bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with octreotide and bromocriptine in patients with acromegaly: an open pharmacodynamic interaction study
Authors: Fredstorp L. , Kutz K. , Werner S. 
Published: March 2008

SummaryOBJECTIVE Several studies suggest that the combination of octreotide and bromocriptine is more effective than octreotide alone in reducing GH levels in patients with acromegaly. However, these studies have evaluated either the acute effects of single doses of octreotide and bromocriptine, or the effects of long‐term combination therapy, in which octreotide was given only twice a day. The aim of the study was to evaluate the effects of the combination of octreotide and bromocriptine compared to octreotide alone, using a treatment scheme of three daily injections of octreotide during a period long enough to ensure a pharmacokinetic and pharmacodynamic steady state.PATIENTS Eleven patients with acromegaly.DESIGN AND MEASUREMENTS Different treatment regimes were performed during three periods. During the first period there was no administration of octreotide or bromocriptine, during the second period 100 μg octreotide was given subcutaneously three times a day, and during the third period 100 /ig octreotide was given subcutaneously three times a day in combination with bromocriptine, given orally 5 mg twice daily. When the patients were without any treatment a single oral dose of 5 mg bromocriptine was given at 0730 h. Individual GH levels were assessed as the mean value of 11 observations during the day, at hourly Intervals from 0730 to 1530 h, and at 1730 and 1930 h, and the GH levels for the whole group were calculated as the mean of the individual mean values. Serum IGF‐I and PRL were measured in fasting samples at 0730 h on the same days as GH. GH, IGF‐I, and PRL were evaluated at the end of each treatment regime.RESULTS Basal mean GH value for all 11 patients was 54.2 ± 17.4 mU/l. During octreotide therapy mean GH value was significantly reduced compared to basal mean GH level; 19.86±6.82 mU/l (P<0 05). The reduction of mean GH during combination therapy was also significant compared to basal, 18.70 ±6.72 mU/l (P<0.05). Basal mean IGF‐I value for all 11 patients was 716 ±96 μg/l. During octreotide therapy mean IGF‐I value was significantly reduced compared to basal mean IGF‐I level; 458 ±100 μg/l (P<0.05). The reduction of mean IGF‐I during combination therapy was also significant compared to basal, 456 ±93 μg/l (P<0.05). There was no difference between the levels of mean IGF‐I during the two treatment periods. One patient, the only patient with hyperprolactinaemia, showed an additional reduction of GH levels of >50% during combination therapy. This was also the patient showing the most pronounced reduction of GH levels after the administration of a single dose of bromocriptine.CONCLUSION When octreotide is administered three times a day, the additive effect of bromocriptine on GH and IGF‐I suppression seems to be negligible in most patients with acromegaly.
Relation between growth hormone and Cortisol spontaneous secretion in children
Authors: Martinelli Carlos E. , Moreira Ayrton C. 
Published: March 2008

SummaryOBJECTIVE Dual effects of corticoids upon GH release in man have been described: a rapid, potentiating effect and a delayed suppressive one. Many investigators have used pharmacological doses of glucocorticoids in an attempt to detect this interaction of corticoids and GH. The aim of the present study was to determine the relationship between GH and Cortisol spontaneous secretion in children under physiological conditions.DESIGN AND PATIENTS Nine children aged 7.5–13.5 years with different growth rates were evaluated over a 24‐hour period. Four were of normal stature (±2 SD) and five were below 2 SO (familial or constitutional short stature). Blood samples were obtained at 20‐minute intervals over a 24‐hour period.MEASUREMENTS GH and Cortisol concentrations were measured by radioimmunoassay in each of the 73 samples collected.RESULTS A significant correlation was obtained between mean 24‐hour Cortisol concentration and mean 24‐hour GH concentration (r= 0.83; P < 0.01), the sum of 24‐hour GH pulse amplitudes (r= 0.85; P < 0.01) and the highest 24‐hour GH concentration (r= 0.88; P < 0.01). A significant positive correlation was also detected between mean 24‐hour Cortisol concentration and the number of GH pulses over a 24‐hour period (r= 0.70; P < 0.05). However, there was no significant correlation between mean 24‐hour GH concentration and number of Cortisol pulses over a 24‐hour period. The correlation between number of Cortisol pulses and number of GH pulses was also non‐significant.CONCLUSION These data suggest an interplay of spontaneous GH and Cortisol secretion in children. Physiological plasma Cortisol levels may play a role in brain‐pituitary regulatory mechanisms of GH secretion.
An audit of the insulin tolerance test in adult subjects in an acute investigation unit over one year
Authors: Jones S. L. , Trainer P. J. , Perry L. , Wass J. A. H. , Besser G. M. , Grossman A. 
Published: March 2008

SummaryOBJECTIVE We audited our practice of insulin tolerance testing (ITT) in terms of safety and technical success. We reviewed the results of those tests performed over a 12‐month period. By relating peak Cortisol response to 0900 h screening Cortisol level, we determined whether we could reduce the number of tests performed.DESIGN The results of all ITTs performed on our unit between 1 January and 31 December 1991 were reviewed.PATIENTS AND MEASUREMENTS Patients were pre‐screened by measurement of serum Cortisol and thyroxine, and recording of an electrocardiogram. A subnormal serum thyroxine (<58 nmoi/l), 0900 h serum Cortisol (<100 nmol/l) or an abnormal ECG were taken as contraindications to the test. Minimum glucose and maximum Cortisol levels were recorded, along with peak GH responses when measured. The peak Cortisol response was compared to the screening and basal Cortisol levels.RESULTS A total of 161 tests were performed, 135 of which fulfilled our inclusion criteria. The test was technically successful in all but 5 of these; a significant adverse event occurred in one patient with full recovery after reversal of hypoglycaemia. Thirty‐two patients had a suboptimal serum Cortisol response to hypoglycaemia: screening Cortisol level ranged from 128 to 493 nmol/l and 0900 h serum Cortisol measured prior to the ITT from 97 to 431 nmol/l. The lowest level of screening Cortisol above which all patients would be expected to achieve the normal peak Cortisol of 580 nmol/l or over is therefore 494 nmol/l. If this cut‐off level had been adopted, 10 (8%) ITTs need not have been performed if their only purpose had been to assess Cortisol reserve. Altering the criterion for the necessary peak Cortisol to 500 nmol/l did not affect the number of ITTs required. Our lower limit for testing could not be revised upwards from 100 nmol/l. Adequacy of Cortisol reserve did not predict a normal GH response to insulin‐induced hypoglycaemia.CONCLUSIONS When performed in an experienced endocrine unit with adequate supervision, the insulin tolerance test is a safe procedure. According to the current sample, fewer tests would be performed without detriment to patient care if those with a screening Cortisol of greater than 500 nmol/l did not proceed to testing, unless the purpose of the test was also to exclude GH deficiency. A lower limit of 100 nmol/l appears reasonable and need not be revised upwards.
Osteopenia as a feature of the androgen insensitivity syndrome
Authors: Soule Steven G. , Conway Gerard , Prelevic Gordana M. , Prentice Malcolm , Ginsburg Jean , Jacobs Howard S. 
Published: March 2008

SummaryOBJECTIVE The syndrome of androgen insensitivity, a paradigm of a hormone resistance syndrome, manifests as failure of masculinization despite normal or high concentrations of serum testosterone. The defect in these 46 XY patients resides in the androgen receptor gene, with consequent defective androgen action and abnormal sexual differentiation. We sought to evaluate whether the adverse sequelae of androgen resistance may extend to skeletal tissue by measuring bone mineral density In SIX patients with androgen Insensitivity.DESIGN A cross‐sectional retrospective study.MEASUREMENTS Bone mineral density was measured by means of a Dexa (Hologic QDR 1000 scanner). The diagnosis of androgen Insensitivity was confirmed in each patient by karyotype and assay of sex hormones.RESULTS The five adult patients with androgen insensitivity had been exposed to both defective androgen action and variable periods of oestrogen deficiency. The latter resulted from the low circulating oestrogen concentrations (for premenopausal females) before gonadectomy and inadequate oestrogen replacement afler gonadectomy. All five adults with androgen insensitivity had osteopenia in both the lumbar spine (T‐score −1.52 to −3.85) and femoral neck (T‐ score −1.34 to −4.91).CONCLUSIONS Osteopenia in patients with androgen insensitivity may relate to defective androgen action, oestrogen deficiency or a combination of the two. These observations have implications for the management of patients with androgen insensitivity and may provide insight into the effects of androgens on the female as well as the male skeleton.
Cardiac flow velocity in women with the polycystic ovary syndrome
Authors: Prelevic Gordana M. , Beijic Teodora , Balint‐Peric Ljiljana , Ginsburg Jean 
Published: March 2008

SummaryOBJECTIVE Women with the polycystic ovary syndrome (PCOS) often have several of the known risk factors for cardiovascular disease, including hyperinsulinaemia. We have therefore investigated variables of cardiac flow in young women with PCOS and related them to blood levels of reproductive hormones (LH, FSH, oestradiol and testosterone) and also of insulin.DESIGN A prospective study.PATIENTS Twenty‐six young women with PCOS (mean age 22.8 ± 0.9 years; mean BMI 23.0 ± 0.8) and 11 healthy age matched women with regular ovulatory cycles (mean age 26.3 ± 1.7 years; mean BMI 22.9 ± 0.9).MEASUREMENTS Cardiac flow was measured by pulsed wave Doppler echocardiography in the follicular phase of the cycle in controls and oligomenorrhoeic women; there was no special timing for amenorrhoeic women. The indicators assessed were: ejection fraction (EF), pre‐ejection time (PEP), ejection time (ET), peak systolic flow velocity (PFV), acceleration time (AT), flow velocity integral (FVI), mean acceleration (MA), diastolic time (DT), early diastolic filling time (EI), atrial filling time interval (AI), peak velocity of the early diastolic filling (PE) and peak velocity of the atrial filling (PA). Serum LH, FSH, oestradiol, testosterone, SHBG and insulin concentrations were analysed by standard RIA.RESULTS Significantly lower PFV (1.055 ± 0.025 vs 1.242 ± 0.054, P= 0.0006) and MA (17.06 ± 0.57 vs 23.00 ± 1.49, P= 0.0001) and longer AT (0.063 ± 0.001 vs 0.056 ± 0.004, P= 0.026) were found in women with PCOS as compared to age matched controls. Significant negative correlation between serum fasting insulin concentration and EF (r=‐0.725, P= 0.002), PFV (r=−0.719, P= 0.0025), FVI (r=−0.654, P= 0.003) and MA (r=−0.757, P= 0.001) was observed In the 15 women with PCOS in whom insulin was measured.CONCLUSION An inverse relation between serum fasting insulin level and left ventricular systolic outflow parameters suggests that insulin is associated with the decreased systolic flow velocity observed in women with PCOS.
High incidence of juvenile Graves’disease in Hong Kong
Authors: Wong Gary W. K. , Kwok M. Y. , Ou Yvonne 
Published: March 2008

SummaryOBJECTIVE Childhood Graves’disease has been reported to be rare and epidemiological data on its incidence are limited. In our Paediatric Endocrine Clinic, Graves’disease was the most common thyroid disorder seen. There is no previous epidemiological study on Graves’disease in Chinese children. This study was performed to determine the incidence of childhood Graves’disease in Hong Kong Chinese.DESIGN AND PATIENTS We established a registry of childhood Graves’disease in 1990 at our centre, which has a catchment population of 1 010 000 with 240 000 under 15 years of age. Graves’disease was diagnosed on clinical features, diffuse thyroid gland enlargement, elevated free thyroxine or trilodothyronine levels with suppressed TSH level. All confirmed cases were recorded prospectively. Population data were obtained from the Statistics Department of the Hong Kong Government. RESULTS Forty‐six Chinese children under 15 years of age had a confirmed diagnosis of Graves’disease during the study period from January 1990 to December 1994. The overall incidence was 3.8/100 000/year with a 95% confidence interval of 1.8–7.3/100 000/year. Incidence was low in children under 4 years. The highest incidence was in girls between 10 and 14 years of age at 15.5/100 000/year. The cumulative incidence for boys and girls of developing Graves’disease during the first 15 years was 11 and 104 per 100 000 respectively.CONCLUSIONS Our data demonstrate a very high incidence of Graves’disease in Hong Kong Chinese children, with an overall incidence about 5 times that reported in Danish children. A female predominance was found in all three age groups (0–4, 5–9 and 10–14 years) and was particularly striking in the adolescent girls.
Neuroendocrine evidence for an association between hypothyroidism, reduced central 5‐HT activity and depression
Authors: Cleare A. J. , McGregor A. , O'Keane V. 
Published: March 2008

SummaryOBJECTIVE The incidence of depression in those with hypothyroidism is increased compared to healthy populations, though the mechanism for this Is unclear. We tested the hypothesis that central 5‐HT activity is reduced in hypothyroidism, and that this subsequently lowers the threshold for developing depression.PATIENTS Twenty subjects entered the study: 10 drug free hypothyroid patients and 10 age, sex, weight and menstrual cycle matched controls.MEASUREMENTS Patients were diagnosed as being depressed using DSM‐IIIR criteria and rated using the Hamilton Rating Scale for Depression (HAM‐D) and Beck Depression Inventory (BDI). Cortisol and prolactin responses to dexfenfluramine, a centrally acting 5‐HT releasing agent, were used as an Index of central 5‐HT responsivity.RESULTS Both cortisol and PRL responses were reduced in the hypothyroid group relative to the controls. Peak cortisol responses were inversely correlated to TSH levels. Four of the 10 patients were clinically depressed. Depressed patients had higher TSH levels than their non‐depressed counterparts, and TSH levels were positively correlated with HAM‐D and BDI scores.CONCLUSIONS These findings support animal work suggesting that hypothyroidism reduces central 5‐HT activity. They also suggest a threshold effect in that higher TSH levels predicted both lower 5‐HT mediated endocrine responses and the presence of clinical depression.
Serum testosterone and its relation to bone mineral density and body composition in normal males
Authors: Ongphiphadhanakul B. , Rajatanavin R. , Challurkit L. , Piaseu N. , Teerarungsikul K. , Sirisriro R. , Komindr S. , Puavilai G. 
Published: March 2008

SummaryOBJECTIVE Bone mineral density (BMD) declines with age in both men and women, predisposing the elderly to osteoporosis and fractures. Although there are extensive data about post‐menopausal osteoporosis, there is relatively little information concerning the decrease in BMD with age in normal men, particularly the contribution of declining gonadal function with age to BMD. In the present study, we investigated the effect of age on the pituitary‐gonadal axis in normal males and its relation to BMD and body composition.SUBJECTS Ninety healthy Thai males in the Bangkok Metropolitan area without a history of smoking or significant alcohol consumption were studied.MEASUREMENTS Serum testosterone (T), free testosterone (FT), LH and FSH were measured by radioimmunoassay in fasting blood samples obtained In the morning between 0600 and 1000h. BMD at anteroposterior L2‐L4, lateral L2‐L4, femoral neck, femoral trochanter and Ward's triangle were determined by dual‐energy X‐ray absorptiometry.RESULTS There were significant declines with age in BMD at lateral L2‐L4 (r= 0.37, P < 0.001), femoral neck (r=−0.49, P<0.0001), Ward's triangle (r=−0.54, P < 0.0001) but not at anteroposterior L2‐L4 or femoral trochanter. Serum FT (r=−0.56, P < 0.0001) but not T (r=−0.19, P= 0.07) decreased with age. Serum LH (r= 0.27, P <0.001) and FSH (r= 0.4, P <0.0001) increased with age suggesting a defect in gonadal androgen synthesis or possibly a secretion of bioinactive LH. Serum FT concentrations were significantly correlated to lateral L2‐L4 (r= 0.27, P<0.05), femoral neck (r= 0.48, P < 0.0001) and Ward's triangle (r= 0.50, P < 0.0001) BMD. After controlling for age, declining FT with age was still associated with a decrease In BMD in femoral neck (P < 0.05) and Ward's triangle (P < 0.05) but not in lateral L2‐L4. The proportion of body fat increased with age (r= 0.3, P < 0.01). Decreased serum T, but not FT, was associated with increased body fat after age was taken into account (P < 0.0001).CONCLUSIONS There is a decline in serum free testosterone together with increases In LH and FSH with age In healthy males. The decrease in serum free testosterone Is partially associated with the age‐related decline in bone mineral density added to the effect of age at the femoral neck and Ward's triangle. Testosterone but not free testosterone Is associated with age‐related increase in body fat.
Autonomous nodular hyperplasia of the adrenal cortex: tertiary hypercortisolism?
Authors: Sturrock Nigel D. C. , Morgan Linda , Jeffcoate William J. 
Published: March 2008

SummaryTwo cases of Cushing's syndrome are reported in which apparently autonomous adrenal adenomata were associated with the presence of pituitary tumours. In one case the patient was apparently cured by unilateral adrenalectomy, although she was noted to have radiological evidence of an intrasellar tumour; serum cortisol was not suppressed by dexamethasone and ACTH was undetectable. Serum ACTH in the second case was initially 31 ng/l but became undetectable during the course of investigation. Transsphenoidal removal of a corticotroph adenoma did not affect serum cortisol and she proceeded to unilateral adrenalectomy. The pathogenesis of autonomous macronodular hyperplasia is discussed, as well as the options for management.
No mutation at codon 918 of the RET gene in a family with multiple endocrine neoplasia type 2B
Authors: Toogood Andrew A. , Eng Charis , Smith Darrin P. , Ponder Bruce A. J. , Shalet Stephen M. 
Published: March 2008

SummaryMultiple endocrine neoplasia type 28 (MEN 28) is a rare cancer syndrome which is inherited in an autosomal dominant manner. The molecular basis of this condition has recently been defined as a mutation of codon 918 of exon 16 of the RET proto‐oncogene.The mutation in codon 918 has been described in 69 out of 72 families with MEN 28. We have studied a brother and sister who undoubtedly have the features of MEN 28 as evidenced by medullary thyroid carcinoma, phaeochromocytoma, mucosal neuromas and skeletal abnormalities. Neither of these patients has the classic gene mutation at codon 918 of exon 16 of the RET proto‐oncogene, and although exons 2–20 have also been sequenced, no abnormality has been foundDNA analysis is a sensitive method of screening families for the MEN 2 syndromes. The absence of the mutation at codon 918 in a phenotypically normal individual would refute the diagnosis of MEN 28, but in an individual with some of the features of MEN 28 would make the clinician reconsider the diagnosis. This family demonstrates that, although it is rare, the absence of the mutation in codon 918 of exon 16 of the RET proto‐oncogene does not always exclude the diagnosis of MEN 28. In such families routine biochemical screening for medullary thyroid carcinoma and phaeochromocytoma must be maintained for all individuals at genetic risk.
Effects of cholinergic modulation on serum insulin‐like growth factor4 and its binding proteins in normal and diabetic subjects*
Authors: Ismall I. S. , Mlell J. P. , Scanlon M. F. , Peters J. R. 
Published: March 2008

SummaryOBJECTIVE We wished to study alterations In serum Insulin‐like growth factor‐I (IGF‐I) and its binding proteins in subjects with insulin dependent diabetes mellitus (IDDM) and possible relations with metabolic and GH secretory status, before and after cholinergic modulation. In addition, we have Investigated whether cholinergic modulation exerts any effects on IGF‐I secretion, Independently of any actions on GH secretory status.DESIGN All subjects received OH releasing hormone (GHRH) 1‐44; 80 μg i.v.) alone and 60 minutes following 120mg of pyridostigmine orally or 200 mg of plrenzepine orally. The three tests were carried out In random order at least one week apart. Blood was sampled at 15‐mInute Intervals over 120 minutes.PATIENTS Twelve male subjects with IDDM and no clinical evidence of complications were selected on the basis of HbA1 levels to provide a wide range of metabolic control. SIX normal male subjects were also studied.MEASUREMENTS Serum IGF‐I, IGF‐binding protein 1 (IGFBP‐1) and IGFBP‐3 were measured at regular intervals throughout the study. Fasting plasma glucose and HbA1 were measured before each study to provide measures of metabolic control.RESULTS Serum IGF‐I and IGFBP‐3 levels were significantly lower while serum IGFBP‐I levels were significantly higher In the diabetic subjects. Plrenzepine had no effect on serum IGF‐I, IGFBP‐1 or IGFBP‐3 In diabetic subjects but caused a significant Increase In serum IGF‐I and IGFBP‐3 levels in normal subjects.Pyridostigmine had no effect on IGF‐I, IGFBP‐1 or IGFBP‐3 In either diabetic or normal subjects. IGFBP‐1 levels were significantly correlated with fasting plasma glucose but no correlation was demonstrated between measures of diabetic control and serum IGF‐I or IGFBP‐3 levels In diabetic subjects, nor was there any correlation between OH responses to GHRH alone or after plrenzepine or pyridostigmine pretreatment and serum levels of IGF‐I, IGFBP‐1 or IGFBP‐3.CONCLUSION These data confirm that subjects with IDDM have reduced serum IGF‐I and IGFBP‐3 and Increased IGFBP‐1 levels, the latter being directly related to the fasting plasma glucose concentrations. The absence of any relation between changes In the IGF‐I system and altered GH neuroregulation after cholinergic modulation suggests that changes In IGF‐I are not the sole contributors to the altered GH neuroregulation which occurs In IDDM. We have also shown an acute stimulatory effect of pirenzepine on serum IGF‐I and IGFBP‐3 In normal subjects which Is not present in IDDM although the underlying mechanism Is unknown.
Autonomous hyperparathyroidism in X‐linked hypophosphataemia
Authors: Knudtzon Jergen , Halse Johan , Monn Elrik , Nesland Aasve , Nordal Knut P. , Paus Povel , Selp Martin , Sund Ståle , Sedall Gunnar 
Published: March 2008

SummaryFour patients with familial hypophosphataemic rickets developed significant hypercalcaemia which persisted after discontinuation of vitamin D therapy. They had increased PTH levels and were operated for hyperparathyroldism at the ages of 18, 20, 24 and 45 years, respectively. Three of the patients had previously received phosphate treatment and one patient developed hyperparathyroldism 7 years after treatment with calcitriol. Histological evaluation revealed different degrees of parathyroid hyperplasia in all patients, with persistently Increased PTH and/or calcium levels after surgery. The possibility of autonomous hyperparathyroldism should be evaluated in the follow‐up of patients with X‐linked hypophosphataemic rickets.