Adrenal gland inclusions in patients treated with aldosterone antagonists (Spironolactone/Eplerenone): incidence, morphology, and ultrastructural findings

Diagnostic Pathology

Debra L Zynger¹  Tibor Nadasdy¹  Edward P Calomeni¹  Kishan A Patel¹ 

[1] Department of Pathology, The Ohio State University Medical Center, 410 W 10th Ave, 401 Doan Hall, Columbus, OH 43210, USA

关键词: Inclusions;    Ultrastructural;    Eplerenone;    Spironolactone;    Adrenal;   

Others  :  1228629
DOI  :  10.1186/1746-1596-9-147

 received in 2014-04-12, accepted in 2014-07-07,  发布年份 2014

【 摘 要 】

Background

Spironolactone is often used to treat hypertension caused by hyperaldosteronism, and as a result, can form concentrically laminated electron dense spironolactone body inclusions within the adrenal gland. Spironolactone bodies have not been investigated in a contemporary cohort or in patients treated with the more recently approved aldosterone antagonist, eplerenone.

Methods

Spironolactone bodies were retrospectively investigated in patients treated for hyperaldosteronism (n = 15) from 2012-2013 that underwent a subsequent adrenalectomy.

Results

Inclusions were identified in 33% of patients treated with aldosterone antagonists, far less than previously reported. Remarkably, 50% of patients treated with spironolactone had inclusions while no patients using eplerenone alone had inclusions. Two patients treated with spironolactone had bodies present longer than the duration described in prior studies. Inclusions unexpectedly persisted in 1 patient despite increased duration of discontinued pharmacological treatment. A spectrum of histologic and ultrastructural findings were encountered within an adrenal cortical adenoma from a patient treated with both spironolactone and eplerenone. Ultrastructural examination revealed laminated electron dense bodies with the appearance of classic spironolactone inclusions as well as electron dense bodies without laminations and laminated bodies without electron dense cores.

Conclusions

Our incidence rate of spironolactone bodies was much lower than previously reported, with no inclusions seen in patients treated solely with the newer aldosterone antagonist, eplerenone. Pathologists should be aware of these infrequently encountered inclusions, particularly as the clinical history of hyperaldosteronism and pharmacologic treatment may not be provided.

【 授权许可】

   
2014 Patel et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Janigan DT: Cytoplasmic bodies in the adrenal cortex of patients treated with spirolactone. Lancet 1963, 1:850-852.
• [2]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, 26:949-957.
• [3]Aiba M, Suzuki H, Kageyama K, Murai M, Tazaki H, Abe O, Saruta T: Spironolactone bodies in aldosteronomas and in the attached adrenals. Enzyme histochemical study of 19 cases of primary aldosteronism and a case of aldosteronism due to bilateral diffuse hyperplasia of the zona glomerulosa. Am J Pathol 1981, 103:404-410.
• [4]Hsu SM, Raine L, Martin HF: Spironolactone bodies: an immunoperoxidase study with biochemical correlation. Am J Clin Pathol 1981, 75:92-95.
• [5]Vacher-Lavenu MC, Lellouch-Tubiana A, Louvel A, Daudet-Monsac M, Abelanet R: Spironolactone bodies. Light and electron microscope study apropos of 4 cases of adrenal adenomas with primary hyperaldosteronism. Ann Pathol 1982, 2:311-319.
• [6]Cohn D, Jackson RV, Gordon RD: Factors affecting the frequency of occurrence of spironolactone bodies in aldosteronomas and non-tumorous cortex. Pathology 1983, 15:273-277.
• [7]Kuramoto H, Kumazawa J: Ultrastructural studies of adrenal adenoma causing primary aldosteronism. Virchows Arch A Pathol Anat Histopathol 1985, 407:271-278.
• [8]Conn JW, Hinerman DL: Spironolactone-induced inhibition of aldosterone biosynthesis in primary aldosteronism: morphological and functional studies. Metabolism 1977, 26:1293-1307.
• [9]Jenis EH, Hertzog RW: Effect of spironolactone on the zona: light and electron microscopy. Arch Pathol 1969, 88:530-539.
• [10]Lack EE: Adrenal Cortical Adenoma. In Tumors of the Adrenal Glands and Extraadrenal Paraganglia, AFIP Atlas of Tumor Pathology, Fourth series, Fascicle 8. Edited by Silverberg SG. Washington, DC: ARP Press; 2007:112-124.
• [11]Mete O, Asa SL: Aldosterone-producing adrenal cortical adenoma with oncocytic change and cytoplasmic eosinophilic globular inclusions. Endocr Pathol 2009, 20:182-185.
• [12]Perrino CM, Prall DN, Calomeni EP, Nadasdy T, Zynger DL: Ultrastructural findings in adrenal cortical adenomas clinically mimicking pheochromocytoma: a comparison with other adrenal tumors and tissue preparation techniques. Ultrastruct Pathol 2012, 36:287-293.
• [13]Graham L, Orenstein JM: Processing tissue and cells for transmission electron microscopy in diagnostic pathology and research. Nat Protoc 2007, 2:2439-2450.
• [14]Shrago SS, Waisman J, Cooper PH: Spironolactone bodies in an adrenal adenoma. Arch Pathol 1975, 99:416-420.