Reduced trypsin binding capacity of alpha 2-macroglobulin in diabetes.

The plasma proteinase inhibitor, alpha 2-macroglobulin, is usually elevated in diabetes. The trypsin binding capacity and the concentration of alpha 2-macroglobulin in 90 diabetics sera were compared with 30 age- and sex-matched normal sera. The mean alpha 2-macroglobulin concentration determined by radial immunodiffusion was 313 mg/dl for the diabetics as compared to 240 mg/dl for the healthy subjects (significantly higher, p less than 0.01). The mean of the ratio, mol trypsin bound/mol alpha 2-macroglobulin (molar binding ratio) for the Type I diabetics (n = 54), 0.82, was significantly lower than the mean of the healthy subjects, 0.87, or the mean of the Type II diabetics, 0.87. No relationship between the molar binding ratios and the levels of glycosylated hemoglobin was found. The alpha 2-macroglobulin was isolated from the plasma of 11 Type I diabetics and 7 normals. The maximum molar trypsin binding capacities of the diabetic alpha 2-macroglobulin were significantly lower. The mean for the diabetic alpha 2-macroglobulin was 1.72 vs. 1.97 for the normal alpha 2-macroglobulin. These results indicate that the trypsin binding function of alpha 2-macroglobulin is moderately impaired in diabetes. No differences were found in the extent of proteolytic cleavage of the 'bait region' of diabetic alpha 2-macroglobulin, autolytic cleavage or the methylamine reaction at the thiolester site between diabetic and normal alpha 2-macroglobulin. Nonenzymatic glucosylation of normal alpha 2-macroglobulin did not lower the trypsin binding capacity. The nature of the modification of alpha 2-macroglobulin leading to reduced trypsin binding capacity or the physiological significance is not yet known.

Treatment of lymphocytic thyroiditis with spontaneously resolving hyperthyroidism (silent thyroiditis).

The duration of the hyperthyroidism associated with lymphocytic thyroiditis (LT) with spontaneously resolving hyperthyroidism (SRH) was serially monitored in groups of patients who were not given any treatment (control subjects) or treated with propylthiouracil and/or propranolol hydrochloride and prednisone. The length of time for the thyroxine tests from diagnosis to the normal range was 57 +/- 17, 45 +/- 13, and 15 +/- 7 days (mean +/- SD) indicating a dramatic response to prednisone therapy but none to propylthiouracil and/or propranolol therapy. Five patients were found who had seven episodes of SRH while receiving thyroid hormone suppression therapy after having verified chronic LT (two patients) and LT-SRH (three patients). This indicates that thyroid suppression with thyroid hormone may be ineffective in preventing this disease. Two patients were treated by subtotal thyroidectomy because of recurrent or prolonged episodes of SRH. From this experience, the therapeutic alternatives available to the clinician are reviewed.

Lymphocytic thyroiditis with spontaneously resolving hyperthyroidism and subacute thyroiditis. Long-term follow-up.

In a one- to 15-year follow-up of 124 patients with a history of subacute thyroiditis (SAT) without and with spontaneously resolving hyperthyroidism (SRH) (SAT and SAT-SRH, respectively), only three cases of thyroid disease probably unrelated to the original episode of thyroiditis were found. However, of the 54 patients with a history of lymphocytic thyroiditis (LT) with SRH (LT-SRH), 26 patients were found to have thyroid disease (three with hypothyroidism and 23 with goiters). Antithyroid antibodies were found to be present in 32% (8/25) of the LT-SRH group and in less than 10% (5/60) of the other three groups. The basal thyroid-stimulating hormone levels were substantially increased in the LT-SRH group only, and the response of thyroid-stimulating hormone to 200 microgram of protirelin was augmented in both SAT-SRH and LT-SRH groups. These findings demonstrate that SAT and SAT-SRH are transient thyroid disease rarely leading to permanent thyroid disease, although some loss of thyroid reserve may occur. However, LT-SRH is a persistent progressive disease similar to or the same as chronic LT, in which goiter formation and thyroid failure are a natural course.

Twelve-hour cycles of adrenocorticotropin and cortisol secretion in Cushing's disease.

A 50-yr-old woman presented with a 7-yr history of Cushing's syndrome. She had high urinary free cortisol levels (711 micrograms/day) and a positive response to metyrapone and suppression with 8 mg dexamethasone, suggesting pituitary ACTH-dependent adrenocortical hyperfunction. Plasma cortisol and ACTH levels showed marked temporal variation. Samples obtained at 2-h intervals revealed that plasma ACTH and cortisol levels surged during periods lasting approximately 12 h and fell to levels below normal during the remainder of the 24-h cycle. When urinary free cortisol was measured in urines collected in 12-h aliquots, the corresponding surge in free cortisol excretion was also evident. These cycles were not affected by a 2.5-month course of cyproheptadine. Pituitary irradiation and mitotane therapy resulted in remission of Cushing's syndrome, with disappearance of the peaks of ACTH and cortisol secretion. This case represents an unusual example of the abnormal circadian rhythm of ACTH secretion on Cushing's disease.

Suppression of insulin secretion by protein deprivation in obesity.

1) Protein restricted diets decrease basal plasma insulin levels in obesity. 2) This effect occurs even in the presence of sufficient calories to maintain body weight and while the diet is high in carbohydrate. 3) The decrease in insulin is accompanied by a fall in plasma glucose and in the I/G ratio, suggesting an increase in insulin sensitivity. 4) Excessive protein intake, in addition to carbohydrate, may play a role in the pathogenesis of the hyperinsulinemia and insulin resistance found in obesity.