Different expression of 11β-hydroxylase and aldosterone synthase between aldosterone-producing microadenomas and macroadenomas.
Aldosterone-producing adenoma is a major subtype of primary aldosteronism. The number of cases of these adenomas, which are below the detection limit of computed tomography but diagnosed by adrenal venous sampling, has recently been increasing. However, the pathophysiology of these adenomas, especially those manifesting clinically overt hyperaldosteronism despite their small size, remains unknown. Therefore, we examined the correlation between tumor size and the status of intratumoral steroidogenic enzymes involved in aldosterone biosynthesis using immunohistochemistry. Forty patients with surgically proven aldosterone-producing adenomas were retrospectively studied. Multidetector computed tomography, adrenal venous sampling, and laparoscopic adrenalectomy were performed in all of the patients studied. The tumor area at the maximum diameter of the sections was precisely measured by ImageJ software. The status of the steroidogenic enzymes was immunohistochemically analyzed, and the findings were evaluated according to the H-score system, based on both the number of immunopositive cells and relative immunointensity. Adrenal masses were not detected by computed tomography in 20 patients. Blood pressure, plasma aldosterone concentration, urinary aldosterone excretion, and the number of antihypertensive agents also decreased significantly after the surgery in these patients, as well as in the patients with adenomas detectable by computed tomography. Maximum tumor area obtained in the specimens was significantly correlated with preoperative plasma aldosterone concentration, urinary aldosterone excretion, and the H score of 11β-hydroxylase and was inversely correlated with the H score of aldosterone synthase. These results demonstrated that small adenomas could produce sufficient aldosterone to cause clinically overt primary aldosteronism because of the significantly higher aldosterone synthase expression per tumor area.
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Yoshikiyo
Y
Ono
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Yasuhiro
Y
Nakamura
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Takashi
T
Maekawa
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Saulo J A
SJ
Felizola
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Ryo
R
Morimoto
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Yoshitsugu
Y
Iwakura
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Masataka
M
Kudo
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Kazumasa
K
Seiji
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Kei
K
Takase
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Yoichi
Y
Arai
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Celso E
CE
Gomez-Sanchez
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Sadayoshi
S
Ito
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.).
Hironobu
H
Sasano
From the Division of Nephrology, Endocrinology, and Vascular Medicine (Y.O., R.M., Y.I., M.K., S.I., F.S.), Department of Pathology (Y.O., Y.N., T.M., S.J.A.F., H.S.), Department of Diagnostic Radiology (K.S., K.T.), and Department of Urology (Y.A.), Tohoku University Hospital, Sendai, Japan; Endocrine Section, G.V. Montgomery VA Medical Center, Jackson, MS (C.E.G.-S.); and Division of Endocrinology, University of Mississippi Medical Center, Jackson (C.E.G.-S.). fsatoh@med.tohoku.ac.jp.
Fumitoshi
F
Satoh
D000306:Adrenal Cortex Neoplasms / Q000378:metabolism* / Q000473:pathology; D018246:Adrenocortical Adenoma / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000368:Aged; D000450:Aldosterone / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism*
D000450:Aldosterone; D019405:Cytochrome P-450 CYP11B2; D013252:Steroid 11-beta-Hydroxylase
CYP11B1; CYP11B2; adrenocortical adenoma; hyperaldosteronism; hypertension; immunohistochemistry