Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Apr;77(4):1063–1070. doi: 10.1172/JCI112405

Stimulation of gonadal steroid synthesis by chronic excess of adrenocorticotropin in patients with adrenocortical insufficiency.

H Vierhapper, P Nowotny, W Waldhäusl
PMCID: PMC424440  PMID: 3007576

Abstract

Analysis of 24-h urinary steroid excretion was performed by capillary gas chromatography in six patients (five men, one woman) with adrenocortical insufficiency. Ten healthy subjects (five men, five women) served as controls. A complete absence of all 21-hydroxylated steroid metabolites was seen in patients with adrenocortical insufficiency, whereas the excretion of several steroids lacking hydroxylation in the 21-position (pregnenolone, pregnenetriol, and 11-ketoandrosterone) was markedly increased. In addition, the presence of 11 beta-hydroxyandrosterone was confirmed by mass-spectrometry in the urine of three patients. This pattern of steroid excretion was unchanged in patients with adrenocortical insufficiency, both after stimulation by 1-24 adrenocorticotropin (ACTH) and after short-term (3-d) suppression with dexamethasone. We conclude that patients with adrenocortical insufficiency present a pattern of steroid excretion characterized by the absence of 21-hydroxylated metabolites. In the absence of functional adrenocortical tissue, long-term pathologically elevated concentrations of ACTH apparently stimulate early steps of steroid synthesis, most likely in the gonads. In addition, the presence of 11-hydroxylated steroid metabolites (11-ketoandrosterone, 11 beta-hydroxyandrosterone) in the urine of patients with adrenocortical insufficiency demonstrates that chronic ACTH excess in this disorder may induce some activity of 11 beta-hydroxylase, an enzyme not found in the gonads under physiological conditions.

Full text

PDF
1063

Selected References

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

  1. Abraham G. E., Chakmakjian Z. H. Serum steroid levels during the menstrual cycle in a bilaterally adrenalectomized woman. J Clin Endocrinol Metab. 1973 Oct;37(4):581–587. doi: 10.1210/jcem-37-4-581. [DOI] [PubMed] [Google Scholar]
  2. BRADLOW H. L., GALLAGHER T. F. Metabolism of 11 beta-hydroxy-delta 4-androstene-3, 17-dione in congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1959 Dec;19:1575–1580. doi: 10.1210/jcem-19-12-1575. [DOI] [PubMed] [Google Scholar]
  3. Beierwaltes W. H., Sisson J. C., Shapiro B. Diagnosis of adrenal tumors with radionuclide imaging. Spec Top Endocrinol Metab. 1984;6:1–54. [PubMed] [Google Scholar]
  4. Bongiovanni A. M. Acquired adrenal hyperplasia: with special reference to 3 beta-hydroxysteroid dehydrogenase. Fertil Steril. 1981 Jun;35(6):599–608. doi: 10.1016/s0015-0282(16)45548-2. [DOI] [PubMed] [Google Scholar]
  5. Chambaz E. M., Horning E. C. Conversion of steroids to trimethylsilyl derivatives for gas phase analytical studies: reactions of silylating reagents. Anal Biochem. 1969 Jul;30(1):7–24. doi: 10.1016/0003-2697(69)90368-6. [DOI] [PubMed] [Google Scholar]
  6. DOMINGUEZ O. V. Biosynthesis of steroids by testicular tumors complicating congenital adrenocortical hyperplasia. J Clin Endocrinol Metab. 1961 Jun;21:663–674. doi: 10.1210/jcem-21-6-663. [DOI] [PubMed] [Google Scholar]
  7. Fore W. W., Bledsoe T., Weber D. M., Akers R., Brooks R. T., Jr Cortisol production by testicular tumors in adrenogenital syndrome. Arch Intern Med. 1972 Jul;130(1):59–63. [PubMed] [Google Scholar]
  8. Goldzieher J. W., Beering S. C. Metabolism of 11-beta-hydroxyandrostenedione, adrenosterone and hydrocortisone to urinary 11-oxy 17-ketosteroids. J Clin Endocrinol Metab. 1969 Feb;29(2):171–178. doi: 10.1210/jcem-29-2-171. [DOI] [PubMed] [Google Scholar]
  9. HAMWI G. J., GWINUP G., MOSTOW J. H., BESCH P. K. ACTIVATION OF TESTICULAR ADRENAL REST TISSUE BY PROLONGED EXCESSIVE ACTH PRODUCTION. J Clin Endocrinol Metab. 1963 Sep;23:861–869. doi: 10.1210/jcem-23-9-861. [DOI] [PubMed] [Google Scholar]
  10. Keutmann E. H., Mason W. B. Individual urinary 17-ketosteroids of healthy persons determined by gas chromatography: biochemical and clinical considerations. J Clin Endocrinol Metab. 1967 Mar;27(3):406–420. doi: 10.1210/jcem-27-3-406. [DOI] [PubMed] [Google Scholar]
  11. LANDING B. H., GOLD E. The occurrence and significance of Leydig cell proliferation in familial adrenal cortical hyperplasia. J Clin Endocrinol Metab. 1951 Dec;11(12):1436–1453. doi: 10.1210/jcem-11-12-1436. [DOI] [PubMed] [Google Scholar]
  12. Luyten J. A., Rutten G. A. Analysis of steroids by high-resolution gas-liquid chromatography. II. Application to urinary samples. J Chromatogr. 1974 Apr 24;91:393–406. doi: 10.1016/s0021-9673(01)97918-x. [DOI] [PubMed] [Google Scholar]
  13. Meikle A. W., Stringham J. D., Wilson D. E., Dolman L. I. Plasma 5 alpha-reduced androgens in men and hirsute women: role of adrenals and gonads. J Clin Endocrinol Metab. 1979 Jun;48(6):969–975. doi: 10.1210/jcem-48-6-969. [DOI] [PubMed] [Google Scholar]
  14. Milewicz A., Vecsei P., Korth-Schütz S., Haack D., Rösler A., Lichtwald K., Lewicka S., von Mittelstaedt G. Development of plasma 21-deoxycortisol radioimmunoassay and application to the diagnosis of patients with 21-hydroxylase deficiency. J Steroid Biochem. 1984 Aug;21(2):185–191. doi: 10.1016/0022-4731(84)90382-0. [DOI] [PubMed] [Google Scholar]
  15. Ney R. L., Dexter R. N., Davis W. W., Garren L. D. A study of mechanisms by which adrenocorticotropic hormone maintains adrenal steroidogenic responsiveness. J Clin Invest. 1967 Dec;46(12):1916–1924. doi: 10.1172/JCI105681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pfaffenberger C. D., Horning E. C. High-resolution biomedical gas chromatography. Determination of human urinary steroid metabolites using glass open tubular capillary columns. J Chromatogr. 1975 Oct 29;112:581–594. doi: 10.1016/s0021-9673(00)99987-4. [DOI] [PubMed] [Google Scholar]
  17. Radfar N., Bartter F. C., Easley R., Kolins J., Javadpour N., Sherins R. J. Evidence for endogenous LH suppression in a man with bilateral testicular tumors and congenital adrenal hyperplasia. J Clin Endocrinol Metab. 1977 Dec;45(6):1194–1204. doi: 10.1210/jcem-45-6-1194. [DOI] [PubMed] [Google Scholar]
  18. Samojlik E., Kirschner M. A., Silber D., Schneider G., Ertel N. H. Elevated production and metabolic clearance rates of androgens in morbidly obese women. J Clin Endocrinol Metab. 1984 Nov;59(5):949–954. doi: 10.1210/jcem-59-5-949. [DOI] [PubMed] [Google Scholar]
  19. Shackleton C. H., Honour J. W. Simultaneous estimation of urinary steroids by semi-automated gas chromatography. Investigation of neo-natal infants and children with abnormal steroid synthesis. Clin Chim Acta. 1976 Jun 1;69(2):267–283. doi: 10.1016/0009-8981(76)90505-2. [DOI] [PubMed] [Google Scholar]
  20. Urban M. D., Lee P. A., Gutai J. P., Migeon C. J. Androgens in pubertal males with Addison's disease. J Clin Endocrinol Metab. 1980 Oct;51(4):925–929. doi: 10.1210/jcem-51-4-925. [DOI] [PubMed] [Google Scholar]
  21. Vierhapper H., Waldhäusl W., Nowotny P. Gonadotrophin-secretion in adrenocortical insufficiency: impact of glucocorticoid substitution. Acta Endocrinol (Copenh) 1982 Dec;101(4):580–585. doi: 10.1530/acta.0.1010580. [DOI] [PubMed] [Google Scholar]
  22. Villee D. B., Fisher J. N. The influence of ACTH on steroid synthesis in normal and abnormal testicular tissues. Adv Enzyme Regul. 1975;13:317–328. [PubMed] [Google Scholar]
  23. Waldhäusl W., Herkner K., Nowotny P., Bratusch-Marrain P. Combined 17 alpha- and 18-hydroxylase deficiency associated with complete male pseudohermaphroditism and hypoaldosteronism. J Clin Endocrinol Metab. 1978 Feb;46(2):236–246. doi: 10.1210/jcem-46-2-236. [DOI] [PubMed] [Google Scholar]
  24. Winkel C. A., Casey M. L., Worley R. J., Madden J. D., MacDonald P. C. Extraadrenal steroid 21-hydroxylase activity in a woman with congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab. 1983 Jan;56(1):104–107. doi: 10.1210/jcem-56-1-104. [DOI] [PubMed] [Google Scholar]
  25. Worgul T. J., Santen R. J., Samojlik E., Wells S. A. How effective is surgical adrenalectomy in lowering steroid hormone concentrations? J Clin Endocrinol Metab. 1982 Jan;54(1):22–26. doi: 10.1210/jcem-54-1-22. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES