their own controls during the spontaneous cycles. MEASUREMENTS Pituitary response to GnRH was calculated as the net Increase in LH at 30 min (ALH30) above the basal value.resultsδLH30 was significantly attenuated 12, 24, 36 and 48 hours after the first FSH injection as compared to the spontaneous cycles. In the latter cycles, ALH30 decreased significantly from day 2 (12 hours) to day 4 (48 hours). Serum oestradiol levels at 12 and 24 hours did not differ significantly between the FSH and the spontaneous cycles.conclusionsThese results demonstrate that in superovulated women, a marked attenuation in the pituitary response to GnRH occurs as early as 12 hours from a single injection of FSH before any significant Increase In serum oestradiol levels. It is suggested that FSH is a potent stimulus of GnSAF production in women.
Meningitis as a late complication of surgically and medically treated pituitary adenoma
Authors: Flad T. M. , McKenna T. Joseph 
Published: March 2008

Summary. objective To report meningitis occurring as a late complication of both medical and surgical treatment of pituitary tumour.design Two case reports.patients One patient developed meningitis 9 years after she underwent transsphenoidal hypophysectomy for Nelson's syndrome. The second patient developed rhinorrhoea while on treatment with bromocriptine for a prolactin‐secreting pituitary adenoma and subsequently developed meningitis.measurementsIn Patient 1, CT scanning identified a small defect in the floor of the sells turcica. In Patient 2, CT scan examinations performed with a 3‐year interval demonstrated marked shrinkage of a pituitary tumour which had invaded the sphenoid sinus so that the tumour no longer plugged the erosion.resultsBoth patients experienced rhinorrhoea for over a year prior to the onset of meningitis. Both patients dismissed the occurrence of rhinorrhoea as insignificant and did not bring it to medical attention. In Patient 1, rhinorrhoea and presumably the entry site for pneumococaal infection was through a defect in the floor of the sella turcica consistent with transsphenoidal hypophysectomy performed 9 years previously. In Patient 2, rhinorrhoea and presumably entry of infection was facilitated by unplugging of a defect in the wall of the sphenoid sinus by bromocriptine‐induced shrinkage of the pituitary adenoma.conclusionsMeningitis can occur as a late complication of surgical or medical treatment of pituitary tumours. This may be preceded by rhinorrhoea which should be regularly enquired for as the symptom may not prompt patients to disclose its presence spontaneously. These reports document only the third occurrence of meningitis as a late complication of transsphenoidal hypophysectomy and the first occurrence of meningitis as a consequence of treatment of a pituitary tumour with bromocriptine.
Changes in concentrations of cortisol, dehydroepiandrosterone sulphate and progesterone in fetal and maternal serum during pregnancy
Authors: Donaldson Amanda , Nicolini Umberto , Symes Elizabeth K. , Rodeck Charles H. , Tannirandorn Yuen 
Published: March 2008

Summary. objective In fetuses, adrenal steroids have been Implicated In organ maturation and in some species in initiation of labour. The fetal adrenal gland differs from the adult in its complement of steroid metabolizing enzymes. This study sought to examine the changes in peripheral cortisol, progesterone and dehydroepiandrosterone sulphate (DHEAS) in unstressed fetuses during pregnancy. DESIGN Paired maternal and fetal samples were collected from 47 patients. Fetal blood samples were collected by transabdominal needling. All fetuses were appropriately grown for age which ranged from 18 to 41 weeks.measurementsHormones were measured using specific, validated Immunoassays.results Fetal progesterone (mean, 822 nmol/l; 95% data Intervals 196–1449 nmol/l) varied considerably between Individuals but there was no significant change In serum concentration with gestational age, nor was there any difference between male and female fetuses. There was a small, but significant (y= 0.339x2–13.5x+ 231; r= 0.72, P= 0.0001) rise in cortisol in the fetal circulation from 32 to 41 weeks gestational age, whereas the mean fetal DHEAS concentration decreased linearly with gestational age from 4.1 μmol/l at 18 weeks to 2.6 μmol/l at 41 weeks (r=–0.41; P= 0.007). Mean progesterone concentration in the maternal serum Increased linearly from 98 nmol/l at 18 weeks to 783 nmolll at 41 weeks. In the fetus there was a significant correlation between progesterone and cortisol concentrations.conclusionsThese results are compatible with the proposed role of cortisol in fetal lung maturation, confirm high levels of progesterone in the fetus from an early stage of gestation, and provide further evidence for placental progesterone being the precursor of fetal cortisol.
Attenuation of gonadotrophin release and reserve in superovulated women by gonadotrophin surge attenuating factor (GnSAF)
Authors: Messinis Loannis E. , Templeton Allan 
Published: March 2008

SummaryIn‐vivo and in‐vitro studies have provided evidence that a non‐steroidal ovarian factor, called gonadotrophin surge attenuating factor (GnSAF), attenuates the endogenous LH surge in superovulated women. To study the mechanism of action of GnSAF, the LH response to two i.v. pulses of GnRH (10 μg each, 2 h apart) was investigated in eight normally ovulating women during the late follicular phase of a spontaneous and an FSH superovulated cycle. The maximal LH increase in response to the first pulse (initial release) was considered as representing the acutely releasable pool and the δLH area under the whole curve (integrated response) the reserve pool of LH. Both the initial release and the integrated response to GnRH were markedly attenuated in the FSH as compared to the spontaneous cycles. The response to the second pulse was significantly greater than the response to the first pulse (self‐priming effect of GnRH) in both the spontaneous and the FSH cycles. However, in the FSH cycles the self‐priming effect of GnRH was markedly reduced as compared to the spontaneous cycles. We conclude that during superovulation induction in women the two pools of pituitary LH are markedly attenuated. It is suggested that GnSAF attenuates both the GnRH‐induced initial release of LH and the self‐priming effect of GnRH on the pituitary.
d‐Fenfluramine/prolactin response throughout the menstrual cycle: evidence for an oestrogen‐induced alteration
Authors: O'Keane V. , O'Hanlon M. , Webb M. , Dinan T. 
Published: March 2008

SummaryThe prolactin (PRL) response to fenfluramine (FEN), a serotonin (S‐HT) releasing agent, is used as an index of 5‐HT sensitivity in studying disorders associated with central S‐HT abnormality. Plasma oestrogen levels are known to augment PRL responses to a variety of stimuli. In order to examine the effect that ovarian steroids have on this response nine, healthy women were tested twice at three time points in the menstrual cycle: early follicular, mid‐cycle and late luteal phase with either d‐FEN, a more specific 5‐HT agent than the racemic mixture, or placebo. Responses to d‐FEN were maximal at mid‐cycle, lowest during the early follicular phase, with responses premen‐strually being intermediate between the two. Responses to placebo did not vary. Plasma oestradiol levels fluctuated In parallel with neuroendocrine responses to d‐FEN. The possible mechanisms are discussed, Including an effect that oestradiol may exert at central serotonin sites.
Serum androgens in intensive‐care patients: correlations with clinical findings
Authors: Luppa P. , Munker R. , Nagel D. , Weber M. , Engelhardt D. 
Published: March 2008

SummarySerum androgen levels were studied In 100 patients (50 male) with varying degrees ot severe illness, determined by Acute Physiological and Chronic Health Evaluation (APACHE). Comparison with normal subjects revealed the following changes:

Basal dehydroeplandrosterone sulphate (DHEAS) values were decreased in the ill female patients (P< 0.001) as well as in the III males (two groups, P<0.01; P<0.05). Androstenedione values did not differ from the controls in patients of either sex. Basal testosterone levels were decreased in ill male patients (P< 0.001), but not in females.
The low testosterone concentrations in the severely ill male patients correlated Inversely with the APACHE score; additionally, a dependence on diagnostic categories could be demonstrated In men, since the lowest values were found in patients suffering from sepsis or liver cirrhosis. Acutely ill males had a moderately decreased testosterone, whereas chronically ill males showed a marked reduction of testosterone compared to the controls. Lowered DHEAS and androstenedione levels could be measured in chronically ill males but not In III females.
17α‐OH‐progesterone and 17α‐OH‐pregnenolone levels in subgroups of the patients suggested a probable enzymatic block In the A5‐pathway of androgen biosynthesis in severe illness. The ratio of 17α‐OH‐pregnenolone to DHEAS was significantly higher in male patients and tended to be high in ill females, whereas the ratio of 17α‐OH‐progesterone to androstenedione showed no difference between healthy and ill subjects.