摘要:

SummaryOBJECTIVE We investigated whether the first patient (L‐F3) reported as having selective pituitary resistance had a mutation in the hTRβgene. We compared the clinical parameters of this case with those of patients with generalized resistance to thyroid hormone.DESIGN The patient, L‐F3, was part of a study at the NIH to identify mutations by sequencing the hTRβgene in kindreds with thyroid hormone resistance. The clinical data of L‐F3 as well as patients with generalized resistance to thyroid hormone were compared and analysed retrospectively.MEASUREMENT We amplified by the polymerase chain reaction and then sequenced exons 5 to 10 of the hTRβgene in L‐F3 and a normal control. Upon finding the mutation in L‐F3, we measured the affinity constant of this mutated hTRβreceptor. Criteria developed previously were used to assess tissue responsiveness to thyroid hormone of L‐F3.RESULTS We identified a C to T transition at base 1297 in codon 333 of the hTRβgene in the first patient (L‐F3) reported as having apparent selective pituitary resistance. This base substitution resulted in more than a fourfold decrease in T3‐binding affinity for the hTRβ1 receptor. The mutation of L‐F3 occurred in the dimerization domain of exon 9, a region where the majority of mutations of kindreds with generalized thyroid hormone resistance have been found. Furthermore, the nucleotide substitution at base 1297 found in the apparent selective pituitary resistant case, L‐F3, was the same as in an unrelated patient (K‐T3) with generalized resistance to thyroid hormone. As a result, we compared the clinical parameters of both patients and found that they had similar patterns of resistance in several tissues. Besides the bone resistance present in both kindreds, the apparent selective pituitary resistance case also had liver and neuromuscular resistance.CONCLUSIONS These findings suggest that apparent selective pituitary resistance and generalized resistance to thyroid hormone are not qualitatively different syndromes. Nevertheless, identification of selective pituitary resistance is a useful clinical distinction since such patients with clinical and biochemical features of hyperthyroidism appear to benefit from reduction in serum thyroid hormone concentrations. In contrast, patients with more conventional forms of thyroid hormone resistance require no treatment or may benefit from increased concen

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb00999.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01000.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE It has recently been shown that patients with growth hormone deficiency have a reduced sweating capacity. We hypothesize that reduced sweating might affect thermoregulation in growth hormone deficiency patients. In the present study we have examined thermoregulation in growth hormone deficiency patients.DESIGN AND PATIENTS Six adult growth hormone deficiency patients and six matched controls were exposed to a 90‐minute heat period (40°C). On a second day the subjects exercised for 30 minutes under standardized conditions.MEASUREMENTS On both occasions changes in GH secretion, sweating and temperature were registered. Heat storage and evaporation were calculated from these data.RESULTS We found that during the moderate heat exposure, evaporation was less (56.7 vs 115.6 W,P= 0.0037) and heat storage greater (60.7 v s 37.0 W,P= 0.025) in growth hormone deficiency patients compared to their matched controls. Two of the six patients reacted with severe clinical symptoms of heat exhaustion, whereas the controls were unaffected. After exercise the patients reached significantly higher core temperatures than their matched controls (38.1vs37.8°C,P= 0.0097).CONCLUSIONS Thus, our findings are indicative of a reduced thermoregulatory function in some patients with G H deficie

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01001.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We investigated the effect of growth hormone (GH) treatment on salt and water metabolism and the renin‐angiotensin‐aldosterone system in children with short stature.DESIGN Randomized, controlled study.PATIENTS Twenty‐nine short, pre‐pubertal children referred to two specialist growth clinics for further assessment.MEASUREMENTS Serial measurements of blood pressure, body weight, plasma renin activity (PRA), aldosterone, electrolytes, insulin and insulin‐like growth factor I (IGF‐I) have been made following the initiation of GH treatment.RESULTS A small and transient increase in systolic blood pressure was observed during the first week of GH treatment. The increase in blood pressure over baseline was −1.1 mmHg in controls compared to +11.5 and +3.0 mmHg in children receiving standard (20 units/m2/week) and high dose (40 units/m2/week) GH respectively (P= 0.004). Over the same time interval body weight also tended to increase with GH compared with controls. These changes were greater in those children receiving the lower dose of GH and were not significantly related to age or prior GH status.PRA did not change with GH treatment. Although plasma aldosterone concentration tended to increase with GH, maximal values did not differ from controls and all remained within our normal range. Plasma IgF‐I levels were increased by a similar amount in both treatment groups (1.5 and 1.12 U/ml compared to 0 44 U/ml in controls at 4 months). No difference in plasma insulin concentration was noted after 7 days of GH.CONCLUSIONS In contrast to adult subjects, treatment with high dose GH in childhood is not associated with activation of the renin‐angiotensin‐aldosterone system. Clinical signs consistent with transient salt and water retention are observed with GH therapy, however, suggesting either a direct effect of GH or of IGF‐I on renal tubular function. Blood pressure, plasma renin activity and plasma aldosterone levels were not increased after more prolonged GH therapy. These data suggest that high dose GH therapy in childhood is unlikely to be associated with the increased risk of hypertension seen in adults w

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01002.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The aim was to evaluate the effect of 3 years treatment with recombinant human growth hormone (rhGH) on height velocity and height in girls with Turner's syndrome (TS) and to study to influence of spontaneous or induced puberty on the growth promoting effect of rhGH.PATIENTS AND DESIGN The investigation was performed in 36 girls with Turner's syndrome treated for 3 years with rhGH in a dose of 1 IU/kg week, administered as daily subcutaneous injections. Fifteen patients remained prepubertal throughout the observation period (Group 1). During the first 2 years of rhGH therapy, four girls developed puberty spontaneously (Group 2). During the 3rd year of rhGH treatment puberty was induced with 100 ng/kg day ethinyl oestradlol orally in 17 girls requesting pubertal development and with a bone age of at least 11‘years' (Group 3).RESULTS During the first year of rhGH therapy height velocity increased significantly in all patients. Mean ± SD height velocity was higher in the four patients with Turner's syndrome who developed spontaneous puberty than in 17 age‐matched girls with Turner's syndrome without puberty (8.9 ± 1.2 vs 7.4 ± 12 cm/year;P<0.05). During the second and third year of rhGH treatment height velocity decreased in all patients but remained above baseline levels. The induction of puberty with 100 ng/kg day ethinyl oestradlol in the patients of Group 3 did not lead to an acceleration of height velocity, but seemed in contrast to decelerate height velocity. After 3 years of rhGH treatment, 21 out of 36 patients have obtained a height at or above the initially calculated projected adult height and five girls are already taller than 150 cm.CONCLUSIONS The onset of spontaneous puberty during the first years of rhGH treatment seems to have an additive effect to rhGH on height velocity. Induction of puberty with oral administration of 100 ng/kg day ethinyl oestradiol did not have any beneficial effect on height velocity and seems therefore not to be the optimal way to induce puberty with an adequate pubertal growth spurt in girls with Turner's syndrome under rhGH therapy. Different doses and routes of oestrogen administration have to be evaluated in order to mimic the growth promoting effect of spontaneous puberty as well as po

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01003.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We have previously reported on 30 patients with Cushing's syndrome suggesting an aetiological role for stressful life events. The investigation about life events in the year before the first signs of disease onset was extended to a larger population of patients with Cushing's syndrome, allowing us to differentiate patients with pituitary‐dependent and pituitary‐independent forms. DESIGN Case‐control study.PATIENTS Sixty‐six consecutive patients with Cushing's syndrome of various aetiologies (46 with pituitary‐dependent forms and 20 with primary adrenal hyperfunction or ectopic ACTH production) and a control group of 66 healthy subjects, matched for sociodemographic variables, were studied.MEASUREMENTS Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered after the acute phase of illness while in remission.RESULTS Patients with Cushing's syndrome reported significantly more stressful life events (P<0.001), both events that had an objective negative impact (P<0.001) and independent events (P<0.001), than controls, confirming previous findings. Patients with pituitary‐dependent Cushing's disease were compared with their matched controls and reported significantly more total events, events with an objective negative impact and independent events (all atP<0.001). There were no significant differences between patients with pituitary‐independent forms and their matched controls.CONCLUSIONS These findings indicate a causal role for stressful life events exclusively in pituitary‐dependent Cushing's disease, and suggest a limbic‐hypothalamic involvement in the pathogenesis of this condition. The results are similar to those obtained in major depression, and add to other analogies between

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01004.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The regulation of 19‐hydroxyandrostenedione secretion has been suggested to be under the control of both the ACTH‐adrenal axis and renin‐angiotensin system. We undertook the present study to evaluate the effect of the chronic excess of ACTH, or the short‐term excess of ACTH due to metyrapone, on 19‐hydroxyandrostenedione secretion in patients with Cushing's diseaseDESIGN AND PATIENTS We measured plasma 19‐hydroxyandrostenedione levels simultaneously with plasma Δ4‐androstenedione, corticosterone, 11‐deoxycorticosterone, aldosterone and Cortisol levels after HPLC separation in 13 patients with Cushing's disease under basal conditions and during a dexamethasone suppression test or metyrapone test. Seven patients with Cushing's syndrome due to adrenal adenoma were used for comparison.RESULTS The basal levels of 19‐hydroxyandrostenedione in Cushing's disease were elevated (mean ± SD; 323 ± 193 pmol/l,n= 13), while those in Cushing's syndrome due to adrenal adenoma were low (92 ± 24 pmol/l,n= 7), compared to those in normal subjects (117 ± 33 pmol/l,n= 54). The basal levels of Δ4‐androstenedione were mildly elevated In Cushing's disease (9.0 ± 6.5vs3.6 ± 2.6 nmol/l of normal subjects) but not in Cushing's syndrome due to adrenal adenoma (3.1 ± 3.0 nmol/l). In the overnight 8 mg dexamethasone suppression test in Cushing's disease (n= 12), plasma levels of 19‐hydroxyandrostenedione and Δ4‐androstenedlone decreased from 277 ± 172 to 156 ± 99 pmol/l and from 9.2 ± 6.8 to 4.7 ± 3.4 nmol/l, respectively, whereas the overnight 1 mg dexamethasone suppression test did not induce significant changes. Metyrapone administration in Cushing's disease (n= 9) increased plasma Δ4‐androstenedione level from 9.5 ± 6.7 to 47.2 ± 28.1 nmol/l, but decreased plasma 19‐hydroxyandrostenedione level from 301 ± 196 to 196 ± 105 pmol/l.CONCLUSIONS These data indicate that plasma levels of 19‐hydroxyandrostenedione in patients with Cushing's disease are elevated due to chronic ACTH excess, and that m

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01005.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE The present study was designed to investigate the prevalence of thyroid dysfunction and Its relation to thyroid autoantibodies and urine iodide concentration in apparently healthy people residing in Sapporo, a city of northern Japan, where the iodine intake is high.DESIGN AND SUBJECTS Serum TSH and thyroid autoantibodies, and urine iodide were measured in 4110 people (2931 men and 1179 women) (age 456 ± 103 years (mean ± SD)) who were recruited at the hospital for medical examinations.RESULTS The thyroid autoantibodies were positive in 6.4% of males and 13.8% of females with an age‐related increase. Of the people with positive antibodies, 87.2% had normal TSH values (0.15–5.0 mU/l) as measured by a sensitive assay. The prevalence of unsuspected hyperthyroidism as defined by suppressed TSH values was 0.61%, of which 64% was diagnosed as Graves' disease based on positive thyrotrophin receptor antibody results. The prevalence of unsuspected hypothyroidism, as evidenced by supranormal TSH, was 0.68% for males and 3.13% for females with an age‐related increase. Of those with hypothyroidism, 45.5% were autoantibody positive. The overall prevalence of Hashimoto's thyroiditis was 13.11% for females and 6.15% for males. The urine iodide levels of hypothyroidism with a positive autoantibody of 38.5 (17.7–83.9)μmol/l and a negative autoantibody of 34.9 (17.9–67.9) μmol/l were both significantly higher than that of normal subjects (26.9 (14.6–49.6) μmol/l) (P<0.01). When iodine intake was restricted for 6–8 weeks for hypothyroid subjects, the elevated TSH and thyroglobulin and low free T4 levels were reversed in the autoantibody negative but not in the positive group.CONCLUSIONS This study provides further information on the prevalence of thyroid dysfunction and autoimmune thyroid diseases in an iodine sufficient area. In addition, it suggests that more than half of the patients with unsuspected hypothyroidism were negative for autoantibodies and that the excessive iodine intake may be involved in causing lat

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01006.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We assessed the changes of bone mass in patients with hyperthyroidism by measuring bone mineral density using a new method, dual energy X‐ray absorptiometry.DESIGN The values of bone mineral density in patients with hyperthyroidism were compared with data obtained from the controls, and we assessed the correlation analysis between bone mineral density and several metabolic parameters.PATIENTS We studied 52 Japanese patients with hyperthyroidism (20 males, 32 females). Healthy normal subjects served to establish the mean bone mineral density In the healthy Japanese population (Shiraki et al. 1991).MEASUREMENT Bone mineral density was assessed by the measurement of lumbar vertebrae and femur by dual energy X‐ray absorptiometry. The bone mineral density of vertebrae for each patient was calculated as the percentage of the mean value (% bone mineral density) obtained from an age and sex‐matched control group. Blood was drawn to measure the levels of serum calcium, phosphorus, creatinine, alkaline phosphatase, free T3, free T4, TSH, TSH receptor antibody, parathyroid hormone, and serum osteocalcin.RESULTS The percentage bone mineral density of vertebrae in patients was 92.6 as compared with that of normal controls, and was inversely correlated with serum TSH receptor antibody, osteocalcin, and alkaline phosphatase.CONCLUSIONS These findings suggest that bone mineral density is decreased in patients with hyperthyroidism and that TSH receptor antibody, osteocalcin, and alkaline phosphatase are sensitive markers of bone metabolism alterations in hyperthyro

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01007.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

SummaryOBJECTIVE We investigated the content and compared the molecular forms of parathyroid hormone‐related protein in tumour tissue, plasma and pleural fluid.DESIGN Measurement of parathyroid hormone‐related protein in tumour extracts and biological fluids and comparison of the elution profiles of parathyroid hormone‐related protein (PTHRP) immunoreactivity following gel filtration chromatography on Bio‐gel P100.PATIENTS Tumours and plasma from patients with humoral hypercalcaemia of malignancy were studied, together with tumours and pleural fluids from patients who were normocalcaemic.MEASUREMENTS Immunoreactivity in column fractions, plasma and tumour extracts was measured by a highly sensitive immunoradiometric assay for PTHRP 1–86 with specificity directed at the 17–61 region of PTHRP.RESULTS Similar levels of PTHRP immunoreactivity were measured in tumours from normocalcaemic and hyper‐calcaemic patients. PTHRP 1–86 (28–4630 fmol/g) was detected in eight of the nine tumours studied. Immunoreactivity in tumour extracts eluted as major peaks in the range 22–33 kDa with an additional peak of 15 kOa in three out of six tumours studied. In contrast, immunoreactivity in plasma and pleural fluid eluted within the range 7–14 kDa.CONCLUSIONS The major species of parathyroid hormone‐related protein in plasma and pleural fluids was consistently smaller than that in tumour tissue (22–33 kOa) suggesting that tumour‐derived parathyroid hormone‐related protein is processed at the COOH‐terminus to form a species of approximately 10 kDa which circulates in patients with humor

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1993.tb01008.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY