triiodothyronine--reverse and Respiratory-Insufficiency

Thyroid hormones are displaced from their binding proteins in serum during nonthyroidal somatic illness, and FFA have been claimed to contribute. It seems mandatory to evaluate this effect using techniques for the measurements of serum free thyroid hormones in which serum remains undiluted. We measured the effect of 7 common human FFA on the free fraction of T4, T3 and rT3 in serum from healthy subjects using an ultrafiltration technique by which serum is diluted only minimally. In addition we measured the effect of oleic acid on the free fractions of the iodothyronines in pooled serum from healthy subjects and in pooled serum from patients with nonthyroidal illness. All FFA tested were able to displace both T4, T3 and rT3, but to a varying degree, arachidonic and linoleic acid being the most potent ones. A 20% increase in the free fractions of T4, T3 and rT3, respectively, was obtained by adding between 1.7-3.3 mmol/l, 1.3-4.6 mmol/l and 1.0-2.4 mmol/l of the different FFA. A serum pool obtained from patients with nonthyroidal somatic illness was more sensitive to oleic acid than a serum pool obtained from healthy subjects, since 2-3 times less oleic acid was necessary to induce a 20% increase in the free fractions of thyroid hormones. It is concluded that FFA are able to displace both T4, T3 and rT3 from their serum binding proteins in healthy subjects as well as in patients with nonthyroidal illness. However, serum from patients with nonthyroidal illness was more sensitive to the displacing activity of oleic acid than serum from healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cerebrovascular Disorders; Fatty Acids, Nonesterified; Hepatic Encephalopathy; Humans; Kidney Failure, Chronic; Neoplasms; Respiratory Insufficiency; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Ultrafiltration

ātients with end-stage chronic renal failure (CRF) and those receiving dialysis therapy have normal or decreased serum total T4 (TT4), reduced serum total T3 (TT3), and normal total reverse T3 (TrT3) levels. Those with nonrenal nonthyroidal illnesses or malnutrition have low TT4 and TT3 but elevated TrT3 values. To evaluate the mechanism(s) for the normal TrT3 levels in CRF, we performed intravenous bolus kinetic studies of rT3 and T4 in patients with CRF, in those treated with chronic hemodialysis, in patients with nonrenal nonthyroidal illnesses, and in normal subjects. The CRF patients were selected to have good nutritional status as indicated by normal serum transferrin, relative body weight, and body mass index values. The CRF patients had normal TrT3, TT4, and free T4 values, increased free fraction of rT3, free rT3, and thyroxine-binding globulin levels, and decreased TT3 concentrations. Noncompartmental analysis of the rT3 kinetics indicated normal production rate, reduced cellular clearance rate, and increased pool size and residence time values in both the CRF and nonrenal patients. In CRF, the serum clearance rate was normal, but the fractional rate of exit, permeability, extravascular binding, and the apparent volume of distribution were increased. In contrast, the nonrenal patients had reduced serum clearance rate, permeability, and extravascular binding, whereas the fractional rate of exit and apparent volume of distribution were not significantly altered. The T4 kinetics in CRF paralleled those of the nonrenal patients, with a reduced fractional rate of exit and permeability in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Body Weight; Chronic Disease; Female; Humans; Infections; Kidney Failure, Chronic; Kinetics; Liver Diseases; Male; Middle Aged; Nutritional Physiological Phenomena; Renal Dialysis; Respiratory Insufficiency; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Uremia

The low thyroxine (T(4)) state of acute critical nonthyroidal illnesses is characterized by marked decreases in serum total T(4) and triiodothyronine (T(3)) with elevated reverse T(3) (rT(3)) values. To better define the mechanisms responsible for these alterations, serum kinetic disappearance studies of labeled T(4), T(3), or rT(3) were determined in 16 patients with the low T(4) state and compared with 27 euthyroid controls and a single subject with near absence of thyroxine-binding globulin. Marked increases in the serum free fractions of T(4) (0.070+/-0.007%, normal [nl] 0.0315+/-0.0014, P < 0.001), T(3) (0.696+/-0.065%, nl 0.310+/-0.034, P < 0.001), and rT(3) (0.404+/-0.051%, nl 0.133+/-0.007, P < 0.001) by equilibrium dialysis were observed indicating impaired serum binding. Noncompartmental analysis of the kinetic data revealed an increased metabolic clearance rate (MCR) of T(4) (1.69+/-0.22 liter/d per m(2), nl 0.73+/-0.05, P < 0.001) and fractional catabolic rate (FCR) (32.8+/-2.6%, nl 12.0+/-0.8, P < 0.001), analogous to the euthyroid subject with low thyroxine-binding globulin. However, the reduced rate of T(4) exit from the serum (Kii) (15.2+/-4.6 d(-1), nl 28.4+/-3.9, P < 0.001) indicated an impairment of extravascular T(4) binding that exceeded the serum binding defect. This defect did not apparently reduce the availability of T(4) to sites of disposal as reflected by the increased fractional disposal rate of T(4) (0.101+/-0.018 d(-1), nl 0.021+/-0.003, P < 0.001). The decreased serum T(3) binding was associated with the expected increases in MCR (18.80+/-2.22 liter/d per m(2), nl 13.74+/-1.30, P < 0.05) and total volume of distribution (26.55+/-4.80 liter/m(2), nl 13.10+/-2.54, P < 0.01). However, the unaltered Kii suggested an extravascular binding impairment comparable to that found in serum. The decreased T(3) production rate (6.34+/-0.53 mug/d per m(2), nl 23.47+/-2.12, P < 0.005) appeared to result from reduced peripheral T(4) to T(3) conversion because of decreased 5'-deiodination rather than from a decreased T(4) availability. This view was supported by the normality of the rT(3) production rate. The normal Kii values for rT(3) indicated a comparable defect in serum and extravascular rT(3) binding. The reduced MCR (25.05+/-6.03 liter/d per m(2), nl 59.96+/-8.56, P < 0.005) and FCR (191.0+/-41.19%, nl 628.0+/-199.0, P < 0.02) for rT(3) are compatible with an impairment of the rT(3) deiodination rate. These alterations in thyroid hormo

Topics: Acute Disease; Adult; Aged; Binding Sites; Female; Humans; Infections; Kinetics; Liver Diseases; Male; Metabolic Clearance Rate; Middle Aged; Respiratory Insufficiency; Thyroxine; Thyroxine-Binding Proteins; Triiodothyronine; Triiodothyronine, Reverse