Shelley A. Klemm

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.

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.

Clinical and pathological diversity of primary aldosteronism, including a new familial variety.

1. Of 93 patients with primary aldosteronism seen during a 20 year period, 52 had an aldosterone‐producing adenoma (APA) removed (five more await surgery), 14 had bilateral adrenal hyperplasia (BAH), three had glucocorticoid‐suppressible hyperaldosteronism (GSH), one had adrenal carcinoma and 18 are yet to be categorized.

Histological and Biochemical Distinctiveness of Atypical Aldosterone-Producing Adenomas Responsive to Upright Posture and Angiotensin

Fifteen patients with primary aldosteronism were classified as anglotensin II‐unresponsive aldosterone‐producing adenoma (All‐U APA, n = 9), or anglotensin II‐responsive aldosterone‐producing adenoma (All‐R APA, n= 6), based on the responsiveness of aldosterone to upright posture and to anglotensin II infusion. Lack of aldosterone response to anglotensin II Infusion immediately post‐operatively In the All‐R APA subtype was consistent with previous responsiveness residing solely within the adenoma. Cortisol levels In five of the six patients with All‐R APA failed to suppress normally with dexamethasone consistent with some autonomous production of cortisol by the adenoma. In contrast, cortisol levels suppressed normally during dexamethasone administration In all patients with All‐U APA. This biochemical distinction can be added to the previously described overproduction of 18‐oxo cortisol in All‐U APA but not in All‐R APA. Histological examination of adenoma sections revealed predominantly (±‐50%) zone fascicuiata type cells in All‐U APA. In contrast, All‐R APA contained less than 20% zona fasciculata type. Thus, biochemical differences between All‐U APA and All‐R APA subtypes of primary aldosteronism may be due to underlying differences In cellular composition of the aldosterone‐producing adenomas.

Primary aldosteronism--some genetic, morphological, and biochemical aspects of subtypes.

Primary aldosteronism is the commonest cause of potentially curable hypertension when diagnosed in both florid and less florid forms. Genetic screening, so far available only for glucocorticoid-suppressible hyperaldosteronism, permits diagnosis from birth, before any biochemical or clinical abnormalities appear. Biochemical screening using the aldosterone-to-renin ratio permits diagnosis in the absence of raised aldosterone or of hypokalemia. Primary aldosteronism occurs in several familial forms. As well as the variety described in 1966 which is ACTH-dependent and glucocorticoid-suppressible, and not so far associated with tumors, another variety described in 1991 is not glucocorticoid-suppressible and is frequently associated with aldosterone-producing adenomas (APAs). Primary aldosteronism due to adrenocortical hyperplasia, adenoma, or carcinoma can also occur as part of the multiple endocrine neoplasia syndromes, where normoplasia, hyperplasia, benign neoplasia, and malignant neoplasia can exist in the same patient in the same endocrine gland(s) at the same time. The morphology of adrenocortical hyperplasia causing primary aldosteronism ranges from glomerulosa-like (idiopathic hyperplasia of the adrenals) to fasciculata-like (glucocorticoid-suppressible hyperaldosteronism). The morphology of adrenocortical neoplasia causing primary aldosteronism can also be either predominantly glomerulosa-like or fasciculata-like, in our experience equally often. Varying morphology of APAs is associated with varying responses of aldosterone to angiotensin II. Tumors predominantly fasciculata-like are unresponsive to angiotensin II, whereas those predominantly glomerulosa-like are responsive to angiotensin II. Both subtypes can be seen in a single family. Primary aldosteronism represents a spectrum of genetic disorders resulting in hyperplasia or neoplasia, but all are associated with some degree of autonomy of aldosterone production, independent of the renin-angiotensin system.

ALDOSTERONE-PRODUCING ADENOMAS RESPONSIVE TO ANGIOTENSIN POSE PROBLEMS IN DIAGNOSIS

1. A subgroup of patients with aldosterone‐producing adenoma (APA) have been identified who lack many of the biochemical features regarded as characteristic of APA and used to distinguish APA from bilateral adrenal hyperplasia.

Adrenal Transitional Zone Steroids, 18-Oxo and 18-Hydroxycortisol, Useful in the Diagnosis of Primary Aldosteronism, Are Acth-Dependent

1. The adrenal cortical ‘hybrid’ steroids 18‐oxocortisol (18‐OF) and 18‐hydroxy‐cortisol (18‐OHF) are elevated in patients with typical angiotensin‐unresponsive aldosterone‐producing adenoma (AII‐unresponsive APA) and fall to normal following surgical removal of the adrenal containing the tumour. Since 18‐OF was six times the upper limit of normal pre‐operatively, the tumour was the site of overproduction of hybrid steroids.

LAPAROSCOPIC ADRENALECTOMY FOR ADRENAL TUMOURS CAUSING HYPERTENSION AND FOR ‘INCIDENTALOMAS’ OF THE ADRENAL ON COMPUTERIZED TOMOGRAPHY SCANNING

1. In a 19 month period from June 1993 to December 1994, 60 patients (mean age 54.8 ±.5 years s.e.m.; 32 males, 28 females) underwent unilateral laparoscopic adrenalectomy by one of us (JCR) for the treatment of hypertension due to primary aldosteronism (n = 48), phaeochromocytoma (n = 3) and cortisol‐producing adenoma (n = 1) or to remove adrenal masses incidentally discovered on abdominal computerized tomography scanning (‘incidentaloma’) performed for other reasons (seven adenomas without biochemical evidence of excessive steroid hormone or catecholamine secretion and one carcinoma autonomously producing cortisol).

PCR‐SSCP ANALYSIS OF THE ANGIOTENSIN II TYPE 1: RECEPTOR GENE IN PATIENTS WITH ALDOSTERONE‐PRODUCING ADENOMAS

1. In patients with primary aldosteronism due to angiotensin‐responsive and andotensin‐unresponsive aldosterone‐producing adenomas, no differences in the coding region of the angiotensin II type 1 (AT1) receptor gene were observed compared to normal subjects in peripheral blood leucocyte DNA.

Effects of Volume Expansion and Contraction On Plasma-Levels of Atrial Natriuretic Peptide in Man

1. Effects of saline infusion and blood removal on atrial natriuretic peptide (ANP) in normal subjects were examined in order to better define the magnitude of acute central volume regulatory influences on ANP.