Malignant aldosterone-producing adrenal tumour: reoccurrence with glucocorticoid excess without hyperaldosteronism

We describe a case of hypokalaemic hypertension due to hyperaldosteronism caused by a unilateral adrenocortical tumour with unfavourable histopathology suggestive of malignancy. After removal, the aldosterone excess disappeared. The patient's clinical course was uneventful, until she presented with extensive metastases of adrenal carcinoma four years later. Biochemical abnormalities were now consistent with glucocorticoid excess without hyperaldosteronism. She died four months later. Although malignant aldosterone-producing adrenal tumours are very rare, the present case underscores that clinicians should be aware that primary hyperaldosteronism can occur in the context of adrenocortical carcinoma.     

ADRENOCORTICAL CARCINOMA PRESENTING AS PRIMARY ALDOSTERONISM IN A YOUNG MAN

A young Polynesian man presented with severe hypertension complicated by an intracerebral hemorrhage. The hypertension was found to be secondary to hyperaldosteronism from a well differentiated adrenocortical carcinoma. Surgical removal of the tumour has resulted in a near normal blood pressure with no evidence of tumour recurrence or hyperaldosteronism after one year.     

Malignant Hypertension Due to an Aldosterone Producing Adrenal Adenoma

Malignant hypertension in Conn's syndrome is rare. We report an 18 year old boy who presented with visual and renal impairment due to malignant hypertension which subsequently proved to be secondary to an aldosterone secreting adrenal adenoma.

Diagnosis was delayed in this patient as plasma renin concentrations (PRC) were not invariably low and it is emphasized that suppression of PRC is not always a feature of primary hyperaldosteronism. The diagnosis of primary hyperaldosteronism is only excluded adequately by the demonstration of suppression of aldosterone secretion.     

Arterial blood pressure and plasma and body electrolytes in idiopathic hyperaldosteronism: a comparison with primary hyperaldosteronism (Conn's syndrome) and essential hypertension

Exchangeable and plasma electrolytes, blood pressure and aldosterone were measured in groups of patients with idiopathic hyperaldosteronism, primary hyperaldosteronism and essential hypertension and in normal subjects. In idiopathic hyperaldosteronism exchangeable sodium was higher than in both essential hypertensive and normal groups but lower than in primary hyperaldosteronism. Plasma sodium results were similar except that no difference existed between the two forms of hyperaldosteronism. Plasma potassium concentration was lower in idiopathic hyperaldosteronism than in either essential hypertensive or in normal groups, but higher than in primary hyperaldosteronism. Blood pressure correlated with age in all groups and with exchangeable sodium in hypertensive patients. This was also the case with exchangeable sodium:exchangeable potassium ratio, but blood pressure did not correlate with aldosterone in any group. In idiopathic hyperaldosteronism, as in essential hypertension, sodium and blood pressure correlated strongly in male and weakly in female patients. The analysis reveals important differences between idiopathic and primary hyperaldosteronism and also between idiopathic hyperaldosteronism and essential hypertension.     

Successful percutaneous angioplasty of renal artery in a patient with severe arterial hypertension and symptoms of hyperaldosteronism: a case report

Arterial hypertension may result from renal artery stenosis. In this type of hypertension renin-angiotensin-aldosterone system is activated and patients often produce signs of hyperaldosteronism. It must be distinguished from primary hyperaldosteronism in order to chose a proper therapy. In this paper we describe a case of a 65-years-old man with severe arterial hypertension, which was difficult to control pharmacologically. The patient revealed symptoms which suggested primary hyperaldosteronism (except normal plasma renin activity). Only imaging techniques allowed diagnose of renal artery stenosis and carry out successful percutaneous angioplasty of renal artery.     

Hyperaldosteronism among black and white subjects with resistant hypertension

Recent reports suggesting that the prevalence of primary hyperaldosteronism may be higher than historically thought have relied on an elevated plasma aldosterone concentration/plasma renin activity ratio to either diagnose or identify subjects at high risk of having primary hyperaldosteronism and have not included suppression testing of all evaluated subjects. In this prospective study of 88 consecutive patients referred to a university clinic for resistant hypertension, we determined the 24-hour urinary aldosterone excretion during high dietary salt ingestion, baseline plasma renin activity, and plasma aldosterone in all subjects. Primary hyperaldosteronism was confirmed if plasma renin activity was <1.0 ng/mL per hour and urinary aldosterone was >12 microg/24-hour during high urinary sodium excretion (>200 mEq/24-hour). Eighteen subjects (20%) were confirmed to have primary hyperaldosteronism. The prevalence of hyperaldosteronism was similar in black and white subjects. Of the 14 subjects with confirmed hyperaldosteronism who have been treated with spironolactone, all have manifested a significant reduction in blood pressure. In this population, an elevated plasma aldosterone/plasma renin activity ratio (>20) had a sensitivity of 89% and a specificity of 71% with a corresponding positive predictive value of 44% and a negative predictive value of 96%. These data provide strong evidence that hyperaldosteronism is a common cause of resistant hypertension in black and white subjects. The accuracy of these results is strengthened by having done suppression testing of all evaluated subjects.     

Re-evaluation of the captopril test for the diagnosis of primary hyperaldosteronism

OBJECTIVE: We aimed to re-evaluate the captopril test in the diagnosis of primary hyperaldosteronism. DESIGN: Serum aldosterone and plasma renin activity were measured supine prior to and 60, 90, 120 minutes after oral captopril, 25 mg. PATIENTS: We have performed this test in ten patients with primary hyperaldosteronism, two with hypertension and secondary hyperaldosteronism and in ten normokalaemic patients with essential hypertension. MEASUREMENTS: Validity was assessed by mathematical prediction methods. RESULTS: Using a ratio of aldosterone to plasma renin activity greater than or equal to 1400 pmol/l per microgram/ml/h as a predictor of primary hyperaldosteronism, the captopril test had a sensitivity of 100%, a specificity of 83% and a predictive value of 82% with a 60-minute post captopril evaluation being sufficient. Nevertheless, this test was only marginally superior to a careful analysis of the supine values where a similar ratio in the presence of a normal or suppressed plasma renin activity predicted primary hyperaldosteronism with a sensitivity also of 100% but a slightly lower specificity of 75% and predictive value of 77%. CONCLUSION: Application of the captopril test to patients identified as abnormal by screening confirms all cases of primary hyperaldosteronism but false positive or equivocal results, necessitating further investigation, may occur in some patients with essential hypertension.     

Primary hyperaldosteronism associated with hypertensive emergencies

There is growing awareness of primary hyperaldosteronism as a cause of secondary hypertension. Usually, it manifests as hypertension and hypokalemia, or as resistant hypertension. Much less often, primary hyperaldosteronism may be detected after a hypertensive emergency has developed. We highlight this association by reporting on eight patients with a clinical diagnosis of primary hyperaldosteronism whose course was complicated by a hypertensive crisis. In all patients, an elevated serum aldosterone, was accompanied by a suppressed plasma renin activity despite the presence of a hypertensive crisis. A good outcome was obtained either with laparoscopic adrenalectomy (1 patient) or with an antihypertensive drug regimen that included an antialdosterone agent (7 patients). The differential diagnosis of hypertensive emergencies should include primary hyperaldosteronism.     

Primary hyperaldosteronism: diagnostic value of the administration of a single dose of captopril

The diagnosis of primary tumoral hyperaldosteronism is based on a series of hormonal parameters, measured under resting conditions and after stimulation. The results of the administration of a single dose of a converting enzyme inhibitor, Captopril (1 mg/kg body weight per os), can support this diagnosis. In contrast to essential hypertension and hyperaldosteronism due to bilateral adrenal hyperplasia, plasma aldosterone levels remain unchanged in tumoral hyperaldosteronism after administrating Captopril. This is a simple test which can be performed in a morning which clearly differentiated 8 cases of primary tumoral hyperaldosteronism from 6 cases of adrenal hyperplasia.     

Body-sodium and blood volume in a patient with licorice-induced hypertension

A 68-year-old man a nine-year history of licorice ingestion had moderate hypertension and low plasma potassium. Exchangeable sodium and blood volume were increased to 128 and 111%, respectively of the expected values; plasma renin and aldosterone levels were suppressed. Plasma norepinephrine concentration was distinctly elevated but the pressor response to infused norepinephrine was normal. After licorice withdrawal, blood pressure, plasma potassium and blood volume reverted to normal levels within three weeks, exchangeable sodium and plasma renin within four months. Exchangeable sodium in our patient with licorice-induced hypertension was increased to a comparable extent as in primary hyperaldosteronism. Moreover, blood pressure in relation to body sodium or plasma potassium did not differ between the exogenous or the endogenous types of mineralocorticoid excess. This observation does not support the possibility that in primary hyperaldosteronism excess aldosterone secretion per se could play an important pressor role independently from sodium retention.     

Primary hyperaldosteronism: A missed diagnosis in ‘essential hypertensives’?

Background: It has been recognised recently that primary hyperaldosteronism may be more common than previously thought, the frequency of diagnosis being improved by screening using a plasma aldosterone concentration to renin activity ratio. Aims: To determine the frequency of primary hyperaldosteronism, screening with both plasma aldosterone to renin concentration (PRC) and activity (PRA) ratios, in normokalaemic subjects previously diagnosed as having essential hypertension. Methods: Plasma potassium, aldosterone and PRCs and PRA and blood pressure (BP) were measured in 74 hypertensive subjects previously diagnosed by one physician as having essential hypertension. A normal range for plasma aldosterone/renin ratios was determined in 147 control subjects. Hypertensive subjects with elevated aldosterone/renin ratios were further assessed for primary hyperaldosteronism using saline loading and fludrocortisone suppression. Those in whom plasma aldosterone concentration exceeded 140 pmol/L after suppression tests underwent adrenal vein sampling for measurement of aldosterone and Cortisol concentrations as well as adrenal CT scanning to diagnose the cause of primary hyperaldosteronism. The main outcome measures were a diagnosis of aldosterone producing adenoma or bilateral adrenal hyperplasia based upon adrenal vein sampling. Results: Four subjects (5%) had an elevated plasma aldosterone to renin ratio using PRC and six (8%) using PRA. Two subjects (2.7%) in this selected population had primary hyperaldosteronism, both of whom had BP > 160/110 mmHg at the time of testing. Conclusions: The frequency of normokalaemic primary hyperaldosteronism appears to be greater than previously thought, though the true incidence in the general population of hypertensive subjects remains unknown. The sensitivity of diagnosis (but not specificity) may be improved by measurement of the plasma aldosterone/renin ratio and PRC is at least as adequate as PRA for this process.     

Study on clinical and endocrine characteristics of dexamethasone-suppressible hyperaldosteronism compared with those in primary aldosteronism owing to aldosterone-producing adenoma

The clinical and endocrine characteristics of 12 Japanese patients with dexamethasone-suppressible hyperaldosteronism were compared with those in 49 Japanese patients with primary aldosteronism due to aldosteronoma. The results were as follows: 1. Most of the laboratory data in the two groups were almost the same. 2. The grade of vascular damage in both uncontrolled (3) and well-controlled (9) patients with dexamethasone-suppressible hyperaldosteronism did not correlate with blood pressure response. 3. The responsiveness of plasma aldosterone to exogenous ACTH in 6 patients with dexamethasone-suppressible hyperaldosteronism was not different from that in 9 patients with aldosteronoma. Even in 3 well-controlled patients in the former group, the plasma aldosterone response was as low as in all the 3 patients with small aldosteronomas. 4. In 4 patients with small aldosteronomas, plasma aldosterone was continuously suppressed with daily dexamethasone to the same degree as in dexamethasone-suppressible hyperaldosteronism. 5. The blood pressure, however, did not improve even in the patients with small aldosteronomas. The possible indistinguishable mechanism in dexamethasone-suppressible hyperaldosteronism and primary aldosteronism with small adenomas and the role of unknown hypertensinogenic steroid(s) other than aldosterone in inducing hypertension in dexamethasone-suppressible hyperaldosteronism are discussed.     

Adrenal mineralocorticoids causing hypertension

The three major adrenal mineralocorticoid hormones are aldosterone, deoxycorticosterone (DOC) and corticosterone (B). To date, there are four recognized types of primary aldosteronism: (1) aldosterone-producing adenoma (APA), (2) idiopathic hyperaldosteronism (IHA), (3) indeterminate hyperaldosteronism (IndHA) and (4) glucocorticoid-remediable hyperaldosteronism (GRHA). Preoperative distinction between APA and IHA is best achieved by plotting the basal recumbent plasma renin concentration against the level of aldosterone production after administration of deoxycorticosterone acetate (DOCA). Preoperative predictability has been accurate in thirteen cases. Adrenalectomy effects cure or a marked improvement of hypertension in patients with APA, whereas the results are poor in patients with IHA although the number of patients still remains small. Patients with IndHA have all the features of hyperaldosteronism except aldosterone excretion is readily suppressed by the administration of DOCA, and the administration of spironolactone, 200 to 400 mg/day, corrects the hypertension. GRHA is readily correctable by replacement doses of dexamethasone.     

Concentration of adrenocorticotrophic hormone and aldosterone secretion in essential hypertension and hyperaldosteronism

The authors studied the effect of adrenocorticotropic hormone (ACTH), potassium and plasma renin activity on blood aldosterone in normal subjects as well as in patients with essential hypertension (of a labile and stable course) and hyperaldosteronism (primary and idiopathic). It was demonstrated that in normal subjects and patients with labile essential hypertension, the secretion of aldosterone was simultaneously stimulated by the renin-angiotensin system (RAS) and the hypothalamus-adenopituitary. The RAS dominated in normal conditions whereas in labile hypertension the hypothalamus-adenopituitary system was predominant. In stable hypertension, the RAS and hypothalamus-pituitary influenced aldosterone secretion in an equal degree. Hyperaldosteronism was associated with the most pronounced deviations in the relationship between stimulants and aldosterone. In addition to decreased plasma levels of renin activity and potassium, the corticotropic activity of the hypothalamus-adenopituitary was increased during the first 10 years of the disease, while later on the function of this system became inhibited. The highest ACTH levels were recorded in idiopathic hyperaldosteronism.     

Rectal potential difference in the diagnosis of aldosterone excess.

Rectal potential difference (pd) is directly related to the plasma aldosterone concentration, and rises when aldosterone is stimulated by sodium deprivation. However, when the measurement of rectal pd was tested at a screening test for hyperaldosteronism in 19 hypertensive subjects, four of the eight with primary hyperaldosteronism had a normal pd and four of the eight without aldosterone excess had an abnormally raised potential difference. The technique cannot therefore be recommended as a routine screening test for hyperaldosteronism. No relationship was found between rectal pd and hypertension associated with excess of deoxycorticosterone. Rectal pd rises in response to the mineralocorticoid-like agent carbenoxolone.     

Feminishing adrenal tumor with primary hyperaldosteronism. Report of a case (author's transl)]

A case of feminishing adrenal tumor with primary hyperaldosteronism is reported. The aim of this report is to emphasize on the terminal evolution of the disease. This phase was marked by malignant hypertension, severe renal insufficiency, and iatrogenic cellular hyperhydration with hyponatremia secondary to spironolactone therapy.     

Primary hyperaldosteronism without suppressed renin due to secondary hypertensive kidney damage

Primary hyperaldosteronism is characterized by high plasma and urinary aldosterone and suppressed PRA. Renin suppression is due to aldosterone-dependent sodium retention and mild extracellular volume expansion. We observed three patients with primary hyperaldosteronism, severe refractory hypertension, and normal to high normal PRA levels whose aldosterone/renin ratios were still elevated because of disproportionately high aldosterone levels. All available medical data on the patients as well as publications on the aldosterone/renin relationship in primary hyperaldosteronism were reviewed to explain the unusual findings. In one patient, histologically proven renal arteriolosclerosis was the probable cause of the escape of PRA from suppression by an aldosterone-producing adenoma. In the other two patients, hypertensive kidney damage due to primary hyperaldosteronism was the most likely explanation for the inappropriately high PRA, as in patient 1. All patients had high normal or slightly elevated serum creatinine levels and responded to 200 mg spironolactone/day with increased serum creatinine and hyperkalemia. Hyperkalemia was probably due to a decreased filtered load of sodium and a spironolactone-induced decrease in mineralocorticoid function. Two patients were cured of hyperaldosteronism by unilateral adrenalectomy but still need some antihypertensive therapy, whereas one patient has probable bilateral adrenal disease, with normal blood pressure on a low dose of spironolactone. In patients with severe hypertension due to primary hyperaldosteronism, PRA can escape suppression if hypertensive kidney damage supervenes. An increased aldosterone/PRA ratio is still useful in screening for primary hyperaldosteronism. These patients may respond to spironolactone therapy with a strong increase in serum creatinine and potassium. Early specific treatment of primary hyperaldosteronism is therefore indicated, and even a patient with advanced hypertension will profit from adrenalectomy or cautious spironolactone treatment.     

Low-renin ("primary") hyperaldosteronism. Differential diagnosis and distinction of sub-groups within the syndrome.

Hypokalemia in a hypertensive patient is commonly diuretic-induced. However, if hypokalemia persists after stopping diuretic therapy, possible mineralocorticoid excess, including primary hyperaldosteronism, must be considered. Hypertension with secondary hyperaldosteronism may occur with malignant-phase hypertension and with renal or renovascular disease. However, secondary hyperaldosteronism is associated with raised circulating levels of renin and angiotensin II, while in primary hyperaldosteronism plasma concentrations of renin and angiotensin II are inappropriately low.Hypertension and hypokalemia may also be associated with an excess of a mineralocorticoid other than aldosterone. Syndromes associated with an apparently isolated excess of 11-deoxycorticosterone, of 18-hydroxy-11-deoxycorticosterone and of corticosterone have been described. Plasma renin may be suppressed as in primary hyperaldosteronism, but aldosterone values are normal or low. Hypertension, hypokalemia, and renin suppression may also occur in Cushing's syndrome, associated with abnormalities of corticosteroid synthesis and during ingestion of licorice-containing drugs. Again, aldosterone values are normal or low.Once the diagnosis of primary hyperaldosteronism has been confirmed, the rare cases of glucocorticoid-remediable hyperaldosteronism and hyperaldosteronism associated with adrenal or ovarian carcinoma must be excluded. There-after, it is necessary to distinguish between the two commonest forms, a unilateral adrenocortical adenoma and bilateral hyperplasia of the zona glomerulosa. The statistical technique of quadric analysis used prospectively has correctly predicted adrenal pathology in 23 of 24 patients. Other methods for differentiating the two groups include comparisons of aldosterone response to sodium loading, comparison of postural and diurnal changes in plasma aldosterone, adrenal venography, and examination of the adrenal glands by ultrasound and by scintillation scanning.     

Diagnosis of hyperaldosteronism

Hyperaldosteronism is associated with hypertension, potassium depletion, and suppressed plasma renin activity. It may involve one or both adrenal glands. This article reviews the different types of hyperaldosteronism and the diagnosis and management of each.     

Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment.

The relationship between arterial hypertension and insulin resistance has long been established. We used primary hyperaldosteronism as a model of the relationship between secondary hypertension and insulin sensitivity. Our group consisted of 9 patients with arterial hypertension caused by primary hyperaldosteronism. Five of these patients with aldosterone producing adenoma were operated on and four patients with idiopathic hyperaldosteronism were treated with spironolactone. Hyperinsulinaemic euglycaemic clamp technique was performed before and at least 6 months following the treatment to evaluate the insulin action. Significantly lower glucose disposal rate (M), insulin sensitivity index (M/I) and decreased metabolic clearance rate of glucose (MCR(G)) were found in patients before treatment as compared to healthy controls. In both treated groups the blood pressure and plasma potassium concentrations returned to normal values, whereas plasma aldosterone levels were normalised only after surgical removal of the adenoma. Significantly improved insulin action (M/I: 30.2 +/- 5.9 vs. 51.4 +/-12.2 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.017) was observed in patients after operation of aldosterone producing adenoma. In contrast, spironolactone treatment of patients with idiopathic hyperaldosteronism did not significantly influence insulin action (M/I: 24.5 +/- 7.3 vs. 18.7 +/- 7.6 micromol.kg(-1).min(-1) per mU.l(-1) x 100, p = 0.198). Since plasma aldosterone concentrations have been normalised only in patients after removal of the adenoma whereas they remained increased in spironolactone treated group, we suppose that aldosterone itself could play a role in the development of impaired insulin action.