摘要:

SummaryobjectivesTo re‐evaluate the associations of HLA types with Japanese patients having hyperthyroid Graves' disease, HLA types and clinical findings were correlated.designFour independent clinical findings (ophthalmopathy, family history, age at onset and size of goitre) and two autoantibody titres, thyrotrophin binding inhibitor immunoglobulin (TBII) and anti‐thyroid microsmall antibody (anti‐M), were analysed.patientsEighty‐eight Japanese patients with hyperthyroid Graves' disease and 186 control subjects were assessed.measurementSerological HLA typing was performed on 73 antigens In HLA‐A, ‐B, ‐C, ‐DR and ‐DQ loci. HLA‐D and ‐DP (29 antigens) were determined by the restricted fragment length polymorphism (RFLP) methods. TBII and anti‐M were measured by commercially available kits.resultsPatients with potent antibody tltres had HLA antigens commonly seen among all the patients with Graves' disease. Interestingly, however, HLA‐B35 and ‐Cw11 were found to relate with negative and/or weak TBII, and HLA‐B7 and absence of HLA‐Aw19 with negative antl‐M. Significant associations were observed between HLA‐DRw8 and large goitre and absence of ophthalmopathy, and between HLA‐DQw4 and a negative family history of diffuse goitre (correctedP<0·05). Several other antigens were also found to be significant. Among these antigens, four pairs of MHC classes I and II were found to relate to the clinical findings independently. HLA‐DQw4 and negative ‐A31 pair was closely related to ophthalmopathy, negative family history and late onset of disease. The HLA‐B5 and ‐Dw12 pair was associated with ophthalmopathy, positive family history and early onset of disease. The HLA‐A11 and negative ‐DPw2 pair was associated with ophthalmopathy, negative family history and early onset of disease. The HLA‐Bw46 and ‐DRw8 pair did not increase in frequency above that seen with HLA‐DRw8 alone. These four antigen groups (HLA‐DRw8, HLA‐DQw4 and negative‐A31, HLA‐B5 and ‐Dw12, and HLA‐A11 and negative ‐DPw2) were observed in the majority (68%) of patients with Graves' disease and at a significantly higher incidence than in the control group (P<0·05).conclusionThere are four subpopulations of Japanese patients with hyperthyroid Graves' disease. This is one of the reasons why the association of HLA types

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02905.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryobjectiveTo investigate in‐vitro thyroid stimulatory activity In the serum of patients with hyperemesis gravidarum and thyrotoxicosis.designSerum from hyperthyroid patients was incubated with cultures of human thyroid cells. Attempts were made to neutralize stimulatory activity with antisera to hCG.patientsFive patients presenting In early pregnancy with hyperemesis and thyrotoxicosis.measurementsSerum concentrations of thyroid hormones (total and free), TSH and hCG. Accumulation of extracellular cAMP in response to serum.resultsAll five patients had biochemical hyperthyroidism with no evidence of an underlying autoimmune disease. The mean cAMP accumulation over 4 hours with sera from 12 non‐pregnant controls was 130·6 (121·1–142·8), from 12 pregnant controls 132·4 (118·1–143·8), compared with values of 144·7, 159·1, 166·2, 178·9 and 320·5 for the thyrotoxic patients. The stimulatory activity could not be neutralized by addition of anti‐hCG or by depleting the sera of hCG.conclusionsThyrotoxicosis may present with hyperemesis in early pregnancy. Clinical and biochemical features may be masked by the pregnancy or by the intercurrent illness. The hypothesis that hCG is a thyroid stimulator in patients with hyperemesis gravidarum is not supported by the immuno‐neutrallzat

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02906.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryobjectiveWe wished to investigate the effects of nicotinamide and 3‐aminobenzamlde, well known as inhibitors of poly(ADP ribose) synthetase, on interferon‐γ‐induced HLA‐DR antigen expression using cultured human thyroid cells from patients with Graves' disease.design and measurementsCultured thyroid cells were Incubated for 3 days with 10–400 U/ml of interferonγin the presence of nicotinamlde, 3‐amlnobenzamlde, superoxide dismutase or catalase. The surface expression of HLA‐DR and HLA‐A, B, C antigen was measured by flow cytometry.resultsNicotinamide and 3‐aminobenzamide dose‐dependently inhibited the induction of HLA‐DR antigen expression by interferonγ, but not HLA‐A, B, C antigen expression on cultured thyroid cells. Neither catalase nor superoxide dismutase, which are free‐radical scavengers, Inhibited the expression of HLA antigens on thyroid cells.conclusionsOur data suggest that inhibitors of poly(ADP ribose) synthetase may have differential effects on interferon‐γ‐induced HLA‐DR and HLA‐A, B, C antigen expression, and suppress the autoimmune reactions associated with autoimmune thyroid disorders via the reduction of HLA‐DR antigen expression on thyroid cells. The mechanism of the suppression of HLA‐DR antigen expression is unlikely

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02907.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryobjectiveThe duration of action of a gonadotrophin releasing hormone (GnRH) agonist implant designed to be effective for 3 months was investigated in women by monitoring drug release and ovarian hormone secretlon. Serum inhibin secretion was measured to determine whether the secondary rise in serum FSH concentrations observed during long‐term GnRH agonist treatment was attributable to changes in inhibin secretion.design and patientsThe implants Of Slowly bio‐degradable polylactide/glycolide (molar ratio 75:25) containing 3·3 mg buserelin,d‐Ser (BUt)8‐GnRH (1–9)‐nonapeptide‐ethylamide, in a rod 1 cm long and 0·13 cm diameter were injected s.c. in patients with endometriosis (3·3 mg busereiin in four patients, 6·6 mg busereiin in six patients).measurementsUrinary secretion of oestrone, pregnanediol, LH and buserelin were determined in daily samples collected for 2 cycles before treatment, during treatment, and for 2 recovery cycles. Oestradiol, progesterone, inhibin, LH and FSH were measured in serum collected once per week.resultsin all patients ovarian hormone secretion was suppressed successfully but considerable varlability occurred in the length of time taken for ovarian function to recommence, time to return to ovulation being 100–194 days (median 118 days) (3·3 mg group) and 79–290 (median 178 days) (6·6 mg group). After implant injection, there was a rapid rise in the urinary buserelin excretion followed by an early fast phase of buserelin release, half life (t1/2) = 9 days for 3·3 mg implant and 11 days for 6·6 mg implant. This was followed by a second phase representing a plateau of release,t1/2= 50 days (3·3 mg implant) and 90 days (6·6 mg implant). During this second phase, an excretion rate of>0·2 nmol buserelin/mol Cr was associated with oestrone excretion at or below early follicular phase values. Once buserelin excretion fell below 0·1 nmol/mol Cr, ovarian function returned in all patients. The period for which buserelin secretion was maintained between 0·1 and 0·2 nmol/mol Cr corresponded to the time taken to recovery of ovulatory cycles in 8/10 of the women. In 9/10 patients serum immunoreactive inhibin concentrations declined at 2 weeks, along with the suppression of oestradiol, and remained suppressed throughout the period of anovulation. Recovery of FSH secretion began after 4–5 weeks.conclusionsWhile this implant should have important clinical application where chronic treatment is indicated, further work is needed on design of long‐term implants so that such preparations can be used when precise return to ovarian activity is required. A fall in inhibin secretion may contribute to the secondary rise in FSH by withdrawal of negative feedback but thes

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02908.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryobjectiveObese women with poiycystic ovary syndrome have a greater frequency of menstrual disturbance and of hirsutism than lean women with the syndrome. initial studies have demonstrated a marked improvement in endocrine function following a short‐term, very low calorie diet. The purpose of this study was to examine the effect of long‐term calorie restriction on clinical as well as biochemical abnormalities in obese women with polycystic ovary syndrome.designWe performed a wlthin‐groupcomparison of ciinical and biochemical indices before and during dietary treatment.patientsTwenty‐four obese women with polycystic ovary syndrome (mean weight 91·5 (SD 14·7) kg) were scheduled for treatment for 6–7 months with a 1000 kcal, low fat diet. Nineteen of the 24 had menstrual disturbances, 12 had infertility and 19 were hirsute.measurements and resultsThirteen subjects lost more than 5% of their starting weight (range 5·9–22%). in this group there was no significant change in gonadotrophin or total serum testosterone levels but there was a marked increase in concentrations of sex hormonebinding globulin (pretreatment: 23·6 (9·5); post‐treatment 36·3 (11·8) nmol/l,P= 0·002) and a reciprocal change in free testosterone levels (77 (26)vs53 (21) pmol/l,P= 0·009). These changes were accompanied by a reduction in fasting serum insulin levels (median (range) 11·2 (5·2–32)vs2·3 (0·1–13·8) mU/l,P= 0·018) and the insulin response to 75 g oral glucose. There were no significant changes in these indices in the group who lost5% of their pretreatment weight, 11 had menstrual dysfunction. Amongst these women, nine of 11 showed an improvement in reproductive function, i.e. they either conceived (five) or experienced a more regular menstrual pattern. There was a reduction in hlrsutism in 40% of the women in this group. By contrast, in the group who lost less than 5% of their initial weight, only one of the eight with menstrual disturbances noted an improvement in reproductive function and none had a signtficant reduction in hirsutism.conclusionsThese data indicate that moderate weight loss during long‐term calorie restriction is associated with a marked clinical improvement which reflects the reduction in insulin concentrations and reciprocal changes in SHBG. The improvement in menstrual function and fertility may therefore be consequent upon an increase in insulin sensitivity which, directly or in

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02909.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryobjectiveWe wanted to measure forearm mineral density and bone‐related biochemical variables in patients with Klinefelter's syndrome.designMeasurements made in patients with Klinefelter's syndrome were compared to those obtained in age‐matched normal male volunteers.patientsWe studied 22 patients with Klinefelter's syndrome (12 of whom had received sex hormone therapy) and 22 control subjects.measurementsWe measured forearm mineral density, forearm fat content, fat‐corrected forearm mineral density, plasma calcium and ionized calcium, serum osteocalcin, testosterone and dehydroepiandrosterone sulphate, and urinary hydroxyproline/creatinine ratio.resultsForearm mineral density was lower in the Klinefelter's group than in the control sublets (P<0·05) and below the control range in 5 patients. The fat content of the forearm was greater in the Klinefelter's group (P<0·002). Serum osteocalcin and testosterone were lower, while ionized calcium and the urinary hydroxyproline/creatinine ratio were higher in the Klinefelter's group (P<0·002). Serum dehydroeplandrosterone sulphate and testosterone were significantly related in the Klinefelter's group (r= 0·64,P<0·001), but not in the controls (r= 0·22, NS). Forearm mineral density and fat‐corrected forearm mineral density were significantly related to serum testosterone in the Klinefelter's group (r<0·63;P<0·01), but not in the control subjects (r<0·03, NS).conclusionsDecreased bone density occurs in about 25% of patients with Klinefelter's syndrome and probably reflects both decreased bone formation and increased

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02910.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Thyroid Disease: The Facts. R. I. S. Bayliss&W. M. G. TunbridgeHormonal Communicating Events in the Testis. Edited by A. Isidori, A. Fabbri&M. L. Dufau.

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02911.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1992.tb02912.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY