Primary aldosteronism treated by trilostane (3,β-hydroxysteroid dehydrogenase inhibitor)

Nakada, Teruhiro; Kazama, T; Koike, Hiroshi; Yoshikawa, Munehide; Ishikawa, Shigeaki; Katayama, Takashi

doi:10.1016/0090-4295(85)90548-5

Cited by 15 publications

(7 citation statements)

References 16 publications

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“…Adrenal surgery in patients with APA improved these values, but trilostane therapy in patients with IHA failed to ameliorate the results of these clear ance studies. Trilostane has been shown to be effective in the amelioration of hypertension and biochemical ab normalities in patients with IHA [18]. However, im paired urinary concentrating ability in patients with IHA will need some form of additional therapy in future.…”

Section: Discussionmentioning

confidence: 99%

“…Subsequent operative procedures were performed in 7 of 8 patients with aldosterone-producing adenoma (APA). The underlying metabolic lesions of these subjects and their treatments have been described elsewhere [ 17,18], Twelve patients with essen tial hypertension (WHO grade II) were also included in this study. The clinical characteristics of the patients are summarized in table I.…”

Section: Methodsmentioning

confidence: 99%

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Evidence for a Defect in Urinary Concentrating Ability in Primary Aldosteronism and Its Reversal by Adrenal Surgery

1987

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Of 15 patients with primary aldosteronism, 7 had idiopathic adrenal hyperplasia (IHA) and 8 had aldosterone-producing adenoma (APA). In order to determine any renal problems involved in the treatment, the renal clearance of these patients was analyzed and the results compared with those obtained from 12 patients with essential hypertension. With water diuresis or under antidiuresis status, levels of urine volume, C_osm and C_H2O in patients with APA were greater (p < 0.05 – p < 0.001) than those of patients with essential hypertension, while the fractional tubular sodium delivery of the former patients was lower than that of the latter patients (p < 0.001 or < 0.05). A similar tendency was observed in clearance studies in patients with IHA, although to a lesser extent. Adrenal surgery for patients with APA normalized these values, but administration of trilostane (3β-hydrosteroid dehydrogenase inhibitor) to patients with IHA failed to improve these values. These results indicate that impaired urinary concentrating ability as well as reduced urinary diluting capability is a common feature of primary aldosteronism. Such impaired renal function was improved only in patients with APA after adrenal surgery.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Evidence for a Defect in Urinary Concentrating Ability in Primary Aldosteronism and Its Reversal by Adrenal Surgery

1987

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“…Trilostane has also been used to treat hyperaldosteronism and has been shown to be a feasible therapeutic option for long-term treatment of hyperaldosteronism in humans, caused by either aldosterone-producing adenomas or adrenal hyperplasia [47,48]. Treatment with 240 mg/day can correct both hypokalaemia and hyperaldosteronism and can reduce diastolic blood pressure [43].…”

Section: Trilostane In Adrenocortical Hyperfunctionmentioning

confidence: 98%

Trilostane in advanced breast cancer

Puddefoot

Barker

Vinson

2006

Expert Opinion on Pharmacotherapy

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Antiestrogens, principally tamoxifen, and aromatase inhibitors have been used as the first- and second-line therapy in patients with advanced postmenopausal breast cancer for many years. However, some patients acquire resistance to these treatments and, at present, further endocrine treatment is achieved by merely substituting the current medication with a different antiestrogen or aromatase inhibitor. Trilostane offers an alternative endocrine treatment due to its unique mode of action. It is an allosteric modulator of the estrogen receptor and targets both the estrogen- and growth factor-dependent pathways through which estradiol stimulates cell proliferation. In clinical trials, trilostane has been shown to be an effective treatment for breast cancer in patients who have relapsed after receiving treatment with one or more forms of endocrine therapy. Ongoing and future clinical trials are examining the potential for the use of trilostane in premenopausal breast cancer, as well as in other malignancies such as prostate cancer.

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“…The increment of Hsd3b6 within the ZG cells of the Cry-null adrenal gland was confirmed at the protein and enzymatic activity levels. 6) Furthermore, pharmacologic inhibition of 3β-HSD enzymatic activity in vivo by treating mice with trilostane (2α-cyano-4α,5α-epoxy-17β-olandrostane-3-one) [53][54][55][56] leads to the reduction of PAC in Cry-null mice. These observations suggest that Hsd3b6 is a rate-limiting enzyme for aldosterone production and that the chronic elevation of its activity instigates abnormally high synthesis of aldosterone in the adrenal gland.…”

Section: Identification Of Hsd3b6 As a New Hypertension Risk Factor Lmentioning

confidence: 99%

“…Broad inhibition of 3β-HSD activity leads to reduced production of all steroids, affecting not only aldosterone but also cortisol and sex hormones. 55,56) Because of the lack of subtype specificity, trilostane (the broad-spectrum inhibitor used for the treatment of Cry-null mice) 6) is not currently available for antialdosterone therapy. Thus, the spatiofunctional specificity of HSD3B1 raises the prospect that the development of a subtype-selective inhibitor of HSD3B1 would help circumvent undesired side effects and create new specific therapies for antialdosterone control.…”

Section: Identification Of a Human Orthologue Of Hsd3b6 As A Key Targmentioning

confidence: 99%

Circadian Clock-Deficient Mice as a Tool for Exploring Disease Etiology

Doi

2012

Biological & Pharmaceutical Bulletin

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One of the most significant conceptual changes brought about by the analysis of circadian clock-deficient mice is that abnormalities in the circadian clock are linked not only to sleep arousal disorder but also to a wide variety of common diseases, including hypertension, diabetes, obesity, and cancer. It has recently been shown that the disruption of the two cryptochrome genes Cry1 and Cry2-core elements of the circadian clock-induces salt-dependent hypertension due to abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal gland. This adrenal disorder occurs as a result of increased expression of Hsd3b6, a newly identified steroidogenic enzyme that regulates aldosterone production within the adrenal zona glomerular cells. Importantly, this enzyme is functionally conserved in humans, and the pathophysiologic condition of human idiopathic hyperaldosteronism resembles that of Cry1/2-deficient mice. This review highlights the potential utility of circadian clock-deficient mice as a tool for exploring hitherto unknown disease etiology linked to the circadian clock.

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Primary aldosteronism treated by trilostane (3,β-hydroxysteroid dehydrogenase inhibitor)

Cited by 15 publications

References 16 publications

Evidence for a Defect in Urinary Concentrating Ability in Primary Aldosteronism and Its Reversal by Adrenal Surgery

Evidence for a Defect in Urinary Concentrating Ability in Primary Aldosteronism and Its Reversal by Adrenal Surgery

Trilostane in advanced breast cancer

Circadian Clock-Deficient Mice as a Tool for Exploring Disease Etiology

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