摘要:

SummaryOBJECTIVE Fasting is known to clearly increase both spontaneous and GHRH‐stimulated GH secretion in normal subjects and this effect is likely to be due to hypothalamic mechanism(s). Our aim was to clarify the effect of a 3 or 4‐day fast, on the GH response to GHRH alone or combined with arginine, an amino acid probably acting via inhibition of hypothalamic somatostatin release.DESIGN Two tests with GHRH (1 μg/kg i.v.), administered either alone or in combination with arginine (ARG, 0.5 g/kg i.v.) were performed, in a randomized order at least 3 days apart. In obese women the two tests were repeated after a 3 or 4‐day fast.PATIENTS Seven obese women (06, aged 17–54 years, BMI 42.4 ± 3.6 kg/m2, waist‐hip ratio (WHR) 0.85±0.01) and ten healthy women, as control subjects (CS, aged 20–44 years, BMI 23.1 ±1.1 kg/m2, WHR 0.79 ± 0.01) were studied.MEASUREMENTS Serum GH and IGF‐I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (mU/l) or as areas under the curve (AUC, mU/l/h) calculated by trapezoidal integration. IGF‐I concentrations were expressed as absolute values (μg/l) with reference to a pure recombinant IGF‐I preparation. Results are expressed as mean ± SEM.RESULTS Basal GH and IGF‐l levels in OB were lower than in CS (0.8 ± 0.2vs4.8±1.0 mU/I,P<0.0001 and 120.1 ± 21.4vs188.7 ± 13.1 μg/l,P<0.02, respectively). The GHRH‐induced GH rise in OB was lower (P<0.00001) than in CS (AUC 340.2 ± 81.0vs2125.0 ± 199.6 mU/l/h). ARG increased the GHRH‐induced GH rise in both groups, but in OB the GH response to ARG + GHRH (1458.4 ± 439.0 mU/l/h,P<0.03vsGHRH alone) remained lower (P<0.0001) than in CS (6396.2 ± 772.2 mU/l/h,P<0.01 vs GHRH alone). In spite of a reduction in body weight and IGF‐I, Insulin and glucose levels, in OB fasting failed to modify both the basal GH levels and the somatotroph responsiveness to GHRH when administered either alone or combined with ARG. An increase in free fatty acids (FFA) was also found after fasting.CONCLUSIONS The results of this study demonstrate that in obesity the somatotroph hyporesponsiveness to GHRH, either alone or combined with arginine, is not improved by short‐term fasting. As fasting is considered a CNS mediated stimulus to GH secretion, its ineffectiveness in obesity does not support a hypothalamic pathogenesis and suggests that long standing metabolic alterations, such as hyperinsulinaemia and/or elevated free fatty acids, could play a major role in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00531.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Fasting is known to clearly increase both spontaneous and GHRH‐stimulated GH secretion in normal subjects and this effect is likely to be due to hypothalamic mechanism(s). Our aim was to clarify the effect of a 3 or 4‐day fast, on the GH response to GHRH alone or combined with arginine, an amino acid probably acting via inhibition of hypothalamic somatostatin release.DESIGN Two tests with GHRH (1 μg/kg i.v.), administered either alone or in combination with arginine (ARG, 0.5 g/kg i.v.) were performed, in a randomized order at least 3 days apart. In obese women the two tests were repeated after a 3 or 4‐day fast.PATIENTS Seven obese women (06, aged 17–54 years, BMI 42.4 ± 3.6 kg/m2, waist‐hip ratio (WHR) 0.85 ± 0.01) and ten healthy women, as control subjects (CS, aged 20–44 years, BMI 23.1 ± 1.1 kg/m2, WHR 0.79 ± 0.01) were studied.MEASUREMENTS Serum GH and IGF‐I levels were measured by radioimmunoassay. The GH secretory responses were expressed either as absolute values (mU/l) or as areas under the curve (AUC, mU/l/h) calculated by trapezoidal integration. IGF‐I concentrations were expressed as absolute values (μg/l) with reference to a pure recombinant IGF‐I preparation. Results are expressed as mean ± SEM.RESULTS Basal GH and IGF‐l levels in OB were lower than in CS (0.8 ± 0.2vs4.8 ± 1.0 mU/I,P<0.0001 and 120.1 ± 21.4vs188.7 ± 13.1 μg/l,P<0.02, respectively). The GHRH‐induced GH rise in OB was lower (P<0.00001) than in CS (AUC 340.2 ± 81.0vs2125.0 ± 199.6 mU/l/h). ARG increased the GHRH‐induced GH rise in both groups, but in OB the GH response to ARG + GHRH (1458.4 ± 439.0 mU/l/h,P<0.03vsGHRH alone) remained lower (P<0.0001) than in CS (6396.2 ± 772.2 mU/l/h,P<0.01 vs GHRH alone). In spite of a reduction in body weight and IGF‐I, Insulin and glucose levels, in OB fasting failed to modify both the basal GH levels and the somatotroph responsiveness to GHRH when administered either alone or combined with ARG. An increase in free fatty acids (FFA) was also found after fasting.CONCLUSIONS The results of this study demonstrate that in obesity the somatotroph hyporesponsiveness to GHRH, either alone or combined with arginine, is not improved by short‐term fasting. As fasting is considered a CNS mediated stimulus to GH secretion, its ineffectiveness in obesity does not support a hypothalamic pathogenesis and suggests that long standing metabolic alterations, such as hyperinsulinaemia and/or elevated free fatty acids, could play a major role in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00532.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

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

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00533.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

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 ± 0.025vs1.242 ± 0.054,P= 0.0006) and MA (17.06 ± 0.57vs23.00 ± 1.49,P= 0.0001) and longer AT (0.063 ± 0.001vs0.056 ± 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 observ

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00534.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryBACKGROUND Octreotide, a synthetic long‐acting analogue of somatostatin, now has an establlshed role in the treatment of acromegaly. In acromegalic patients treated with octreotide there is an increased incidence of gallstones and possibly gastritis.OBJECTIVES (1) To compare the seroprevalence ofHelicobacter pylori (H. pylori) infection, in acromegalic patients treated with octreotide to that in patients given other treatment modalities. (2) To study retrospectively the temporal relatlon betweenH. pyloriacquisition and octreotide treatment.PATIENTS Three groups of acromegalic patients were studied; 35 (20 M) had been treated wlth octreotide, 17 (10 M) with bromocriptine and 19 (12 M) had received no pharmacological intervention (untreated, surgically treated or treated with radiotherapy).DESlGNlMEASUREMENTS The presence ofH. pyloriinfection was assessed serologically (Bio‐Rad GAP test for IgG), using stored serum, on the most recent sample from each patient and on serial samples from patients treated with octreotlde.RESULTS The prevalence ofH. pyloriseropositivity was similar in each treatment group, 34, 35 and 37%, respectively. Mean age and duration of acromegaly were similar in the first two groups. Patients who had never received medical treatment were slightly younger. GH levels were similar in all three groups. Patients on octreotide who were seropositive forH. pyloridid not differ from those with negative serology with respect to age, duration of acromegaly, duration of octreotide treatment or serum GH level. Serial samples in octreotide treated patients showed a change in status in only one patient; 18 patients continued with negative serology during a mean period of 30 (range 4–62) months. In each of the 6 patients with persistently positive serology during octreotide treatment, stored samples predating octreotide therapy were shown to have already been positive.CONCLUSIONS The seroprevalence ofH. pyloriinfection in acromegalic patients does not appear to be increased in a manner dependent on the type or duration of medical treatment. In particular, octreotide therapy, while causing the development of histological gastritis in some patients, does not appear to induce the development ofH. pyloriinfe

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00535.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Adults with GH deficiency (GHD) exhibit changes in body composition. Studies of the effects of GH substitution on body composition have been short‐term or not adequately controlled. The purpose of this study was to evaluate the long‐term effects of GH on soft tissue using dual‐energy X‐ray absorptlometry (DEXA). This technique enables assessment of whole body as well as regional soft tissue composition.DESIGN A double‐blind, randomized, placebo‐controlled study in patients with acquired GHD. The therapeutic regime consisted of biosynthetic human GH (2.0 lU/m2per day) or placebo, given as a daily subcutaneous injection at 2000 h for 12 months.PATIENTS Twenty‐nine patients with acquired GHD (GH<10 μg/l (<20 mU/I) following standard provocative tests) in whom additional hormone replacement was maintained.MEASUREMENTS Soft tissue determinations by DEXA scan, height, weight, foot volume and finger clrcumference were recorded together with serum IGF‐I at baseline and after 12 months.RESULTS Twelve months of GH therapy induced a total fat mass (FM) reduction of (mean ± SEM) 4.88 ± 0.58 kg (P<0–002) (n= 13) corresponding to 21.5% of the total FM. The reduction in fat was most marked in the trunk, i.e. 3.07 ± 0.29 kg (P<0–002) corresponding to 61% of the total FM reduction. Total lean soft tissue mass (LSTM) increased by 3.31 ± 0.81 kg (P<0.001). Regional changes for arm and leg in the GH group amounted to 0.32 ± 0.08 kg (P<0002) and 0.71 ± 0.14 kg (P<0.002), respectively, without accompanying significant changes in truncal LSTM between the groups.The foot volume was Increased by 55.8 ± 15.7 ml (P<0007) and the finger circumference by 2.67 ± 0.5 mm (P<0005) on active treatment with no significant changes in the placebo group.CONCLUSIONS Twelve months of GH therapy induced marked changes in soft tissue; fat mass was reduced, particularly in the trunk (61 % of total fat mass reduction) whereas lean soft tissue mass increased more in the extremities. The data imply that GH‐induced changes in body composition are mai

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00536.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

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 strik

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00537.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE The importance of iodine intake and thyroiditis in the pathogenesis of thyroid cancer remains controversial. We have investigated the natural history of thyroid cancer and thyroiditis in a goitrous region before and after iodine prophylaxis over a 31‐year period.DESIGN For the analysis of thyroid cancer the material was divided in two periods. The first 15 years (59 cases), including 5 years before prophylaxis, was compared with the second 16 years (85 cases), a period well after iodine supplementation of salt. Histological diagnosis of the tumours was based on the WHO system. Moderate to severe thyroiditis in the non‐tumoral surrounding thyroid from female patients was recorded. For this, the material was analysed in the two periods In relation to the introduction of iodine prophylaxis in 1963, taking account of the age of the patients.RESULTS Papillary carcinomas formed the largest group of tumours in both periods, with nearly twice as many in the second period as the first, while the numbers of follicular and medullary carcinomas remained about the same. The ratio of papillary to follicular carcinoma rose from 1.7:1 in the first period to 3.1:1 in the second. All three thyroid lymphomas were of the non‐Hodgkin's type, and all occurred in the second period in females aged over 50. A severe lymphoid thyroiditis was present in the two cases with assessable background thyroid tissue.The frequency of lymphoid infiltrate in females rose from 8% 11/12) before 1963 to 25% (18172) after prophylaxis in the whole series. After salt prophylaxis, thyroiditis was more frequent in patients with papillary carcinoma in general (31%), and clinically significant papillary carcinomas in particular (35%), than in those with non‐papillary tumours (6%) (X2,P<0.05 andP<0.025, respectively).CONCLUSIONS Our observations indicate that a high dietary intake of iodine may be associated with a high frequency of papillary carcinoma and thyroiditis, and that thyroiditis is more commonly associated with papillary carcinoma than with other thyroid tumours. The occurrence of non‐Hodgkin's lymphomas only in the post‐prophylaxis period may be linked to an increase in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00538.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

SummaryOBJECTIVE Increased levels of free thyroid hormones have been previously described in prepubertal blind subjects and have been thought to be a consequence of a partial target organ refractoriness due to the early and prolonged lack of light perception. The aim of this study was to clarify whether this abnormality is permanent or transient and the interrelationships between melatonin and thyroid hormone secretion.MEASUREMENTS Total and free thyroid hormones, TSH, thyroxine‐binding globulin (TBG), reverse trilodothyronine (rT3) and melatonin were measured In plasma samples obtained at 0800 h (two hours after lights‐on) In a group of 11 totally (group 1) and 16 partially (group 2) blind adult patients and in 10 age‐matched healthy subjects.RESULTS Both totally and partially blind patients showed melatonin levels higher than in controls (330 ± 106 pmol/l, group 1 and 361 ± 159 pmol/l, group 2, respectively; controls: 53 ± 12 pmol/l,P<0.001vsboth groups), but fT4, fT3, T4, T3 TSH, rT3 and TBG concentrations showed no significant differences from controls.CONCLUSIONS A possible resetting of pltuitary‐thyroid axis regulation can occur in blindness after puberty; variations of melatonin secretion could play a role in this. The inhibitory effect of melatonin on thyroid gland function found in animals does not seem to occur in humans. Elevated melatonin levels, both in patients with total blindness and in those with light perception only, suggest that more complex mechanisms other than light signalling are involved in the changes of melatonin secretion in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00539.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

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 cl

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1995.tb00540.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY