Skip to main content

Pituitary-adrenal and pituitary-thyroid function during administration of difluocortolone and dexamethasone to human subjects

Summary

In a comparative study in humans pituitary-adrenal and pituitary-thyroid function have been assessed following oral administration of difluocortolone and dexamethasone to groups of volunteers. The results of single dose and multi-dose studies demonstrate that on an equal dose basis difluocortolone is a less potent inhibitor of both functions than dexamethasone. During administration of the former drug adrenal steroids were less suppressed and following multi-dose administration recovery of pituitary adrenal function was more rapid than was the case with dexamethasone.

This is a preview of subscription content, access via your institution.

Abbreviations

Dexamethasone:

1,2-dehydro 9α-fluoro-16α-methylcortisol

Fluocortolone:

1

Difluocortolone:

1,2-dehydro-6α, 9α-dilluoro-16α-methylcorticosterone

References

  • Arimura, A., Bowers, C. Y., Schally, A. V., Saito, M. and Miller, M. C. 1969. Effect of corticotrophin releasing factor, dexamethasone and actinomycin D on the release of ACTH from rat pituitary in vivo and in vitro. Endocrinology, 85, 300.

    PubMed  CAS  Google Scholar 

  • Beardwell, C. G., Burke, C. W. and Cope, C. L. 1968. Urinary free cortisol measured by competitive protein binding. J. Endocrinol. 42, 79.

    CAS  Google Scholar 

  • Beisel, W. R., DiRaimonds, V. C. and Forsham, P. H. 1964. Cortisol transport and disappearance. Ann. Intern. Med. 60, 641.

    PubMed  CAS  Google Scholar 

  • Christy, N. P., Wallace, E. Z. and Jailer, J. H. 1956. Comparative effects of prednisone and cortisone in suppressing the response of the adrenal cortex to exogenous adrenocorticotrophin. J. Clin. Endocrinol. 16, 1059.

    CAS  Article  Google Scholar 

  • Cope, C. L. 1956. Diagnostic use of adrenal inhibition. Brit. Med. J. ii, 193.

    Google Scholar 

  • Cope, C. L. and Black, E. G. 1959. The reliability of some adrenal function tests. Brit. Med. J. ii, 1117.

    Google Scholar 

  • Cope, C. L. and Hurlock, B. 1954. Some aspects of adrenal cortical metabolism. Clin. Sci. 13, 69.

    PubMed  CAS  Google Scholar 

  • Critchlow, V. and Zimmermann, E. 1969. Negative feedback and pituitary-adrenal function in female rats. Amer. J. Physiol. 216, 148.

    PubMed  Google Scholar 

  • Dallman, M. F. and Yates, F. E. 1969. Dynamic asymmetries in the corticosteroid feedback path and distribution-metabolism-binding elements of the adrenocortical system. Ann. N.Y. Acad. Sci. 156. 696.

    PubMed  Article  CAS  Google Scholar 

  • De Kloet, E. R., Van Der Vies, J. and De Wied, D. 1974. The site of the suppressive action of dexamethasone on pituitary-adrenal activity. Endocrinology, 94, 61.

    PubMed  Google Scholar 

  • De Wied, D. 1964. The site of the blocking action of dexamethasone on ACTH release. J. Endocrinol. 29, 29.

    Google Scholar 

  • Duick, D. S., Warren, D. W., Nicoloff, J. T., Otis, C. L. and Croxson, M. S. 1975. Effect of single dose dexamethasone on the concentration of serum triiodothyronine in man. J. Clin. Endocrinol, 39, 1151.

    Google Scholar 

  • Faglia, G. C., Ferrari, P., Beck-Peccoz, P., Spada, A., Travaglini, P. and Ambrosi, B. 1973. Reduced plasma thyrotropin response to thyrotropin-releasing hormone after dexamethasone administration in normal subjects. Hormone Metab. Res. 5, 289.

    CAS  Google Scholar 

  • Few, J. D. 1961. A method for the analysis of urinary 17-hydroxy-corticosteroids. J. Endocrinol. 22, 31.

    PubMed  CAS  Google Scholar 

  • Ganong, W. F. 1970. In ‘The Hypothalamus’ ed by L. Martini, M. Motta and F. Franschini. New York, Academic Press, p. 317.

    Google Scholar 

  • Haigler, E. D., Pittman, J. A., Hershman, J. M. and Baugh, C. M. 1971. Direct evaluation of pituitary thyrotropin reserve utilizing synthetic thyrotropin releasing hormone. J. Clin. Endocrinol. 33, 573.

    CAS  Google Scholar 

  • Hesch, R. D. and Evered, D. 1973. Radioimmunoassay of triiodothyroinine in unextracted human serum. Brit. Med. J. i, 645.

    Google Scholar 

  • Ingbar, S. H. and Freinkel, N. 1955. The influence of ACTH, cortisone and hydrocortisone on the distribution and peripheral metabolism of thyroxine. J. Clin. Invest. 34, 1375.

    PubMed  Article  CAS  Google Scholar 

  • Ingbar, S. H. and Freinkel, N. 1956. ACTH, cortisone and the metabolism of iodine. Metabolism 5, 652.

    PubMed  CAS  Google Scholar 

  • Jacobson, T., Sundberg, M., Kotovirta, M. L. and Strandstrom, L. 1968. Pituitary adrenal function in patients given long-term adrenal steroid treatment. Acta Endocrinol. 59, 76.

    Google Scholar 

  • Jasani, M. K., Boyal, J. A., Greig, W. R., Dalakos, T. G., Browning, M. C. K., Thompson, A. and Buchanan, W. W. 1967. Corticosteroid induced suppression of the hypothalamic-pituitary-adrenal axis: observation on patients given oral corticosteroids for rheumatoid arthritis. Quart. J. Med. 36, 261.

    PubMed  CAS  Google Scholar 

  • Jeffries, W. McK. 1967. Low dose glucocorticoid therapy. Arch. Intern. Med. 119, 265.

    Article  Google Scholar 

  • Jones, M. T., Brush, F. R. and Neame, R. L. B. 1972. Characteristics of fast feedback control of corticotrophin release by corticosteroids. J. Endocrinol. 55, 489.

    PubMed  CAS  Google Scholar 

  • Kendall, J. W., Matsuda, K., Duyck, C. and Greer, M. A. 1963. Neural control of ACTH secretion: effect of acute decrebration in the rat. Endocrinology, 72, 845.

    PubMed  Google Scholar 

  • Lambe, R. F., Tormey, P. D. and Darragh, A. 1971. The early detection of luteal activity. Irish J. Med. Sci. 140, 316.

    PubMed  Article  CAS  Google Scholar 

  • Livanou, T., Ferriman, D. and James, V. H. T. 1967. Recovery of hypothalamo-pituitary-adrenal function after corticosteroid therapy. Lancet ii, 856

    Article  Google Scholar 

  • Mangili, G., Motta, M. and Mortini, L. 1966. In Neuroendocrinology, vol. I, ed. by L. Martini and and W. F. Ganong New York, Academic Press, p. 297.

    Google Scholar 

  • Meikle, A. W., Lagerquist, L. G. and Tyler, F. H. 1973. A plasma dexamethasone radioimmunoassay. Steroids, 22, 193.

    PubMed  Article  CAS  Google Scholar 

  • M.R.C. Committee on Clinical Endocrinology, Memorandum. 1963. Determination of 17-oxosteroids in urine. Lancet i, 1415.

    Google Scholar 

  • Murphy, B. E. P. 1967. Some studies of the protein-binding of steroids and their application to the routine micro and ultramicro measurement of various steroids in body fluids by competitive protein-binding assay. J. Clin. Endocrinol. 27, 973.

    CAS  Google Scholar 

  • Nishida, S., Matsumara, S., Horino, M., Oyama, H. and Atusko, T. 1976. Single-dose 4 hour dexamethasone suppression test in normal men and its application for the diagnosis of Cushings syndrome. Steroids, 28, 411.

    PubMed  Article  CAS  Google Scholar 

  • Odell, W. D., Wilber, J. F. and Paul, W. E. 1965. Radioimmunoassay of thyrotropin in human serum. J. Clin. Endocrinol. Metab. 25, 1179.

    PubMed  CAS  Article  Google Scholar 

  • Ortega, E., Burdick, K. H. and Segre, E. J. 1975. Adrenal suppression by clobetasol propionate. Lancet ii, 1200

    Article  Google Scholar 

  • Otsuki, M., Dakoda, M. and Baba, S. 1973. Influence of glucocorticoids on TRF-induced TSH response in man. J. Clin. Endocrinol. Metab. 36, 95.

    PubMed  CAS  Google Scholar 

  • Paris, J. 1961. Pituitary-adrenal suppression after protracted administration of adrenal cortical hormones. Proc. Mayo Clin. 36, 305.

    CAS  Google Scholar 

  • Robinson, B. H. B., Mattingly, D. and Cope, C. L. 1962. Adrenal function after prolonged corticosteroid therapy. Brit. Med. J. i, 1579.

    Google Scholar 

  • Rodbard, D. and Lewald, J. E. 1970. Computer analysis of radioligand assay and radioimmunoassay data. Acta Endocrinol. Suppl. 147, 79.

    Google Scholar 

  • Rosner, J. M., Cos, J. J., Biglieri, E. G., Hane, S. and Forsham, P. H. 1963. Determination of urinary unconjugated cortisol by glass fibre chromatography in the diagnosis of Cushing's syndrome. J. Clin. Endocrinol. 23, 820.

    CAS  Google Scholar 

  • Smelik, P. G. 1969. The regulation of ACTH secretion. Acta Physiol. Pharmacol. Neerl. 15, 123.

    PubMed  CAS  Google Scholar 

  • Straughton, R. C. D. and August, P. J. 1975. Cushing's syndrome and pituitary-adrenal suppression due to clobetasol proprionate. Brit. Med. J. ii, 419.

    Google Scholar 

  • Taaffe, W. P., O'Kelly, D. A. and Darragh, A. 1975. Simple inexpensive procedure for the measurement of serum thyroxine. Clin. Chim. Acta. 60, 263.

    PubMed  Article  CAS  Google Scholar 

  • Tan, R. S. H. and Samman, P. D. 1974. Pustular psoriasis with adrenal suppression following topical corticosteroids. Proc. Roy. Soc. Med. 67, 8.

    Google Scholar 

  • Vigneri, R., Pezzino, V., Filetti, S., Squatrito, S., Galbiati, A. and Polosa, P. 1975. Effect of dexamethasone on thyroid hormone response to TSH. Metabolism, 24, 1209.

    PubMed  Article  CAS  Google Scholar 

  • Watanabe, H. 1975. Dexamethasone-binding receptor in bovine pituitary cytosol. J. Steroid Biochem. 6, 27.

    PubMed  Article  Google Scholar 

  • Woolf, P. D., Gonzales-Barcena, D., Schalch, D. S., Lee, L. A., Arzac, J. P., Schally, A. Y. and Kastin, A. J. 1973. Lack of effect of steroids on thyrotrophin releasing hormone (TRH) mediated thyrotrophin (TSH) release in man. Neuroendocrinology, 13, 56.

    PubMed  Article  CAS  Google Scholar 

  • Yates, F. E. 1967. In “The Adrenal Cortex” ed. by A. B. Eisenstein. London, J. and A. Churchill Ltd. p. 133.

    Google Scholar 

  • Zimmermann, E. and Critchlow, V. 1972. Shortlatency suppression of pituitary-adrenal function with physiological plasma levels of corticosterone in the female rat. Neuroendocrinology, 9, 235.

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lambe, R.F., O'Kelly, D.A. & Darragh, A. Pituitary-adrenal and pituitary-thyroid function during administration of difluocortolone and dexamethasone to human subjects. I.J.M.S. 147, 15 (1978). https://doi.org/10.1007/BF02939362

Download citation

  • DOI: https://doi.org/10.1007/BF02939362

Keywords

  • Cortisol
  • Dexamethasone
  • Thyroid Stimulate Hormone
  • Plasma Cortisol
  • IRISH Journal