Serum Lp(a) lipoprotein concentrations in insulin dependent diabetic patients with microalbuminuria.

OBJECTIVE: To compare the serum concentrations of lipoproteins and apolipoproteins in insulin dependent diabetic patients with and without microalbuminuria. DESIGN: Cross sectional study. SETTING: Paediatric and medical outpatient clinic at a university hospital. PATIENTS: 76 insulin dependent diabetic patients: 41 with microalbuminuria (20 males, 21 females) and 35 controls without microalbuminuria (18 males, 17 females). The two groups were similar with respect to age, duration of disease, and haemoglobin A1c concentrations before the study. MAIN OUTCOME MEASURES: Serum concentrations of Lp(a) lipoprotein, total cholesterol, high density lipoprotein cholesterol, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoproteins A-I, A-II, and B. RESULTS: Median serum Lp(a) lipoprotein concentration was 10.0 mg/100 ml in the microalbuminuric group and 4.9 mg/100 ml in the control group (p = 0.007). 17 (41%) of the microalbuminuric patients and five (14%) of the control patients had Lp(a) lipoprotein values above the upper quartile of a normal population. Median serum triglycerides concentrations in the microalbuminuric and control groups were 1.15 mmol/l and 0.88 mmol/l respectively (p = 0.03). Median very low density lipoprotein cholesterol concentration was 0.52 mmol/l in the microalbuminuric group and 0.40 mmol/l in the control group (p = 0.03). No significant differences in serum concentrations of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, or apolipoproteins A-I, A-II, and B were found between the groups. CONCLUSIONS: Serum concentrations of Lp(a) lipoprotein are twice as high in insulin dependent diabetic patients with microalbuminuria as in those without microalbuminuria. Increased concentrations of Lp(a) lipoprotein might partly explain the increased morbidity and mortality from cardiovascular disease observed among patients with diabetic nephropathy.

In vivo and in vitro inhibition by ketoconazole of ACTH secretion from a human thymic carcinoid tumour.

We treated a patient with an ectopic ACTH-producing thymic carcinoid tumour with ketoconazole. The treatment decreased blood levels of ACTH and cortisol and relieved the patient's symptoms. Tumour explants secreted ACTH to the culture medium for at least 11 days. The tumour cells responded to high extracellular K+ concentration with increased ACTH secretion, whereas the hypothalamic ACTH-releasing hormone (CRH) and cortisol had no effect on ACTH secretion. Addition of ketoconazole to the culture medium decreased ACTH secretion showing that ketoconazole had a direct effect on the tumour cells.

Appropriate replacement dose of thyroxine in primary hypothyroidism.

An ultrasensitive thyrotropin (TSH) assay was used to determine how many of 65 patients with primary hypothyroidism on thyroxine (T4) replacement therapy had suppressed serum TSH. In 13 patients (20%) TSH levels less than or equal to 0.1 mIU/l were found, indicating an overdose of thyroxine. After correction of the dose, 48 patients had normal TSH values. Their mean dose of thyroxine was 119 micrograms/24 hours, and the appropriate replacement dose tended to decline with advancing age. The serum level of thyroid hormones during replacement therapy with thyroxine very imperfectly reflected serum TSH values. It is concluded that overdose of thyroxine is common when suppressed serum TSH is used as an end point. Biochemical follow-up of replacement therapy with thyroxine in primary hypothyroidism therefore requires the use of an ultrasensitive TSH assay in order to detect such suppression. Serum levels of thyroxine or triiodothyronine (T3) during thyroxine therapy are poor indicators of pituitary TSH secretion and are therefore not useful as parameters of adequate thyroxine dosage.

Triiodothyronine (T3) binding to immunoglobulin G subclasses in a slightly hypothyroid woman.

A 44-year-old woman, with an earlier history of myxoedema, had stopped taking thyroxine and was found to have both a slightly elevated basal TSH level and an increased TSH response after thyroliberin stimulation. The T4 value was low borderline, and using a radioimmunoassay that separated free and antibody-bound hormone by polyethylene glycol precipitation, the T3 value was found to be less than zero. This last finding was explained by the existence of T3 antibodies in the patient's serum. The antibodies, being of the IgG class, did not bind T4, thyroglobulin or cytoplasmic thyroid antigen. The subclass IgG2, and to a lesser extent IgG1, IgG3 and IgG4, did bind T3. A Scatchard plot gave an antibody avidity constant of 4.28 x 10(8) l/mol and a binding site concentration of 3.8 x 10(-9) mol/l. Radioimmunoassay of total T3, after extraction with ethanol gave a high value. The concentration of free T3 was, however, just above the lower reference limit.