Analysis of mRNA expression for steroidogenic enzymes in the remaining adrenal cortices attached to adrenocortical adenomas.

Shigematsu, Kazuto; Nakagaki, Takehiro; Yamaguchi, Naohiro; Kawai, Kioko; Sakai, Hideki; Takahara, Osamu

doi:10.1530/eje-07-0626

Cited by 12 publications

(13 citation statements)

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“…In addition to two adenomas, minute nodules with aldosterone production were observed in bilateral normal-appearing adrenal cortex. These nodules are similar to the lesions often found in cases of unilateral [18] and bilateral adrenal hyperplasia. Furthermore, spironolactone bodies were clearly found in these minute nodules, indicating continuous aldosterone production by the Surgical removal of the tumors is a therapy of choice in cases of functional adrenal tumor.…”

Section: Discussionsupporting

confidence: 80%

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Cushing's Syndrome by Left Adrenocortical Adenoma Synchronously Associated with Primary Aldosteronism by Right Adrenocortical Adenoma: Report of a Case

et al. 2009

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mal range; 30-159) pg/ml and 10 (4.4-17.4) µg/dl, respectively. Although her plasma renin activity (PRA) and ACTH was suppressed to an undetectable level, no further examination was conducted or followedup. One year later, hypertension and progressive edema in the lower extremities gradually appeared. Reexamination revealed hypopotassemia and elevation of plasma aldosterone level as high as 216 (normal range; 30-159) pg/ml, with low PRA as 0.3 (0.5-2.0) ng/ml/ hr. Magnetic resonance imaging demonstrated that the right adrenal mass did not enlarge. Abstract. Synchronous associations of Cushing's syndrome (CS) and primary aldosteronism (PA) with multiple adrenocortical adenomas secreting each hormone independently have rarely been reported. Herein, we describe a unique case of PA associated with CS with detailed clinical and pathological investigations. bilateral adrenal masses with clinical symptoms of CS and PA were found in a 43-year-old woman. Venous sampling demonstrated excess secretion of cortisol, and aldosterone from right, and left tumor, respectively. A bilateral laparoscopic partial adrenalectomy was undergone. The right adrenal tumor (3 cm) was yellow in color with abundant lipofuscin granules, and was composed of both eosinophilic compact cells and clear cells. In situ hybridization showed that both mRNAs for HSd3b2 and CYP17A1 were strongly expressed in the tumor, suggesting cortisol synthesis. Left adrenal tumor (2.4 cm) was golden-yellow in color, and composed of clear cells only. expression of HSd3b2 and CYP11b mRNAs were observed in the tumor compatible with the aldosterone synthesis. Furthermore, minute nodules were found at the surface of normal-appearing cortex on both sides of the adrenal glands, and the expression of HSd3b2 and CYP11b mRNAs was clearly demonstrated within the nodules, indicating aldosterone synthesis. we diagnosed that the present case had 1) cortisol-producing right adrenocortical adenoma, 2) aldosterone producing left adrenocortical adenoma, and 3) cortical minute nodules with aldosterone production in both adrenal glands compatible with idiopathic adrenal hyperplasia. we reviewed the cases reported, and discussed the significance of the minute nodules in the adrenal cortex, often found in association with the adrenocortical adenoma.Key words: Adrenal gland, Cushing's syndrome, primary aldosteronism, bilateral adrenocortical adenomas, Laparoscopic adrenalectomy (Endocrine Journal 56: [495][496][497][498][499][500][501][502] 2009) A JApAnese woman was admitted to a local hospital for the treatment of her depression when she was age 35. Right adrenal mass of less than 20 mm was demonstrated by imaging studies during her workup. At this time, both plasma aldosterone and plasma cortisol levels were within normal limits, at 72 (nor-

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Section: Discussionsupporting

confidence: 80%

“…could be found not only in cases with aldosteroneproducing adenoma, but also that with cortisol-producing adenoma or incidentaloma when investigated by ISH [18]. The pathogenesis and the clinical relevance of this functioning minute nodule have yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

Cushing's Syndrome by Left Adrenocortical Adenoma Synchronously Associated with Primary Aldosteronism by Right Adrenocortical Adenoma: Report of a Case

et al. 2009

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“…In situ hybridization was performed as described previously [6]. cDNA fragments of melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR), CYP11A1, HSD3B2, CYP11B, CYP17A1, and CYP21A2 were obtained by reverse transcriptase-polymerase chain reaction and subcloned into pT-NOT vector [6].…”

Section: Methodsmentioning

confidence: 99%

Primary Aldosteronism with Aldosterone-Producing Adenoma Consisting of Pure Zona Glomerulosa-Type Cells in a Pregnant Woman

et al. 2009

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C a 2+ is a critical signal for adrenal and gonadal steroid synthesis 1 acting within 2 cellular compartments; Ca 2+ is generated in the cytosol 2,3 and transferred to the mitochondria 4-7 where it activates matrix dehydrogenases to generate reducing equivalents (NAD(P)H) that are essential cofactors for steroid hydroxylation. 8 In aldosterone-producing zona glomerulosa (ZG) cells of the adrenal cortex, the dominant pathway for extra-cellular Ca 2+ entry into the cytoplasmic compartment is plasma membrane voltage-gated Ca 2+ channels, 9 whereas the principal pathway for mitochondrial Ca 2+ uptake is via the mitochon-drial uniporter, a Ca 2+-selective channel. 10 Membrane voltage across each of these compartments regulates Ca 2+ transport and thus the rate of steroid production. Because other ion channels resident in each membrane (plasma and mitochondrial) can change membrane voltage, they too are capable of altering Ca 2+ uptake by mitochondria. 11 Accordingly, it is not surprising that genetic variation in genes encoding ion channels and transporters is now considered central to the pathophysiology of 1 common subtype of primary hyperaldosteronism, unilateral aldosterone-producing adenoma. 12 In aldosterone-producing adenoma, aldosterone synthesis is not strictly controlled by the renin-angiotensin II system and thus is characterized by a large increase in the aldosterone/renin ratio. 13 Yet, the cause of other common endocrine hypertensive disorders in which aldosterone production is inappropriate for the level of renin, such as bilateral adrenal hyperplasia and low renin essential hypertension, 14,15 still remains poorly understood. Our laboratory and that of Barhanin et al have generated mouse models of aldosterone overproduction evoked by deletion of leak potassium channels that generate background currents to establish a negative resting cell membrane voltage. 16-20 The combined deletion of TASK-1 and TASK-3 channels (tandem pore domain acid-sensitive K + channels) leads to excessive aldosterone overproduction and low renin in mice. By contrast, deletion of TASK-3 alone evokes mild hyperal-dosteronism and low renin, 19 whereas that of TASK-1 elicits mild hyperaldosteronism without an accompanying suppression of renin. 21 Genetic variations in the human TASK-1 gene (KCNK3) 21-23 are associated with measures of hypertension (rs1275988, rs13394970) and elevated plasma aldosterone (rs2586886), and KCNK3 mRNA is abundantly expressed in mouse and human adrenal cortex. 24 By contrast, the KCNK9 gene product, TASK-3, is principally expressed in the rodent adrenal cortex, 25 although low levels of message are detected in the human adrenal cortex. 26 The function of TASK-3 in adrenal cortical cells remains unknown. We previously reported that global deletion of TASK-3 in mice produces a mild hyperaldosteronism even though the cell Abstract-Ca 2+ drives aldosterone synthesis in the cytosolic and mitochondrial compartments of the adrenal zona glomerulosa cell. Membrane potential across each of these compartments regu...

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“…Total RNA was collected from frozen adenoma tissues using GenElute Mammalian Total RNA kit (Sigma-Aldrich). After the reverse transcriptase reaction, LightCycler Quick System 330 (Roche Diagnostics K K) was used for the real-time PCR (7). Sequence-specific primers were designed and assigned the following GenBank accession numbers: SYP (X06389: 225-249 and 357-333), 140-kDa NCAM (M17410: 919-937 and 993-972), CYP11B2 (X54741: 2637-2658 and 2724-2699), and CYP17A1 (M14564: 1203-1226 and 1339-1315).…”

Section: Real-time Pcrmentioning

confidence: 99%

Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression

Shigematsu

Nishida²,

Sakai³

et al. 2009

European Journal of Endocrinology

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Design and methods: The adrenal cortex is not considered to be an intrinsic part of the diffuse neuroendocrine system, but adrenocortical neoplasms possess neuroendocrine properties. In this study, we examined synaptophysin (SYP) and neural cell adhesion molecule (NCAM) expression in adrenocortical adenomas in relation to adrenal function. Results: Immunohistochemical analysis showed that 50.7 and 98.6% of the cortical adenomas showed SYP and NCAM immunoreactivities respectively. There was no apparent difference in NCAM immunoreactivity among the adenomas. However, the immunostaining for SYP was significantly stronger in cortisol-producing adenomas (CPA) than in aldosterone-producing adenomas (APA), nonfunctioning adenomas (NFA), showing no clinical or endocrinological abnormality, or adenomas associated with preclinical Cushing's syndrome (preCS). Western blotting and real-time PCR demonstrated that the expression level of SYP protein and mRNA was significantly higher in CPA than in APA or NFA. Additionally, the SYP mRNA level showed a positive correlation with CYP17A1 mRNA. In addition to the plasma membrane, mitochondria, and smooth endoplasmic reticulum, SYP immunoreactivity was detected in the Golgi area, which is known to be involved in the regulation of mitochondrial cholesterol and the transport of steroid intermediates. It was unexpected that the ratio of positive cells for SYP in preCS was less than that in APA and NFA. However, further examination is required, because the number of preCS cases we investigated was very small. Conclusions: We propose that SYP expression in adrenocortical cells may be involved in some aspect of adrenal function such as transport or secretion of glucocorticoids.European Journal of Endocrinology 161 939-945

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Analysis of mRNA expression for steroidogenic enzymes in the remaining adrenal cortices attached to adrenocortical adenomas.

Cited by 12 publications

References 30 publications

Cushing's Syndrome by Left Adrenocortical Adenoma Synchronously Associated with Primary Aldosteronism by Right Adrenocortical Adenoma: Report of a Case

Cushing's Syndrome by Left Adrenocortical Adenoma Synchronously Associated with Primary Aldosteronism by Right Adrenocortical Adenoma: Report of a Case

Primary Aldosteronism with Aldosterone-Producing Adenoma Consisting of Pure Zona Glomerulosa-Type Cells in a Pregnant Woman

Synaptophysin immunoreactivity in adrenocortical adenomas: a correlation between synaptophysin and CYP17A1 expression

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