William L. Green

Separation of iodo compounds in serum by chromatography on Sephadex columns

Abstract The migration of iodothyronines through Sephadex columns is greatly influenced by the pH and ionic strength of the eluents. By controlling these variables, a method has been developed for separating the iodo compounds of serum into four discrete fractions: iodoprotein, iodide, triiodothyronine and thyroxine, during a single passage through a column of Sephadex G-25. The method is relatively rapid (less than 3 h per column run), and cam be employed with large samples of serum. Recovery of labeled iodothyronines added to serum is essentially complete. Chromatography of purified labeled compounds showed less than 0.2% deiodination; no conversion of thyroxine to triiodothyronine during the procedure could be demonstrated.

Thyroid function and lipids in patients with chronic renal disease treated by hemodialysis: With comments on the “free thyroxine index”

Abstract It is known that hypertriglyceridemia and abnormal thyroid function tests are common in patients with chronic renal disease treated by hemodialysis, but a possible association between these abnormalities has not been investigated. We measured serum thyroid hormone and lipid levels in one hundred patients receiving chronic hemodialysis. There were ten patients with elevations in serum thyrotropin (TSH). In the remaining patients with normal TSH, those receiving no drugs known to affect thyroid function had low mean values for thyroxine (T 4 ) and triiodothyronine (T 3 ), while the mean T 3 resin uptake (fraction of T 3 bound to resin, T 3 U) was normal, resulting in low mean values for free T 4 index (FT 4 I = T 4 × T 3 U) and free T 3 index (FT 3 I = T 3 × T 3 U). The depression in T 3 was greater than the depression in T 4 , so that T 3 T 4 ratios were also low. Androgen-treated male patients had the lowest T 3 and T 4 levels; their T 3 Us were high, presumably reflecting androgen-induced depression of T 4 -binding globulin, but their mean FT 4 I and FT 3 I were still lower than those of the other patients. Evidence is presented that the conventional T 3 U underestimates the proportion of free hormone when binding protein levels are low, and that a “new T 3 U,” the ratio of resin-bound T 3 to serum protein-bound T 3 , more accurately reflects the proportion of free hormone. Computing a “new FT 4 I,” as new T 3 U × T 4 , yielded values in the androgen-treated group similar to those of the other patients. Patients receiving propranolol had lower T 3 T 4 ratios than the other patients, presumably due to propranolols inhibitory effect on peripheral conversion of T 4 to T 3 . No relationship was found between indexes of thyroid function and lipid levels. Subjects with high TSH levels had levels of triglyceride and cholesterol similar to the remaining patients. Among those with normal TSH levels, low levels of T 3 or T 4 did not correlate with abnormal lipid levels. It is concluded that thyroid hormone abnormalities do not explain the hypertriglyceridemia of patients on chronic hemodialysis. The frequency of low T 4 and T 3 values in such patients, in the absence of clinical evidence of hypothyroidism and, in most instances, in the absence of TSH hypersecretion, remains unexplained.

Interactions of iron deficiency, anemia, and thyroid hormone levels in the response of rats to cold exposure

We have earlier shown that iron-deficient rats have increased urinary norepinephrine (NE) excretion. They also have an exaggerated rise in urinary NE when placed in the cold, a stimulus known to cause increased NE excretion in normal rats. Nonetheless, they fall to maintain body temperature. We have now examined the thyroidal response to cold in iron-deficient rats. As others have shown, control rats had a rise in plasma levels of thyroxine (T4) and triiodothyronine (T3) soon after entering the cold environment (4 degree C); they also maintained a rectal temperature above 36 degree C. In the iron-deficient rats, basal levels of T3 and T4 were normal, but there was little or no increase after 6 hr in the cold, and, as before, body temperatures fell. Injections of T3, 10 microgram/kg, 15 min before cold exposure improved the ability of iron-deficient rats to maintain body temperature, but they still did not do as well as the controls. We conclude that the inability of iron-deficient rats to increase T3 levels after cold exposure is one factor in their poor resistance to cold. The defect could involve inability to augment thyroid secretion, imparied ability to convert T4 to T3 in peripheral tissues, or both. Preliminary data suggest that anemia is an important and perhaps critical factor in the cold sensitivity of iron deficiency. Transfusing iron-deficient rats from their usual hematocrit of 15-20 to one of 30 restores cold resistance to normal. Transfusion also allows a more normal thyroid response, with a rise in T3 and T4 levels, so thyroid hormones may be a factor in the improvement produced by transfusion.

Sudden infant death syndrome and hypertriiodothyroninemia: comparison of neonatal and postmortem measurements.

Serum triiodothyronine concentrations in victims of sudden infant death syndrome, when compared with those of both living and dead controls, were found to be elevated to a degree comparable to those found in a previous study. Thyroxine, thyroid-stimulating hormone, and thyroglobulin values were not elevated. Neonatal triiodothyronine and thyroxine values, determined on specimens collected within a few days of birth for most of the sudden infant death syndrome victims, did not differ significantly from those of comparable peers in their birth cohort. These results indicate that hypertriiodothyroninemia may serve as a useful postmortem diagnostic marker for the syndrome but not as a premortem predictor. Parenthetically, thyroid hormones appear to remain stable in either a frozen or dried state for up to two years.

Thyrotropin levels in hyperlipidemic survivors of myocardial infarction

In an earlier investigations, the prevalence of hyperlipidemia in a group of patients who survived myocardial infarction was determined, and family studies were performed to allow genetic classification of patients with hyperlipidemia. Radioimmunoassay for thyrotropin (TSH) has now been performed on plasmas from most of these hyperlipidemic survivors. Elevated TSH values were found in five of the 18 hyperlipidemic women over age 60, and in seven of the remaining 104 hyperlipidemic subjects. Among the various genetically defined types of hyperlipidemia, the highest prevalence of TSH elevations was seen in women with sporadic (nonfamilial) hypertriglyceridemia; four of the ten had an abnormal TSH level, and two of the remainder were receiving thyroid medication. Hypercholesterolemia was not strongly correlated with TSH abnormalities. These data support the hypothesis that clinically inapparent thyroid damage may be associated with coronary artery disease.

Hypothermia and Adrenocortical Function

Excerpt To the editor: In his review of hypothermia in the October 1978 issue, Reuler (1) includes a diagram that suggests cold exposure stimulates the pituitary gland, which in turn stimulates sec...

A model of sustained activation of the symphatetic nervous system (SNS) using anterior hypothalamic cooling in the baboon

Abstract A model has been developed to simulate central activation of the sympathetic nervous system (SNS) in unanesthetized baboons. By continuously cooling the preoptic anterior hypothalamus with an implanted thermode, a chronic heat production response is generated. In the primate, SNS activation is a major feature of the response to cold stress. During central cooling, oxygen consumption and catecholamine excretion doubled. These responses have been sustained for 30 days. Metabolic and endocrine changes accompanying chronic SNS activation include (1) an early period of basal hyperinsulinemia followed by restoration of normal insulin sensitivity, (2) an unexpected maintenance of normal (or even increased) responsiveness to isoproterenol (heart rate, insulin secretion and lipolysis, (3) increased glucagon levels throughout, (4) a persistent and progressive fall in T3 without change in T4 which was not explained by decreased food intake since this did not diminish, and weight was maintained. The model may prove useful in characterizing the adaptations and maladaptations which accompany sustained increases in central SNS activity in primates.

A Homogeneous Time-Resolved Fluorescence Immunoassay Method for the Measurement of Compound W

Objective: Using compound W (a 3,3′-diiodothyronine sulfate [T2S] immuno-crossreactive material)-specific polyclonal antibodies and homogeneous time-resolved fluorescence immunoassay assay techniques (AlphaLISA) to establish an indirect competitive compound W (ICW) quantitative detection method. Method: Photosensitive particles (donor beads) coated with compound W or T2S and rabbit anti-W antibody were incubated with biotinylated goat anti-rabbit antibody. This constitutes a detection system with streptavidin-coated acceptor particle. We have optimized the test conditions and evaluated the detection performance. Results: The sensitivity of the method was 5u2009pg/mL, and the detection range was 5 to 10u2009000u2009pg/mL. The intra-assay coefficient of variation averages <10% with stable reproducibility. Conclusions: The ICW-AlphaLISA shows good stability and high sensitivity and can measure a wide range of compound W levels in extracts of maternal serum samples. This may have clinical application to screen congenital hypothyroidism in utero.