Abstract. Twenty‐one patients with increased, thyroid‐stimulating‐hormone (TSH) concentrations in the serum while fasting were studied before and after substitution with l‐thyroxine. Nine patients had TSH values < 40 mU/1 and an average serum‐thyroxine value of 64 nmol/1. Twelve patients with TSH‐values > 40 mU/1 had an average serum‐thyroxine value of 23 nmol/1. On treatment TSH and thyroxine normalized (reference limits < 8 mU/1 and 65–160 nmol/1 respectively) as did also the response to a load with thyroid‐releasing hormone (TRH). In the group with severe thyroid dysfunction (TSH > 40 mU/1) the lipoprotein‐lipase activities in both adipose and skeletal‐muscle tissue were subnormal before therapy and increased during substitution treatment. This was also reflected in a significant increase of the post‐heparin, lipoprotein‐lipase activity in the plasma and of the fractional removal rate of an i.v. injected fat emulsion. Ten out of twelve patients showed a decrease of the triglyceride concentration in whole serum, which reflected changes of the triglyceride concentrations in low‐density lipoproteins (LDL) and high‐density lipoproteins (HDL) more than changes in very‐low‐density lipoproteins, in which the triglyceride concentration was unchanged during treatment. In LDL, both the cholesterol and triglyceride concentrations were elevated before therapy and decreased by 22% and 32% of the pretreatment values, respectively, during treatment. Furthermore, the serum‐apolipoprotein‐B concentration decreased by 16%. The serum‐apolipoprotein‐A‐I concentration was subnormal before treatment and the lipid composition of the HDL particle was changed towards an enrichment of triglycerides. During treatment, the HDL‐triglyceride concentration decreased, whereas that of HDL cholesterol was unchanged. The fasting serum‐insulin concentration increased significantly during the treatment period. In the group with mild hypothyroidism (TSH < 40 mU/1), there were no significant changes similar to those found in severe hypothyroidism.

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Chromogranin A is a well-known protein constituent in granules of neuroendocrine cells. It is also known that plasma levels of chromogranin A increase considerably in patients with neuroendocrine tumours and thus chromogranin A is used as a marker for these tumours. In the present study, we have shown that fragments of chromogranin A are excreted into the urine in some patients with carcinoid tumours. The chromogranin A molecule appeared in the urine N-terminally cleaved at amino acid positions 116 and 210, which are previously reported cleavage sites of the molecule. The fragments identified were mainly of about 35 kDa in size. The unprocessed chromogranin A molecule was not excreted in the urine. Five out of 40 patients excreting the fragments had slight tubular dysfunction in the kidneys. We also showed that these renally excreted split products of chromogranin A were immunogenic and could be used for production of antibodies against chromogranin A. These antibodies were used both for immunocytochemistry and for the development of a specific and sensitive radioimmunoassay for chromogranin A and its fragments. Measurements of plasma chromogranin A by radioimmunoassay appeared to be a better marker for tumour growth than were measurements of chromogranin A in the urine.

Tissue samples were taken from the gastrocnemius muscle of 26 randomly selected, glucose-tolerant, 48-yr-old men. Hexokinase, phosphorylase, lactate dehydrogenase (LDH), succinate dehydrogenase, and lipoprotein lipase activity (LPLA), as well as the area per fiber type and capillary density, were determined. Mean fiber area correlated positively with relative body weight (r equals 0.53, P less than 0.01), but capillary density did not. The result is that, in cases of high body weight, each capillary supplies a larger muscle fiber area. Serum insulin concentration in the fasting state correlated positively with body weight (r equals 0.77, P less than 0.001) and with mean fiber area per capillary (r equals 0.87; P less than 0.001). Only during the latter part of an oral glucose tolerance test (OGTT) did blood glucose concentrations correlate with relative body weight and mean fiber area per capillary (r equals 0.42, r equals 0.51, P less than 0.05). A stepwise multiple regression analysis showed that the different muscle morphology measurements could account for 3/4 of the variation in the fasting serum insulin concentration, the fasting insulin/glucose ratio, and the blood glucose concentration at 120 min in the OGTT. Of the intracellular enzymes, only LDH (r equals -0.71, P less than 0.001) correlated with the mean fiber area per capillary. LPLA correlated with capillary density (r equals 0.66, P less than 0.001), and, long with the muscle morphology measurements, could account for 3/4 of the variation in serum triglyceride concentrations. The results show that a large mean muscle fiber area/capillary ratio indicates a morphologic imbalance, which is related to both glucose tolerance and various degrees of insulin sensitivity.

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