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. 1980 Sep;66(3):451–456. doi: 10.1172/JCI109875

Variable Thyrotropin Response to Thyrotropin-releasing Hormone after Small Decreases in Plasma Free Thyroid Hormone Concentrations in Patients with Nonthyroidal Diseases

Susan J Maturlo 1,2, Robert L Rosenbaum 1,2, Chao Pan 1,2, Martin I Surks 1,2
PMCID: PMC371672  PMID: 6772675

Abstract

Although a normal serum thyrotropin (TSH) concentration is generally considered to be the most important finding to support the clinical impression of euthyroidism in patients with nonthyroidal diseases and decreased serum triiodothyronine (T3), the regulation of TSH secretion in sick patients has not been studied previously. Accordingly, we studied the regulation of TSH secretion in 23 patients with nonthyroidal diseases; 15 of the patients had decreased serum T3. TSH regulation was studied by measuring the TSH response to injected thyrotropin-releasing hormone (TRH) before and after effecting a small decrease in serum thyroxine (T4) and/or T3 concentrations by iodide treatment, 262 mg daily for 10 d. Iodide treatment significantly decreased (> 10%) the free T4 index (FT4-I) and/or free T3 index (FT3-I) in all patients. FT4-I values were correlated (0.611, P < 0.001), with free T4 concentration determined by equilibrium dialysis. Despite decreased FT4-I and/or FT3-I after iodide treatment in all patients, the TSH response to TRH after iodide treatment was augmented in only 8 of 15 patients who had decreased serum T3 (group 1) and in only 5 of 8 patients who had a normal serum T3. Mean base-line TSH concentration was increased significantly (P < 0.05) from 0.9±0.1 to 1.5±0.3 μU/ml in group 1 only. Comparison of the mean TSH response to TRH showed that there was no significant difference between groups 1 and 2. Moreover, no significant difference in thyroidal parameters was observed between patients who had augmented TSH response to TRH after iodides and those who had either similar or decreased TSH response irrespective of the initial serum T3. These studies show that an augmented TSH response to TRH in response to a small reduction in serum T4 and T3 concentration occurred in only 57% of the entire group of patients with nonthyroidal diseases and that the presence or absence of a normal TSH response to this stimulus did not seem to be related to the base-line serum T3 concentration. Because an increase in serum TSH in response to decreased serum T4 and T3 did not occur in about one-half of patients with nonthyroidal diseases, normal serum TSH may not be a reliable index of the euthyroid state in these patients.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bermudez F., Surks M. I., Oppenheimer J. H. High incidence of decreased serum triiodothyronine concentration in patients with nonthyroidal disease. J Clin Endocrinol Metab. 1975 Jul;41(1):27–40. doi: 10.1210/jcem-41-1-27. [DOI] [PubMed] [Google Scholar]
  2. Burrows A. W., Cooper E., Shakespear R. A., Aickin C. M., Fraser S., Hesch R. D., Burke C. W. Low serum L-T3 levels in the elderly sick: protein binding, thyroid and pituitary responsiveness, and reverse T3 concentrations. Clin Endocrinol (Oxf) 1977 Oct;7(4):289–300. doi: 10.1111/j.1365-2265.1977.tb01328.x. [DOI] [PubMed] [Google Scholar]
  3. Burrows A. W., Shakespear R. A., Hesch R. D., Cooper E., Aickin C. M., Burke C. W. Thyroid hormones in the elderly sick: "T4 euthyroidism". Br Med J. 1975 Nov 22;4(5994):437–439. doi: 10.1136/bmj.4.5994.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carter J. N., Eastman C. J., Corcoran J. M., Lazarus L. Effect of severe, chronic illness on thyroid function. Lancet. 1974 Oct 26;2(7887):971–974. doi: 10.1016/s0140-6736(74)92070-4. [DOI] [PubMed] [Google Scholar]
  5. Cathcart E. S., Idelson B. A., Scheinberg M. A., Couser W. G. Beneficial effects of methylprednisolone "pulse" therapy in diffuse proliferative lupus nephritis. Lancet. 1976 Jan 24;1(7952):163–166. doi: 10.1016/s0140-6736(76)91272-1. [DOI] [PubMed] [Google Scholar]
  6. Chopra I. J., Solomon D. H., Chopra U., Wu S. Y., Fisher D. A., Nakamura Y. Pathways of metabolism of thyroid hormones. Recent Prog Horm Res. 1978;34:521–567. doi: 10.1016/b978-0-12-571134-0.50018-1. [DOI] [PubMed] [Google Scholar]
  7. Chopra I. J., Solomon D. H., Chopra U., Young R. T., Chua Teco G. N. Alterations in circulating thyroid hormones and thyrotropin in hepatic cirrhosis: evidence for euthyroidism despite subnormal serum triiodothyronine. J Clin Endocrinol Metab. 1974 Sep;39(3):501–511. doi: 10.1210/jcem-39-3-501. [DOI] [PubMed] [Google Scholar]
  8. Croxson M. S., Hall T. D., Kletzky O. A., Jaramillo J. E., Nicoloff J. T. Decreased serum thyrotropin induced by fasting. J Clin Endocrinol Metab. 1977 Sep;45(3):560–568. doi: 10.1210/jcem-45-3-560. [DOI] [PubMed] [Google Scholar]
  9. Gardner D. F., Kaplan M. M., Stanley C. A., Utiger R. D. Effect of tri-iodothyronine replacement on the metabolic and pituitary responses to starvation. N Engl J Med. 1979 Mar 15;300(11):579–584. doi: 10.1056/NEJM197903153001102. [DOI] [PubMed] [Google Scholar]
  10. Gavin L. A., McMahon F. A., Castle J. N., Cavalieri R. R. Alterations in serum thyroid hormones and thyroxine-binding globulin in patients with nephrosis. J Clin Endocrinol Metab. 1978 Jan;46(1):125–130. doi: 10.1210/jcem-46-1-125. [DOI] [PubMed] [Google Scholar]
  11. Grajower M. M., Surks M. I. Effect of decreased hepatic nuclear L-triiodothyronine receptors on the response of hepatic enzymes to L-triiodothyronine in tumor-bearing rats. Endocrinology. 1979 Mar;104(3):697–703. doi: 10.1210/endo-104-3-697. [DOI] [PubMed] [Google Scholar]
  12. Hershman J. M., Pittman J. A., Jr Utility of the radioimmunoassay of serum thyrotrophin in man. Ann Intern Med. 1971 Apr;74(4):481–490. doi: 10.7326/0003-4819-74-4-481. [DOI] [PubMed] [Google Scholar]
  13. Hoffman D. P., Surks M. I., Oppenheimer J. H., Weitzman E. D. Response to thyrotropin releasing hormone: an objective criterion for the adequacy of thyrotropin suppression therapy. J Clin Endocrinol Metab. 1977 May;44(5):892–901. doi: 10.1210/jcem-44-5-892. [DOI] [PubMed] [Google Scholar]
  14. Ingbar S. H., Braverman L. E. Active form of the thyroid hormone. Annu Rev Med. 1975;26:443–449. doi: 10.1146/annurev.me.26.020175.002303. [DOI] [PubMed] [Google Scholar]
  15. Lim V. S., Fang V. S., Katz A. I., Refetoff S. Thyroid dysfunction in chronic renal failure. A study of the pituitary-thyroid axis and peripheral turnover kinetics of thyroxine and triiodothyronine. J Clin Invest. 1977 Sep;60(3):522–534. doi: 10.1172/JCI108804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Odell W. D., Wilber J. F., Utiger R. D. Studies of thyrotropin physiology by means of radioimmunoassay. Recent Prog Horm Res. 1967;23:47–85. doi: 10.1016/b978-1-4831-9826-2.50005-2. [DOI] [PubMed] [Google Scholar]
  17. Ramirez G., O'Neill W., Jr, Jubiz W., Bloomer H. A. Thyroid dysfunction in uremia: evidence for thyroid and hypophyseal abnormalities. Ann Intern Med. 1976 Jun;84(6):672–676. doi: 10.7326/0003-4819-84-6-672. [DOI] [PubMed] [Google Scholar]
  18. Reichlin S., Bollinger J., Nejad I., Sullivan P. Tissue thyroid hormone concentration of rat and man determined by radiommunoassay: biologic significance. Mt Sinai J Med. 1973 May-Jun;40(3):502–510. [PubMed] [Google Scholar]
  19. Saberi M., Utiger R. D. Augmentation of thyrotropin responses to thyrotropin-releasing hormone following small decreases in serum thyroid hormone concentrations. J Clin Endocrinol Metab. 1975 Mar;40(3):435–441. doi: 10.1210/jcem-40-3-435. [DOI] [PubMed] [Google Scholar]
  20. Schimmel M., Utiger R. D. Thyroidal and peripheral production of thyroid hormones. Review of recent findings and their clinical implications. Ann Intern Med. 1977 Dec;87(6):760–768. doi: 10.7326/0003-4819-87-6-760. [DOI] [PubMed] [Google Scholar]
  21. Snyder P. J., Jacobs L. S., Rabello M. M., Sterling F. H., Shore R. N., Utiger R. D., Daughaday W. H. Diagnostic value of thyrotrophin-releasing hormone in pituitary and hypothalamic diseases. Assessment of thyrotrophin and prolactin secretion in 100 patients. Ann Intern Med. 1974 Dec;81(6):751–757. doi: 10.7326/0003-4819-81-6-751. [DOI] [PubMed] [Google Scholar]
  22. Snyder P. J., Utiger R. D. Inhibition of thyrotropin response to thyrotropin-releasing hormone by small quantities of thyroid hormones. J Clin Invest. 1972 Aug;51(8):2077–2084. doi: 10.1172/JCI107014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Snyder P. J., Utiger R. D. Response to thyrotropin releasing hormone (TRH) in normal man. J Clin Endocrinol Metab. 1972 Feb;34(2):380–385. doi: 10.1210/jcem-34-2-380. [DOI] [PubMed] [Google Scholar]
  24. Spector D. A., Davis P. J., Helderman J. H., Bell B., Utiger R. D. Thyroid function and metabolic state in chronic renal failure. Ann Intern Med. 1976 Dec;85(6):724–730. doi: 10.7326/0003-4819-85-6-724. [DOI] [PubMed] [Google Scholar]
  25. Surks M. I., Schadlow A. R., Oppenheimer J. H. A new radioimmunoassay for plasma L-triiodothyronine: measurements in thyroid disease and in patients maintained on hormonal replacement. J Clin Invest. 1972 Dec;51(12):3104–3113. doi: 10.1172/JCI107137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Vagenakis A. G., Rapoport B., Azizi F., Portnay G. I., Braverman L. E., Ingbar S. H. Hyperresponse to thyrotropin-releasing hormone accompanying small decreases in serum thyroid hormone concentrations. J Clin Invest. 1974 Oct;54(4):913–918. doi: 10.1172/JCI107831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vinik A. I., Kalk W. J., McLaren H., Hendricks S., Pimstone B. L. Fasting blunts the TSH response to synthetic thyrotropin-releasing hormone (TRH). J Clin Endocrinol Metab. 1975 Mar;40(3):509–511. doi: 10.1210/jcem-40-3-509. [DOI] [PubMed] [Google Scholar]
  28. Walfish P. G., Orrego H., Israel Y., Blake J., Kalant H. Serum triiodothyronine and other clinical and laboratory indices of alcoholic liver disease. Ann Intern Med. 1979 Jul;91(1):13–16. doi: 10.7326/0003-4819-91-1-13. [DOI] [PubMed] [Google Scholar]

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