Atsushi Ogo

Atrial and brain natriuretic peptide in adrenal steroidogenesis

We elucidated the role of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in human and bovine adrenocortical steroidogenesis. The urinary volume, sodium excretion and cyclic GMP (cGMP) excretion and plasma cGMP were markedly increased by the synthetic alpha-human ANP (alpha-hANP) infusion in healthy volunteers. Plasma arginine vasopressin (AVP) and aldosterone levels were significantly suppressed. Both ANP and BNP inhibited aldosterone, 19-OH-androstenedione, cortisol and DHEA secretion dose-dependently and increased the accumulation of intracellular cGMP in cultured human and bovine adrenal cells. alpha-hANP significantly suppressed P450scc-mRNA in cultured bovine adrenal cells stimulated by ACTH. Autoradiography and affinity labeling of [125I]hANP, and Scatchard plot demonstrated a specific ANP receptor in bovine and human adrenal glands. Purified ANP receptor from bovine adrenal glands identified two distinct types of ANP receptors, one is biologically active, the other is silent. A specific BNP receptor was also identified on the human and bovine adrenocortical cell membranes. The binding sites were displaced by unlabelled ANP as well as BNP. BNP showed an effect possibly via a receptor which may be shared with ANP. The mean basal plasma alpha-hANP level was 25 +/- 5 pg/ml in young men. We confirmed the presence of ANP and BNP in bovine and porcine adrenal medulla. Plasma or medullary ANP or BNP may directly modulate the adrenocortical steroidogenesis. We demonstrated that the lack of inhibitory effect of alpha-hANP on cultured aldosterone-producing adenoma (APA) cells was due to the decrease of ANP-specific receptor, which caused the loss of suppression of aldosterone and an increase in intracellular cGMP.

Markedly increased expression of cytochrome P-450 17α-hydroxylase (P-450c17) mRNA in adrenocortical adenomas from patients with Cushing's syndrome

We studied the contents of cortisol (F) and dehydroepiandrosterone (DHEA) and the expression of mRNA of cytochrome P-450 for side-chain cleavage (P-450scc), 17 alpha-hydroxylase (P-450c17), 21 alpha-hydroxylase (P-450c21) and 11 beta-hydroxylase (P-450c11) in adrenocortical adenomas from three patients with Cushings syndrome. The F content was significantly higher in adrenocortical adenomas than in normal adrenal glands, while the DHEA level was similar to that in normal adrenal glands. The adrenal adenomas showed a markedly higher level of P-450c17 mRNA, and a slightly but not significantly increased level of P-450c21 mRNA, compared with normal adrenal glands. The expression of P-450scc and P-450c11 mRNA in the adenomas was similar to that in normal adrenal glands. These results suggest that the overproduction of cortisol in adrenocortical adenomas associated with Cushings syndrome results from an increased expression of P-450c17 and P-450c21 mRNA.

EXPRESSION OF CYTOCHROME P-450 MRNAS IN STEROIDOGENESIS OF ADRENOCORTICAL ADENOMAS FROM PATIENTS WITH PRIMARY ALDOSTERONISM

We studied the contents of aldosterone and cortisol (F) and the expression of mRNA of cytochrome P-450 for side-chain cleavage (P-450scc), 17 alpha-hydroxylase (P-450c17), 21-hydroxylase (P-450c21) and 11 beta-hydroxylase (P-450c11) in adrenocortical adenomas from three patients with primary aldosteronism. The aldosterone content was significantly higher in adrenocortical adenomas than in normal adrenal glands, while F content in adenomas was similar to the level in normal adrenal glands. The aldosterone-producing adenomas showed a markedly higher level of P-450c11 mRNA, a slightly but not significantly increased level of P-450c21 mRNA and a significantly decreased level of P-450c17 mRNA, compared with those in normal adrenal glands. The expression of P-450scc mRNA in adenomas was similar to the level in normal adrenal glands. These results suggested that the renin-independent overproduction of aldosterone in adrenocortical adenomas from the patients with primary aldosteronism results from increasing expression of the mRNA for P-450c11 and decreasing expression of the mRNA for P-450c17.

Importance of contralateral aldosterone suppression during adrenal vein sampling in the subtype evaluation of primary aldosteronism

Adrenal vein sampling (AVS) is the standard criterion for the subtype diagnosis in primary aldosteronism (PA). Although lateralized index (LI) ≥4 after cosyntropin stimulation is the commonly recommended cut‐off for unilateral aldosterone hypersecretion, many of the referral centres in the world use LI cut‐off of <4 without sufficient evidence for its diagnostic accuracy.

Chronic kidney disease score for predicting postoperative masked renal insufficiency in patients with primary aldosteronism.

Chronic kidney disease (CKD) is sometimes unmasked after unilateral adrenalectomy in patients with primary aldosteronism (PA) without expectation.

Decreased Expression of Cytochrome P450 17α-Hydroxylase mRNA in Senescent Bovine Adrenal Gland

To investigate the mechanisms of age-related decline in synthesis of adrenal androgen, we studied the contents of cortisol (F) and dehydroepiandrosterone (DHEA) and the amounts of cytochrome P450 17α-

Adrenal Venous Sampling in Patients With Positive Screening but Negative Confirmatory Testing for Primary Aldosteronism

Adrenal venous sampling is considered to be the most reliable diagnostic procedure to lateralize aldosterone excess in primary aldosteronism (PA). However, normative criteria have not been established partially because of a lack of data in non-PA hypertensive patients. The aim of the study was to investigate aldosterone concentration and its gradient in the adrenal vein of non-PA hypertensive patients. We retrospectively studied the results of cosyntropin-stimulated adrenal venous sampling in 40 hypertensive patients who showed positive screening testing but negative results in 2 confirmatory tests/captopril challenge test and saline infusion test. Plasma aldosterone concentration, aldosterone/cortisol ratio, its higher/lower ratio (lateralization index) in the adrenal vein with cosyntropin stimulation were measured. Median plasma aldosterone concentration in the adrenal vein was 25 819 pg/mL (range, 5154–69 920) in the higher side and 12 953 (range, 1866–36 190) pg/mL in the lower side (P<0.001). There was a significant gradient in aldosterone/cortisol ratio between the higher and the lower sides (27.2 [5.4–66.0] versus 17.3 [4.0–59.0] pg/mL per &mgr;g/dL; P<0.001) with lateralization index ranging from 1.01 to 3.87. The aldosterone lateralization gradient was between 1 to 2 in 32 patients and 2 to 4 in 8 patients. None of the patients showed lateralization index ≥4. The present study demonstrated that plasma aldosterone concentration in the adrenal veins showed significant variation and lateralization gradient even in non-PA hypertensive patients. Adrenal venous sampling aldosterone lateralization gradients between 2 and 4 should be interpreted with caution in patients with PA because these gradients can be found even in patients with negative confirmatory testing for PA.

Optimum position of left adrenal vein sampling for subtype diagnosis in primary aldosteronism

Although adrenal vein sampling (AVS) is the standard method for subtype diagnosis in primary aldosteronism (PA), protocol details including the sampling position in the adrenal vein are not standardized.

Comparison of cystatin C- and creatinine-based estimated glomerular filtration rate to predict coronary heart disease risk in Japanese patients with obesity and diabetes

The aim of this study is to determine which indicator of chronic kidney disease most closely correlates with 10-year Framingham coronary heart disease (CHD) risk among serum creatinine, serum cystatin C (S-CysC), urine albumin-creatinine ratio (UACR), estimated creatinine-based GFRs (eGFRcre), and estimated CysC-based GFRs (eGFRcys) in patients with obesity and diabetes. Serum creatinine, S-CysC, UACR, and cardio-ankle vascular index (CAVI) were examined in 468 outpatients with obesity and type 2 diabetes, free of severe renal dysfunction or previous history of cardiovascular disease, as a cross-sectional survey using baseline data from the multi-centered Japan Diabetes and Obesity Study. S-CysC and eGFRcys had significantly stronger correlations with the 10-year Framingham CHD risk than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.318; S-CysC, ρ = 0.497; UACR, ρ = 0.174; eGFRcre, ρ = -0.291; eGFRcys, ρ = -0.521; P < 0.01 by Fishers z-test). S-CysC and eGFRcys had significantly stronger correlations with CAVI than serum creatinine, eGFRcre, and UACR (creatinine, ρ = 0.198; S-CysC, ρ = 0.383; UACR, ρ = 0.183; eGFRcre, ρ = -0.302; eGFRcys, ρ = -0.444; P < 0.05 by Fishers z-test). The receiver operating characteristic curves to distinguish the high-risk patients for CHD revealed significantly larger areas under the curve of S-CysC and eGFRcys than those of serum creatinine, UACR, and eGFRcre (serum creatinine, 0.64; S-CysC, 0.75; UACR, 0.56; eGFRcre, 0.63; eGFRcys, 0.76; P < 0.01). The data suggested that eGFRcys can be more predictive of the 10-year CHD risk than eGFRcre in Japanese patients with obesity and diabetes.

Accuracy of adrenal computed tomography in predicting the unilateral subtype in young patients with hypokalaemia and elevation of aldosterone in primary aldosteronism

The current Endocrine Society Guideline suggests that patients aged <35 years with marked primary aldosteronism (PA) and unilateral adrenal lesions on adrenal computed tomography (CT) scan may not need adrenal vein sampling (AVS) before proceeding to unilateral adrenalectomy. This suggestion is, however, based on the data from only one report in the literature.