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Biomedical subjects

L Wartofsky

Publications and source records attributed to L Wartofsky.

At least 127 records · Page 7Linked to original sources
PubMed1980

Thyroid hormone homeostasis in states of relative caloric deprivation.

Starvation is accomplished by significant changes in the hypothalamic-pituitary-thyroid axis and in peripheral thyroid hormone metabolism. Less well studied, however, are the effects on thyroid hormone economy produced by hypocaloric feeding. We explored these changes in obese patients fed 200, 400, or 600 cal/day of either carbohydrate of protein for 28 days. T4' T3' reverse T3 and the TSH response to TRH were measured at frequent intervals. Each patient demonstrated a transient rise in reverse T3 and a fall in T2 that returned to near basal levels by the end of the study period. The TSH response to TRH on the other hand, declined to approximately 50% of control values and remained at that level throughout the course of study, regardless of the type of substrate or calorie level chosen. The results indicated that hypocaloric feeding is associated with changes in thyroid hormone economy similar to those in starvation and that peripheral (changes in T3 and rT3) and central (TRH response) events are controlled by separate mechanisms.

Diet↗
PubMed1980

Ipodate and 8-anilino-1-naphthalene sulfonic acid block receptor binding of T3 in rat liver.

We have determined that 8-anilino-1-naphthalene sulfonic acid (ANS) and ipodate are effective inhibitor in vitro of 125I-T3 binding to rat hepatic nuclei receptors. Both of these agents are estimated to have a Kd for the T3 receptor of about 1--2 x 10(-4) M. Indirect preliminary studies suggest that ANS is a non-competitive inhibitor and ipodate is a competitive inhibitor of T3 binding. Compounds such as tyropanoate and diatrizoate and iodide had no effect on T3 receptor binding. Further in vivo studies with ipodate suggested that T3 receptor binding inhibition also occurred when ipodate was given intravenously to rats.

Anilino Naphthalenesulfonates↗
PubMed1980

Free T4, free T3, and reverse T3 in critically ill, thermally injured patients.

A prospective study of thyroid function was performed in 25 thermally injured patients. These patients are divided into two groups. The first group contains five patients with greater than 50% burn size studied longitudinally during the first 15 days following thermal injury. Significant suppression of serum concentrations of 3,5,3'-triiodothyronine (T3) and elevation of serum concentrations of 3,3',5'-triiodothyronine (rT3) were seen. The free thyroxine index and serum TSH concentrations remained within the normal range. To assess the clinical significance of these alterations in peripheral thyroid hormone concentrations, a second group of 20 patients was studied. We measured the free serum levels of T4 (FT4) and T3 (FT3) in ten patients, mean age 34 years, mean burn size 56%, studied during a period of clinical deterioration, and in ten patients of comparable age and burn size who were clinically stable. Both FT4 and T3 values were significantly lower in the unstable patients (p < 0.01). All FT3 values for the unstable patients (M +/- SE), 193 +/- 14 pg/dl, were below the normal range for FT3 of 230 to 669 pg/dl, and significantly lower than those observed in the stable patients (M +/- SE), 430 +/- 59 pg/dl (p < 0.001). This correlation of biochemical hypothyrodisim with clinical deterioration may have functional significance for the critically ill trauma patient.

Adolescent↗
PubMed1980

Uremia decreases nuclear 3,5,3'-triiodothyronine receptors in rats.

The maximal binding capacity (MBC) of hepatic T3 nuclear receptors was decreased in uremic rats (132 +/- 37 fmol/mg DNA) compared to sham-operated controls (212 +/- 44 fmol/mg DNA; P < 0.025), while the equilibrium affinity constants (Ka) remained unaltered (1.8 +/- 0.4 and 1.5 +/- 0.3 X 10(9) M-1 in the uremic and control rats, respectively, P = NS). There was also a reduction in the MBC of the kidney T3 receptors, from 73 +/- 14 fmol/mg DNA in the control animals to 32 +/- 7 fmol/mg DNA in the uremic rats (P < 0.10), while the Ka values were identical in both groups (1.9 +/- 0.5 X 10(9) M-1). In addition, there were significant reductions in serum T4 (1.5 +/- 0.7 microgram/dl) and T3 (92 +/- 10 ng/dl) in the uremic rats compared to control rats, whose T4 levels averaged 4.4 +/- 0.1 microgram/dl (P < 0.005) and whose T3 levels averaged 140 +/- 13 ng/dl (P < 0.005). Further, insulin levels averaged 83 +/- 21 microU/ml in uremic rats and 38 +/- 7 microU/ml in control rats (P < 0.025), while glucagon levels averaged 457 +/- 114 pg/ml in the uremic rats and 101 +/- 30 pg/ml in the control animals (P < 0.0125). These data suggest that 1) in addition to starvation and hepatectomy, uremia is another pathological condition associated with the modification of the number of T3 receptors, 2) the reduction in MBC observed may be generalized rather than organ specific for hepatic nuclear receptors, and 3) elevated glucagon levels are associated with reduced MBC in uremia, but it is indeterminate whether hyperglucagonemia is the etiology of the decrease.

Animals↗
PubMed1980

Solubilized nuclear thyroid hormone receptors in circulating human mononuclear cells.

In order to assess iodothyronine receptor interactions in man, we have developed a receptor assay for T3 and T4 in solubilized nuclear extracts from circulating mononuclear cells. This assay utilizes the technique of salt solubilization to isolate nuclear receptors and employs standard saturation analysis for T3 and T4 to determine maximal binding capacity (MBC) and equilibrium dissociation constants (Kd). We have determined that 11 normal subjects had a MBC for T3 of 1.20 +/- 0.20 pmol/mg DNA (+/- SE) and a Kd of 3.4 +/- 0.2 X 10(-10) M; the T4 MBC was 8.44 +/- 1.22 pmol/mg DNA and the Kd was 2.7 +/- 0.3 X 10(-10) M. Hypothyroid patients had a mean T3 MBC of 7.32 +/- 2.28 pmol/mg DNA and a mean T4 MBC of 40.04 +/- 21.36 pmol/mg DNA (P less than 0.05 compared to normal). Obese subjects (n = 12) had a basal fed MBC that was 0.66 +/- 0.13 pmol/mg DNA for T3 (P less than 0.05 compared to normal) and was 3.58 +/- 0.56 pmol/mg DNA for T4 (P less than 0.01 compared to normal). During fasting, the average T3 MBC increased to 1.43 +/- 0.31 pmol/mg DNA and the average T4 MBC increased to 9.63 +/- 2.46 pmol/mg DNA, values that are both significantly higher than those in the fed period; the dissociation constants were unaltered in obese subjects (compared to normals) in fed and fasting states. Gel filtration with 0.5 M agarose was employed to ascertain if the physicochemical properties of the solubilized mononuclear human cell receptor were similar to those previously observed in rat and human liver and kidney receptors. The elution profile obtained was similar to that reported earlier. The major binding activity has an estimated Stokes radius of 35 A and a molecular weight ratio of approximately 50,000 daltons. These studies indicate that: 1) high affinity T3 and T4 receptors exist in human mononuclear cells and have properties similar to those for T3 and T4 described previously in rat liver; 2) T3 and T4 receptor number tends to increase in hypothyroid subjects and tend to be lower in obese patients than in normal weight control subjects; 3) fasting is associated with an increase in both T3 and T4 MBC; and 4) despite their apparent physicochemical similarity, T3 receptors in rat liver and human mononuclear cells may be regulated differently, at least during fasting since hepatic T3 receptors decrease in the fasted rat. Collectively, these observations support the concept that human white cell T3 nuclear receptor binding is capable of rapid fluctuations, suggesting a mechanism for homeostatic regulation of T3 action.

Adult↗
PubMed1980

Glucagon kinetics in fasting: physiological elevations in serum 3,5,3'-triiodothyronine increase the metabolic clearance rate of glucagon.

We have attempted to determine if the elevated plasma glucagon concentration and delayed MCR of glucagon (MCRg) observed during caloric restriction are related to the decreased serum T3 that also occurs during fasting. Twelve obese subjects received a 3-h iv glucagon infusion during a 4-day fed period (1000 kCal/day) and again on approximately the third fasting day. Five patients fasted without receiving exogenous T3 (control group), whereas seven subjects fasted but also received 5 micrograms T3 orally every 4 h (T3 group) to maintain approximately the same serum T3 levels in the fed and fasting periods. Glucagon production rates (GPR) were derived by multiplying the MCRg by the respective basal plasma glucogon concentrations. In the control group, the MCRg was 442 +/- 55 ml/m2 . min in the postabsorptive state and decreased to 312 +/- 49 ml/m2 . min (P < 0.025) during fasting, whereas in the T3-treated group, the postabsorptive MCRg was 304 +/- 22 ml/m2 . min and increased during fasting to 417 +/- 47 ml/m2 . min (P < 0.025). The GPRs in the control group were statistically unaltered between the fed (27.7 +/- 3.0 ng/m2 . min) and fasted (22.9 +/- 1.8 ng/m2 . min) intervals, but GPR increased from 37.9 +/- 6.1 ng/m2 . min during fasting to 49.2 +/- 9.1 ng/m2 . min when T3 was administered (5 micrograms every 4 h). The net plasma glucose increment in response to glucagon decreased from 18 mg/dl (fed) to 5 mg/dl (fast) in the control patients and from 10 mg/dl (fed) to 7 mg/dl (fast) in the T3-treated subjects. In the T3-treated patients, serum T3 averaged 124 ng/dl during both feeding and fasting, and rT3 was 55 +/- 6 ng/dl during feeding and 49 +/- 5 ng/dl during fasting. In summary, the results from this study indicate that during fasting 1) slight physiological alterations in serum T3 influence the MCRg, and 2) T3 increases the GPR and blocks the customary fasting-induced rise in rT3. Conceivably, decreased T3 is an early event in the fasting state which serves to decrease the MCRg, a process which subsequently regulates glucose homeostasis.

Adult↗
PubMed1979

The effect of T3 and reverse T3 administration on muscle protein catabolism during fasting as measured by 3-methylhistidine excretion.

Since recent studies have indicated that measurement in urine of the amino acid, 3-methylhistidine, accurately reflects the extent of muscle catabolism, and because it has been suggested that thyroid hormones may influence muscle breakdown, especially during fasting, the effect of T3 and reverse T3 (rT3) administration on the excretion of 3-methylhistidine was examined in obese subjects during fasting. The mean (+/- SE) 3-methylhistidine excretion in patients fed an egg protein diet (devoid of meat protein) was 256 +/- 35 mumoles/day and decreased to 190 +/- 14 mumoles/day during fasting. T3 administration (100 microgram/day x 5 days) increased 3-methylhistidine excretion to 304 +/- 37 mumoles/day during its ingestion and to 485 +/- 46 mumoles/day in the T3 posttreatment interval. T3 doses of 10 microgram every 4 hr (q4h) for the first 6 days of fasting also appeared capable of increasing 3-mehis excretion whereas 5 microgram T3 q4h administered during the first 6 days of fasting did not increase 3-mehis excretion. Reverse T3 administration (80 microgram q6h) during fasting was associated with a mean 3-methylhistidine of 130 +/- 13 mumoles/day, a value no higher than in patients fasted alone. These observations suggest that: (1) skeletal muscle catabolism decreases during fasting: and (2) pathophysiologic doses of T3 (60 microgram/day or more), but not reverse T3, enhance muscle catabolism during fasting.

Adult↗
PubMed1978

Failure of 3,3'-diiodothyronine administration to alter TSH and prolactin responses to TRH stimulation.

In order to determine whether elevations in serum 3,3'-diiodothyronine (3,3'T2) concentrations influence the hypothalamic-pituitary--thyroid axis, thyrotropin (TSH) and prolactin responses to thyrotropin-releasing hormone (TRH) were assessed in five patients both prior to and during 3,3'T2 administration. Mean (+/- SE) peak TSH responses to TRH were 168 +/- 64 microU/ml during 3,3'T2 administration and 168 +/- 65 muU/ml during 3,3'T2 administration. Mean basal and peak prolactin concentrations after TRH were 6 +/- 3 ng/ml and 54 +/- 26 ng/ml, whereas during 3,3'T2 administration the basal and peak prolactin levels were 6 +/- 2 ng/ml and 55 +/- 28 ng/ml, respectively. Hypothyroid rats administered triiodothyronine (10 migrogram b.i.d.) for 5 days had a mean TSH response to TRH stimulation of 0.051 +/- 0.003 mU/ml, whereas rats to whom saline or 3,3'T2 (50 microgram b.i.d.) had been given for the same time interval had mean TRH-induced TSH responses of 1.127 +/- 0.179 mU/ml and 1.324 +/- 0.286 mU/ml, respectively. None of the TSH or prolactin responses to TRH, in either human or rat studies, were apparently altered by 3,3'T2. These observations suggest that elevation of serum 3,3'T2 levels are not associated with alterations in the hypothalamic--pituitary--thyroid axis in the experimental systems employed.

Animals↗
PubMed1978

Parameters of thyroid function in patients with active acromegaly.

In order to determine if acromegaly per se may be associated with abnormalities in thyroidal economy, serum thyroxine-binding globulin (TBG), resin T3 uptake, total and free T4, T3, and reverse T3 concentrations were measured in 21 patients with active acromegaly. Mean (+/- SE) total T4, T3, and reverse T3 levels were 7.1 +/- 0.2 microgram/dl, 111 +/- 4 ng/dl, and 45 +/- 2 ng/dl, respectively, and the mean TBG concentration was 3.6 +/- 0.2 mg/dl. Similarly, mean free T4, T3, and reverse T3 concentrations were 2.4 +/- 0.09 ng/dl, 383 +/- 22 pg/dl, and 118 +/- 7 pg/dl, respectively. None of these values is significantly different from normal and the thyrotropin response to thyrotropin-releasing hormone was also normal. In contrast to several earlier reports, these data suggest that parameters of thyroid function are generally normal in patients with active acromegaly.

Acromegaly↗
PubMed1978

Serum triiodothyronine in undernourished rats: dependence on dietary composition rather than total calorie or protein intake.

Serum triiodothyronine (T3) in rats did not change if food intake was restricted without altering the composition of the diet. Feeding a hypocaloric low-protein high-carbohydrate diet caused increases in serum T3, while feeding a hypocaloric high-protein low-carbohydrate diet caused decreases in serum T3. These changes were not related to reductions in intake of either calories or protein, and concomitant changes in serum thyroxine (T4) were not observed. Reduction in the dietary content of valine, without changes in the percentage of carbohydrate in the diet, caused increases in serum T3 when compared to growth-matched controls on a diet with normal valine concentration. Serum T3 in undernourished rats depends on the composition of the diet and not on total intake of calories or protein.

Animals↗