The proposed research is an interdisciplinary effort involving collaboration among the Divisions of Nephrology, Endocrinology and Nuclear Medicine. The research proposals are aimed at: 1) the evaluation of the derangements in serum thyroid hormone levels, thyroid hormone metabolism and distribution and the quantitation of specific tissue uptake of T4, T3 and rT3 in patients with renal diseases in the presence and absence of renal failure; and 2) the elucidation of the potential role of malnutrition in altering T4 and T3 metabolism and of parathyroid hormone in inducing the changes in rT3 metabolism in hyperparathyroid states. Studies will be carried out in normal subjects, in healthy euthyroid individuals with altered serum thyroxine binding globulin levels, in patients with acute and chronic renal failure, nephrotic syndrome and normal glomerular filtration rates, patients with primary hyperparathyroidism and those with hypercalcemia and undetectable parathyroid hormone levels. In addition, serum rT3 kinetic studies and direct tissue quantitation of rT3 content will be carried out in normal dogs, parathyroidectomized animals and in acutely and chronically uremic dogs with intact parathyroid glands and in those subjected to parathyroidectomy. The data obtained from serum disappearance and liver and forearm uptake of 131-I labeled T4, T3 and rT3 in the human studies will be subjected to compartmental analysis using the simultation, analysis and modeling program. The serum rT3 kinetic data from the dog studies will be analyzed by both noncompartmental and compartmental methods. It is anticipated that the results of these studies will provide enhanced definition of the specific nature and tissue sites of the alterations in thyroid hormone metabolism as well as elucidating the factors responsible for inducing these changes. These, in turn may shed light on the mechanisms and clinical significance of the disturbances in thyroid hormone metabolism in nonthyroid illnesses and specifically in renal diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
1R01AM031431-01A3
Application #
3152276
Study Section
Endocrinology Study Section (END)
Project Start
1984-12-01
Project End
1988-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Medicine
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90033
Kaptein, E M; Hoopes, M T; Pattabhiraman, R et al. (1989) Separation of iodothyronines from iodinated metabolites in serum from reverse T3 tracer kinetic studies in man and dog: a comparison of two methods. Horm Metab Res 21:678-81
Kaptein, E M; Quion-Verde, H; Chooljian, C J et al. (1988) The thyroid in end-stage renal disease. Medicine (Baltimore) 67:187-97
Kaptein, E M; Egodage, P M; Hoopes, M T et al. (1988) Amiodarone alters thyroxine transfer and distribution in humans. Metabolism 37:1107-13
Tang, W W; Kaptein, E M; Massry, S G (1987) Diagnosis of hypothyroidism in patients with end-stage renal disease. Am J Nephrol 7:192-7
Kaptein, E M; Kaptein, J S; Chang, E I et al. (1987) Thyroxine transfer and distribution in critical nonthyroidal illnesses, chronic renal failure, and chronic ethanol abuse. J Clin Endocrinol Metab 65:606-16