E. G. Black

Relation between serum interleukin‐6 and thyroid hormone concentrations in 270 hospital in‐patients with non‐thyroidal illness

OBJECTIVES Non‐thyroidal illness (NTI) is frequently accompanied by alterations in circulating thyroid hormone concentrations, despite patients remaining clinically euthyroid. The mechanisms accounting for these changes in circulating thyroid hormone concentrations remain unknown. Much attention has focussed on the role of inflammatory cytokines which are known to be important mediators of disease. The aim of this study was to investigate the role of the cytokine interleukin‐6 (IL‐6) in alterations of thyroid hormone metabolism seen in NTI.

The inter-relationship of thyroid hormones, vitamin A and their binding proteins following acute stress.

The effects of surgical stress on the metabolism of the retinol‐binding‐protein‐thyroxine‐binding‐prealbumin complex were investigated. The immediate post‐surgical period was characterized by a rapid decline in the serum concentration of retinol, retinol binding protein and triiodothyronine and an increase in the 24 h urinary excretion of retinol, retinol‐binding‐protein and thyroxine. Similar, but less pronounced, changes were seen in other subjects suffering acute myocardial infarction but were not observed in normal healthy euthyroid males or in pre‐operative euthyroid patients. The preparation of specific anti‐retinol binding protein anti‐serum and the use of this in ‘monorocket’ immunoelectrophoresis are also described.

SERIAL SERUM THYROGLOBULIN MEASUREMENTS IN THE MANAGEMENT OF DIFFERENTIATED THYROID CARCINOMA

Serum thyreoglobulin (Tg) was measured on repeated occasions in 416 patients with differentiated thyroid cancer for up to 7 years after initial therapy. All patients had thyroidectomy and/or ablative 131I therapy and all measurements were done while patients were receiving T4 replacement. Tg was measured using a double‐antibody radioimmunoassay. Overall correlation between serum Tg concentration and presence or absence of cancer was 95‐9%. At the time of initial measurement 295 patients had serum Tg <5 μg/1, and in the latest analysis only 1‐7% of these patients showed evidence of disease. Initially there were 19 patients of a total of 121 with serum Tg > 5 μg/l in whom no cancer was apparent. In eight of these 19 subjects recurrent or metastatic disease has been diagnosed up to 3‐5 years after the first measurement indicating that in these cases serum Tg values were ‘predictive’. Serum Tg appears to be a sensitive and specific means of detecting residual, recurrent or metastatic thyroid cancer and in most situations can replace routine, expensive and inconvenient radioactive thyroid scans; these should be performed when serum Tg values are elevated or when there is clinical evidence suggesting recurrence.

SHOULD ONE MEASURE SERUM THYROGLOBULIN IN THE PRESENCE OF ANTI-THYROGLOBULIN ANTIBODIES?

Thyroglobulin auto‐antibodies (anti‐Tg) may affect measurement of serum thyroglobulin (Tg). We have assayed sera for Tg by RIA regardless of presence or absence of anti‐Tg, and this study was designed to assess the influence of anti‐Tg on the results. Binding of human anti‐Tg by the second antibody in our RIA (sheep anti‐rabbit immunoglobulin) is very low and sera containing anti‐Tg of varying titres do not systematically affect assay of Tg regardless of concentration. In our follow‐up study of patients with thyroid cancer, correlation between clinical state and Tg concentration is greater than 97% whether anti‐Tg is present or absent. These results indicate that in our assay anti‐Tg positive sera do not need to be excluded.

Glycosylation of human thyroglobulin and characterization by lectin affinity electrophoresis

Thyroglobulin, a 660 kDa glycoprotein, is the major product of protein synthesis in the thyroid gland. It has been suggested that modifications of thyroglobulin glycosylation occur in various thyroid disorders. In order to study possible changes in glycosylation of tissue thyroglobulin associated with thyroid disease, we have developed a lectin affinity electrophoresis system which allows characterization of small (less than 1 microgram) quantities of thyroglobulin. Human thyroglobulin was extracted and purified. Agarose gels were cast containing concanavalin A, Ricinus communis agglutinin, L-phytohaemagglutinin and pokeweed mitogen at various concentrations. Purified human thyroglobulin was serially diluted, loaded onto lectin gels and electrophoresed. Concanavalin A, R. communis agglutinin and phytohaemagglutinin all bound thyroglobulin in a concentration-dependent manner. Pokeweed mitogen did not bind thyroglobulin. Purified thyroglobulin was treated with neuraminidase and endoglycosidase H. Two-dimensional immunoelectrophoresis revealed the migration of thyroglobulin to be modified by neuraminidase but not by endoglycosidase H. Lectin affinity electrophoresis of purified human thyroglobulin with and without enzyme treatment indicated the presence of: oligomannose structures as shown by concanavalin A reactivity and modification by endoglycosidase H, and complex oligosaccharides as shown by affinity for R. communis agglutinin and modification by neuraminidase. These structures are in keeping with the proposed patterns of glycosylation of human thyroglobulin and indicate suitability of the method for characterizing the glycosylation of small quantities of thyroglobulin.