ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01907.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Although the nature of the side‐effects of G H replacement In adults are well described, the factors Influencing their development are III understood. The aim of this study was to determine whether there were any characteristics of adults with G H deficiency that predicted whether or not they developed side‐effects of G H replacementDESIGN A 12‐month study (double blind placebo controlled for the first 6 months and open for the second 6 months) of G H replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) In adultsPATIENTS Sixty‐three adults (27 men, 36 women, aged 34.9 ±1.4 (mean ± SE, range 20.1‐59.5 years)) with G H deficiency (peak serum G H response to provocative testing of less than 10mU/l) who took part In a 12‐month study of G H replacement. Twenty‐five patients (40%) did not develop side‐effects, 19 patients (30%) developed side‐effects which did not necessitate a reduction In dose of G H, and 19 patients (30%) required a reduction In dose of G H because of side‐effectsMEASUREMENTS The three groups of patients were compared according to age, height, weight and body mass index (BMI) at entry Into the study and to pretreatment peak serum G H response to provocative testing. They were also compared according to serum concentration of Insulin‐like growth factor (I G F)‐I and IGF binding proteln‐3, and age‐adjusted serum IGF‐I standard deviation score (SDS), at entry Into the study and by change In these measurements after 6 months of GH replacement. The patient's sex, whether GH deficiency was of childhood or adult onset, estimated duration of G H deficiency, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder and previous therapeutic Interventions were also compared In the three groups of patientsRESULTS Those patients who required a reduction In dose of G H because of side‐effects were more likely to have a peak serum G H response of greater than 1 mU/l (P=0.005) and to have adult onset G H deficiency (P = 0‐04) than those who did not develop side‐effects or who did not require a reduction In dose of G H because of side‐effects. In addition, those who needed a reduction In G H dose were older (P = 0‐002), heavier (P = 0‐04) and had a greater BMI (P = 0‐003) than those who did not develop side‐effects. Those who developed side‐effects but did not require a reduction In dose of GH had a greater increment in I G F‐I S D S after 6 months of G H replacement than those who did not develop side‐effects (P‐0‐03). CONCLUSION Side‐effects of G H replacement are more likely to occur In older patients, In those with a peak serum G H response to provocative testing of greater then 1 mU/l, In those with a greater increment In serum I G F‐I S D S whilst receiving G H replacement, In those with gre

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01908.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Growth hormone replacement In adults may be considered beneficial by clinicians, but patients may not perceive any benefits. The purpose of this study was to determine whether there were any factors which Influenced whether an adult wished to continue on long‐term GH replacement after taking part In a study of GH replacement.DESIGN A 12‐month study (double‐blind placebo controlled for the first 6 months and open for the second 6 months) of GH replacement (0.125 IU/kg/week for the first month and 0.25 IU/kg/week thereafter) In adults.PATIENTS Sixty‐three adults (27 men, 36 women, aged 34.9 ±1.4 (mean ± SE, range 20.1‐59.5) years) with GH deficiency (peak serum GH response to provocative testing less than 10mU/I) who entered a 12‐month study of GH replacement. Thirty patients (48%) wished to continue on GH replacement and 33 patients (52%) did not wish to continue on GH replacement after the study.MEASUREMENTS Biochemical, anthropometric and demographic characteristics, and well‐being, were compared In those patients who wished to continue on long‐term GH replacement and in those who did not. In the two groups of patients the age, height, weight, body mass Index, serum insulin‐like growth factor (IGF)‐I, IGF binding protein (IGFBP)‐3 and IGF‐I age matched standard deviation score (SDS) were compared at entry Into the study, and changes In IGF‐I, IGFBP‐3 and IGF‐I SDS were compared after 6 months of GH replacement. The patients were compared according to pretreatment peak serum GH response to provocative testing, sex, estimated duration of GH deficiency, whether GH deficiency was of childhood or adult onset, presence or absence of additional pituitary hormone deficiencies, underlying pathological disorder, previous therapeutic Interventions, employment status, marital status and living arrangement, and according to development of side‐effects of GH replacement and the requirement for reduction In dose of GH because of side‐effects during the study. Scores on two questionnaire measures of well‐being or distress, the Nottingham Health Profile (NHP) and the Psychological General Weil‐Being Schedule (PGWBS), were compared at entry Into the study In the two groups, as were change in scores on these questionnaires after 6 months of GH replacement.RESULTS Those who continued on GH replacement tended to have a greater severity of GH deficiency (median peak serum GH concentration 0.7 vs 2.3mU/I, P = 0.06), tended to have greater distress in terms of energy (NHP,P= 0.06) and vitality (PGWBS,P= 0.06) at entry Into the study and showed an improvement In energy during the study compared with no change In those who did not wish to continue on GH replacement (NHP,P= 0 06).CONCLUSION Those adults who wished to continue on GH replacement tended to have a greater severity of GH deficiency, to experience more distress in terms of energy and vitality at entry into the study and to experience an improvement in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01909.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVES The aim of this study was to examine (1) the diurnal variation In SHBG and (2) the Inter‐relatlonshlps of Insulin, IGF‐I, SHBG and IGFBP‐1 over 24 hours In 10 women with anovulatory PCOS and compare them with weight‐matched ovulatory controls.PATIENTS AND METHODS The two groups comprised 10 anovulatory women with PCOS (as defined by clinical, ultrasound and biochemical criteria) and 10 weight matched controls. Serum samples were taken at two‐hourly Intervals for 24 hours and stored for measurement of SHBG, IGFBP‐1, insulin and IGF‐I. Differences between the groups were compared using the Wllcoxon ranked paired tests of the Individual peak and trough concentrations in each group. The variation In Insulin, IGFBP‐1 and SHBG concentrations over 24 hours was tested using two‐way analysis of variance with the factors time and subject. Spearman's correlation coefficient was calculated from the subjects’median value over 24 hours.RESULTS The median (interquartile range) body mass Index (BMI) was 25‐2 (22‐2‐29‐3) in the PCOS group and 24‐3 (23‐2‐25‐7) kg/m2 In the control group. Serum testosterone (T) and LH levels were significantly raised in the PCOS group compared to the control group; T 3‐8 (2‐9‐5‐6) vs 1‐9 (1‐9‐2‐5) nmol/l (P<0‐007) and LH 12 (10‐15) vs 4‐1 (3‐6‐4‐5) IU/I (P<0‐005) respectively. There was no diurnal variation In SHBG. The median (interquartile ranges) of the peak SHBG concentrations was lower In the PCOS group: 29‐4 (14‐9‐39‐4) vs 52‐1 (39‐4‐61) nmol/l In the control group (P<0‐01). The fasting levels of Insulin at 0600 h (median (Interquartile ranges)) were not significantly different between the groups; 6‐6 (5‐4‐9‐8) and 6‐2 (1‐9‐7‐6) mU/l, respectively, although the peak median concentrations were significantly different; PCOS 66‐1 (50‐9‐129‐2) vs 40 (36‐1‐74‐2) mU/l (P<005). Two‐way analysis of variance showed a diurnal variation In Insulin concentrations In the control group (P=0‐001) but not in the PCOS group (P=0‐1). The diurnal variation In IGFBP‐1 was similar in the two groups but the peak median levels were lower In the women with PCOS 54‐9 (22‐3‐79‐2) vs 71‐5 (60‐5‐99‐3) μg/I (P<003). The decline In IGFBP‐1 concentrations correlated with the increase In insulin concentrations. The IGF‐I concentrations were similar In the two groups. There was a significant negative correlation between SHBG and insulin (P<0‐05) and between Insulin and IGFBP‐1 (P<001).CONCLUSION This study demonstrates that there Is no diurnal variation In SHBG concentrations and confirms the finding of a marked diurnal variation in the concentration of IGFBP‐1. Women with PCOS who are anovulatory have an abnormal pattern of Insulin secretion with an absence of diurnal variation compared to weight matched controls. This provides further evidence of the relative Insulin resistance which is independent of weight found In women with anovulatory PCOS. The inverse correlations of insulin concentrations with SHBG and IGFBP‐1 support the role of Insulin as a possible regulator of the ci

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01910.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Correction of anaemia with recombinant human erythropoietin (rHu‐EPO) Improves the responsiveness of thyroidal and gonadal axes to exogenous TRH and GnRH In chronic haemodialysis patients, but the mechanisms remain to be fully elucidated. In order to assess the Influences of endogenous erythropoietin on the hypothalamo‐hypophyseal thyroidal and gonadal axes, we studied the response of polycythaemic and anaemic patients, In comparison to normal controls, after the administration of exogenous TRH and GnRH.DESIGN Exogenous hypothalamic factors, 500μg TRH and 100μg GnRH, were administered as a bolus and blood samples were obtained over a 3‐hour period at 30, 60, 90, 120 and 180 minutes.PATIENTS Five male polycythaemic patients (low EPO), three male anaemic patients (high EPO) and six normal age and sex matched controls were studied.MEASUREMENTS Blood samples were centrifuged Immediately and the serum was stored at −20°C until assayed for total T4, free T4, free T3, TSH, prolactin, growth hormone (TRH test), and FSH, LH, testosterone (GnRH test). Haematological parameters and biochemical profiles were also measured.RESULTS After TRH administration, both patient groups showed a normal TSH response; however, their free T4 and free T3 secretion was blunted compared to controls. Normal basal PRL levels Increased in an exaggerated fashion, whereas, when compared to chronic renal failure patients on chronic haemodialysls, we did not see a paradoxical GH response or a basal GH Increase in these 5 patients. GnRH administration In the study groups elicited a normalization In the LH response without an increase in testosterone levels; however, an exaggerated FSH response was found in the polycythaemic patients (low EPO)CONCLUSIONS Thus by Investigating the role of low endogenous EPO levels In non‐anaemic and anaemic patients with high EPO levels, our study suggests that the underlying chronic disease state may be the major contributing factor in the regulation of the hypothalamo‐hypophyseal thyroid and gonadal axes, rather than

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01911.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summaryobjective The Incidence of sleep apnoea Is Increased In acromegaly. The aim of the study was to determine the occurrence of nocturnal breathing abnormalities and upper airway morphology In acromegalic patients some years after adenomectomyDESIGN A case‐control studyPATIENTS Eleven patients with treated acromegaly and two control groups: (1) sleep studies: 197 subjects randomly selected from the population, (2) cephalometry: 27 healthy subjects and 17 patients with obstructive sleep apnoeaMEASUREMENTS Nocturnal breathing was monitored with a static charge‐sensitive bed. The upper airway soft tissues and bone morphology were assessed by cephalometrlc X‐ray photography. The upper airway collapslblllty was Investigated with dynamic nasopharyngoscopy. Endocrinological investigations were also performedRESULTS Nocturnal breathing abnormalities were present In all but one acromegalic patient (91%), which was far more frequent than In the general population (29‐4%, P<0‐0001). Treated acromegaly was the most powerful predictor of breathing abnormalities, Independent of the other significant predictors, age and body mass Index. The predominant breathing abnormality was periodic breathing with symmetrically waxing and waning respiratory effort without a major body movement component. Episodes of complete obstruction with repetitive arousals were rare. Except for the longer soft palate, the cephalometrlc findings were similar to normal. In comparison to obstructive sleep apnoea, the treated acromegalic patients had rather prognathic than retrognathlc mandibles. Flbreoptlc endoscopy in the acromegalic patients revealed collapsible upper airways at the level of the soft palate, whereas at the base of the tongue little, If any, dynamic narrowing was observed.CONCLUSION Our study confirms that nocturnal breathing abnormalities are common In treated acromegaly, and may persist years after the removal of the G H secreting tumour. The breathing abnormalities and the upper airway morphology in acromegalic patients after adenomectomy are different from those observed In primary obstructive sleep apnoea, suggesting a different pathophysiology of the airway o

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01912.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryThe molecular basis for male pseudohermaphroditism produced by the 5α‐reductase deficiency is becomining Increasingly understood.OBJECTIVE We have performed biochemical and molecular analyses of the 5α‐reductase type 2 gene In a Turkish family with a 5α‐reductase deficiency.PATIENT A 46,XY prepubertal Turkish patient with female phenotype showing clltoral hypertrophy, high plasma testosterone and dihydrotestosterone, and normally differentiated and developed testosterone‐dependent internal genitalia.MEASUREMENTS 5α‐Reductase activity, measured by the conversion of3H‐T Into 5α‐reduced compounds, was determined from cultured genital skin fibroblasts by both Intact monolayer assay and cell‐free extracts at various pH values. The five exons of the 5α‐reductase type 2 gene were sequenced after enzymatic amplification (PCR) of the patient's genomic DNA. Labelled PCR of the consanguineous parents’DNA was submitted to electrophoresis on a sequencing gel.RESULTS A marked decrease In the transformation of T into 5α‐reduced compounds by Intact cells and a diminished 5α‐reductase activity at acidic pH by sonicated cell extracts strongly suggested a 5α‐reductase type 2 deficiency. Molecular analysis of the 5α‐reductase type 2 gene showed a trinucleotide deletion straddling codons 156 and 157, responsible for a methionine residue deletion at position 157 of the protein. The parents’DNA contained both normal and deleted alleles.CONCLUSIONS This Is the third deletion described in the 5α‐reductase type 2 gene. The deleted methionine 157 Is conserved in both types 1 and 2 of human and rat 5α‐reductase, which suggests Its crucial role In the functioning of the enzyme. This gene rearrangement was thus clearly responsible for the reduced 5α‐reductase activity

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01913.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Previous studies, using a variety of methods, have reported growth‐promoting Immunoglobulins (IGs) In a large proportion of patients with endemic goitre. We sought to determine whether thyroid growth‐promoting Immunoglobulins (TGI) are present in the serum of Indian patients with endemic goitre.DESIGN IgG was prepared by protein G‐Sepharose affinity purification and added to FRTL‐5 thyroid cells In the presence of suboptimal concentrations of TSH.PATIENTS We studied 30 sequential patients with endemic goitre and 16 euthyroid controls without a goitre from the same areaMEASUREMENTS Two assays for thyroid cell growth were used:3H‐thymldine Incorporation, and flow cytometric measurement of the proportion of cells in the S phase and G2/M phase of the cell cycle.RESULTS Both assays were shown to detect growth produced by TSH and by thyroid stimulating antibodies in IgG preparations from 3 patients with Graves' disease. There was no significant Increase In either3H‐thymldine Incorporation or the distribution of cells In S or G2/M phase with IgGs from endemic goitre patients, and no difference between the effects of these IgGs and those from the normal subjects.CONCLUSIONS Thyroid growth‐promoting immunoglobulins cannot be detected In Indian patients with e

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01914.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Activation of the hypothalamic‐pituitary‐adrenal axis is of vital importance during critical Illness. We have studied the adaptive mechanisms which occur at the level of the glucocorticoid receptor in glucocorticoid target tissues in patients with sepsis or septic shock.DESIGN The effects of hypercortlsolaemia, hyperthermia and cellular composition on number of glucocorticoid receptors per cell and their affinity were evaluated, bothIn vitroandIn vivo, In peripheral blood mononuclear leucocytes of control subjects and In patients with sepsis or septic shock.SUBJECTS Fifteen patients (age 25‐79) with sepsis or septic shock who were admitted to an Intensive care unit were studied. The control group consisted of 24 healthy laboratory employees.MEASUREMENTS The binding capacity and affinity of the glucocorticoid receptors were measured and compared to clinical data and the plasma Cortisol concentrations.RESULTS Hypercortlsolaemia,in vitro, resulted in a decreased affinity and a decreased binding capacity of the glucocorticoid receptor.In vitro, hyperthermia as well as variations In the cellular composition did not Influence the glucocorticoid receptor.In vivo, there was no change In the number of receptors per cell In patients with sepsis or septic shock as compared to healthy controls. However, a decreased affinity of the glucocorticoid receptor was observed. There was a weak but significant negative correlation between body temperature and the number of glucocorticoid receptors In the patient group. There was no relation between circulating Cortisol concentrations and glucocorticoid receptor affinity and number.CONCLUSIONS There Is no obvious regulation of the number of glucocorticoid receptors by plasma Cortisol concentrationsIn vivo.The decreased affinity of the glucocorticoid receptor together with the negative correlation between hyperthermia and the number of glucocorticoid receptors In patients with sepsis or septic shock suggest that hypo‐thalamlc‐pitultary‐adrenal axis activation during critical illness Is accompanied by peripheral adaptation in glucocorticoid receptor number a

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01915.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVES In adults with growth hormone deficiency (GHD) social problems have been reported, but so far the relative contributions of GHD, additional pituitary deficiencies and short stature have not been distinguished.We therefore compared social data from GHD patients with social data from controls with short or normal stature. Furthermore we Investigated whether social problems are caused solely by the deficiency of GH or also by the associated absence of other pituitary hormones.DESIGN A questionnaire was sent to patients and controls with Items on education, profession, Income, partner and living situation.PATIENTS Two hundred and ten GHD patients treated In childhood but not In adulthood with GH (93 Isolated GHD (IGHD), 111 patients with multiple pituitary deficiency (MPD)) were compared with 53 short controls (height In childhood

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb01916.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY