bluuebunny/crossref_metadata_2025_split huggingface dataset:
The regulation of insulin‐like growth factor binding protein (IGFBP)‐1 during prolonged fasting
Authors: Cotterill Andrew M. , Holly Jeffrey M. P. , Wass John A. H. 
Published: March 2008

SummaryOBJECTIVE Insulin‐like growth factor binding protein (IGFBP)‐1 levels increase overnight, being inversely related to changes in insulin. With prolonged fasting IGFBP‐1 levels increase further. In animal studies high IGFBP‐1 levels increase plasma glucose levels possibly by regulating the insulin‐like actions of ‘bio‐available’ plasma IGF. Following prolonged fasting, there is an increase in insulin requirement. A proportion of this reversible insulin resistance may be due to inhibitory effects of high IGFBP‐1 levels on IGF action. This study examined the regulation of IGFBP‐1 in the presence of reversible insulin resistance.SUBJECTS Nine normal adult volunteers, seven female and two male (mean age 27.6 ± SD 2.6 years, range 21.7–46.0 years) of normal body mass index were studied.METHODS Subjects fasted from 2200 h day 0 to 0900 h day 3 (59 hours), the fast being completed with a 75‐g glucose meal. At least one week later, an 11‐hour overnight fast was performed, followed by a repeat glucose meal. Blood samples were taken at regular intervals from 0900 h day 1 and for 5 hours during both glucose meal studies via an indwelling cannula.MEASUREMENTS Serum levels of IGFBP‐1, insulin, GH, glucose, IGF‐I and cortisol were measured at varying intervals during the fast and both glucose meal studies.RESULTS Following the initial 11‐hour overnight fast IGFBP‐1 levels rose from (mean ± SEM) 32 ± 5 μg/l to reach a maximum of 144 ± 24μg/l after 32 hours of fasting. IGFBP‐1 levels then fluctuated, falling in the morning (93 ± 8μ/l) and then rising overnight (126 ± 9μ/l), but not regaining the initial peak levels. The increase of IGFBP‐1 from overnight fasting levels was associated with a fall in plasma insulin from 5.7 ± 0.7 to 2.2 ± 0.2 mU/l.In comparison, 30 minutes after termination of the fast with the glucose meal, IGFBP‐1 levels fell from 120 ± 11 to 24 ± 2 μg/l within 4 hours. After an overnight fast IGFBP‐1 levels fell from 35 ± 5 to 13 ± 2 μg/l within 3 hours. There was glucose intolerance and increased insulin levels following the glucose meal preceded by the 59‐hour fast when compared with the overnight fast. The fall of IGFBP‐1 levels after the glucose meal was best expressed, taking into account subject variation, by the following regression equations: Glucose meal preceded by 11‐hour fast: log [IGFBP‐1] = 1 64–0 255 log [1 h previous insulin] (R2 0.51); Glucose meal preceded by 59‐hour fast: log [IGFBP‐1] 1.41–0.265 log [1 h previous insulin] ± 0.557 log [current glucose] (R2 0.82).CONCLUSION In man, insulin appears to regulate circulating IGFBP‐1 levels in all circumstances, this regulation being unaffected by the resistance to insulin action induced by prolonged fasting. The high IGFBP‐1 levels were statistically related to the higher glucose levels and may have directly contributed to the increased insulin requirement observed after prolonged fasting.
ACTH‐independent Cushing's syndrome in pregnancy with spontaneous resolution after delivery: control of the hypercortisolism with metyrapone
Authors: Close C. F. , Mann M. C. , Watts J. F. , Taylor K. G. 
Published: March 2008

SummaryA 25‐year‐old primigravid woman presented with Cushing's syndrome at 23 weeks gestation; serum Cortisol was 1090 nmol/l at 0900 h, 1230 nmol/l at 2200 h; basal urinary free Cortisol excretion was 3680 nmol/24 h, and 8830 nmol/ 24 h after dexamethasone 8 mg daily for 48 hours; plasma ACTH was <1.1 pmol/l. CT scan of the adrenal glands showed bilateral adrenal hyperplasia. The hypercortisolism was controlled with metyrapone until elective delivery of the fetus by Caesarian section at 34 weeks gestation because of a decline in growth. No adverse fetal effects of metyrapone treatment were apparent, maternal outcome was uncomplicated and wound healing was unimpaired. Maternal adrenocortical function had returned to normal within 4 weeks of the cessation of pregnancy and biochemical remission has been maintained up to 9 months post‐partum. Metyrapone therapy is effective in controlling the hypercortisolism in certain cases of Cushing's syndrome complicating pregnancy.
Isolated congenital ACTH deficiency: a cleavage enzyme defect?
Authors: Nussey S. S. , Soo Shlu‐Ching , Gibsonf S. , Gout I. , White A. , Bain M. , Johnstone A. P. 
Published: March 2008

SummaryThe pro‐opiomelanocortin (POMC) gene encodes adreno‐corticotrophin (ACTH) which is derived from precursors by proteolytic cleavage. Congenital, isolated ACTH deficiency is rare but may be familial and fatal. The aetiology is unknown though defects at both hypothalamus and adenohypophysis have been postulated. We have studied a female presenting with hypoglycaemia in the neonatal period. When studied at 6 weeks of age, ACTH was unmeasurable even after injection of corticotrophin releasing hormone (CRH,_41). ACTH precursors, quantitated by two‐site immunuradiometric assay, were clearly measurable prior to treatment and were stimulated by CRH, 4, and suppressed by glucocorticoid administration. Concentrations of POMC, N‐terminal pro‐opiocortin (N‐POC) and β‐endorphin (β‐EP) were within the normal adult range during glucocorticoid replacement therapy; ACTH and βMipotrophin remained undetectable. The secretion of glucagon, measured by radioimmunoassay, in response to hypoglycaemia was normal. By sequencing polymerase chain reaction products from the patient's genomic DNA, the entire coding region of the POMC gene was established to be normal. The results are compatible with a cleavage enzyme defect.
Growth hormone dose regimens in adult GH deficiency: effects on biochemical growth markers and metabolic parameters
Authors: Møller Jens , Jørgensen Jens O. L. , Lauersen Torben , Frystyk Jan , Næraa Rune W. , Øsrskov Hans , Christiansen Jens S. 
Published: March 2008

SummaryOBJECTIVE We examined the effects of different doses of GH on insulin‐like growth factor I (IGF‐I), IGF binding protein 3 (IGFBP‐3), body composition, energy expenditure, and various metabolites in GH deficient adults, in order to approach a metabolically appropriate GH dosage in young GH deficient adults.DESIGN Ten GH deficient patients (age 21–43) were studied after 4 weeks without GH followed by three consecutive 4‐week periods, where the patients received in a fixed order GH 1,2 and 4 IU/m2 s.c. per day. At the end of each period the patients were hospitalized for a 24‐hour examination.RESULTS Mean 24‐hour levels of GH (mIU/l) were 2.7±0.3 (0 GH), 7 2±0.9 (1), 10.8±1.5 (2) and 18.9±2.7 (4 IU/m2) (mean ±SEM) (P<0.01). Likewise, IGF‐I levels increased dose dependently from 61 ± 21 to 206 ± 65, 260 ± 70 and 468 ± 171 /μg/l (P < 0 05); serum IGF‐I in an age and sex matched control group was 248 ± 25 /μg/l. Corresponding serum IGFBP‐3 levels also increased from 1860 ±239 to 3261 ±379, 3762 ±434 and 4384 ±652 /μg/l (P = 001) respectively. Significant increases in diurnal serum insulin levels after 4 IU/m2 were recorded, whereas plasma glucose levels remained unchanged. Lipid intermediates increased dose independently during GH administration. GH caused a significant increase in resting energy expenditure, whereas the respiratory exchange ratio was unaltered. Fat mass was increased without GH therapy and decreased during the study. Four patients made complaints during 4 IU/m2 GH administration, probably related to GH induced fluid retention.CONCLUSION Based primarily on IGF‐I and IGFBP‐3 levels our data suggest that a GH replacement dose in young GH deficient adults in the order of 1–2 IU/m2 per day is adequate. This is a relatively low dose as compared to dose regimens in children and adolescents.
Delta‐5‐androstenediol and its sulphate in serum and urine of normal adults and patients with endocrine diseases
Authors: Dikkeschei L. D. , Willemse P. H. B. , Wolthers B. G. , de Ruyter‐Buitenhuis A. W. , Nagel G. T. 
Published: March 2008

SummaryOBJECTIVES We evaluated the role of delta‐5‐androste‐nediol (adiol) and its sulphates in health and endocrine diseases.DESIGN Serum and urine samples from healthy adult men and pre and post‐menopausal women were analysed by gas chromatography‐mass spectrometry to establish reference values. In patients who were either evaluated or treated for endocrine diseases, sequential serum samples were collected and analysed.PATIENTS Reference values were obtained from 24 healthy male, 23 premenopausal and 30 post‐menopausal female volunteers. Adiol and delta‐5‐androstenediol‐3‐sulphate (adiol‐3S) concentrations were determined in combination with other relevant steroids in patients with either pituitary (n= 5), adrenal (n= 2) or gonadal dysfunction (n= 1), or testicular carcinoma (n= 19).MEASUREMENTS After addition of deuterated adiol as internal standard, serum and urine samples were extracted. Steroid sulphates were hydrolysed. The extracts and hydrolysates were purified on HPLC, adiol was derivatized and finally quantified by gas chromatography‐mass spectrometry.RESULTS The calculated reference ranges for adiol and adiol‐3S concentrations in serum are respectively: in men 1.78–7.24 and 123–579 nmol/l, in premenopausal women 0 65–6 93 and 21 2–298 nmol/l and in post‐menopausal women 0 29–2 90 and 61–184 nmol/l. Urinary values varied considerably. In the population with endocrine abnormalities serum adiol and adiol‐3S concentrations were compared with other relevant steroids.CONCLUSIONS The wide concentration range of adiol and adiol‐3S in urine makes analysis of these steroids in urine of little clinical value. Serum concentrations of adiol and adiol‐3S are higher in men than in women. Premenopausal values are higher than post‐menopausal. Adiol and adiol‐3S in serum are significantly correlated in pre and post‐menopausal women, r= 0 51 and r= 0–69 respectively, but not in men. In endocrine patients the serum concentrations of adiol show an ACTH or LH dependency in women; adiol correlates with Cortisol, dehydroepian‐drosterone or androstenedione and, in males, additionally with testosterone. However, in several situations adiol correlates with none of these steroids. Although adiol secretion can be stimulated by ACTH and LH, the level of serum adiol is also determined by other factors. Finally, in adrenal carcinoma serum adiol and adiol‐3S may be used as tumour markers.
Combined 17α‐hydroxylase/17,20‐lyase deficiency caused by heterozygous stop codons in the cytochrome P450 17α‐hydroxylase gene
Authors: Rumsby G. , Skinner C. , Lee H. A. , Honour J. W. 
Published: March 2008

SummaryOBJECTIVE To determine the genetic defect underlying congenital adrenal hyperplasia due to 17α‐hydroxylase deficiency in a genetic female.DESIGN Blood samples were used as a source of genomic DNA. A library of size selected genomic DNA sequences was prepared. In addition, portions of the 17α‐hydroxylase gene were amplified by the polymerase chain reaction and the gene products sequenced.PATIENTS Samples were obtained from a patient with sexual infantilism, lack of secondary sexual characteristics and hypertension. Streak gonads were found on laparoscopy.RESULTS Two point mutations were found, one in exon 3 and one in exon 4 which generate premature stop codons at codons 194 and 239 in place of glutamate and arginine respectively. The mutation in exon 3 has not previously been reported in patients with 17α‐hydroxylase deficiency.CONCLUSION The protein product of these defective genes could be expected to be severely truncated with no catalytic activity. This is in keeping with the complete lack of Cortisol and sex steroid output in this patient. The polymerase chain reaction provides faster access to gene sequence information than previous procedures based on library screening prior to sequencing.
Pregnancy associated osteoporosis
Authors: Dunne Fidelma , Walters Boni , Marshall Tim , Heath David A. 
Published: March 2008

SummaryOBJECTIVE Previous literature reports have suggested that osteoporosis associated with pregnancy is a rare event. We have examined the prevalence of this condition and compiled data on the largest group of such patients in the literature.PATIENTS AND DESIGN With the help of the National Osteoporosis Society 35 women with pregnancy associated osteoporosis were identified. These women were matched with a control group from our already established computer data bank for age, weight, height and calcium status. Detailed questionnaires were sent to the osteoporotic sufferers enquiring about their present condition, past medical and drug history, and their menstrual, lactational and obstetric histories. They were also asked to complete a detailed dietary history to establish their calcium status. A questionnaire was also completed by the parents of these women and the parents of the control group, asking specifically about fracture history.RESULTS Twenty‐nine women had idiopathic osteoporosis associated with pregnancy, while in six, the condition may have resulted from drug therapy or associated diseases. Pain occurring late in the first full term pregnancy was the most common presentation. The natural history was for the condition to improve with time. There was a significantly higher prevalence of adult related fractures (P < 02) occurring at an earlier age in the mothers of these women compared to a control population.CONCLUSION We have identified 35 women who have developed osteoporosis during or shortly after pregnancy and in only six of them could a recognized underlying cause be suggested. These findings would suggest that idiopathic osteoporosis associated with pregnancy may be more common than the current literature suggests. The higher prevalence of fractures in the mothers of our population compared to controls raises the question of a possible associated genetic factor in the aetiology of this condition.
Two different pathogenetic mechanisms may play a role in acne and in hirsutism
Authors: Toscano Vincenzo , Balducci Rina , Bianchi Patrizia , Guglielmi Rinaldo , Mangiantini Adele , Rossi Fabia G. , Colonna Loredana M. , Sciarra Francesco 
Published: March 2008

SummaryOBJECTIVE Acne is one of the most common skin disorders. Androgens are known to play an important and possibly central role. Androgens secreted from ovaries and adrenal glands (androstenedione, dehydroepiandro‐sterone and its sulphate, testosterone) and target tissue‐produced androgens (testosterone and its 5α‐reduced metabolite, dihydrotestosterone) have been implicated. Although the sebaceous gland and the hair follicle form a single morphological entity, the pilosebaceous unit, acne and hirsutism do not always appear concomitantly, thus leading to the supposition that these two structures may have different degrees of sensitivity to similar androgenic stimulation.DESIGN AND PATIENTS To determine whether acne and hirsutism are the clinical expression of a different androgen metabolism at target tissue levels we studied 90 randomly selected patients who came to our Out‐patient Department for diagnosis and treatment during the last 2 years with isolated acne of mild to severe degree and 52 patients with idiopathic hirsutism without acne or history of acne.Twenty‐four women without acne or hirsutism and without a history of endocrine disease were studied as controls.MEASUREMENTS In both groups of patients, plasma levels of sex hormone binding globulin, of dihydrotestosterone, and of 3α‐androstanediol and of its glucuronide were evaluated. In all patients the percentage of free testosterone and the testosterone/sex hormone binding globulin ratio were also calculated.RESULTS Patients with acne and those with isolated hirsutism showed significantly decreased sex hormone binding globulin plasma levels. The values of the percentage free testosterone and those of the testosterone/sex hormone binding globulin ratio were, on the contrary, higher with respect to the controls, although there were no statistically significant differences between the two groups. Significantly increased plasma levels of dihydrotestosterone with respect to the controls were observed in patients with acne or in those with hirsutism. However, while all patients with hirsutism showed increased plasma values of 3α‐androstanediol and its glucuronide, all patients with acne showed plasma levels within the normal range, independently of the precursor plasma levels.CONCLUSIONS Our results demonstrate that dihydrotestosterone is further reduced to 3α‐androstanediol and its glucuronide only in hirsute patients but not in acne patients. These results suggest that dihydrotestosterone may undergo different metabolic pathways at skin levels and support the hypothesis that the two clinical manifestations may be the expression of the different metabolic fate of dihydrotesterone itself. Moreover, our results demonstrate that 3α‐androstanediol and its glucuronide cannot be used as plasma markers of target‐tissue produced androgens in all hyperandrogenic conditions.
Plasma 19‐hydroxyandrostenedione is elevated in patients with high renin essential hypertension
Authors: Sekihara Hisahiko , Yonemitsu Keiko , Yazaki Yoshio 
Published: March 2008

SummaryOBJECTIVES We have reported that 19‐hydroxyandrostenedione (19‐OH‐A‐dione) functions as an amplifier of the sodium‐retaining and hypertensive action of aldosterone. We therefore measured 19‐hydroxyandrostenedione in hypertensive patients.PATIENTS AND MEASUREMENTS We studied 53 normal male control subjects and 63 male patients with essential hypertension (48 patients with normal renin essential hypertension and 15 patients with high renin essential hypertension). Plasma 19‐OH‐A‐dione levels were measured by RIA.RESULTS Plasma 19‐OH‐A‐dione concentrations in control subjects and patients with normal and high renin essential hypertension were 115 ± 46 (meaniSD), 112 ± 49 and 201 ± 79 pmoI/I, respectively. Patients with high renin essential hypertension showed significantly higher 19‐OH‐A‐dione concentrations than did control subjects. The evaluation of the correlation between plasma 19‐OH‐A‐dione concentrations and plasma renin activity revealed that plasma 19‐OH‐A‐dione concentrations in hypertensive subjects rose gradually with an increase in plasma renin activity. Therefore, a significant correlation was found between plasma renin activity and plasma 19‐OH‐A‐dione (r= 0 586, P < 0001). In contrast, in control subjects, no significant correlation was found between plasma renin activity and plasma 19‐OH‐A‐dione (r=0 059, P<0 05). conclusions The secretion of 19‐OH‐A‐dione from the adrenal cortex is under the control of the renin‐angiotensin system in hypertensives but not in normotensives.
Impact of 2 weeks high dose growth hormone treatment on basal and insulin stimulated substrate metabolism in humans
Authors: Meller N. , Møller J. , Jørgensen J. O. L. , Ovesen P. , Schmitz O. , Albert K. G. M. M. , Christiansen J. S. 
Published: March 2008

SummaryOBJECTIVE Short‐term, high dose growth hormone (GH) treatment has been advocated in many catabolic disease states. It is likely that some of the anabolic effects of GH are mediated through activation of lipolysis, but the metabolic impact of therapeutically relevant GH exposure is not known in detail. The present study was accordingly designed to assess the effects of such GH exposure on basal and insulin stimulated intermediary metabolism.DESIGN, PATIENTS AND MEASUREMENTS Six healthy young females were examined following daily injections of GH (12 IU/day) or saline for 2 weeks in a placebo controlled design. Each study consisted of a 3 hour basal period and a 2 hour hyperinsulinaemic euglycaemic clamp.RESULTS GH treatment caused (1) increased levels of IGF‐I (382 ± 46 vs 294 ± 22 /μg/l, P < 0 05) and (2) increased basal values of free fatty acids (714 ±40 (GH) vs 634 ±64 (placebo) μmol/l, P<0 05), 3‐hydroxybutyrate (118 3 ± 42 8 (GH) vs 57 7 ± 21 6 (placebo) μmol/l, P < 0 05), glycerol (54–3 ±8–2 (GH) vs 41–4 ±8–4 (placebo) μmol/l, P<0 05) and forearm uptake of 3‐hydroxybutyrate, together with increments of plasma glucose (5 28 ±0–11 (GH) vs 4 87±0 16 (placebo) mmol/l, P<0 05). Basal forearm uptake of glucose, isotopically determined glucose turnover and serum levels of GH, insulin and C‐peptide were unaltered.During the clamp GH treatment was associated with (1) a 40% decrease in the administered amount of glucose (M‐value) (P<0 05) and (2) a 70% decrease in forearm glucose uptake (P<0 05).Indirect calorimetry revealed a 15% increase in resting energy expenditure (P<0 05) and a decreased basal respiratory exchange ratio (0 75 (GH) vs 0 80 (placebo), P<0 05), presumably reflecting increased lipid oxidation. CONCLUSIONS Administration of GH in a therapeutic dose for 2 weeks, despite apparently normal daytime levels of major metabolic hormones, induces significant increases in circulating lipid fuel substrates, increased energy expenditure and lipid oxidation, together with insulin resistance. Such effects should be considered when applying GH treatment schedules clinically.
Abnormal twenty‐four hour pattern of pulsatile luteinizing hormone secretion and the response to naloxone in women with hyperprolactinaemic amenorrhoea
Authors: Tay Clement C. K. , Glasier Anna F. , Illingworth Peter J. , Baird David T. 
Published: March 2008

SummaryOBJECTIVE Hyperprolactinaemic amenorrhoea is associated with disturbances of pulsatile gonadotrophin secretion. The underlying mechanism remains unclear and the aim of this study was to investigate the 24‐hour secretory pattern of gonadotrophins in women with hyperprolactinaemic amenorrhoea. The effect of opioid blockade using naloxone infusion on LH secretory pattern was also studied.DESIGN The secretory patterns of LH, FSH, PRL and their responses to naloxone infusion were studied by serial blood samples collected at 10‐minute intervals for 24 hours. On the following day, naloxone was infused at a dose of 1 6 mg per hour for 4 hours.PATIENTS Eight women with hyperprolactinaemic amenorrhoea, two women hyperprolactinaemic but with normal ovarian cycles, and nine control subjects in the early follicular phase of menstrual cycle.MEASUREMENTS Concentrations of LH, FSH and PRL were measured in plasma samples obtained at 10‐minute intervals for 24 hours. In one woman, concentrations of urinary oestrone glucuronide were measured daily during treatment with pulsatile GnRH.RESULTS The number of LH pulses per 24 hours was significantly fewer in women with hyperprolactinaemic amenorrhoea than in those with hyperprolactinaemia with normal cycles or control subjects (mean ± SEM 4.5 ± 2.4 vs 13.5 ± 2.5 vs 17 3±0 8, P<0 001). The magnitude of each episode of secretion was significantly higher in the hyperprolactinaemic amenorrhoeic women (P<005) so the overall mean concentrations of LH throughout the 24‐hour period was similar in the three groups (5 2±1 1, 4.8±0 8 and 5.2 ±0.4 U/I respectively). In women with hyperprolactinaemic amenorrhoea there was no significant change in the pattern of LH secretion during sleep in contrast to the control women in whom there was a slowing in the LH pulse frequency during the night. There was no significant change in the mean concentrations of LH, FSH and PRL during the naloxone infusion. There were also no significant changes in the LH pulse frequency in response to naloxone infusion when compared with an equivalent period of time in the previous 24 hours. In one hyperprolactinaemic amenorrhoeic woman, follicular development, ovulation and pregnancy were induced when gonadotrophin releasing hormone (GnRH) was infused in a pulsatile manner at a dose of 5 μg every 90 minutes.CONCLUSIONS The suppression of normal ovarian cycles in women with hyperprolactinaemic amenorrhoea is due to a significant reduction in frequency of LH (GnRH) secretion which is not due to an increase in hypothalamic opioid activity. As normal ovarian cycles can occur or be induced by exogenous GnRH in hyperprolactinaemia, it is unlikely that a high level of prolactin by itself inhibits follicular development and ovulation.