摘要:

SUMMARYUsing a recently developed sensitive enzyme immunoassay (EIA) for TSH, serum TSH levels in normal subjects and patients with various thyroid disorders were measured. The minimum detectable concentration was less than 0.005 mU/l. An excellent correlation was observed between TSH values measured by EIA and by sensitive radioimmunoassay (r= 0.932). In 26 normal subjects, serum TSH ranged from 0.30 to 2‐65 mU/l (geometric mean 0.97 raU/l). In 27 untreated hyperthyroid Graves' patients, serum TSH was detected in all but one, ranging from 0.005 to 0.19 mU/l (geometric mean 0.040). These values were proved to be specific for human TSH by absorption, recovery, cross‐reactivity and dilution studies; non‐specific serum effects were also ruled out. In 10 patients with destructive thyroiditis, similar TSH values (0.005‐0.20 mU/l, mean 0.032) were observed. However, no significant correlations between TSH and circulating thyroid hormone levels were observed in these thyrotoxic conditions. Furthermore, 9 untreated Graves' patients did not respond to a single i.v. injection of TRH. In 13 hypothyroid patients with hypothalamopituitary disorders, 10 had basal TSH levels of less than 0.4 mU/l, and TRH tests in five gave peak TSH values of more than 0.8 mU/l, which were associated with significant increases in serum T3. In three patients with Sheehan's syndrome, elevated basal TSH levels were observed. Two of them responded to TRH, but these TSH elevations were not associated with T3 increases. In conclusion, this sensitive EIA could measure TSH levels in most patients with thyrotoxicosis and central hypothyroidism. However, the true significance of these measured values needs to be elucidated by future studies.The conventional radioimmunoassay (RIA) for TSH cannot fully discriminate low TSH levels from those of euthyroid subjects, but recently developed sensitive RIA and immunoradiometric assay (IRMA) have been reported to be able to discriminate between them (Pekaryet al., 1975; Smithet al., 1979; Moriet al., 1983; Sethet al., 1984). However, even these assays cannot detect serum TSH in patients with thyrotoxicosis. Detectable amounts of TSH have been observed in the pituitary of hyperthyroid Graves' patients (Kumaharaet al., 1967; Mori, 1973). We could expect them, therefore, to secrete some TSH into the circulation, but to detect low TSH levels, it is necessary to apply a very sensitive assay. Cytochemical bioassay of TSH has been reported to be of sufficient sensitivity (Bitenskyet al., 1974). However, the assay is not suitable for routine use, and is known to be interfered with by certain non‐specific serum effects (Condliffe&Weintraub, 1979).We have recently reported the development of a highly sensitive enzyme immunoassay (EIA) for TSH which could detect 0.005 mU/l or even less (Inoueet al., 1986). This paper deals with clinical application of the EIA, and discusses the significance of TSH values measured in cases of decreased TSH

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00833.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThe in‐vivo reaction of the plasma GH concentration to the administration of the somatostatin analogue SMS 201‐995, bromocriptine and their combination were compared with the in‐vitro effects of both compounds and their combination on GH release and the GH tumour cell content of 9 acromegalic patients. Exposure of cultured GH‐secreting pituitary tumour cells for 4–96 h to SMS 201‐995 showed a variable, but in all instances during longer incubations statistically significant inhibition of GH release, which paralleled the sensitivity of GH secretion to the drugin vivo.This inhibitory effect on GH release was in two of the eight tumours accompanied by a decrease in the GH tumour cell content after 24‐72 h of culture. These changes either reflect an inhibition of GH synthesis and/or an increase in intracellular breakdown (crinophagy) of GH and might be the basis for the tumour shrinkage which has been observed in about half of the acromegalic patients during long‐term SMS 201‐995 therapy. The inhibitory effects of bromocriptine on GH secretion were antagonized by haloperidol, while the inhibitory effect of SMS 201‐995 was not affected by the dopamine receptor antagonist. This suggests that the effects of SMS 201‐995 and bromocriptine are mediated via separate mechanisms involving different receptors. Additive but no potentiating inhibitory effects of both drugs on GH release were observed in a group of six patientsin vivoand in three o

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00834.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYFour patients with various endocrine deficiences of a predominantly hypothalamic nature are described, in whom computed topographic scans demonstrated pituitary stalk enlargement. In one, a disseminated papular skin eruption with regional pleomorphism and spontaneous regression appeared 4 years after the development of the initial symptoms of diabetes insipidus, and led to a diagnosis of xanthoma disseminatum, a rare type of histiocytosis. It is suggested that this patient's endocrine dysfunction is also due to histiocytic involvement of the hypothalamus and/or pituitary stalk. In view of the prolonged lapse of time between the initial endocrine manifestations and the eventual diagnosis, even though no cause is apparent in the other three patients, it is suggested that close follow‐up be carried out to rule out such a possibility in patients with this endocrine‐radiological ent

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00835.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYCombined therapy with systemic corticosteroids and orbital cobalt radiotherapy has been shown to be an effective treatment of severe Graves' ophthalmopathy. The potentially serious side‐effects of large doses of systemic corticosteroids prompted us to evaluate the use of retrobulbar corticosteroids instead of systemic corticosteroids. Forty‐four patients with active Graves' ophthalmopathy were given orbital cobalt irradiation (total dose 2000 rads) and retrobulbar methylprednisolone acetate (14 bilateral injections at 20‐30 d intervals). The degree of ocular involvement and responses to treatment were evaluated by numerical scoring (ophthalmopathy index, OI) and clinical assessment. Excellent or good responses were observed in 11 out of 44 patients (25%), 24 (55%) showed slight responses, and no change was found in 9 patients (20%). The initial OI mean score was 5‐9; the final score was 3‐2, with a change of ‐ 2.7 (P<0001). Regression or partial improvement was observed in most cases (35/44, 80%) with soft tissue changes, and in all 9 cases with sight loss due to optic neuropathy. Proptosis, corneal lesions and extra‐ocular muscle involvement were less responsive, since regression or partial improvement was observed in 39% (12/31), 50% (8/16) and 31% (13/42), respectively. No major side‐effects were observed. The effects of this type of therapy and those obtained by combined therapy with systemic corticosteroids and orbital radiotherapy were compared in two groups of 30 patients each, randomly assigned to either treatment. The results obtained in the group receiving systemic corticosteroids were more satisfactory both clinically (excellent and good responses being observed in 60% vs 30% of cases) and in terms of changes of the OI (mean decrease 3.5 vs 2.6,P<0.02). In conclusion, the combination of orbital irradiation with retrobulbar corticosteroids may be used in the treatment of severe Graves' ophthalmopathy, but appears to be less effective than orbital irradiation used with systemic corticosteroids. Thus, the use of retrobulbar corticosteroids should be limited to patients with contra‐indications to

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00836.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYIn acromegaly a direct relationship has been demonstrated between GH responsiveness to TRH and to the dopaminergic agent bromocriptine (Br). Recent data show an inverse relationship between GH responsiveness to Br and to GH releasing hormone (GHRH), but not between the GH responses to GHRH and TRH. Thirty‐one acromegalic patients, 18 women and 13 men (age 46‐2 ±(SD) 13 years) were studied. Four patients had been treated, but all still had active disease. The GH responses to GHRH (hpGHRH1‐44Bachem 100 μg i.v. bolus), TRH (Thyroliberin, Hoechst 200 μg i.v. bolus) and Br (Parlodel 5 mg orally) were assessed in most of the patients. The GH responses to GHRH showed a wide interindividual variation (δGH 1‐995 ng/ml), which correlated significantly with the basal GH levels (r=+0.85,P<0.0001,n= 31). GH increments in response to GHRH were inversely related to the responses to Br, i.e. the lower the GH increase after GHRH the greater the GH decrease after Br (r=−0.49,P<0.01,m= 30). This decrease correlated with the basal PRL level (r=+0.45,P<0.02,n= 29) and also the GH response to TRH (r=+0.66,P<0.0001,n= 30). An inverse correlation was also found between the GH responses to TRH and to GHRH (r=−0.43,P<0.02,n= 29). The data are consistent with the existence of GH‐secreting adenomas which are more sensitive to GHRH and less to Br and TRH (pure somatotroph adenomas) and of mixed (lactotroph‐like adenomas) responsive to TRH and Br but less

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00837.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYWe report two female siblings (ages 4 and 9 years) and one 8‐year‐old male with the syndrome of apparent mineralocorticoid excess (AME) presenting with low renin hypertension and hypoaldosteronism. The deficiency of 11β‐hydroxysteroid dehydrogenase results in a defect of the peripheral metabolism of Cortisol (F) to cortisone (E). As a result, the serum Cortisol half‐life (T½) is prolonged, ACTH is suppressed, and serum F is normal. The specific diagnosis of the disorder was made by the decreased ratio of the urinary metabolites of E (tetrahydrocortisone, THE) and F (tetrahydrocortisol, THF). Continuous i.v. hydrocortisone administration caused an increase in blood pressure and decrease in serum potassium demonstrating the abnormal mineralocorticoid activity of Cortisol in these patients. Addition of spironolactone resulted in a decrease in blood pressure, rise in serum potassium and a gradual increase in plasma renin activity. These studies suggest that an abnormality in Cortisol action or metabolism results in Cortisol behaving as a potent mineralocorticoid and causing the syndro

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00838.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYA patient with autoimmune Addison's disease treated with hydrocortisone and fludrocortisone became mineralocorticoid‐deficient whilst taking lithium carbonate for a bipolar illness. During an in‐patient metabolic balance study she required 1.0 mg fludrocortisone daily and dietary sodium supplementation to make plasma renin activity and serum potassium normal, and to abolish postural hypotension. We present data to suggest that lithium carbonate inhibits the action of fludrocortisone on the distal renal tub

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00839.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYAn i.v. bolus injection of 500 μg TRH caused a prompt increase in plasma calcitonin (CT) in two patients with medullary thyroid carcinoma (MTC). In case 1 with a sporadic MTC, plasma CT increased from 0.32 ng/ml to 0.70 ng/ml 2 min after TRH. In the second case with multiple endocrine neoplasia (MEN) type II, plasma CT increased from 0.39 ng/ml to 4.7 ng/ml 2 min after the injection. None of five normal healthy subjects and a patient with thyroid follicular adenocarcinoma had significant changes in plasma CT levels after TRH. Studies with monolayer cultures of MTC cells derived from one patient revealed that TRH stimulated CT release. Incubation of the cells with TRH of 10−6mor 10−5mfor 1 h increased CT concentration in the medium to 140% or 182% of the control level, respectively. Under the same conditions, pentagastin (10−6m) increased CT concentration in the medium to 156%. These results indicate the direct stimulatory effect of TRH on CT secretion in the patients wi

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00840.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThis study represents an international double‐blind collaborative study of abnormal immunoglobulin activity in untreated Graves' disease. Laboratories in two countries participated in a comparison of thyrotrophin binding inhibiting (TBII), thyroid stimulating (TSAb), and growth stimulating (TGI) immunoglobulins with clinical data, including ultrasonically measured thyroid size. The correlation between TGI and thyroid volume (n= 25, Rs= 0.54,P<0‐05) and the fact that 9 of 10 patients with high range TGI values had large goitres establish the relationship between TGI and goitre, confirming that the in‐vitro activity of these antibodies is related to an in‐vivo action. In addition, both TBII and TSAb correlated with serum free T3 indices (TBII:n= 60, Rs= 0.46,P<0.001, and TSAb:n= 60, Rs= 0.64,P<0001). Moreover, both TBII and TSAb correlated with thyroid volume (TBII:n= 60, Rs= 0.37,P<0.01, and TSAb:n= 60, Rs= 0.41,P<0001) suggesting that these antibodies are also important in development of goitre in Graves' disease. Finally, some correlation between the antibodies was observed. TBII correlated with TSAb (n= 60, Rs= 0.47,P<0.001), and in the 16 patients with positive TGI results, this activity correlated with TBII (Rs= 0.54,P<0.05), but not with TSAb. Also some cases were found with corresponding high range TBII and TGI, while negative for TSAb, suggesting a close relationship between the in‐vitro measurement of TSH bindin

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00841.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY

摘要:

SUMMARYThe aim of this study was to evaluate the effect of T4 replacement therapy on plasma insulin‐like growth factor 1 (IGF‐1) levels in patients with primary hypothyroidism to see whether recovery of pituitary GH responsiveness to GRF was associated with increased plasma IGF‐1 levels. IGF‐1 levels and GH responses to GRF (1 μg/kg) were measured in 21 patients with primary hypothyroidism before and after T4 replacement therapy. T4 increased plasma IGF‐1 levels (57.2 ± 4.4 vs 75.9 ± 8‐8 ng/ml, mean ± SEM,P<0.05) and GH responses to GRF as assessed both by peak GH levels (9 ± 1.5 ng/ml before treatment vs 16.7 ± 3 ng/ml after treatment, mean ± SEM,P<0.05) and area under curve (496 ± 92 before treatment vs 896 ± 161 after treatment, mean‐± SEM,P<0.05). Linear regression analysis showed a positive correlation between free T3 and IGF‐1 levels after treatment (r= 0‐37,P<0.05) and a negative relationship between plasma IGF‐1 levels before treatment and a IGF following T4 replacement therapy (r= 0.45,P<0.025). However, no correlation was found between plasma IGF‐1 levels and GH responses to GRF, suggesting that GH responses to GRF are of no predictive value in relation to the recovery of plasma’ IGF‐1 levels following T4 replacem

ISSN:0300-0664    

DOI:10.1111/j.1365-2265.1987.tb00842.x

出版商:Blackwell Publishing Ltd    

年代:1987

数据来源: WILEY