Abstract
Studies of the effect of norethandrolone on the transport and peripheral metabolism of thyroxine were carried out in four patients lacking thyroxine-binding globulin. Before norethandrolone administration, values for serum protein-bound iodine (PBI) were decreased (1.8 ±0.5 μg/100 ml) and the proportion of free thyroxine increased (0.036 ±0.008%). As a result, values for the absolute concentration of free thyroxine iodine were at the lower end of the normal range (0.63 ±0.12 mμg/100 ml). During the control thyroxine-turnover study, the thyroxine distribution space was strikingly increased (18.2 ±7.9 liters) and the fractional rate of thyroxine turnover moderately increased (17.1 ±11.3%/day), as compared to the expected mean values for normal subjects. Therefore, calculated values for the daily rate of thyroxine clearance were increased even more, ranging between 255 and 500% of normal values. However, owing to the low PBI in these patients, the daily disposal of thyroxine iodine was similar to that expected in normals on the basis of age and weight. During the administration of norethandrolone, the thyroxine-binding capacity of the thyroxine-binding prealbumin increased strikingly in all patients, values averaging 162% of those found during the control period. This increase was associated with a highly significant increase in PBI (133% of control values) and a small but significant decrease in the proportion of free thyroxine, resulting in no significant change in the absolute concentration of free thyroxine iodine. In all four patients, administration of norethandrolone was associated with a pronounced decrease in the thyroxine distribution space to values which averaged 69% of those found during the control period. Values for the fractional rate of thyroxine turnover increased slightly. As a result, thyroxine-clearance rate decreased in all patients. Owing to the reciprocal changes in clearance rate and PBI, no significant change in total daily thyroxine disposal was observed. The present studies reveal that when the thyroxine-binding prealbumin is increased in patients lacking thyroxine-binding globulin, several indices of peripheral thyroxine transport and metabolism are altered. However, these changes were small, even in the absence of thyroxine-binding globulin. It is suggested, therefore, that the effect of changes in thyroxine-binding prealbumin would be even smaller in individuals in whom thyroxine-binding globulin is present.
Full text
PDF





Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- BEISEL W. R., ZAINAL H., HANE S., DIRAIMONDO V. C., FORSHAM P. H. Low thyroidal iodine uptake with euthyroidism associated with deficient thyroid-binding globulin but normal cortisol binding. J Clin Endocrinol Metab. 1962 Dec;22:1165–1170. doi: 10.1210/jcem-22-12-1165. [DOI] [PubMed] [Google Scholar]
- Bellabarba D., Inada M., Varsano-Aharon N., Sterling K. Thyroxine transport and turnover in major nonthyroidal illness. J Clin Endocrinol Metab. 1968 Jul;28(7):1023–1030. doi: 10.1210/jcem-28-7-1023. [DOI] [PubMed] [Google Scholar]
- Bernstein G., Hasen J., Oppenheimer J. H. Turnover of 131-I-thyroxine in patients subjected to surgical trauma. J Clin Endocrinol Metab. 1967 May;27(5):741–744. doi: 10.1210/jcem-27-5-741. [DOI] [PubMed] [Google Scholar]
- Braverman L. E., Foster A. E., Ingbar S. H. Thyroid hormone transport in the serum of patients with thyrotoxic Graves' disease before and after treatment. J Clin Invest. 1968 Jun;47(6):1349–1357. doi: 10.1172/JCI105827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braverman L. E., Ingbar S. H. Effects of norethandrolone on the transport in serum and peripheral turnover of thyroxine. J Clin Endocrinol Metab. 1967 Mar;27(3):389–396. doi: 10.1210/jcem-27-3-389. [DOI] [PubMed] [Google Scholar]
- Braverman L. E., Socolow E. L., Woeber K. A., Ingbar S. H. Effect of norethandrolone on the metabolism of 125-I-labeled thyroxine-binding prealbumin. J Clin Endocrinol Metab. 1968 Jun;28(6):831–835. doi: 10.1210/jcem-28-6-831. [DOI] [PubMed] [Google Scholar]
- Cavalieri R. R., Searle G. L. The kinetics of distribution between plasma and liver of 131-I-labeled L-thyroxine in man: observations of subjects with normal and decreased serum thyroxine-binding globulin. J Clin Invest. 1966 Jun;45(6):939–949. doi: 10.1172/JCI105409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis P. J., Gregerman R. I. Separation of thyroxine(T4)-binding proteins of human serum in polyacrylamide gel at pH 7.4. I. Effect of pH on distrubution of tracer quantities of T4. J Clin Endocrinol Metab. 1970 Feb;30(2):237–245. doi: 10.1210/jcem-30-2-237. [DOI] [PubMed] [Google Scholar]
- Fisher D. A., Oddie T. H. Effect of methyl testosterone on thyroxine metabolism and on triiodothyronine kinetics. J Clin Endocrinol Metab. 1968 Dec;28(12):1690–1698. doi: 10.1210/jcem-28-12-1690. [DOI] [PubMed] [Google Scholar]
- Gregerman R. I., Solomon N. Acceleration of thyroxine and triiodothyronine turnover during bacterial pulmonary infections and fever: implications for the functional state of the thyroid during stress and in senescence. J Clin Endocrinol Metab. 1967 Jan;27(1):93–105. doi: 10.1210/jcem-27-1-93. [DOI] [PubMed] [Google Scholar]
- INGBAR S. H., FREINKEL N. Simultaneous estimation of rates of thyroxine degradation and thyroid hormone synthesis. J Clin Invest. 1955 Jun;34(6):808–819. doi: 10.1172/JCI103136. [DOI] [PMC free article] [PubMed] [Google Scholar]
- INGBAR S. H. Observations concerning the binding of thyroid hormones by human serum prealbumin. J Clin Invest. 1963 Feb;42:143–160. doi: 10.1172/JCI104701. [DOI] [PMC free article] [PubMed] [Google Scholar]
- INGBAR S. H. The interaction of the thyroid hormones with the proteins of human plasma. Ann N Y Acad Sci. 1960 Apr 23;86:440–453. doi: 10.1111/j.1749-6632.1960.tb42821.x. [DOI] [PubMed] [Google Scholar]
- Ingbar S. H. CLINICAL AND PHYSIOLOGICAL OBSERVATIONS IN A PATIENT WITH AN IDIOPATHIC DECREASE IN THE THYROXINE-BINDING GLOBULIN OF PLASMA. J Clin Invest. 1961 Nov;40(11):2053–2063. doi: 10.1172/JCI104431. [DOI] [PMC free article] [PubMed] [Google Scholar]
- NICOLOFF J. T., DOWLING J. T., PATTON D. D. INHERITANCE OF DECREASED THYROXINE-BINDING BY THE THYROXINE-BINDING GLOBULIN. J Clin Endocrinol Metab. 1964 Mar;24:294–298. doi: 10.1210/jcem-24-3-294. [DOI] [PubMed] [Google Scholar]
- Nikolai T. F., Seal U. S. X-chromosome linked inheritance of thyroxine-binding globulin deficiency. J Clin Endocrinol Metab. 1967 Nov;27(11):1515–1520. doi: 10.1210/jcem-27-11-1515. [DOI] [PubMed] [Google Scholar]
- OPPENHEIMER J. H., SQUEF R., SURKS M. I., HAUER H. BINDING OF THYROXINE BY SERUM PROTEINS EVALUATED BY EQUILIBRUM DIALYSIS AND ELECTROPHORETIC TECHNIQUES. ALTERATIONS IN NONTHYROIDAL ILLNESS. J Clin Invest. 1963 Nov;42:1769–1782. doi: 10.1172/JCI104862. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Oddie T. H., Meade J. H., Jr, Fisher D. A. An analysis of published data on thyroxine turnover in human subjects. J Clin Endocrinol Metab. 1966 Apr;26(4):425–436. doi: 10.1210/jcem-26-4-425. [DOI] [PubMed] [Google Scholar]
- Oppenheimer J. H. Role of plasma proteins in the binding, distribution and metabolism of the thyroid hormones. N Engl J Med. 1968 May 23;278(21):1153–1162. doi: 10.1056/NEJM196805232782107. [DOI] [PubMed] [Google Scholar]
- Oppenheimer J. H., Werner S. C. Effect of prednisone on thyroxine-binding proteins. J Clin Endocrinol Metab. 1966 Jul;26(7):715–721. doi: 10.1210/jcem-26-7-715. [DOI] [PubMed] [Google Scholar]
- Refetoff S., Selenkow H. A. Familial thyroxine-binding globulin deficiency in a patient with Turner's syndrome (XO). Genetic study of a kindred. N Engl J Med. 1968 May 16;278(20):1081–1087. doi: 10.1056/NEJM196805162782002. [DOI] [PubMed] [Google Scholar]
- WOEBER K. A., INGBAR S. H. THE EFFECTS OF NONCALORIGENIC CONGENERS OF SALICYLATE ON THE PERIPHERAL METABOLISM OF THYROXINE. J Clin Invest. 1964 May;43:931–942. doi: 10.1172/JCI104979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Woeber K. A., Ingbar S. H. The contribution of thyroxine-binding prealbumin to the binding of thyroxine in human serum, as assessed by immunoadsorption. J Clin Invest. 1968 Jul;47(7):1710–1721. doi: 10.1172/JCI105861. [DOI] [PMC free article] [PubMed] [Google Scholar]
