摘要:

OBJECTIVE The optimal dosage regimen for carbimazole (CBZ) in the treatment of hyperthyroidism remains uncertain, despite clinical use of the drug for approximately fifty years. We have compared the early clinical and biochemical responses to 20 or 40 mg/day of CBZ given as initial treatment for hyperthyroidism.DESIGN Prospective open multicentre trial.PATIENTS Sixty‐three patients presenting with hyperthyroidism.MEASUREMENTS Serum total and free thyroid hormones, serum TSH and SHBG were measured at baseline and at 4 and 10 weeks after start of therapy. Weight, pulse and a symptom questionnaire were also monitored at 6 and 12 weeks.RESULTS Patients randomized to a starting dose of 40 mg/day CBZ had lower total (98 ± 10it158 ± 11 nmol/l,P < 0.001) and free T4 (19.4 ± 2.6vs35.2 ± 3.7 pmol/l,P < 0.001) and total (2.6 ± 0.3vs4.3 ± 0.4 nmol/l,P < 0.001 and free T3 (8.3 ± 1.0vs13.7 ± 1.2 pmol/l,P  260 nmol/l.CONCLUSIONS In treating hyperthyroidism, 20 mg/day carbimazole is effective, convenient and has a lower risk than 40 mg/day of iatrogenic hypothyroidism in patients with

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00800.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00866.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Spontaneous improvement occurs in about one‐half of patients with primary hypothyroidism who reside in an iodine‐sufficient area of Japan, but the pathogenetic factors related to reversible hypothyroidism are still not fully understood. We therefore investigated the clinical features and prognosis of patients with reversible hypothyroidism with or without iodine excess and antithyroid antibodies.DESIGN Amelioration of hypothyroidism was diagnosed when the elevated serum TSH concentrations (serum TSH concentration ≥ 40 mU/l) decreased by 50% or more during an iodine restriction period of 2–15 weeks without replacement therapy. Reversible hypothyroidism occurred in a post‐partum group (n = 20) and a non‐post‐partum group (n = 91).The latter was then further classified into chemical (n = 28), immunological (n = 20), and mixed (n = 43) groups, according to the presence of iodine excess (serum non‐hormonal iodine level>50 μg/l or a history of excess iodine ingestion), antithyroid autoantibody, or both, respectively.MEASUREMENTS Clinical characteristics and long‐term prognosis were compared among the four groups. The rate at which hypothyroidism recovered was expressed as the number of days required for a 50% decrease in the serum TSH concentration. The level of thyroid echogenicity was measured by 10‐MHz ultrasonography.RESULTS In the chemical group, the mean age, male : female ratio, and serum non‐hormonal iodine concentrations were all higher than those in the immunological group. The estimated rate at which hypothyroidism recovered was rapid (6.1 ± 3.1 (mean ± SD) days), the levels of thyroid echogenicity were near normal, and a histological examination (n = 7) revealed either colloid goitre or a normal thyroid in the chemical group. In the immunological and post‐partum groups, the recovery rate was slow (16.8 ± 9.6 days and 16.2 ± 5.8 days, respectively). The levels of thyroid echogenicity were markedly reduced but increased after the spontaneous recovery of the thyroid function in both groups. Aspiration cytology suggested lymphocytic infiltration in all patients examined in the immunological (n = 6) and post‐partum groups (n = 4). Relapse to overt hypothyroidism was observed more frequently in the immunological (38%) and mixed groups (35%) than in the chemical group (5%).CONCLUSION Thyroid damage was more severe, recovery slower and the rate o

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00858.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

BACKGROUND Elevation of plasma renin activity (PRA) is a feature of mineralocorticoid deficiency in patients with primary adrenal insufficiency. This study was designed to assess the usefulness of PRA as an index of adequacy of fludrocortisone (FC) replacement in patients with primary adrenal failure, paying particular attention to the variability in PRA levels during FC and glucocorticoid treatment.METHODS Twenty‐two patients with mineralocorticoid deficiency due to primary adrenal disease were studied at 3 time points: 8, 24 and 32 hours following the administration of FC replacement. Body weight, blood pressure while supine and erect, PRA, and plasma or serum levels of aldosterone, urea, sodium and potassium were measured at each time. The clinical and biochemical consequences of adjusting the FC dose were monitored in 5 patients with PRA levels above the range seen in normal subjects and in one hypokalaemic patient with normal PRA levels.RESULTS At 8 and 32 hours following FC administration, PRA levels were not significantly different. PRA levels were significantly higher at 32 hours following FC administration (4.7 ±1.1 nmol/l/h) than at 24 hours (4.2 ±1.1 nmol/l/h, mean ± SEM,P <0.05). At 8 and 32 hours following FC administration, potassium levels were similar. Potassium levels were significantly higher at 32 hours following FC administration (3.9 ± 0.1 mmol/l) than at 24 hours (3.6 ±0.1 mmol/l,P < 0.05). No changes in measurements of sodium, urea, mean supine and erect arterial pressure or body mass index were noted at the different study points. Attempted lowering of elevated PRA in 5 normokalaemic subjects by raising the dose of FC led to normalization of PRA in all of these patients but 2 developed hypokalaemia and oedema. Lowering of FC dose in one hypokalaemic patient with normal PRA levels led to the PRA levels rising to a supranormal value while the hypokalaemia was corrected.CONCLUSIONS These results indicate that when plasma renin activity is estimated in patients with primary adrenal insufficiency replaced with daily doses of fludrocortisone, the time of day of blood sampling is not critical. Lowering elevated plasma renin activity levels to normal in patients who were considered to be otherwise normal may lead to over‐treatment in some patients. Therefore, optimal fludrocortisone replacement may be associated with mildly elevated plasma renin activity levels. The information obtained by monitoring plasma renin activity adds little to the assessment of patients based on clinical evaluation and measure

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00838.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

BACKGROUND AND OBJECTIVE Glucocorticoid replacement is the most effective therapy for patients with congenital adrenal hyperplasia (CAH). It has been reported that excessive steroid therapy leads to bone loss and osteoporosis, but it is uncertain whether steroid replacement therapy affects bone turnover and bone mineral density (BMD) in adult patients with CAH.DESIGN Case‐control study: patients with CAH were compared to normal subjects, individually matched for age and body weight.PATIENTS Eleven patients, aged 19–65 years, were evaluated in this study. The age at diagnosis of CAH was 0–26 years. Nine patients (6 females and 3 males) were diagnosed with 21‐hydroxylase deficiency and 2 male patients with 11‐hydroxylase deficiency. 17‐Hydroxyprogesterone levels in patients had never been below the reference range in the previous 2 years. These patients were individually matched for sex, age and weight to 11 healthy controls.MEASUREMENTS Total body, lumbar spine and femoral neck BMD was measured by dual‐energy X‐ray absorptiometry. Serum bone Gla‐protein (BGP, osteocalcin) and bone alkaline phosphatase (BAP) were measured to assess bone formation whereas serum tartrate‐resistant acid phosphatase (TRAP) and urinary cross‐linked N‐telopeptides of type I collagen (NTx) were measured to assess bone resorption. NTx was expressed as a fraction of urinary creatinine excretion (NTx/Cr). Serum dehydroepiandrosterone sulphate (DHEA‐S) and androstenedione levels were measured to assess adrenal androgen status.RESULTS Serum DHEA‐S, androstenedione, BGP and BAP and urinary NTx/Cr were decreased in patients when compared with controls (pairedt‐test,P = 0.005, 0.0003, 0.002, 0.03 and 0.03, respectively). BMD was not significantly decreased in patients. The difference of total body BMD between patients and controls (i.e. BMD in patients minus BMD in controls) was negatively correlated with age. There was no correlation between androgen levels and either BMD or bone turnover. The total dose of steroid taken in the previous 2 years was not correlated with BMD, bone turnover or androgen levels. The was no correlation between BMD adjusted by age and bone turnover or initial age at diagnosis.CONCLUSIONS We conclude that (1) bone turnover is decreased in congenital adrenal hyperplasia, (2) bone mineral density is not decreased in congenital adrenal hyperplasia and (3) patients initially have higher bone mineral density but later have lower bone miner

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00851.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE GH deficiency, either in children or in adults, is a clinically relevant problem. The diagnosis is based on dynamic tests of GH secretion, which are clear cut on a group basis but highly problematic for individual diagnosis. The controversy surrounding the diagnosis of GH deficiency reflects the absence of a gold standard dynamic test. The synthetic hexapeptide hexarelin and GHRH stimulate GH secretion using different mechanisms. A sequential test has been devised using the administration of GHRH as first stimulus followed 120 minutes later by hexarelin. The two aims of the study were (a) to evaluate the interaction of GHRH and hexarelin, and (b) to devise a sequential test of GH reserve.DESIGN The GH stimuli used were GHRH (1 μg/kg i.v.) as a pituitary stimulus, and hexarelin (1 μg/kg i.v.) as a GH stimulus whose main action is hypothalamic. Each subject was tested twice in order to serve as his own control. Three different studies, each with two duplicate tests, were performed on separate groups of individuals: (a) GHRH followed 120 minutes later by hexarelin and on the second day hexarelin followed 120 minutes later by GHRH; (b) GHRH followed 120 minutes later by GHRH and on the other day hexarelin followed 120 minutes later by hexarelin; (c) GH 0.5 IU i.v. followed 120 minutes later by GHRH and on the other day, the same dose of GH followed 120 minutes later by hexarelin.PATIENTS Eighteen normal volunteers (12 women, 6 men) after giving informed consent.MEASUREMENTS Plasma GH levels were measured by time‐resolved fluoroimmunoassay; each value shown is the mean ± SEM ofn = 6.RESULTS GHRH followed 120 minutes later by hexarelin induced two episodes of GH secretion (expressed as mean GH peak, mU/l). The GHRH‐mediated GH release showed a mean GH peak of 38.2 ± 13.6 mU/l and after hexarelin 120 minutes later of 56.7 ± 18.0 mU/l. The contrary sequence blocked the second stimulus, i.e. the hexarelin‐stimulated GH mean peak was 54.7 ± 18.4, and the GH release 120 minutes later after GHRH was 4.8 ± 1.9 (P < 0.05vsGHRH used as first stimulus).In the two sequential tests using the same stimulus, the second GH peak was reduced. In fact, GHRH induced a GH mean peak of 63.8 ± 21.1 mU/l as first stimulus, greater (P < 0.05) than when GHRH was administered again 120 minutes later (22.0 ± 5.9 mU/l). Similar results were obtained with hexarelin, with a first mean peak of 70.6 ± 10.3 mU/l, and a second one 120 minutes later of 13.4 ± 4.6 mU/l (P < 0.05).The blockade of the second stimulus was not due to the feed‐back action of the GH released by the first stimulus. In fact, the i.v. administration of exogenous GH induced a mean GH peak of 168.0 ± 89.7 and reduced the action of GHRH administered 120 minutes later (26.1 ± 8.1). The previous administration of GH (mean peak 115.5 ± 42.0) did not alter the action of hexarelin injected 120 minutes later, showing a mean peak of 71.9 ± 11.2.The large variability in the stimulatory action of GHRH contrasted vividly with the reproducibility of hexarelin. Furthermore, individually analysed, only one of the 12 subjects tested first with hexarelin, compared to 4 out of 12 tested with GHRH as first stimulus, presented a blunted response (<13 mU/l). After the sequential stimulus there were no false negatives.CONCLUSION The sequential administration of GHRH in normal subjects and of hexarelin 120 minutes later provides separate information regarding pituitary GH reserve, of both secretagogues without mutual interference. There were not false negative results to the combi

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00841.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE The recognition of the syndrome of adult GH deficiency suggests that young GH deficient adults, deprived of GH replacement at completion of linear growth, may suffer effects of GH deficiency. We assessed GH reserve in young adults previously diagnosed as having idiopathic GH insufficiency, who were treated with hGH replacement (14 IU/m2/week) in childhood.DESIGN Eight patients (7 males, 1 female) diagnosed as having GH insufficiency by insulin tolerance test (ITT) in childhood (ages 8.5–15.6 years) were retested by ITT at completion of linear growth (ages 15.1–19.6 years), 3 months after discontinuation of hGH therapy.MEASUREMENTS GH reserve was measured during ITT at diagnosis and at retesting. Height velocity (HV) and HV SDS were calculated before and during GH therapy.RESULTS At diagnosis, the mean peak GH response to ITT was 10.5 ± 2.0 mU/l (range 7.7–13.6). At retesting, mean GH was 52.4 ± 33.2 mU/l (range 10.4–100), 7/8 subjects having peak GH levels greater than 15 mU/l. During hGH therapy mean HV increased from 4.0 ± 1.5 cm/year at diagnosis to 7.3 ± 1.9 cm/year during the 1st year (P = 0.004) and 6.9 ± 2.3 cm/year during the 2nd year (P = 0.02). Mean HVSDS increased from −1.6 ± 2.1 at diagnosis to 3.1 ± 2.9 during the 1st year (P = 0.004) and 2.2 ± 4.2 during the 2nd year (P = 0.05, NS) of treatment.CONCLUSIONS Seven out of 8 children diagnosed as having idiopathic GH insufficiency had normal GH secretion at completion of linear growth. Children with GH insufficiency cannot be assumed to become GH deficient adults and should not continue on GH therapy into adult life without reinvestigation. All who were GH insufficient children should be retested at completion of linear growth to ide

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00850.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE In adults, there are few data regarding GH responses to provocative stimuli other than insulin‐induced hypoglycaemia. We have compared the GH response to four different growth hormone secretagogues and placebo in normal healthy adult males.DESIGN This was a prospective, randomized, placebo‐controlled study in 18 normal male subjects. After an overnight fast, an intravenous cannula was inserted into the arm of each subject and a blood sample was taken for GH at −30, −15, and 0 minutes. Four provocative agents (intravenous insulin 0.2 IU/kg; intravenous arginine 20 g/m2as an infusion over 30 minutes; oral clonidine, either 100 or 200 μg; intramuscular glucagon 1 mg) and placebo were administered to each subject in a randomized manner on different days. Further blood samples were taken at 15‐minute intervals for 180 minutes for GH estimation.RESULTS The median (range) GH peak response for each agent was insulin 107.7 (28.1–200) mU/l; arginine 22.3 (3.1–72.9) mU/l; glucagon 42 (11.8–200) mU/l; 100 μg clonidine 7.2 (<1–22.2) mU/l; 200 μg clonidine 8.2 (1.1–88) mU/l and placebo 2.4 (<1–30.2) mU/l. The peak GH response to insulin‐induced hypoglycaemia (ITT) was significantly greater than for any other agent (P<0.0001). The peak GH response to glucagon was significantly greater than for arginine (P<0.05), clonidine at 100 and 200 μg (P<0.01) and placebo (P<0.01). The peak GH response following administration of arginine was significantly greater than for clonidine 100 and 200 μg (P<0.05), and placebo (P20 mU/l to glucagon, arginine and clonidine respectively. In complete contrast only one subject achieved a peak response of less than 40 mU/l (28.1 mU/l) to ITT.CONCLUSIONS The most profound GH release is seen after insulin‐induced hypoglycaemia. Glucagon appears to be more effective at inducing GH release than

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00855.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVES Sleep apnoea is common in active acromegaly. It is associated with increased morbidity and mortality but can be treated effectively. The objective of this study was to determine the largely unknown relative frequency of, and the predictive factors for, sleep apnoea in treated acromegalic patients.DESIGN Retrospective cohort study.SETTING Tertiary referral hospital.PATIENTS Fifty‐four of 100 patients with treated acromegaly. If sleep apnoea had been diagnosed before acromegaly, the patient was excluded.MEASUREMENTS Sleep studies (using the MESAM‐4 device measuring oxyhaemoglobin saturation, heart rate, snoring sounds and body position to determine presence and severity of sleep apnoea); GH and IGF‐I levels; body mass index, neck and index‐finger circumference; daytime symptoms of sleep apnoea, duration of acromegaly before treatment, shoe and neck‐size difference since beginning of acromegaly; age, sex and treatment modes of acromegaly.RESULTS The relative frequency of sleep apnoea was 39% in the 54 patients with sleep studies and at least 21% in the entire study population of 100 patients.In patients with sleep apnoea, statistically significant higher values were observed for GH (P = 0.002), IGF‐I (P = 0.029), age (P = 0.014) and neck circumference (P = 0.016). An index‐finger circumference of ≥8.5 cm was associated with a significantly higher desaturation index (P = 0.012, Mann–WhitneyItest). Adenomectomy had been performed significantly less frequently in patients with sleep apnoea (P < 0.001, χ2test). The body mass index was non‐significantly higher in the patients with sleep apnoea.CONCLUSIONS The relative frequency of sleep apnoea in patients with treated acromegaly is at least 21%. Parameters of predictive value for the presence of sleep apnoea in this population are neck and index‐finger circumference as measures of soft tissue hypertrophy, age, GH and

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00852.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

OBJECTIVE Verapamil has been associated with hyperprolactinaemia, but there have been no population‐based studies. Our objective was to determine the prevalence and degree of hyperprolactinaemia associated with verapamil in the clinical setting.DESIGN Observation with cross‐sectional and longitudinal components in the setting of an urban teaching hospital and its satellite out‐patient clinics.PATIENTS Male out‐patients excluding those taking other drugs known to raise PRL, renal failure and known primary hypothyroidism (1265 eligible subjects). Control subjects were drawn from eligible out‐patients not taking verapamil.MEASUREMENTS Serum PRL levels, frequency of persistent hyperprolactinaemia and total testosterone levels.RESULTS Prolactin levels were obtained in 449 subjects on verapamil (35.5% response rate) and 166 controls. The proportions of individuals with hyperprolactinaemia (PRL> 460 mU/l) were 0.085 and 0.030 in the verapamil and control groups, respectively (P = 0.012, χ2‐test). The mean (±SD) serum PRL levels were 267 ± 205 and 203 ±118 mU/l in the verapamil and control groups, respectively (P  120,P < 0.00001). The ± SD serum testosterone levels at follow‐up were significantly lower in Group 1 (6.16 ± 2.52 nmol/l) than in Group 2 (9.42 ± 3.92 nmol/l,P = 0.029, independentt‐test).CONCLUSIONS The prevalence of hyperprolactinaemia associated with verapamil use in this study of male out‐patients was .5% (95% Cl 5.9–11.1%). The persistence of hyperprolactinaemia when verapamil was continued (Group 1) and the return to normal PRL levels when verapamil was discontinued (Group 2) confirm verapamil’s causal role in the development of hyperprolactinaemia. While low testosterone levels were common in both groups, testosterone levels were lower in patients on verapamil. Our data suggest tha

ISSN:0300-0664    

DOI:10.1046/j.1365-2265.1996.00859.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY