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Mitsuhide Naruse

Publications and source records attributed to Mitsuhide Naruse.

30 records · Page 2Linked to original sources
PubMed2004

Adrenocortical hyperplasia associated with ACTH-dependent Cushing's syndrome: comparison of the size of adrenal glands with clinical and endocrinological data.

Diffuse or nodular hyperplasia of adrenal glands is associated frequently with ACTH-dependent Cushing's syndrome. We carried out a retrospective analysis of 28 patients with ACTH-dependent Cushing's syndrome admitted to our institution between 1984 and 1999 in order to clarify the incidence of adrenal hyperplasia in ACTH-dependent Cushing's syndrome and also to determine the correlation between adrenal gland images and clinical, biochemical and endocrinological data. Of the 28 patients, 16 (57%) showed diffuse adrenal hyperplasia while only 3 had focal adrenal nodules in the hypertrophied adrenals. There was a positive, significant correlation between the width of the adrenal glands measured on CT and circulating plasma ACTH, cortisol levels and urinary free cortisol (UFC) levels. Duration of the disease also correlated positively with adrenal width. No correlation was found between age and adrenal size and there was no difference in the prevalence of diffuse hyperplasia between normotensive and hypertensive patients. These results suggest that chronic ACTH hypersecretion may lead to diffuse adrenal hyperplasia in patients with ACTH-dependent Cushing's syndrome.

ACTH Syndrome, Ectopic↗
PubMed2004

[Aldosterone].

Aldosterone is one the representative cardiovascular hormones involved in the blood pressure and body-fluid homeostasis. Elevation of aldosterone leads to systemic hypertension through its action on the mineralocorticoid receptor (MR) in the kidney. More recent studies demonstrated that aldosterone may produce target organ damage through its direct actions on the non-epithelial MR of the heart in addition to its systemic effects. Clinical experience in primary aldosteronism supports the concept that aldosterone is a risk factor of cardiovascular complications, since concentric type of cardiac hypertrophy is most common in primary aldosteronism among various types of endocrine hypertension. Clinical mega-trial in congestive heart failure (RALES study, EPHESUS study) demonstrated blocking angiotensin II action is not sufficient for cardioprotection unless aldosterone action is equally blocked. An important phenomenon related to this issue is the aldosterone breakthrough which implies a reelevation of plasma aldosterone during chronic administration of ACE inhibitors and Angiotensin receptor antagonists. Normal level of aldosterone could still be a risk factor. Combination of ACE inhibitor or ARB with aldosterone antagonist could result in a better cardioprotection in cardiovascular diseases. Although spironolactone has been the only one aldosterone antagonist, a new antagonist eplerenone has been developed. Eplerenone is specific to MR and is practically devoid of the major side effect gynecomastia of spironolactone. Another topic of aldosterone is its very quick cardiovascular effect presumably via a non-genomic action. All these recent findings support that this adrenocortical steroid hormone is as important as angiotensin II. Determining aldosterone levels is therefore much morel important than before in the diagnosis and treatment of cardiovascular diseases.

Aldosterone↗
PubMed2003

Effectiveness of aldosterone blockade in patients with diabetic nephropathy.

It has been reported that continuous ACE inhibitor therapy does not necessarily produce a maintained decrease in plasma aldosterone levels, which may remain high or increase eventually during long-term use (aldosterone escape). We have examined the role of aldosterone escape in 45 patients with type 2 diabetes and early nephropathy treated with an ACE inhibitor for 40 weeks. With treatment, there was a 40% reduction in average urinary albumin excretion, although urinary albumin excretion in patients with aldosterone escape (18 patients) was significantly higher than that in patients without escape (27 patients). In the 18 patients with escape, spironolactone (25 mg/d) was added to ACE inhibitor treatment in 13. After a 24-week study period, urinary albumin excretion and left ventricular mass index were significantly reduced without blood pressure change. In conclusion, the present study demonstrates that aldosterone escape is observed in 40% of patients with type 2 diabetes with early nephropathy despite the use of ACE inhibitors. Our study suggests the possibility that aldosterone blockade may represent optimal therapy for patients with early diabetic nephropathy who show aldosterone escape during ACE inhibitor treatment and who no longer show maximal antiproteinuric effects of ACE inhibition. Additional, larger, prospectively randomized, double-blind studies will be needed before adaptation of this strategy.

Albuminuria↗
PubMed2003

Variability in the renin/aldosterone profile under random and standardized sampling conditions in primary aldosteronism.

An increased plasma aldosterone concentration (PAC) with decreased plasma renin activity (PRA) is the abnormal endocrine finding in primary aldosteronism (PA). However, it remains unknown whether this profile is universal when blood samples are obtained in a random manner. We retrospectively evaluated the renin/aldosterone profile in 71 patients with PA due to unilateral adrenal adenoma. Blood samples were obtained randomly at an out-patient clinic and under standardized conditions during hospitalization before surgery. The frequency of PAC above 15 ng/dl, PRA below 0.5 ng angiotensin I/ml x h, and a PAC/PRA ratio greater than 35 was determined. These three variables showed a large intra- and interpatient variation. At least one measurement of PAC, PRA, and PAC/PRA ratio was in the normal range in 39%, 48%, and 31% of patients, respectively. Only 37% of patients always had the characteristic profile associated with PA. The mean values of PAC at the out-patient clinic were slightly, but significantly, lower than those in the hospital. These results clearly demonstrated that the renin/aldosterone profile in PA is not always abnormal due in part to conditions for blood sampling. We conclude that a single normal PAC, PRA, or PAC/PRA ratio does not excluded the diagnosis of PA in a hypertensive patient, but repeated measurements yields one or more abnormal parameters in the vast majority of patients. The PAC/PRA ratio is recommended to use as a screening, but other testing is required to arrive at the correct diagnosis.

Adenoma↗
PubMed2002

Aldosterone breakthrough during angiotensin II receptor antagonist therapy in stroke-prone spontaneously hypertensive rats.

Aldosterone breakthrough during ACE inhibitor therapy has been reported. This study investigates changes in plasma aldosterone concentration (PAC) and its mechanism and effects on target organ damage during long-term angiotensin II type 1 (AT1) receptor antagonist (AT1A) therapy in hypertensive rats. An AT1A (candesartan, 1 mg/kg per day PO) was administered in stroke-prone spontaneously hypertensive rats from 4 weeks of age for 34 weeks. PAC was significantly decreased during the first 4 weeks but showed aldosterone breakthrough after 8 weeks of AT1A administration. Plasma angiotensin II concentration was significantly elevated, whereas no change was seen in plasma ACTH or serum potassium. The mechanism(s) of aldosterone breakthrough were investigated by giving high doses of candesartan (3 mg/kg per day PO), dexamethasone (200 microg/kg per day IP), or the AT2 antagonist (PD123319, 10 mg/kg per day SC) during the last week of the 24-week AT1A treatment period. Dexamethasone and AT2 antagonist but not high-dose AT1A produced a significant decrease in PAC, with a larger decrease produced by the AT2 antagonist. To clarify the effects of the residual aldosterone, effects of coadministration of low-dose spironolactone (10 mg/kg per day SC), an aldosterone antagonist, on left ventricular hypertrophy and expression of brain natriuretic peptide mRNA were determined. Low-dose spironolactone further improved left ventricular hypertrophy and brain natriuretic peptide mRNA expression despite no additional depressor effect. These results suggest that aldosterone breakthrough occurs during long-term AT1A therapy, mainly by an AT2-dependent mechanism. Residual aldosterone may attenuate the cardioprotective effects of AT1A.

Adrenocorticotropic Hormone↗
PubMed2002

[Significance of combining spironolactone during long-term administration of ARB].

Blocking aldosterone action has been of clinical interest in the treatment of hypertension and related target organ damage. Although we have previously demonstrated aldosterone escape during long term administration of AT1 antagonist, pathological significance of aldosterone remains unknown. We investigated the effects of co-administration of spironolactone(SPRL) on the cardioprotective effects of AT1A in SHR-SP. Administration of AT1A alone resulted in a significant decrease in cardiac weight, cardiac transverse section area, cardiac fibrosis, and mRNA expression of BNP, type I and type III collagen, while cardiac ET-1 mRNA showed a significant increase. Co-administration of AT1A with SPRL resulted in a significant decrease in all the parameters including ET-1 mRNA expression. These results provide theoretical rationale for combination therapy of AT1A and SPRL in hypertension.

Angiotensin Receptor Antagonists↗