No abstract

Patients with ESRD have multiple alterations of thyroid hormone metabolism in the absence of concurrent thyroid disease. These may include elevated basal TSH values, which may transiently increase to greater than 10 mU/liter, blunted TSH response to TRH, diminished or absent TSH diurnal rhythm, altered TSH glycosylation, and impaired TSH and TRH clearance rates. In addition, serum total and free T3 and T4 values may be reduced, free rT3 levels are elevated while total values are normal, serum binding protein concentrations may be altered, and disease-specific inhibitors reduce serum T4 binding. Changes in T4 and T3 transfer, distribution, and metabolism resemble those of other nonthyroidal illnesses, while changes in rT3 metabolism are disease specific. Dialysis therapy minimally affects thyroid hormone metabolism, while zinc and erythropoietin administration may partially reverse thyroid hormone abnormalities. Thyroid hormone metabolism normalizes with renal transplantation; however, glucocorticoid therapy may induce additional changes. ESRD patients may have an increased frequency of goiter, thyroid nodules, thyroid carcinoma, and hypothyroidism. Goiter and hypothyroidism may be induced by iodide excess, due to reduced renal iodide excretion, and may be reversed with iodide restriction in some patients. The increased frequency of thyroid nodules and malignancies in ESRD may relate to secondary hyperparathyroidism. After renal transplantation, the higher frequency of thyroid malignancies may relate to the immunosuppressed state. Clinical symptoms and signs and biochemical features of hypothyroidism and hyperthyroidism may be altered by concurrent ESRD. ESRD patients with hyperthyroidism or follicular neoplasms require reduced dosages of Na 131-I depending upon type, frequency, and duration of dialysis therapy.

Patients with ESRD have multiple alterations of thyroid hormone metabolism in the absence of concurrent thyroid disease. These may include elevated basal TSH values, which may transiently increase to greater than 10 mU/liter, blunted TSH response to TRH, diminished or absent TSH diurnal rhythm, altered TSH glycosylation, and impaired TSH and TRH clearance rates. In addition, serum total and free T3 and T4 values may be reduced, free rT3 levels are elevated while total values are normal, serum binding protein concentrations may be altered, and disease-specific inhibitors reduce serum T4 binding. Changes in T4 and T3 transfer, distribution, and metabolism resemble those of other nonthyroidal illnesses, while changes in rT3 metabolism are disease specific. Dialysis therapy minimally affects thyroid hormone metabolism, while zinc and erythropoietin administration may partially reverse thyroid hormone abnormalities. Thyroid hormone metabolism normalizes with renal transplantation; however, glucocorticoid therapy may induce additional changes. ESRD patients may have an increased frequency of goiter, thyroid nodules, thyroid carcinoma, and hypothyroidism. Goiter and hypothyroidism may be induced by iodide excess, due to reduced renal iodide excretion, and may be reversed with iodide restriction in some patients. The increased frequency of thyroid nodules and malignancies in ESRD may relate to secondary hyperparathyroidism. After renal transplantation, the higher frequency of thyroid malignancies may relate to the immunosuppressed state. Clinical symptoms and signs and biochemical features of hypothyroidism and hyperthyroidism may be altered by concurrent ESRD. ESRD patients with hyperthyroidism or follicular neoplasms require reduced dosages of Na 131-I depending upon type, frequency, and duration of dialysis therapy.

As bstract. The present study was undertaken to define the source of endogenous triiodothyronine (T3) production responsible for maintaining serum T3 levels in euthyroid subjects with depressed serum thyroxine (T4) values. After withdrawal from 4 wk of exogenous T3 administration, a 22% decline in serum T3 values (from 129±6 to 99±4 ng/dl) was observed in six euthyroid subjects, despite a twofold reduction in serum T4 concentrations (from 7.5±0.5 to 3.2±0.5 ug/dl). This was accompanied by a nearly twofold increase in serum T3/T4 ratio values (17±1 to 29±6) but no significant alteration in reverse T3/T4 ratio values. This phenomenon did not appear to be thyroid stimulating hormone (TSH) dependent, since base-line serum TSH values were subnormal. Nor was it dependent on changes in thyroid gland function, since a blunted T3 response to exogenous bovine TSH occurred and pharmacologic doses ofiodide did not influence the phenomenon. The finding in three athyreotic subjects that serum T3/T4 ratio values increased from 14±1 on T4 therapy (mean serum T4, 9.6±0.8 ug/dl and T3, 132±8 ng/dl) to 40±2 after withdrawal from 2 wk of T3 administration (serum T4 1.2±0.1 ttg/dl and T3 46±3 ng/dl) provided direct evidence that an alteration in peripheral thyroid hormone metabolism was probably responsible for these findings previously observed in euthyroid subjects. The results of this study support the possible existence in euthyroid man of a peripheral tissue autoregulatory mechanism for maintaining serum T3 values in states of T4 deficiency. Whether this process

A B S T R A C T The low thyroxine (T4) state of acute critical nonthyroidal illnesses is characterized by marked decreases in serum total T4 and triiodothyronine (T3) with elevated reverse T3 (rT3) values. To better define the mechanisms responsible for these alterations, serum kinetic disappearance studies of labeled T4, T3, or rT3 were determined in 16 patients with the low T4 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 T4 (0.070±0.007%, normal [nl] 0.0315±0.0014, P <0.001), T3 (0.696±0.065%, nl 0.310±0.034, P <0.001), and rT3 (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 T4 (1.69±0.22 liter/d per m2, 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 T4 exit from the serum (Kii) (15.2±4.6 d-1, nl 28.4±3.9, P < 0.001) indicated an impairment of extravascular T4 binding that exceeded the serum binding defect. This defect did not apparThis work was presented in part at the 6th International Congress of Endocrinology, Melbourne, Australia, February, 1980 (Abstract No. 364), and at the 61st Annual Endocrine Society Meeting, Wash., D. C., June, 1980 These alterations in thyroid hormones indices and kinetic parameters for T4, T3, and rT3 in the low T4 state of acute nonthyroidal illnesses can be accounted for by: (a) decreased binding of T4, T3, and rT3 to vascular and extravascular sites with a proportionately greater impairment of extravascular T4 binding, and (b) impaired 5'-deiodination activity affecting both T4 and rT3 metabolism.