EVALUATION OF A SENSITIVE CHEMILUMINESCENT ASSAY FOR TSH IN THE FOLLOW-UP OF TREATED THYROTOXICOSIS

We have studied 21 patients treated for thyrotoxicosis to evaluate a highly sensitive chemiluminescent thyrotrophin (TSH) assay in the assessment of changing thyroid status. Serum TSH was generally suppressed with high serum thyroid hormone concentrations and invariably rose when free T4 and T3 fell substantially below the normal range. However TSH values in 14 of the 21 patients remained undetectable or subnormal for variable periods despite normal or even slightly subnormal free T4 and T3 values. The level of free T4 and T3 at which TSH concentrations rose was highly variable, suggesting differing degrees of hypothalamo-pituitary suppression. Sensitive TSH assays are likely to provide useful information regarding physiological regulation of TSH secretion in man, but our data indicate that in certain circumstances these assays used alone will be inadequate for biochemical assessment of thyroid status.     

HUMAN SERUM THYROTROPHIN MEASUREMENT BY ULTRASENSITIVE IMMUNORADIOMETRIC ASSAY AS A FIRST-LINE TEST IN THE EVALUATION OF THYROID FUNCTION

An ultrasensitive immunoradiometric assay (IRMA) using two monoclonal anti-TSH antibodies has been used for TSH measurements in basal conditions and after TRH stimulation. The results have been compared with those obtained by conventional radioimmunoassay (RIA). The IRMA method had very high sensitivity (0.07 microU/ml). Detectable serum TSH concentrations were found in all normal subjects by IRMA, but in only 76% by RIA. No overlap was observed with the results obtained by IRMA in untreated overtly hyperthyroid patients, in whom serum TSH was below the limit of detection. The relationship between basal and TRH-stimulated serum TSH concentrations by IRMA and RIA was evaluated in 176 subjects including normals and patients with untreated and treated hyperthyroidism, functioning thyroid adenoma, nontoxic goitre and patients on L-thyroxine therapy. A normal TSH response to TRH was observed in virtually all patients with detectable basal serum TSH by both methods. When patients with undetectable basal serum TSH levels were considered, all but one (98%) had no TSH response to TRH by IRMA. On the contrary using RIA, an absent response was found only in 47% of subjects, a blunted responses in 10% and a normal response in 42%. These data indicate that basal serum TSH measurements by IRMA allows a complete discrimination of normal from hyperthyroid patients and can avoid the need for TRH stimulation tests.     

EFFECT OF A LARGE DOSE OF THYROTROPHIN RELEASING FACTOR ON PITUITARY AND THYROID FUNCTION IN PATIENTS WITH PARKINSONISM

Thyrotrophin releasing factor (TRF) was given intravenously in doses of 0.5 mg and 20 mg to six patients with Parkinsonism treated with l -dopa. Plasma thyrotrophin (TSH), prolactin, luteinizing hormone (LH), follicle stimulating hormone (FSH), thyroxine (T4) and triiodothyronine (T3) were measured before and after TRF infusion. The observation that FSH and LH did not change in response to either dose of TRF confirmed specificity of the effects of TRF for certain anterior pituitary functions. The plasma TSH and prolactin levels achieved after 20 mg TRF were considerably greater and were maintained longer than those after 0.5 mgTRF. However, despite a seven fold increase in the overall TSH response, the T4 and T3 responses to 20 mg TRF were not significantly greater than those to 0.5 mg TRF. The explanation for this discrepancy between immunoreactive TSH levels and apparent biologic effect is unclear.     

ROLE OF BASE-PAIRING IN THE CONTROL OF AN ENZYME REACTION

In an attempt to ascertain whether specific base-pairing could have a regulating function in an enzyme system in which nucleotides serve as the substrate, we studied the effects of the addition of the various homopolymers of the ribonucleotide series on the action of adenylate kinase on ADP or CDP, and found that the results support this possibility. Poly U strongly inhibits the enzyme action on ADP, and poly G that on CDP, both to the extent of about 70 per cent. Lesser effects are shown when poly G is used with ADP and poly U with CDP. The other homopolymers tested, poly A and poly C, are ineffective.     

IMMUNOASSAY OF PLATELET-DERIVED GROWTH FACTOR IN THE PLASMA OF PATIENTS WITh SCLERODERMA

It has been postulated that platelet—derived growth factor(PDGF) is responsible for the abnormal fibroblast proliferationobserved in scleroderma. In one previous study, plasma samplesfrom patients with scleroderma caused increased mitogenesisin cultured fibroblasts, suggesting that the pathogenesis ofscleroderma is related to increased plasma PDGF concen trations.To test this hypothesis, we used a sensitive, monoclonal antibody—basedELISA to measure PDGF in the plasma of 12 scleroderma patients.A rigorous sampling protocol prevented false elevations in plasmaPDGF levels from ex vivo platelet degranulation: ß-thromboglobulinconcentrations were measured in each plasma sample to monitorplatelet lysis. Plasma PDGF concentrations in the sclerodermapatients were not statistically different from those observedin age- and sex—matched normal controls, and patientswith RA. While it is possible that changes in PDGF activityat a local level alter fibroblast function, we cannot concludethat elevated plasma concentrations of PDGF play a role in thepathogenesis of scleroderma. KEY WORDS: Scleroderma, Systemic sclerosis, Rheumatoid arthritis, Platelet-derived growth factor, ß-Thromboglobulin, Enzyme-linked immunoassay, monoclonal antibody     

THE CIRCADIAN VARIATION OF THYROTROPHIN IN PATIENTS WITH PRIMARY THYROIDAL DISEASE

We have used a highly sensitive immunochemiluminometric assay (ICMA) for human TSH to study the effect of thyroid status on the circadian variation in TSH levels. Three subjects with Graves' disease, three with toxic multinodular goitre and three with euthyroid multinodular goitre were sampled every hour for 24 h. The results obtained were compared to those from five euthyroid control subjects. It was found that some patients with hyperthyroidism and suppressed basal TSH levels exhibited a 24 h secretory pattern similar to that seen in normal subjects with peak TSH levels occurring at night. In addition two subjects with a euthyroid multinodular goitre demonstrated levels of TSH below the normal range despite being clinically and biochemically euthyroid. TSH suppression in these subjects is probably related to some degree of thyroid autonomy and possible development of hyperthyroidism in the future.     

A HIGHLY SENSITIVE CYTOCHEMICAL BIOASSAY FOR PLASMA ANGIOTENSIN II

A highly sensitive cytochemical bioassay has been developed for measuring angiotensin II in human plasma. The assay depends on the ability of angiotensin II to alter the reducing potency of the zona glomerulosa as measured by Prussian blue staining and microdensitometry. An inverse correlation between the intensity of the stain and the logarithm of concentration existed over the range 0.05-5.0 fmol/l of angiotensin II. The limit of sensitivity of the assay in plasma was 50 fmol/l; the index of precision was 0.07 ± 0.04 (mean ± SD; n = 15); and the coefficient of variation of a quality control sample was 34%. The response was specific for angiotensin II; approximately 10² times more angiotensin III and approximately 10⁶ times more ACTH was required to produce a similar effect. Angiotensin I had no significant activity. A significant inverse relationship existed between sodium intake and bioactive angiotensin II in 5 normal subjects studied on low, normal and high sodium diets. Extremely low levels of angiotensin II were detected in anephric subjects.     

ALTERED DOPAMINERGIC REGULATION OF THYROTROPHIN RELEASE IN PATIENTS WITH PROLACTINOMAS: COMPARISON WITH OTHER TESTS OF HYPOTHALAMIC-PITUITARY FUNCTION

This study was carried out to test the hypothesis that sustained hyperprolactinaemia in patients with prolactinomas stimulates hypothalamic dopaminergic activity via a short loop positive feedback effect of prolactin (PRL). The intensity of dopamine (DA) effects on the pituitary around the adenoma was evaluated by measuring thyroid stimulating hormone (TSH) responses to intravenous injection of domperidone (10 mg) a new DA receptor blocking drug that does not penetrate the blood-brain barrier. TSH responses have been compared with those of PRL to the same agent. Eight females with prolactinomas showed greater TSH release after domperidone than nine normal females (sum of TSH increments over 120 min 17·5 ± 1·7 v. 8·9±1·5 mu/l, P < 0·001) whilst PRL release was reduced (sum of PRL increments over 120 min 5·9 ± 2·4 v. 21·8 ± 3·8 mu/l ± 10^?3, P < 0·01). Amongst nineteen hyperprolactinaemic females with apparently normal pituitary fossae (plain skull X-ray), ten showed an exaggerated TSH response (ΔTSH, 4·2 ± 0·6 mu/l, range 2·5–9·40 mu/l) and reduced PRL response to domperidone, comparable with established tumour cases. In the remaining nine normal fossa hyperprolactinaemic females, the TSH and PRL responses to domperidone were similar to normal females. These results support the initial hypothesis and indicate the coexistence of a defect in the dopaminergic inhibition of PRL release and increased dopaminergic inhibition of TSH release in patients with prolactinomas. The presence of an exaggerated TSH response to DA antagonism in a euthyroid, radiologically normal (plain skull X-ray), hyperprolactinaemic patient is compatible with the presence of an autonomously-functioning, PRL secreting, pituitary microadenoma and the TSH changes seen in these patients after DA antagonist administration can be readily detected by sensitive TSH radioimmunoassay.     

PITUITARY—ADRENOCORTICAL FUNCTION IN PATIENTS DURING TREATMENT WITH THE ANGIOTENSIN-CONVERTING ENZYME INHIBITOR CAPTOPRIL

To study effects on pituitary-adrenocortical activity of a sustained block of angiotensin II formation, six 'drug-resistant' patients with essential hypertension were studied before and during treatment with an inhibitor of the angiotensin-converting enzyme (Captopril, SQ 14,225). The drug was given in increasing doses (100-400 mg/day) for 2 weeks whilst patients received a moderately restricted sodium intake (60-80 mmol/day). Immunoreactive ACTH, cortisol, aldosterone, plasma renin activity (PRA) and the activity of the angiotensin-converting enzyme (ACE) were measured in blood samples drawn at 0800-0900 h. Urinary excretion of cortisol and aldosterone were measured in 24-h urine collections. Further information on pituitary-adreno-cortical function was obtained by measuring serial plasma corticosteroid levels after submaximal stimulation with a synthetic ACTH preparation. ACTH and cortisol did not change an observation which does not support the hypothesis that glucocorticoid activity is influenced by a decrease in plasma angiotensin II concentrations.     

腹腔镜在老年人腹膜后肿瘤诊治中的作用

目的探讨腹腔镜在老年病人腹膜后肿瘤疾病诊治中的价值。方法自2000年6月至2004年3月,收治12例老年腹膜后肿瘤病人,行腹腔镜腹腔探查和腹膜后肿瘤活检,其中2例术中同时行肠粘连松解术。结果12例患者均完成腹腔探查和术中肿瘤活检。术中分别取出1～3枚0．4-1．0cm大小的肿瘤组织,行术中冰冻和术后病理检查。5例病人根据快速冰冻病理结果终止手术,7例病人完成肿瘤切除手术。结论腹腔镜可以对老年腹膜后肿瘤疾病的病人进行诊断和分类。减少盲目的剖腹手术。     

辛伐他汀对急性冠状动脉综合征患者高敏C-反应蛋白的影响

目的探讨调脂对急性冠状动脉综合征(ACS)患者冠脉病变炎症的影响。方法采用随机、单盲、对照方法将125例ACS患者分为辛伐他汀治疗组(n=63)非辛伐他汀治疗组(n=62),另选健康对照组(n=60),测定治疗前、治疗后8周血浆高敏C-反应蛋白(hs-CRP)水平的变化。结果ACS患者的hs-CRP水平明显增高,经辛伐他汀治疗8周后其血浆hs-CRP水平明显下降,非他汀治疗组各项指标无明显变化。结论他汀调脂可阻滞ACS患者冠脉病变的炎症反应。     

STUDIES ON THE ROLE OF HISTAMINE IN HUMAN PITUITARY FUNCTION

To elucidate further the role of histamine in pituitary regulation, TRH and L-DOPA stimulation tests were performed with and without diphenhydramine, cimetidine, or betazole pre-treatment. Betazole blunted the GH response to L-DOPA and slightly enhanced the T3 response to TRH without altering the TSH or PRL increments. Neither diphenhydramine nor cimetidine had any acute effect on the hormonal responses examined. Histamine appears to play only a limited role in these aspects of human pituitary regulation.