Severity of alcoholic liver disease and markers of thyroid and steroid status.

Alcoholic liver disease is associated with abnormalities in circulating levels of thyroid, adrenal and gonadal steroid hormones. The relative importance of ethanol consumption and severity of liver disease in the aetiology of these changes and their relationship to clinical abnormalities are unclear. We studied 31 subjects with alcohol-induced liver disease divided into three groups according to the severity of histological features: fatty change, hepatitis and cirrhosis.

HLA class II gene polymorphism contributes little to Hashimoto's thyroiditis.

Unlabelled: Previous studies of HLA and Hashimoto's thyroiditis have shown weak associations between the disease and various HLA-DR antigens.

Objective: To define better the contribution of HLA class II alleles to susceptibility to Hashimoto's thyroiditis.

Design And Measurements: Comparison of HLA-DRB, DQA and DQB restriction fragment length polymorphisms in patients with Hashimoto's thyroiditis and control subjects, and meta-analysis of this and other published studies.

Long-term thyroxine treatment and bone mineral density.

Studies of the effect of thyroxine replacement therapy on bone mineral density have given conflicting results; the reductions in bone mass reported by some have prompted recommendations that prescribed doses of thyroxine should be reduced. We have examined the effect of long-term thyroxine treatment in a large homogeneous group of patients; all had undergone thyroidectomy for differentiated thyroid cancer but had no history of other thyroid disorders. The 49 patients were matched with controls for age, sex, menopausal status, body mass index, smoking history, and calcium intake score; in all subjects bone mineral density at several femoral and vertebral sites was measured by dual-energy X-ray absorptiometry.

The thyroid and osteoporosis.

Increasingly sophisticated tests of thyroid function have indicated that minor degrees of hyperthyroidism are common, especially in patients taking thyroxine (T(4)) therapy. Several recent reports have suggested that such patients have reduced bone density as a consequence of their hyperthyroidism. Further studies are required to determine whether these changes are found in all age groups and both sexes and whether they are clinically relevant in terms of risk of osteoporotic fractures.

The significance of TSH values measured in a sensitive assay in the follow-up of hyperthyroid patients treated with radioiodine.

Use of sensitive assays for TSH in the follow-up of patients treated with radioiodine (131I) for thyrotoxicosis has led to questions regarding the significance of abnormal TSH values found in association with normal circulating thyroid hormone levels, especially TSH results below normal. We have investigated the relationship between serum TSH and the likelihood of maintenance of euthyroidism, as well as the relationship between serum TSH and free T4, in 389 subjects treated with 131I 2-35 years previously who had free T4 and free T3 values within the normal range and who were not receiving thyroxine or antithyroid therapy. In those with undetectable TSH (less than 0.

Tissue localization of 11 beta-hydroxysteroid dehydrogenase and its relationship to the glucocorticoid receptor.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) dictates specificity for the mineralocorticoid receptor (MR) by converting the active steroid cortisol to cortisone in man (corticosterone to 11-dehydrocorticosterone in rodents), leaving aldosterone to occupy the MR. However cortisol is the principal circulating glucocorticoid in man and 11 beta-HSD, distributed in a tissue specific fashion, may represent a powerful mechanism in regulating exposure of active steroid to the glucocorticoid receptor (GR). A detailed localization study of 11 beta-HSD gene expression and activity in numerous rat tissues has been performed and compared with the presence of GR mRNA.

Thyroid hormone regulation of human pituitary alpha subunit gene expression.

The thyroid hormone T3 exerts an inhibitory effect upon pre-translational expression of the alpha subunit gene in the anterior pituitary. In the intact animal oestrogen alone is without effect upon alpha gene expression but oestrogen modulates the influence of T3 deficiency upon the alpha gene. T3 effects upon alpha transcription are mediated via sequences within 98 bp of the transcriptional start site of the gene and similar 5' flanking sequences of the alpha gene mediate both T3 regulation and oestrogen modulation of T3 inhibition.

Assessment of a screening process to detect patients aged 60 years and over at high risk of hypothyroidism.

General practitioners are increasingly expected to screen elderly patients for common disorders, such as hypothyroidism, and the identification of at-risk patients by simple means would reduce the financial and other costs of such screening. A general practice based study of 1193 patients aged 60 years and over has been carried out to investigate the usefulness of the following factors in identifying those in whom biochemical testing for hypothyroidism would be indicated: personal history or family history of thyroid disease, symptoms of thyroid disease and body mass index. Of the 190 patients with either a personal or family history of thyroid disease, 28 (14.

Thyroid hormone and glucocorticoid regulation of receptor and target gene mRNAs in pituitary GH3 cells.

We have examined the effects of triiodothyronine (T3), in dose-response and time-course studies, on T3 receptor (T3R) alpha and beta and glucocorticoid receptor (GR) mRNAs in rate pituitary GH3 cells, in parallel with T3 actions on expression of the growth hormone (GH) target gene. Modulatory influences of dexamethasone (dex) on T3 action were studied by treatment with dex before and during T3 treatment. T3 treatment (1-100 nM) for 24 h reduced T3R alpha mRNA, while the presence of dex (1 microM) enhanced the T3 effect on T3R alpha mRNA and induced T3 inhibition of T3R beta mRNA.

Regulation by thyroid status of c-myc, c-fos and H-ras mRNAs in the rat myocardium.

Effects of thyroid status on expression of a variety of myocardial genes, such as those encoding contractile proteins, have been reported, as well as interactions between thyroid hormones and developmental and haemodynamic regulation of contractile protein synthesis. In addition, it is clear that developmental and haemodynamic factors regulate expression of specific proto-oncogenes, including c-myc, c-fos and H-ras, in the myocardium but the effect of thyroid status on such proto-oncogene products, which are proposed to play a critical signal-transducing role in the heart, has been previously unexplored. In order to determine whether changes in thyroid status are associated with changes in expression of these putative intracellular signals, we examined the effect of hypothyroidism and tri-iodothyronine (T3) treatment on myocardial levels of c-myc, c-fos and H-ras mRNAs in the rat.

Localization of renal 11 beta-dehydrogenase by in situ hybridization: autocrine not paracrine protector of the mineralocorticoid receptor.

In the kidney, 11 beta-dehydrogenase (11 beta-DH) converts the active steroid cortisol to inactive cortisone (corticosterone to 11-dehydrocorticosterone in the rat). In man, congenital and acquired deficiency of 11 beta-dehydrogenase are rare causes of hypertension in which cortisol acts as a potent mineralocorticoid. Observations from these clinical studies indicate that 11 beta-DH conveys specificity for the mineralocorticoid receptor in distal tubules and collecting ducts.

Prevalence and follow-up of abnormal thyrotrophin (TSH) concentrations in the elderly in the United Kingdom.

Increasing use of assays for TSH with improved sensitivity as a first-line test of thyroid function has raised questions regarding prevalence and clinical significance of abnormal results, especially values below normal. We have assessed the thyroid status of 1210 patients aged over 60 registered with a single general practice by measurement of serum TSH using a sensitive assay. High TSH values were more common in females (11.

Long-term follow-up of treatment of thyrotoxicosis by three different methods.

In view of continuing debate regarding the best definitive therapy for thyrotoxicosis, we examined the long-term outcome of radioiodine (131I) or surgical treatment of 1918 thyrotoxic patients divided into three groups: those given 131I at a dose calculated from thyroid size, 131I uptake and effective half-life to administer a fixed radioactivity dose to the thyroid; those treated with a dose of 131I (110, 185 or 370 MBq) chosen empirically; and those treated by partial thyroidectomy. A minimum 10-year follow-up was achieved for 1119 patients treated with a calculated 131I dose; a single dose resulted in control of disease in 90.5%.

The effects of drugs on tests of thyroid function.

Many drugs affect tests of thyroid function through alterations in the synthesis, transport and metabolism of thyroid hormones, as well as via influences on thyrotrophin (TSH) synthesis and secretion. Despite effects on circulating thyroid hormone and TSH levels, few drugs result in important changes in clinical thyroid state, but difficulty in interpretation of thyroid function tests often results. Commonly prescribed drugs including anti-convulsants, non-steroidal anti-inflammatory drugs, beta-adrenoceptor antagonists, steroid hormones and heparin may result in abnormal thyroid function tests in the absence of clinical features of thyroid dysfunction.

Regulation of alpha and thyrotrophin-beta subunit mRNA levels by androgens in the female rat.

Thyroid and steroid hormones act by similar mechanisms to influence gene expression in the anterior pituitary gland. The genes encoding the common alpha and TSH-beta glycoprotein subunits are known to be regulated by thyroid hormones; we report here the effects of androgen administration on levels of alpha and TSH-beta mRNA in pituitary cytoplasm in the euthyroid and hypothyroid female rat. Dihydrotestosterone (DHT) suppressed both alpha and TSH-beta mRNAs to levels lower than those found in untreated animals; a similar reduction was seen in hypothyroid animals treated with DHT.

Multiple DNA elements determine basal and thyroid hormone regulated expression of the human glycoprotein alpha subunit gene in pituitary cells.

Basal and thyroid hormone-regulated expression of constructs containing varying lengths of 5' flanking sequence of the human glycoprotein hormone alpha subunit gene ligated to the reporter gene encoding chloramphenicol acetyl transferase (CAT) were examined in transfected pituitary GH3 cells. CAT gene expression was quantified by measurement of CAT enzyme activity. In addition, an RNase protection assay was used to confirm changes in CAT mRNA levels and to verify regulation of transcription from the authentic alpha gene start site.

Insulin autoantibodies in Graves' disease--before and after carbimazole therapy.

Insulin autoantibodies (IAA) are well documented in patients with insulin-dependent diabetes (IDDM) prior to the administration of insulin and in patients with reactive hypoglycaemia--the insulin autoimmune syndrome (IAS). It has been suggested that IAA can be induced by the administration of drugs containing sulphydryl groups, such as carbimazole, and they have been frequently described in Graves' disease. An alternative explanation is the clustering of autoantibodies in autoimmune disease.

Thyroid hormone receptor expression in the "sick euthyroid" syndrome.

To explore the hypothesis that alteration of T3 receptor expression may be an important mechanism controlling the tissue effects of thyroid hormones in the "sick euthyroid" syndrome, specific triiodothyronine (T3) receptor mRNAs were measured in tissues from normal subjects and from patients with liver disease, chronic renal failure, or with multiple organ failure on an intensive care unit (ICU). In all patient groups circulating free thyroxine and free T3 were reduced, while thyroid stimulating hormone remained normal. In patients with liver or renal disease, there were significant increases in levels of both alpha and beta T3 receptor mRNAs in peripheral mononuclear cells (PMNCs); in ICU patients there was a significant increase in beta mRNA.

Thyroid and steroid hormone regulation of proto-oncogene expression.

In contrast to the established effects of peptide growth factors on specific proto-oncogene expression, the actions of steroid and thyroid hormones are less clearly defined. However, there is increasing evidence that these hormones, acting through structurally related DNA-binding nuclear receptor proteins, influence proto-oncogene expression. This influence may determine the function of steroid and thyroid hormones in regulation of cell proliferation and maturation, and provide insight into the role of these hormones in oncogenesis.