Summary
Seven adrenal glands removed from 4 patients suffering from a central-type Cushing's syndrome after various periods of aminoglutethimide (AGL) treatment were subjected to conventional morphological and histochemical, particularly enzyme histochemical, studies and to biochemical incubation studies.
The adrenal glands of the AGL-treated patients showed marked lipoid adrenocortical hyperplasia with an excessive cholesterol or cholesterol ester accumulation leading to cholesterol crystallization and focal dystrophic and necrotic changes in the adrenocortical periphery. Histochemically, the foci of adrenocortical tissue so affected showed an increase in acid phosphatase reaction and a severe reduction of dehydrogenase activity. In chronically treated cases, the adrenal cortex showed some reduction in weight and the necrotic foci were replaced by cicatricose tissue.
The biochemical findings confirmed the blockade of cholesterol side chain cleavage, but the biosynthesis of corticosteroids from pregnenolone was unaffected.
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Camacho, A. M., Brough, A. J., Wilroy, R. S.: Inhibition of adrenal steroidogenesis by amino-glutethimide and the mechanism of action. J. Amer. med. Ass. 202, 114–120 (1967).
Cash, R., Brough, A. J., Cohen, M. N. P., Satoh, P. S.: Aminoglutethimide (Elipten Ciba) as an inhibitor of adrenal steroidogenesis: mechanism of action and therapeutic trial. J. clin. Endocr. 27, 1239–1248 (1967).
Cohen, M. P.: Aminoglutethimide inhibition of adrenal desmolase activity. Proc. Soc. exp. Biol. (N.Y.) 127, 1086–1090 (1968).
Dexter, R. N., Fishman, L. M., Ney, R. L., Liddle, G. W.: Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: Studies on the mechanism of action. J. clin. Endocr. 27, 473–480 (1967).
Elleder, M., Lojda, Z.: Remarks on the “OTAN” reaction. Histochemie 14, 47–64 (1968).
Fishman, L. M., Liddle, G. W., Island, D. P., Fleischer, N., Küchel, O.: Effects of aminoglutethimide on adrenal function in man. J. clin. Endocr. 27, 481–490 (1967).
Frederickson, D. S., Petterson, R. E., Steinberg, D.: Inhibition of adrenocortical steroid secretion by A4-cholestenone. Science 127, 704–705 (1958).
Givens, J. R., Camacho, A., Patterson, P.: Effect of aminoglutethimide and reserpine on the human pituitary-adrenal axis: Remission of a case of Cushing's disease. Metabolism 19, 818–830 (1970).
Givens, J. R., Coleman, S., Britt, L.: Anatomical changes producted in the human adrenal cortex by aminoglutethimide. Clin. Res. 16, 441 (1968).
Hardonk, M. J.: A new method for the histochemical demonstration of steroid-producing cells in human tissues. Histochemie 5, 234–243 (1965).
Hertz, R., Allen, M. J., Schricker, J. A., Dhyse, F. G., Hallman, L. F.: Studies on amphenone and related compounds. Recent Progr. Hormone Res. 11, 119–141 (1955).
Horký, K., Küchel, O., Gregorová, I., Jiránková, J., Matys, Z.: Klinische Erfahrungen mit Aminoglutäthimid (Elipten), einem neuen Inhibitor der Steroidbiosynthese in der Nebenniere. Schweiz. med. Wschr. 98, 1843–1851 (1968).
Hradec, E., Motlík, K.: Morphology of surgically removed adrenals in Cushing's syndrome. XVe Congrés de la Soc. Internat. d'Urol., Tokyo 12–18 Juillet 1970, Tome 2, 211–225 (1970).
Hughes, S. W. M., Burley, D. M.: Aminoglutethimide: A “side effect” turned to therapeutic advantage. Postgrad. med. J. 46, 409–416 (1970).
Kahnt, F. W., Neher, R.: Über die adrenale Steroid-Biosynthese in vitro. III. Selektive Hemmung der Nebennierenrinden-Funktion. Helv. chim. Acta 49, 725–732 (1966).
Kovács, K., Blascheck, J. A., Yeghiayan, E., Hatakeyama, S., Gardell, C.: Adrenocortical lipid hyperplasia induced in rats by aniline: A histologic and electron microscopic study. Amer. J. Path. 62, 17–34 (1971).
Kovács, K., Yeghiayan, E., Hatakeyama, S., Selye, H.: Adrenocortical lipoid hyperplasia induced in rats by aniline. Experientia (Basel) 26, 1014–1015 (1970).
Kracht, J.: Die Nebennierenrinde bei chemischer Adrenostase. Allergie u. Asthma 7, 264–271 (1961).
Lojda, Z., Papoušek, F.: Základy histochemické\(\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle\smile}$}}{h} \)o průkazu enzymů (Fundamentals of enzyme histochemistry) [In Czech]. Brno 1970.
Marek, J., Horký, K., Gregorová, I., Motlík, K.: Further experience with long-term aminoglutethimide treatment of hyperfunctional adrenocortical conditions [In Czech]. Sborn. lék. in press (1973).
Marek, J., Thoenes, W., Motlík, K.: Lipoide Transformation der Mitochondrien der Nebenniere durch Aminoglutethimid. Naturwissenschaften 57, 250–251 (1970a).
Marek, J., Thoenes, W., Motlík, K.: Lipoide Transformation der Mitochondrien in Nebennierenrindenzellen nach Aminoglutethimid (Elipten® Ciba). Virchows Arch. Abt. B 6, 116–131 (1970b).
Motlík, K.: Některé problémy obecné morfologie kůry nadle dvin (Some problems of general adrenocortical morphology) [In Czech]. Acta Univ. Carol. Med. (Praha) Monographia XVII, p. 1–277 (1964).
Motlík, K., Šilha, V., Marek, J.: Adrenocortical, ovarian and thyroid changes in rats following peroral aminoglutethimide (Elipten® Ciba). Acta Univ. Carol. Med. (Praha) in press (1972).
Motlík, K., Stárka, L.: Morphological changes in the endocrine glands of female rats injected with aminoglutethimide (Elipten® Ciba). Acta Univ. Carol. Med. (Praha) in press (1972).
Pearse, A. G. E.: Histochemistry, theoretical and applied. London: Churchill, ed. 2 1960 and 3 1968.
Racela, A., Azarnoff, D., Svoboda, D.: Mitochondrial cavitation and hypertrophy in rat adrenal cortex due to aminoglutethimide. Lab. Invest. 21, 41–60 (1969).
Siebenmann, R. E.: Die kongenitale Lipoidhyperplasie der Nebennierenrinde mit Nebennierenrinden-Insuffizienz. Schweiz. Z. Path. 20, 77–84 (1957).
Smilo, R. P., Earll, J. M., Forsham, P. H.: Suppression of tumorous adrenal hyperfunction by aminoglutethimide. Metabolism 16, 374–377 (1967).
Stárka, L., Motlík, K.: The influence of injected aminoglutethimide on the morphology of the rat adrenal cortex and adrenal metabolism of progesterone. Endokrinologie 58, 75–86 (1971).
Šulcová, J., Stárka, L.: Chromatographische Untersuchungen über den Stoffwechsel im Ovargewebe, J. Wagner, Hrsg..: Chromatographie in der klinischen Biochemie. Leipzig: A. Barth in press 1971.
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Motlík, K., Pinsker, P., Stárka, L. et al. Effects of aminoglutethimide (Elipten® Ciba), a steroid biosynthesis blocking agent, on adrenal glands in Cushing's syndrome. Virchows Arch. Abt. A Path. Anat. 360, 11–26 (1973). https://doi.org/10.1007/BF00548654
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DOI: https://doi.org/10.1007/BF00548654