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To examine the hypothesis that glaucoma may be a manifestation of unrecognized hypothyroidism, we studied 25 consecutive patients with newly diagnosed hypothyroidism who presented to an endocrinology clinic. Using tonography and tonometry, we demonstrated a reduction in facility of outflow in the hypothyroid state. With treatment of the hypothyroidism alone there was a statistically significant improvement in facility of outflow, intraocular pressure and Po/C (p0.002). Our results support the hypothesis that secondary open-angle glaucoma may be a manifestation of hypothyroidism and that the glaucoma will resolve on treatment of the primary disease.

Hypothyroidism was diagnosed in a 62-year-old woman with poorly controlled primary open-angle glaucoma, including a disc hemorrhage and a documented arcuate scotoma. After 1 year of thyroxine therapy the glaucoma was easily controlled, pilocarpine treatment was stopped and the visual fields were completely normal. To our knowledge this is the first report in the modern literature of reversal of open-angle glaucoma with treatment of hypothyroidism.

A program designed to achieve normal plasma glucose concentrations before meals was tested in 83 insulin-dependent diabetic women during 110 pregnancies. The women rigidly controlled their carbohydrate intake but not their total energy intake, and twice daily they injected a combination of short-acting (Toronto) and intermediate-acting (NPH or Lente) insulin. Obstetric care was highly individualized and was aimed at avoiding or minimizing the impact of complications, such as hypertension, on the fetus and ensuring fetal lung maturity before delivery. The mean plasma glucose levels before meals (+/- standard error of the mean) were 136 +/- 9, 117 +/- 5 and 101 +/- 2 mg/dl during the first, second and third trimesters respectively. Obstetric complications included hypertensive disease of pregnancy (in 30.0%) and hydramnios (in 16.4%). The mean gestational age (+/- standard deviation [SD]) was 38.1 +/- 1.8 weeks, the cesarean section rate 45.4% and the mean stay in hospital for diabetes control before delivery (+/- SD) 15.7 +/- 9.6 days. The perinatal mortality rate was 0.9%. Neonatal problems included congenital anomalies in 3.6%, somatomegaly in 24.6%, hypoglycemia in 26.5%, hypocalcemia in 17.3% and hyperbilirubinemia in 39.4%. There were nine cases (8.2%) of the respiratory distress syndrome, four (3.6%) of which were severe. These findings lend support to the importance of a policy aimed at achieving normoglycemia and fetal lung maturity before delivery, goals that are attainable without lengthy antenatal hospitalization.

Propranolol alone was used to prepare 20 thyrotoxic patients, 19 women and 1 man, for subtotal thyroidectomy. Serum thyroxine (T4) and triiodothyronine (T3) concentrations were measured immediately before, at several stages during and after the surgical procedure. As judged primarily by the cardiovascular response, an average of 80 mg (range 40 to 120 mg) of propranolol qid for 8 days (range 3 to 18 days) was required to prepare the patients. During the various stages of surgical removal there was no change from the initial mean (+/- SEM) T4 concentration of 25.0 +/- 2.5 microgram/dl (321.8 +/- 32.2 nmol/l) or T3 concentration of 4.2 +/- 0.6 microgram/l (6.45 +/- 0.92 nmol/l) (P greater than 0.2). At discharge on the fifth postoperative day values were significantly lower, 12.9 +/- 1.5 microgram/dl (166.0 +/- 19.3 nmol/l) and 1.9 +/- 0.2 microgram/l (2.9 +/- 0.31 nmol/l), respectively (P less than 0.001). There were no operative complications but four patients had transient hypoparathyroidism. After 1 year 2 of 18 patients had permanent hypoparathyroidism and 4 of the 18 followed up for 1 year had permanent hypothyroidism requiring thyroid hormone replacement. There was no instance of recurrent thyrotoxicosis. The authors conclude that during surgical manipulation of the gland no release of thyroid hormones into the circulation was detected and that, using propranolol as the sole agent, thyrotoxic patients can be rapidly and safely prepared for subtotal thyroidectomy.

The plasmas of four patients with SLE were found to contain two anti-DNA antibody populations of widely varying affinity. The addition of double-stranded DNA to the anti-DNA plasmas resulted in formation of precipitating (insoluble) and soluble immune complexes. Human platelets suspended at physiologic concentrations in the anti-DNA plasmas during the immune complex formation underwent aggregation and release that correlated positively with precipitating (insoluble) immune complex formation but not with soluble complex formation. Preformed insoluble immune complexes induced platelet aggregation and release in a significant linear fashion, and release was inhibited by increasing concentrations of soluble immune complexes or Fc-fragments. The release reaction was completely inhibited by blocking the Fc-pieces of the preformed insoluble DNA-anti-DNA immune complexes. Soluble complexes of DNA-anti-DNA and A-anti-A at equimolar IgG concentrations produced similar degrees of inhibition, which were much greater than equimolar concentrations of Fc-fragments. The ability of increasing concentrations of soluble immune complex formed at fixed antibody concentration to cause greater inhibition of platelet release suggests that occupancy of the antigen binding sites of the antibody increases its ability to block the platelet Fc-receptor. The inhibition is similar for soluble complexes of varying antigen molecular size. This is compatible with the concept that a conformational change in the antibody occurs after antigen binding and results in an increase in binding strength at the platelet Fc-receptor site. We conclude that insoluble DNA-anti-DNA immune complexes induce aggregation and release of human platelets at physiologic concentrations in plasma via the platelet Fc-receptor.

The correlation between the formation of immune complexes and platelet aggregation and release was studied in pig plasma. The pigs were hyperimmunized with a multivalent antigen, horse ferritin. The ability of the antisera to form precipitating (insoluble) and soluble immune complexes was measured and correlated with the concomitant platelet aggregation and release of serotonin and LDH. Aggregation ws measured by aggregometry, differential centrifugation, and electron microscopy, and release by [14C]serotonin and LDH loss. Aggregation correlated with release (r = 0.84, p0.001), but no correlation was found between antibody titer or varying antigen concentrations and platelet [14C]serotonin release. A positive correlation was found between platelet [14C]serotonin release and precipitating immune complexes (r = 0.68, p0.001) and a negative correlation with soluble complexes (r = -0.78, p0.001). Maximal precipitation of insoluble complexes was complete within 30 sec or less, was independent of temperature, and obeyed the laws of mass action and of optimal ratios of antigen and antibody concentrations (equivalence zone). Platelet aggregation and serotonin release in plasma and precipitating immune complex formation were both maximal at antigen-antibody equivalence and undetectable at marked antigen or antibody excess. These results suggest that immune complex precipitation may initiate platelet aggregation and release in plasma and that the reaction may be at least partially blocked by soluble immune complexes.

The effectiveness of combining the subcutaneous administration of short- and intermediate-acting insulin with the intravenous infusion of glucose in maintaining normoglycemia during labour and delivery in insulin-dependent diabetic women was tested. Fifty women were given intermediate-acting insulin twice daily in doses that were fractions of their usual dose, based on the projected duration of labour. In addition, they were given regular (i.e., short-acting) insulin every 6 hours, the dose being 1% of their total daily insulin dose for every increase of 10 mg/dl above 100 mg/dl (5.6 mmol/l) in the plasma glucose level 1 hour previously; the levels were measured every 3 hours. All the patients were fasting and received a basal intravenous infusion of 6 g/h of glucose; the rate of infusion was increased by 1 g/h for every decrease of 10 mg/dl in the plasma glucose level below 100 mg/dl. The mean plasma glucose levels (+/- standard deviation) were 90 +/- 46 mg/dl after 3 hours of labour, 92 +/- 35 mg/dl after 6 hours, 97 +/- 49 mg/dl after 9 hours and 107 +/- 65 mg/dl after 12 hours. With only one exception, in a premature infant, the 5-minute Apgar scores were identical to those of the infants of nondiabetic women.

A program of screening cord blood for evidence of primary neonatal hypothyroidism was implemented in a general hospital. In 13 months 3456 newborns were screened: the thyroxine (T4) and triiodothyronine (T3) concentrations were measured in cord blood samples, and when the T4 level was below 8.0 micrograms/dl thyrotropin was also assayed in the sample. The two-tier program was effective. One hypothyroid newborn was detected and treated. More boys than girls had T4 levels below 8.0 micrograms/dl (9.7% v. 4.7%). The T4 level correlated with birth weight slightly better in the boys (r = 0.28 v. 0.21), and in the boys this correlation was stronger when the birth weight was lower. Regression analysis of the data for 54 sets of twins indicated that the T4 level was more strongly related to gestational age than to birth weight.

We have described the calcium dependence of the IgG Fc receptor (Fc-R) on human platelets by analyzing the direct binding of radiolabelled Fc fragments, monomers and dimers of IgG. Specific binding to platelets was undetectable at 37 degrees C in a calcium-free preparation but readily detected when calcium was restored. Scatchard analysis of the binding data for the calcium-restored platelets permitted calculation of the available Fc-R and the Ka of binding for the different IgG ligands. The mean Ka of binding for 12 normal subjects varied from 10(7) to 10(8) L/M, with an equal receptor number measured by Fc fragments and dimers of IgG, but a lesser amount for monomeric IgG. There was no apparent difference in Fc-R number for platelets from 6 normal male versus 6 normal female subjects. At 4 degrees C binding was detectable for dimers and polymers of IgG in a calcium-free preparation and this was markedly increased with recalcification. Thus, our data are consistent with an Fc receptor population on human platelets whose avidity for binding is significantly enhanced in a calcium-restored medium.

We have evaluated an affinity-chromatographic procedure for determination of glycated albumin (GA) and glycated total serum protein (GSP). Recovery of these analytes was inversely related to free glucose concentration, thus necessitating removal of free glucose. For this we used molecular-exclusion chromatography on G-25 Sephadex, or dialysis, the latter procedure resulting in significantly (p less than 0.05) lower concentrations of GSP and GA. Total protein concentration and percent glycation are also inversely related, and so protein concentrations must be standardized before the assay. Within- and between-run CVs for both GSP and GA were less than 6.5 and 18%, respectively, the determination of GA being generally the more precise of the two. Labile glycated fractions, lipemia, icterus, hemolysis, and type of anticoagulant did not affect the results, but assay temperature did. Diabetic subjects showed substantially higher concentrations of GA and GSP than did normal subjects. Because of the life span of these analytes in circulation, their measurement may provide a short-term index of glycemic control.