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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

At least 73 records · Page 4Linked to original sources
PubMed1994

Association of restriction fragment length polymorphism at the atrial natriuretic peptide gene locus with aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

Primary aldosteronism is an important, potentially curable, form of hypertension. We examined the possible association between restriction fragment length polymorphisms in the atrial natriuretic peptide (ANP) gene and responsiveness of aldosterone to angiotensin II in 59 patients with primary aldosteronism due to aldosterone-producing adenoma (APA). Significant differences in the allelic frequencies of the BglI, TaqI and XhoI polymorphic sites at the ANP gene locus (chromosome 1; 1p36) between angiotensin II-unresponsive and angiotensin II-responsive tumors were observed. Variation in the ANP gene between the two groups may result in altered expression of ANP within the adrenal gland, and may contribute to the biochemical regulation of aldosterone production of these two subgroups of patients with APA.

Adenoma↗
PubMed1994

The renin gene and aldosterone-producing adenomas.

Approximately one half of the aldosterone-producing adenomas (APA) removed from patients with primary aldosteronism in the Hypertension Unit at Greenslopes Hospital belong to a subgroup in which aldosterone levels are responsive to the renin-angiotensin system (angiotensin-responsive APA; AII-R-APA), unlike classical APAs in which aldosterone is unresponsive (AII-U-APA). Renin mRNA levels in AII-R-APA were elevated when compared with those in AII-U-APA or normal adrenal cortices. Renin mRNA levels in some adrenal cortices surrounding AII-R-APA (but never in AII-U-APA) were raised, suggesting that a genetic defect is not confined to the tumor. Renin gene RFLP analysis in peripheral blood DNA revealed a significant difference in allelic frequencies between patients with AII-R-APA and AII-U-APA, suggesting an association between an alteration in the renin gene and aldosterone responsiveness to the renin-angiotensin system in patients with APAs.

Adenoma↗
PubMed1994

Genetics of primary aldosteronism.

1. In 1991 we described a familial variety of primary hyperaldosteronism which was not glucocorticoid-suppressible and was associated with adenoma formation, and called it familial hyperaldosteronism type II (FH-II) in order to distinguish it from the glucocorticoid-suppressible variety described in 1966, familial hyperaldosteronism type I (FH-I). 2. In 1992 the genetic basis of FH-I was clarified by description of a hybrid gene. 3. Primary aldosteronism due to bilateral adrenocortical hyperplasia or to aldosterone-producing tumour can be part of the multiple endocrine neoplasia type I syndrome (MEN I), in which loss of heterozygosity has been described on chromosome 11q13. Loss of heterozygosity at the MEN I locus was found in five of 26 aldosterone-producing tumours from our series (by Japanese collaborators). These included two with adrenal cancer and two with FH-II. 4. We recently described an association of aldosterone responsiveness of aldosterone-producing adenomas with renin gene restriction fragment length polymorphisms, suggesting a possible role for renin genotype and intra-adrenal renin gene expression in the development and biochemical expression of some aldosterone-producing tumours. 5. We found abnormal karyotypes in 13 of 32 benign aldosterone-producing adenomas.

Family↗
PubMed1994

Renal extraction of atrial natriuretic peptide in unilateral renal artery stenosis.

1. Elevated peripheral atrial natriuretic peptide (ANP) levels were observed in 12 patients with unilateral renal artery stenosis (U-RAS). 2. Renal extraction of ANP was higher across the affected than the unaffected kidney in U-RAS, provided the glomerular filtration rate in the affected kidney was not severely reduced (> 12 mL/min). As ANP is a high clearance compound, reduced flow on the affected side may result in increased renal extraction of ANP. 3. When glomerular filtration rate (GFR) in the affected kidney was severely reduced (< 12 mL/min), renal extraction of ANP was also reduced, possibly contributing to increased circulating ANP levels in this subgroup. 4. Overall, renal extraction of ANP was inversely correlated to peripheral ANP levels in patients with U-RAS. This might be explained by progressive sodium retention as GFR falls leading to volume expansion and increased ANP secretion.

Adult↗
PubMed1994

Renin gene polymorphism associated with aldosterone responsiveness to the renin-angiotensin system in patients with aldosterone-producing adenomas.

1. Aldosterone levels in patients with unilateral aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system, with the former often previously misdiagnosed as bilateral adrenal hyperplasia. 2. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. 3. We compared the frequency of four renin gene polymorphisms in peripheral blood DNA from the two subgroups and found significant associations between BglI, TaqI and HinfI restriction fragment length polymorphisms (RFLP) and aldosterone responsiveness. 4. Allelic variation in the constitutive renin gene was associated with a specific cause of hypertension.

Adrenal Gland Neoplasms↗
PubMed1994

An association of primary aldosteronism and adrenaline-secreting phaeochromocytoma.

1. Two patients with adrenaline-only secreting phaeochromocytomas and primary aldosteronism were studied. 2. Urinary adrenaline levels were raised and plasma adrenaline was not suppressed normally following administration of clonidine. Plasma aldosterone to plasma renin activity ratios were repeatedly elevated. 3. Both had large intra-adrenal phaeochromocytomas visible on computerized tomography (CT) scanning. Surrounding adrenal cortical tissue contained an adenoma in one and nodular hyperplasia in the other. 4. Following removal of the adrenal gland containing the phaeochromocytoma, plasma and urinary adrenaline levels, and plasma aldosterone to plasma renin activity ratios returned to normal. 5. Adrenaline-only secreting phaeochromocytomas and primary aldosteronism have been rarely diagnosed even as separate entities, but reliable screening tests are now available. 6. Simultaneous presence of these two conditions of hormone excess is probably a chance occurrence. Alternatively, there may be a genetic predisposition to endocrine dysplasia, or an interaction between the contiguous medullary and cortical tissues, particularly after the normal architecture has been disturbed by an enlarging phaeochromocytoma.

Adrenal Cortex↗
PubMed1994

High incidence of primary aldosteronism in 199 patients referred with hypertension.

1. This study sought to assess the incidence of primary aldosteronism in 199 hypertensives who were normokalaemic and in whom the question of primary aldosteronism had never been raised. 2. The screening test applied was the aldosterone to renin ratio in plasma, which was raised in 40 and normal in 159 patients. A second ratio was normal in 14 of these 40. 3. Twenty-two patients with two further raised ratios required fludrocortisone suppression testing. This has been completed in 17, and failure to suppress led to a diagnosis of primary aldosteronism in all. 4. A dexamethasone suppression test (DST) excluded ACTH-dependent hyperaldosteronism and laterality of aldosterone production was determined by adrenal vein sampling. 5. Unilaterality in five patients led to adrenalectomy in four and spironolactone in one. Bilaterality in six patients led to spironolactone. 6. This study so far provides a proven (minimum) incidence for primary aldosteronism of 8.5%, a probable incidence of 12.0% (including two raised ratios) and a possible (maximum) incidence of 13.0% (leaving out those with second ratio normal). Exclusion of hypokalaemic hypertensives will lead to an underestimation of the true incidence of primary aldosteronism. 7. Based on this and other evidence, it is estimated that the incidence of primary aldosteronism in the 'essential hypertensive' population is between 5 and 15%, and is probably around 10%.

Adolescent↗
PubMed1994

Response to unilateral adrenalectomy for aldosterone-producing adenoma: effect of potassium levels and angiotensin responsiveness.

1. Normokalaemic primary aldosteronism (PA) masquerades as 'essential hypertension', and 50% of patients with aldosterone-producing adenoma (APA) are normokalaemic at presentation to this unit. 2. Angiotensin-responsive (AII-R) APA is as common as angiotensin-unresponsive (AII-U) APA, and requires adrenal venous sampling for differentiation from bilateral adrenal hyperplasia (BAH). 3. From 1981 to 1992, 55 patients with APA underwent unilateral adrenalectomy and were followed up for at least 12 months postoperatively. Hypertension was cured in 55% and improved in the remainder. 4. Cure rate was lower (P < 0.001) in males (11/32, 34%) vs females (19/23, 83%), lower (P < 0.005) in patients over 45 years of age (13/33, 39%) vs those 45 years or younger (17/22, 77%), lower (P < 0.05) in AII-R APA (11/28, 39%) vs AII-U APA (19/27, 70%) and tended to be lower (not significant) in normokalaemic APA (7/17, 41%) vs hypokalaemic APA (23/38, 61%). 5. A higher proportion (P <0.001) of AII-R APA patients were males (23/28, 82%) vs AII-U APA (9/27, 33%), and a higher proportion were from the older age group AII-U APA 13/27, 48%; P < 0.05). Females with AII-U APA who were hypokalaemic had a very high cure rate (16/17, 94%). 6. Since unilateral adrenalectomy cures or improves blood pressure in normokalaemic and AII-R as well as in hypokalaemic and AII-U patients, all hypertensives should be screened for PA, and AII-R APA differentiated from BAH in proven PA.

Adrenal Cortex Neoplasms↗
PubMed1993

Renin gene polymorphism associated with aldosterone responsiveness to the renin-angiotensin system in patients with aldosterone-producing adenomas.

Aldosterone-producing adenomas may be responsive or unresponsive to the renin-angiotensin system. In tumours from patients in the responsive subgroup, renin mRNA is expressed in greater amounts than in tumours from patients in the unresponsive subgroup, or in normal adrenals. We compared the frequency of two renin gene polymorphisms in peripheral blood DNA from the two subgroups and found a significant association (allele frequency X2 = 7.67, p < 0.006) between BglI polymorphism and aldosterone responsiveness. This may be a significant determinant of the biochemical behaviour of these tumours.

Adenoma↗
PubMed1993

Karyotypic abnormalities in benign adrenocortical tumors producing aldosterone.

Because familial hyperaldosteronism type II (FH-II) includes tumor formation, we examined the karyotypes of benign adrenocortical aldosterone-producing adenomas (APAs), including those from patients with FH-II. Cell culture was successful in 12 of 14 tumors removed, two of which were from patients with FH-II. Five of the 12 tumors cultured (one from a patient with FH-II) had abnormal karyotypes. All were from male patients, and loss of the Y chromosome was observed in each. One showed loss of chromosome 19, and another showed an unbalanced t(6;7) producing partial trisomy 7q. Oncogenes are present at these breakpoints, and loss of the Y chromosome and monosomy 19 have previously been reported in neoplasia. This is the first report of cytogenetic abnormalities in benign adrenocortical tumors.

Adrenal Gland Neoplasms↗
PubMed1993

Cortisol production by aldosterone-producing adenomas in vitro.

1. In vitro short-term production of cortisol by dispersed tumour and non-tumourous adrenal cortical cells was measured with and without added angiotensin II (AII) or adrenocorticotrophin (ACTH) in adrenals removed from five patients with primary aldosteronism. 2. Aldosterone-producing adenomas (APA) were classified as angiotensin responsive (AII-R) or angiotensin unresponsive (AII-U) based on pre-operative behaviour in vivo. 3. Cortisol was produced by both tumour and cortex in vitro without stimulation, and significantly more cortisol was generated by the cortex. 4. Addition of AII significantly increased cortisol production by both tumour and cortex to an equal extent. 5. Addition of ACTH also significantly increased cortisol production by both tumour and cortex, but tumours were more responsive than cortex. The response to ACTH exceeded the response to angiotensin in both tumour and cortex. 6. There was no obvious difference between AII-R and AII-U APA in terms of cortisol production.

Adenoma↗
PubMed1993

Evidence that primary aldosteronism may not be uncommon: 12% incidence among antihypertensive drug trial volunteers.

1. Six (12%) out of 52 respondents to newspaper advertisements for antihypertensive drug trials had elevated aldosterone to renin ratio, confirmed by repeated measurement. 2. Failure to suppress aldosterone with fludrocortisone acetate administration and oral salt loading confirmed the presence of primary aldosteronism in all six patients. 3. Two of the six patients have already had aldosterone-producing adenomas removed, one has commenced spironolactone, and one has an adrenal mass on computerized tomography but investigation is incomplete. 4. None of the six patients with primary aldosteronism had unprovoked hypokalaemia. 5. Plasma aldosterone levels did not distinguish those patients with subsequently proven primary aldosteronism from the others. Plasma renin activity (PRA) was a better discriminator, but not as good as the aldosterone to renin ratio. 6. The incidence of primary aldosteronism is probably much higher than the 1% currently quoted in texts, with earlier, normokalaemic forms accounting for the majority of cases.

Adult↗
PubMed1993

Angiotensin-responsive aldosterone-producing adenomas: postoperative disappearance of aldosterone response to angiotensin.

1. Nineteen out of 47 patients (40%) with confirmed unilateral aldosterone-producing adenoma (APA) were responsive to low-dose angiotensin II infusion (AII-R), as defined by an increase in plasma aldosterone concentration of > 50% over basal at 2 ng/kg per min for 60 min. 2. Seven to ten days after unilateral adrenalectomy, aldosterone was no longer responsive to angiotensin infusion in AII-R APA (100%, n = 17). Therefore, angiotensin responsiveness resides within the adenoma in AII-R APA. 3. The upright posture test for the differentiation of adenoma from hyperplasia was unreliable for the AII-R APA (26%), but generally reliable in the angiotensin-unresponsive subtype, (AII-U APA, 96%). 4. The reported predominance of females in APA was seen in AII-U APA (68%), but was reversed in AII-R APA (37%).

Adenoma↗
PubMed1993

Ageing and blood pressure regulation: dose-response relationships for angiotensin, blood pressure, atrial natriuretic peptide and aldosterone in normal subjects of varying ages.

1. Infusion of increasing doses of angiotensin II (AII) in normal subjects sequentially increased blood pressure, aldosterone and atrial natriuretic peptide (ANP) levels. 2. The slope of ANP response to AII was positively correlated with basal ANP and with the slope of blood pressure response to AII (pressor slope) but not with age. 3. This is consistent with the response of ANP to AII being mediated partly by the rise in blood pressure, independent of ageing. 4. As expected in a selected normotensive population, there was no correlation between basal blood pressure and age, but pressor slope was positively correlated with age. 5. Thus, dose-response relationships may be an index of age-induced alterations in pressure regulatory mechanisms.

Adult↗
PubMed1993

Effect of positive family history of hypertension on the blood pressure and catecholamine responses to a 6 hour adrenaline infusion.

1. The effects of 6 h infusion of adrenaline (INF-A) or dextrose (INF-D) and of post-infusion cold pressor test (CPT) were compared in normal subjects, with (FH+) and without (FH-) a family history of hypertension. 2. Increased urinary excretion rates suggested facilitated noradrenaline (NA) release during and after INF-A in both FH+ and FH-. 3. Urinary adrenaline (UADR) excretion increased during INF-A, as expected, and was also slightly higher after INF-A than INF-D. 4. The effect of INF-A on systolic blood pressure (SBP) was greater in FH- than in FH+ but diastolic blood pressure (DBP) did not fall as quickly with nocturnal recumbency after INF-A in FH+. 5. A significantly greater response in plasma NA to CPT was seen in FH+ than in FH- after INF-A. A similar trend was also seen after INF-D. 6. Increases in DBP due to CPT were higher in FH+ than in FH- after both infusions. 7. This study provides evidence of increased noradrenergic activity during and after INF-A, and also of a difference in response to sympathetic stimulation between FH+ and FH-.

Adult↗