Abstract
The formation of spironolactone (S) bodies, eosinophilic laminated cytoplasmic inclusions, is induced in the aldosterone-producing cells of the human adrenal cortex after the administration of spironolactone. The aim of this study was to define the enzyme histochemical characteristics of S bodies, S-body-containing cells, and the apparently hyperplastic zona glomerulosa (zG) of adrenal tissues attached to aldosteronomas. S bodies were found in 14 of 19 aldosteronomas, in 10 of 19 adrenal tissues attached to aldosteronomas, and in the adrenal tissues in a patient with aldosteronism due to bilateral diffuse zG hyperplasia. The S bodies themselves exhibited most intense 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) activity but did not exhibit glucose-6-phosphate dehydrogenase (G6PD), NADP-dependent isocitrate dehydrogenase (NADP-ICDH), or succinate dehydrogenase (SDH) activity, confirming histochemically the origin of S bodies in the smooth endoplasmic reticulum. In two adenomas, S bodies were found to be surrounded by reaction products of acid hydrolase but were not found in the other adenomas and the remaining adrenal tissues. S-body-containing cells, irrespective of being neoplastic or not, showed enhanced 3 beta HSD, G6PD, and NADP-ICDH activity and weak SDH activity (Type I pattern of enzyme activity). Though zG was hyperplastic in most of the adrenal tissues attached to the adenomas, zG cells that did not contain S bodies showed the opposite pattern (Type II pattern) of enzyme activity (ie, weak 3 beta HSD, G6PD, and NADP-ICDH activity and intense SDH activity), in contrast to those in the adrenal tissues in a patient with aldosteronism due to bilateral diffuse zG hyperplasia (which showed the Type I pattern). The results are consistent with the view that hyperplastic zG cells, except S-body-containing cells, in the case of aldosteronoma are not hyperfunctioning. The latter cells may have enhanced but possibly abortive steroidogenic activity.
Full text
PDF![404](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2468/1903848/15bc203d139a/amjpathol00219-0072.png)
![405](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2468/1903848/a0725e133fb9/amjpathol00219-0073.png)
![406](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2468/1903848/497619c2055e/amjpathol00219-0074.png)
![407](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2468/1903848/eab53d4277d1/amjpathol00219-0075.png)
![408](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2468/1903848/843ec3801084/amjpathol00219-0076.png)
![409](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2468/1903848/aa5683a22c1d/amjpathol00219-0077.png)
![410](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2468/1903848/71bcfba10250/amjpathol00219-0078.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aiba M., Kameya T., Suzuki H., Nakamura H., Mizuno Y., Kanno T. Enzyme histochemical and electron microscopic study of a virilizing adrenocortical adenoma. Acta Pathol Jpn. 1978 Jul;28(4):615–626. doi: 10.1111/j.1440-1827.1978.tb00900.x. [DOI] [PubMed] [Google Scholar]
- BURSTONE M. S., KEYES P. H. Studies on calcification. I. The effect of inhibition of enzyme activity on developing bone and dentin. Am J Pathol. 1957 Nov-Dec;33(6):1229–1235. [PMC free article] [PubMed] [Google Scholar]
- Cain D. R., Van de Velde R. L., Shapiro S. J. Spironolactone inclusions in an aldosteronoma. Am J Clin Pathol. 1974 Mar;61(3):412–416. doi: 10.1093/ajcp/61.3.412. [DOI] [PubMed] [Google Scholar]
- Cheng S. C., Suzuki K., Sadee W., Harding B. W. Effects of spironolactone, canrenone and canrenoate-K on cytochrome P450, and 11beta- and 18-hydroxylation in bovine and human adrenal cortical mitochondria. Endocrinology. 1976 Oct;99(4):1097–1106. doi: 10.1210/endo-99-4-1097. [DOI] [PubMed] [Google Scholar]
- Conn J. W., Hinerman D. L. Spironolactone-induced inhibition of aldosterone biosynthesis in primary aldosteronism: morphological and functional studies. Metabolism. 1977 Dec;26(12):1293–1307. doi: 10.1016/0026-0495(77)90026-9. [DOI] [PubMed] [Google Scholar]
- Davis D. A., Medline N. M. Spironolactone (aldactone) bodies: concentric lamellar formations in the adrenal cortices of patients treated with spironolactone. Am J Clin Pathol. 1970 Jul;54(1):22–32. doi: 10.1093/ajcp/54.1.22. [DOI] [PubMed] [Google Scholar]
- Erbler H. C. The effect of saluretics and spironolactone on aldosterone production and electrolyte excretion in man. Naunyn Schmiedebergs Arch Pharmacol. 1974;286(2):145–156. doi: 10.1007/BF00501608. [DOI] [PubMed] [Google Scholar]
- HAYASHI M. HISTOCHEMICAL DEMONSTRATION OF N-ACETYL-BETA-GLUCOSAMINIDASE EMPLOYING NAPHTHOL AS-BI N-ACETYL-BETA -GLUCOSAMINIDE AS SUBSTRATE. J Histochem Cytochem. 1965 May-Jun;13:355–360. doi: 10.1177/13.5.355. [DOI] [PubMed] [Google Scholar]
- HAYASHI M., NAKAJIMA Y., FISHMAN W. H. THE CYTOLOGIC DEMONSTRATION OF BETA-GLUCURONIDASE EMPLOYING NAPHTHOL AS-BI GLUCURONIDE AND HEXAZONIUM PARAROSANILIN; A PRELIMINARY REPORT. J Histochem Cytochem. 1964 Apr;12:293–297. doi: 10.1177/12.4.293. [DOI] [PubMed] [Google Scholar]
- Headon D. R., Hsiao J., Ungar F. The intracellular localization of adrenal 3beta-hydroxysteroid dehydrogenase/delta5-isomerase by density gradient perturbation. Biochem Biophys Res Commun. 1978 Jun 14;82(3):1006–1012. doi: 10.1016/0006-291x(78)90883-5. [DOI] [PubMed] [Google Scholar]
- JANIGAN D. T. Cytoplasmic bodies in the adrenal cortex of patients treated with spirolactone. Lancet. 1963 Apr 20;1(7286):850–852. doi: 10.1016/s0140-6736(63)91624-6. [DOI] [PubMed] [Google Scholar]
- Jenis E. H., Hertzog R. W. Effect of spironolactone on the zona. Light and electron microscopy. Arch Pathol. 1969 Nov;88(5):530–539. [PubMed] [Google Scholar]
- Kovacs K., Horvath E., Singer W. Fine structure and morphogenesis of spironolactone bodies in the zona glomerulosa of the human adrenal cortex. J Clin Pathol. 1973 Dec;26(12):949–957. doi: 10.1136/jcp.26.12.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mori M. Histochemical evaluation of NADP-dependent glucose-6-phosphate and isocitrate dehydrogenases in steroid producing organs and tumors. Arch Histol Jpn. 1967 Feb;28(1):45–57. doi: 10.1679/aohc1950.28.45. [DOI] [PubMed] [Google Scholar]
- NACHLAS M. M., TSOU K. C., DE SOUZA E., CHENG C. S., SELIGMAN A. M. Cytochemical demonstration of succinic dehydrogenase by the use of a new p-nitrophenyl substituted ditetrazole. J Histochem Cytochem. 1957 Jul;5(4):420–436. doi: 10.1177/5.4.420. [DOI] [PubMed] [Google Scholar]
- Okano K., Matsumoto K., Koizumi T., Mizushima T., Mori M. Histochemical comparison of oxidative enzymes in adrenal glands of mammals. Histochemie. 1965 Mar 5;4(6):494–501. doi: 10.1007/BF00281902. [DOI] [PubMed] [Google Scholar]
- Shrago S. S., Waisman J., Cooper P. H. Spironolactone bodies in an adrenal adenoma. Arch Pathol. 1975 Aug;99(8):416–420. [PubMed] [Google Scholar]
- Sundsfjord J. A., Marton P., Jorgensen H., Aakvaag A. Reduced aldosterone secretion during spironolactone treatment in primary aldosteronism: report of a case. J Clin Endocrinol Metab. 1974 Oct;39(4):734–739. doi: 10.1210/jcem-39-4-734. [DOI] [PubMed] [Google Scholar]
- WATTENBERG L. W. Microscopic histochemical demonstration of steroid-3 beta-ol dehydrogenase in tissue sections. J Histochem Cytochem. 1958 Jul;6(4):225–232. doi: 10.1177/6.4.225. [DOI] [PubMed] [Google Scholar]