The Effects of Noncalorigenic Congeners of Salicylate on the Peripheral Metabolism of Thyroxine*

Summary. Studies of the metabolism of thyroxine in 14 cases of cirrhosis revealed a variety of deviations from normal. In addition to radiothyroxine turnover studies, determinations were made of the free thyroxine fractions and free thyroxine iodine concentrations in serum (magnesium precipitation method) as well as the maximal binding capacities of thyroxine-binding alpha globulin (TBG) and thyroxine-binding prealbumin (TBPA) by reverse flow paper electrophoresis in a glycine acetate system at pH 8.6.All cases of cirrhosis exhibited diminutions in TBPA capacities but their TBG capacities showed a wide scatter (13.4 to 41.6 jug/100 ml). The free thyroxine fraction was quite variable, with distinct elevations in nine of the 17 sera. The binding proteins appeared to be determinants of the free thyroxine fraction, which in turn, appeared to be a direct determinant of the half-time of turnover. These inferences did not exclude other possible factors including diminished hepatic uptake and metabolism of the hormone in liver disease.Despite considerable alterations in biological half-times, free thyroxine values, and binding proteins, it was remarkable that the absolute hormone disposal was normal in all 14 patients with cirrhosis.

Section: Discussionsupporting

confidence: 93%

Thyroxine Turnover and Transport in Laennec's Cirrhosis of the Liver*

Inada

Sterling²

1967

“…Paper chromatography of dialyzed, unhydrolyzed specimens of I131-TBPA revealed mainly immobile, organic I131 and small amounts of inorganic I131; no free labeled amino acids were detected.8 After hydrolysis of the I131-TBPA, la- 7 Iodination yields were consistently greater during experiments with HSA. In four experiments, over-all yields averaged 24%.…”

Section: Resultsmentioning

confidence: 95%

“…Despite some early doubts concerning its presence in plasma and its physiological function (1)(2)(3)(4), the thyroxine-binding prealbumin of human serum (TBPA) is now known to play a significant role in the transport of thyroxine (T4) (5)(6)(7)(8). Normally, as assessed by in vitro techniques, TBPA appears to bind at least 25 to 35%o of T4 in serum (5,6).…”

mentioning

confidence: 99%

Preparation of I-131-labeled human serum prealbumin and its metabolism in normal and sick patients.

Socolow¹,

Woeber²,

Purdy³

et al. 1965

117

Despite some early doubts concerning its presence in plasma and its physiological function (1-4), the thyroxine-binding prealbumin of human serum (TBPA) is now known to play a significant role in the transport of thyroxine (T4) (5-8). Normally, as assessed by in vitro techniques, TBPA appears to bind at least 25 to 35%o of T4 in serum (5,6). In the serum of many patients with severe acute or chronic illness, however, the proportion of endogenous T4 in serum bound by TBPA and the T4-binding capacity of TBPA decline (8,9). The recent availability of substantial quantities of a highly purified preparation of TBPA has made possible an investigation of the in vivo metabolism of this protein in normal patients and in patients with a variety of disorders that lead to decreased binding of T4 by TBPA in serum. In addition, the cause of this decrease in T4 binding in the serum of such "sick" patients has been evaluated. A portion of the findings has been presented in abstract form (10). While these studies were in progress, Oppenheimer, Surks, Bernstein, and Smith reported similar studies in abstract form (11,12). MethodsHighly purified TBPA was prepared from plasma Fraction IV-6 (method 6) of Cohn and colleagues (13).* Submitted for publication April 9, 1965; accepted June 16, 1965. This The method of purification of the protein and details of its characterization will be described in detail elsewhere (14). Additional characterization of the specific batch of protein employed in the present studies was carried out. Solutions of TBPA (2.0 g per 100 ml), enriched with I'-labeled T4,1 were subjected to electrophoresis in acrylamide gel in a Tris-maleate buffer system,2 pH 9.2. Gel concentrations of 5.0, 7.0, and 8.0 g per 100 ml were employed, and, in some instances, two dimensional gel electrophoretic studies were conducted (15). After electrophoresis, gels were radioautographed and then stained with amido black 10 B.Iodination of TBPA. To minimize the possibility of denaturing the TBPA during the iodination process, a technique was developed for iodinating protein by a microdiffusion process. The technique, an adaptation of that described by Banerjee and Ekins (16), was first employed in tests with human serum albumin (HSA) or with purified TBPA for relatively low specific activity labeling. When the method had been standardized, it was employed for higher specific activity labeling of the TBPA used in the present studies. This was performed as follows. All glassware and buffer media employed were autoclaved before use. A 2.0 g per 100 ml solution of TBPA was prepared in 0.01 M phosphate buffer, pH 7.5, and 200 Al was pipetted into the center well of a single side-armed Warburg flask of 5.0 ml capacity. NaI' (10 to 15 mc, free of carrier iodide and reducing agent),8 together with 60 Ag of unlabeled NaI, was introduced into the main compartment of the vessel in approximately 1 ml of phosphate buffer. Five hundred Al of fresh 3% H202 4 was added to the side arm, and the vessel was closed with a greased ground-glass stopp...

“…In addition to acute bacterial infection, accelerated disappearance of To has been observed to occur during several other hypermetabolic states including muscular exercise (19), cold exposure (20), acute adaptation to high altitude (21), leukemia (12), active acromegaly (22), treated Graves' disease (23), and salicylate administration (24,25). In many of these circumstances (19,(21)(22)(23), as during acute bacterial sepsis, the acceleration of To disappearance could not be ascribed to a decrease in the binding of hormone in plasma, suggesting that cellular metabolism was primarily increased.…”

Section: Resultsmentioning

confidence: 99%

Accelerated Cellular Uptake and Metabolism of L-Thyroxine during Acute Salmonella typhimurium Sepsis

DeRubertis¹,

Woeber²

1973

Self Cite

A B S T R A C T The effects of acute Salmonella typhimurium sepsis on the kinetics of peripheral L-thyroxine (T4) distribution and metabolism and on serum total and free T4 concentrations were studied in rhesus monkeys inoculated i.v. with either heat-killed or viable organisms. The rate of disappearance of labeled T4 from serum was increased within 8 h after inoculation of monkeys with either heat-killed or viable Salmonella. The effects of the heat-killed organisms were transient and no longer evident by 16 h postinoculation. The monkeys inoculated with the viable Salmonella experienced a 2-3 day febrile, septic illness that was accompanied by an increase in the absolute rate of T4 disposal. In the infected monkeys, serum total T4 and endogenously labeled protein-bound iodine concentrations fell significantly during the period of acute sepsis and then rose during convalescence to values that exceeded the preinoculation values, suggesting that thyroidal secretion of hormone had increased in response to a primary depletion of the peripheral hormonal pool. Total cellular and hepatic uptakes of T4 were enhanced by 4 h after inoculation of monkeys with either heatkilled or viable Salmonella, but the increase in total cellular uptake persisted for 24 h only in the monkeys inoculated with the viable organisms. These alterations in T4 kinetics could neither be correlated with changes in the binding of T4 in plasma nor attributed to an increase in vascular permeability. Moreover, they could not be ascribed to an in vitro product of bacterial growth, suggesting that the presence of the organisms themselves was required. An acceleration of T4 disappearance was also observed during Escherichia coli and Diplococcus pneumioniae bacteremias. Our findings are Dr. Woeber's present address is the