[Effect of portalization of blood outflowing from the adrenal glands on the development of secondary hyperaldosteronism and ascites].
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Aldosterone↗
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[Myxedema with inappropriate antidiuresis and hyperaldosteronism].
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Aged↗
[Diagnosis and treatment outcome in primary aldosteronism based on a retrospective analysis of 187 cases].
INTRODUCTION: Primary aldosteronism is the most common form of mineralocorticoid hypertension. The disease has been described by Jerome W. Conn in 1955; since that time there has been a great progress in the knowledge concerning the prevalence, diagnostics and treatment of the disease. AIMS: The authors retrospectively analyzed the efficacy of diagnostic procedures and the outcome of treatment by the analysis of data of 187 patients with primary aldosteronism examined between 1958 and 2004 at the 2nd Department of Medicine of Semmelweis University. METHODS: The efficacy of different methods used for the diagnosis, the frequency of the different subtypes of primary aldosteronism, as well as the surgical outcomes in patients with surgically treated subtypes of primary aldosteronism were studied. RESULTS: Aldosterone-producing adenoma was detected in more than two thirds of patients (n = 135), whereas idiopathic hyperaldosteronism was found in 46 patients. Other subtypes of primary hyperaldosteronism occurred less frequently (unilateral primary adrenocortical hyperplasia in 5 patients and adrenocortical carcinoma in one patient). For the diagnosis of familial hyperaldosteronism type I, molecular biological studies of the aldosterone-synthase/11beta-hydroxylase gene chimera were carried out in 30 patients but none of them showed the presence of the chimeric gene. When comparing the clinical parameters of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism, no significant differences were found in the time period between the diagnosis of hypertension and the diagnosis of primary aldosteronism, or in the systolic and diastolic blood pressure values. The mean of the lowest documented serum potassium concentration was slightly lower in patients with aldosterone-producing adenoma (2.8 +/- 0.1 mmol/l) compared to those with idiopathic hyperaldosteronism (3.1 +/- 0.2 mmol/l), but the difference was not significant. Normokalemic primary hyperaldosteronism was found in 7 cases. The ratio of plasma aldosterone concentration (ng/dl) to plasma renin activity (ng/ml/h) was above 20 in all patients with aldosterone-producing adenoma and in all but 5 cases with idiopathic hyperaldosteronism. To confirm the diagnosis and to differentiate the subtypes of primary aldosteronism, the postural test combined with furosemide administration was performed in the majority of patients. When cases showing an elevation of plasma cortisol level during the test were excluded, this test differentiated patients with aldosterone-producing adenoma from those with idiopathic hyperaldosteronism with a sensitivity of 69% and a specificity of 92%. In cases of adrenocortical adenomas not or not clearly detectable by radiological imaging techniques, as well as in cases with bilateral adrenocortical adenomas, selective adrenal vein sampling was performed (n = 55). All but 4 patients with aldosterone-producing adenoma underwent adrenalectomy. Histology and postoperative hormone results confirmed the preoperative diagnosis in all operated patients. After surgery serum potassium concentration returned to normal in all patients showing low serum potassium levels before surgery. Also, the moderate to severe preoperative hypertension disappeared or improved after surgery. CONCLUSIONS: These observations are in contrast with the results of international studies which showed a high frequency of normokalemic primary aldosteronism and a more frequent occurrence of idiopathic hyperaldosteronism well treatable with aldosterone-antagonists. Therefore, it can be presumed that a significant number of primary aldosteronism cases that are not accompanied with severe hypokalemia remain undetected in Hungary.
Adenoma↗
Use of the saline infusion test to diagnose the cause of primary aldosteronism.
Angiotensin II has a major effect on mineralocorticoid hormone synthesis in patients with idiopathic hyperaldosteronism; it has little or no effect in those with an aldosterone-producing adenoma. To determine if this difference could be of use in clinically separating these two forms of primary aldosteronism, saline infusion tests were performed in 20 patients--14 with surgically proved aldosterone-producing adenoma and six with idiopathic hyperaldosteronism. With the patients receiving a balanced diet containing 120 meq of sodium, 1,250 ml of isotonic saline was infused intravenously between 8 A.M. and 10 A.M. after overnight recumbency. Plasma samples were obtained immediately before and after the infusion. Plasma cortisol level decreased appropriately in both groups, but plasma renin concentration decreased only in those patients with idiopathic hyperaldosteronism (p less than 0.05). Aldosterone and 18-hydroxycorticosterone levels decreased in both groups. To account for the circadian variation in adrenocorticotropin levels during the course of saline infusion, 18-hydroxycorticosterone/cortisol and aldosterone/cortisol ratios were examined. Both ratios increased in every patient with aldosterone-producing adenoma (p less than 0.01 and p less than 0.001, respectively), but these ratios remained unchanged or decreased in the patients with idiopathic hyperaldosteronism. This divergent variation in ratios after saline infusion allows for the differentiation of patients with an aldosterone-producing adenoma from those with idiopathic hyperaldosteronism. In patients with primary aldosteronism, an 18-hydroxycorticosterone/cortisol ratio of less than 3.0 or an aldosterone/cortisol ratio of less than 2.2 after saline infusion is diagnostic of idiopathic hyperaldosteronism.
18-Hydroxycorticosterone↗
Review of surgical management of aldosterone secreting tumours of the adrenal cortex.
AIMS: To evaluate the investigation and surgical management of primary hyperaldosteronism. Retrospective case note analysis of thirty-three patients who underwent adrenalectomy for primary hyperaldosteronism between 1982 and 2001 and a current relevant literature review. METHODS: The records of twelve male and twenty-one female patients, age range 18 to 81 (mean 48 years) were reviewed. Eleven operations were performed by an open approach and twenty-two laparoscopically. Preoperative investigations included computed tomography (CT), magnetic resonance imaging (MRI), selective venous sampling and seleno-cholesterol isotope scanning, along with biochemical and hormonal assays. Twenty-six benign adenomas, three nodular hyperplastic lesions, one primary adrenal hyperplasia and three functional carcinomas were excised. Mean follow up was 12 months. RESULTS: Patients had a mean blood pressure of 185/107 mmHg for 6.2 years mean duration. The mean severity of hypokalaemia was 2.7 mmol/l. Sensitivity of CT scanning was 85%, and of MRI 86%. Fifty percent of seleno-cholesterol scans were accurate. Mean operating time was 158 min for laparoscopic adrenalectomy whilst open surgery took 129 min (p=0.2, NS). Two cases commenced laparoscopically required open access for control of primary haemorrhage whilst one other bleed was managed via the operating ports. Mean postoperative stay was significantly shorter for the laparoscopic group (3 days compared with 7.9 days, p<0.0001). Thirty day mortality was zero. There were three infective complications in the open group (two chest, one wound) with no postoperative complications in the laparoscopic group. All patients were cured of hypokalaemia, whilst 62% cure of hypertension was achieved. Of those patients whose blood pressure was improved preoperatively by spironolactone 78% were cured by adrenalectomy. Adrenalectomy led to an overall reduction in the mean number of anti-hypertensive medications (2.3 drugs preoperative to 0.6 postoperative, p<0.0001). Of those not cured, 58% had improved blood pressure control requiring less medication on average (1.6 drugs compared with 2.6 drugs, p=0.08). Mean age of patients not cured by surgery was 55 years, whilst those cured was 44 years (p=0.03). CONCLUSIONS: Primary hyperaldosteronism is a rare but important cause of hypertension. Selective venous sampling is a useful tool where investigations are inconclusive and fail to lateralise secretion. Patients with primary hyperaldosteronism enjoy lower complication rates and earlier discharge with the advent of laparoscopic surgery. Most patients will be cured of their hypertension and all of hypokalaemia. Laparoscopic adrenalectomy is now the accepted method of surgery for benign hyperaldosteronism. Those with bilateral disease due to idiopathic hyperaldosteronism (IHA) are not candidates for surgery and should be treated medically.
Adenoma↗
High prevalence of thyroid ultrasonographic abnormalities in primary aldosteronism.
The study was performed to evaluate the prevalence of thyroid abnormalities detected by ultrasonography and, in particular, of multinodular nontoxic goiter in primary aldosteronism. We analyzed 80 consecutive of patients with primary hyperaldosteronism (40 with unilateral adenoma and 40 with idiopathic hyperaldosteronism) and 80 normotensive healthy controls, comparable for age, sex, iodine intake, and geographical area. Blood pressure, thyroid palpation, thyroid function, and ultrasonography were evaluated. The prevalence of ultrasonographic thyroid abnormalities was 60% in primary aldosteronism and 27% in controls (p < 0.0001). There was a statistically significant difference in prevalence of these abnormalities in unilateral adenoma and idiopathic hyperaldosteronism with respect to controls (p < 0.05 and p < 0.0001, respectively). The prevalence of multinodular nontoxic goiter in idiopathic hyperaldosteronism was higher than in controls (p < 0.001) and, in particular, in female patients. From these data it seems to be worth considering the existence of primary hyperaldosteronism in patients with multinodular goiter and hypertension.
Adult↗
Biochemical markers of endothelial dysfunction in patients with endocrine and essential hypertension.
The aim of our study was to evaluate potential differences in the concentration of biochemical markers of endothelial dysfunction between essential hypertension, endocrine hypertension (pheochromocytoma, primary hyperaldosteronism) and control healthy group and to assess a potential relationship between these markers of endothelial dysfunction and vasopressor substances overproduced in endocrine hypertension. We have investigated 21 patients with moderate essential hypertension, 29 patients with primary hyperaldosteronism, 24 subjects with pheochromocytoma and 26 healthy volunteers. Following parameters of endothelial dysfunction were measured, von Willebrand factor (vWf), plasminogen activator (t-PA) and E-selectin (E-sel). Clinical blood pressure was measured according to the European Society of Hypertension recommendations. We found significantly higher levels of the von Willebrand factor in patients with essential hypertension in comparison with a control group (114+/-20 IU/dl vs 90+/-47 IU/dl; P=0.04) and patients with primary hyperaldosteronism (114+/-20 IU/dl vs 99+/-11 IU/dl; P=0.01). Patients with endocrine hypertension revealed increased levels of vWF compared to the control group, but these differences did not reach statistical significance. Levels of t-PA were increased in patients with pheochromocytoma in comparison with the control group (4.6+/-1.9 ng/ml vs 3.4+/-0.9 ng/ml; P=0.01) and with primary hyperaldosteronism (4.6+/-1.9 ng/ml vs 3.4+/-1.1 ng/ml; P<0.01). In case of E-selectin we found lower levels in patients with pheochromocytoma in comparison with other groups, but they differed significantly only with primary hyperaldosteronism (40.2+/-15.0 ng/ml vs 51.3+/-23.0 ng/ml; P=0.05). Our study did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between essential and endocrine hypertension. No correlation between the biochemical markers of endothelial dysfunction and vasopressor substances activated in endocrine hypertension was found.
Adrenal Gland Neoplasms↗
[The localization of aldosterone-producing adenoma on computed tomography--a comparative study with adrenal scintigraphy and plasma aldosterone concentration in the adrenal or renal vein].
The evaluation of computed tomography (CT) for detecting aldosterone-producing adenoma in primary aldosteronism was performed by comparison with adrenal scintiscan; determination of aldosterone in adrenal or renal veins, retroperitoneal pneumography and adrenal venography was reliable for diagnosis of adrenal tumors in pheochromocytoma or Cushing's syndrome, but not so effective for small adenoma of primary aldosteronism. An abdominal CT scan was performed on six patients with primary aldosteronism, one with idiopathic hyperaldosteronism and one with glucocorticoid responsive hyperaldosteronism; in an attempt to evaluate the utility of this noninvasive procedure. Diagnosis of hyperaldosteronism was made by demonstrating the elevated plasma aldosterone concentration and aldosterone secretion rate, normal excretion rate of urinary 17-OHCS and 17-KS, and low plasma renin activity. The CT scan correctly predicted unilateral adrenal adenoma in all the patients with primary aldosteronism of which the findings were identical to those demonstrated by surgery. The diameter of these tumors ranged from 10 X 7 X 6 to 19 X 17 X 14 mm. Also the CT scan in idiopathic hyperaldosteronism and glucocorticoid responsive hyperaldosteronism showed bilateral adrenal hyperplasia and bilateral normal adrenal glands, respectively. The pathological findings in these two cases disclosed the adrenal hyperplasia of zona glomerulosa and adrenal hyperplasia of zona subglomerulosa accompanied by a normal thickness of the adrenal gland, respectively. The precision of the CT scan, adrenal scintigraphy and determination of plasma aldosterone in the adrenal or renal veins were almost equal to the diagnosis of the localization of adrenal adenoma. It is concluded that the CT scan is a noninvasive and most useful method for the localization of aldosterone-producing adenoma and helpful in distinguishing adrenal adenoma from adrenal hyperplasia.
Adenoma↗
The role of aldosterone antagonists in the management of resistant hypertension.
Resistant hypertension is an increasingly common problem faced by primary care physicians and specialists and will undoubtedly become even more common as the adult population ages and gains weight. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), at least 8% of subjects were resistant to treatment based on the need for three or more antihypertensive agents. Characteristics of patients with resistant hypertension include being older, black, obese, and diabetic, and having chronic kidney disease as well as untreated sleep apnea. Hyperaldosteronism is common in patients with resistant hypertension, with a prevalence of approximately 20%. This, however, is likely an underestimation of the role aldosterone excess plays in causing drug resistance. In subjects with resistant hypertension, suppressed renin levels are common, exceeding 75% in our studies, suggesting aldosterone excess effects beyond cases of true primary hyperaldosteronism. Recent studies indicate that aldosterone antagonists provide significant blood pressure reduction when added to antihypertensive regimens of patients with resistant hypertension. Interestingly, the blood pressure reduction with use of spironolactone is not limited to patients with hyperaldosteronism, consistent with the concept of aldosterone excess as a continuum from low-renin hypertension with normal aldosterone levels to true primary hyperaldosteronism.
Drug Resistance↗
Plasma concentration of neuropeptide Y in patients with adrenal hypertension.
The mechanisms of hypertension during primary hyperaldosteronism and Cushing's syndrome are not completely understood. An enhanced vascular sensitivity to noradrenaline has been described in both situations. Neuropeptide Y (NPY) induces direct vasoconstriction and potentiates the action of noradrenaline. Sodium retention and dexamethasone have been shown to increase circulating NPY levels in animals and the expression of NPY in neuroendocrine cells. In order to determine if NPY could be involved in the enhanced vascular sensitivity to noradrenaline associated with adrenocortical hyperactivity, we measured plasma NPY in patients with Cushing's syndrome (n = 26) and primary hyperaldosteronism (n = 15) and compared it with that of hypertensive patients with pheochromocytomas (n = 13) or essential hypertension (n = 51) and with normotensive controls (n = 47). The concentration of NPY-Like immunoreactivity (NPY-Li) (mean +/- S.E.) in controls was 39.6 +/- 3.0 pg/ml. Elevated concentrations were found in 77% of the samples collected from pheochromocytoma patients (1180.4 +/- 394.0 pg/ml). NPY-Li levels in patients with essential hypertension (35.0 +/- 2.6 pg/ml), primary hyperaldosteronism (31.3 +/- 3.9 pg/ml) and Cushing's syndrome (33.1 +/- 4.8 pg/ml) were not different from that of controls. NPY-Li levels in hypertensive and normotensive patients with Cushing's syndrome were similar (38.5 +/- 7.5 vs 24.2 +/- 3.7 pg/ml). No correlation was found between the NPY-Li level and the mean blood pressure at the time of sampling. Our results suggest that NPY is unlikely to be involved in the pathogenesis of hypertension associated with primary hyperaldosteronism and Cushing's syndrome.
Adolescent↗
Accuracy of CT scanning and adrenal vein sampling in the pre-operative localization of aldosterone-secreting adrenal adenomas.
In primary hyperaldosteronism, it is important to distinguish between unilateral and bilateral disease, as management strategies differ. In the period 1983-95, we identified 34 patients with primary hyperaldosteronism. Following further investigations, a diagnosis of aldosterone-secreting adenoma was made in 17 patients, and surgery was performed. Computed tomography clearly localized an apparent adenoma (discrete adenoma=1 cm diameter; normal contralateral gland) in only 10 of these patients (59%); two of these 'adenomas' were subsequently shown to be hyperplastic glands without adenomas. Histological examination showed adrenal adenomas in the remaining 15 patients. An 'adenoma' also appeared to be clearly localized in 3/17 patients later classified as having bilateral adrenal hyperplasia by adrenal vein sampling. CT scanning, therefore clearly localizes adenomas in only 50% of histologically proven cases, and can also produce misleading results. Adrenal vein sampling results altered our management approach in one third of cases. On the basis of our detailed results we would recommend surgery if there is clear evidence of unilateral aldosterone secretion along with CT findings which may not be strictly localizing but are in keeping with the dominant side on adrenal vein sampling. The decision to refer for surgery in primary hyperaldosteronism can be difficult, and we would caution against too heavy a reliance on CT results when recommending adrenalectomy, and suggest that adrenal vein sampling should remain a routine part of the investigation of patients with primary hyperaldosteronism.
Adenoma↗
Primary aldosteronism: learning from the study of familial varieties.
Primary aldosteronism (PAL) has been traditionally regarded as a rare cause of hypertension and not worth looking for in the absence of hypokalemia. However, the availability of the aldosterone/renin ratio as a screening test and its application to a wider population of hypertensives has resulted in a marked increase in detection rate, suggesting that PAL is common, with most patients being normokalemic. The spectrum of PAL has been expanded further by the study of familial varieties, in which family screening efforts have permitted the recognition of earlier, sometimes even pre-clinical, stages of disease. Familial hyperaldosteronism type I(FH-I) In FH-I, inheritance of a 'hybrid' 11beta-hydroxylase/aldosterone synthase gene causes adrenocorticotrophic hormone (ACTH)-regulated aldosterone and 'hybrid steroid' (18hydroxy-cortisol and 18-oxo-cortisol) overproduction. Genetic testing, by Southern blot or polymerase chain reaction-based techniques, has greatly facilitated detection, being more convenient and more reliable than dexamethasone suppression testing, and has led to a fuller appreciation of the marked phenotypic variability in this disorder. The demonstration of excessive, abnormally regulated aldosterone production in normotensive subjects with FH-I suggests that absence of hypertension in such individuals cannot merely be attributed to lack of expression of the hybrid gene. Determinants of hypertension severity may include patient gender, gender of affected parent, degree of hybrid gene expression, and interactions with other genetic and environmental factors. Detailed biochemical studies, including analyses of aldosterone/PRA/cortisol 'day-curve' levels, have led to a fuller understanding of aldosterone regulation both before and in response to glucocorticoid treatment in this condition, and prompted a re-examination of current approaches to treatment Unless ACTH is completely suppressed by glucocorticoid treatment, the hybrid gene dominates over the wild-type aldosterone synthase genes in terms of aldosterone production, both in untreated and treated FH-I. This may in part be due to an abnormality affecting the functional expression of the 'wild-type' genes. Demonstration of persisting hybrid gene expression in patients rendered normotensive by very low doses of glucocorticoids suggests that currently recommended doses, aimed at normalizing aldosterone regulation (rather than blood pressure), may be too high, and may therefore place patients at unnecessary risk of developing Cushingoid side effects. Familial hyperaldosteronism type II (FH-II) Like FH-I, FH-II is associated with hyperaldosteronism and probable autosomal dominant inheritance. Unlike FH-I, hyperaldosteronism in FH-II is not dexamethasone suppressible, and is not associated with the hybrid gene mutation. Detection of adrenal mass lesions, which are frequently (17 of 57 patients in the Greenslopes Hospital series) responsible for PAL in FH-II, does not help to differentiate FH-II from FH-I, since mass lesions may also be common in that condition (detected in seven of 21 patients). Biochemically and morphologically, FH-II is indistinguishable from apparently non-familial PAL, and demonstrates similar variability even among individuals of the same family. In one informative family available for linkage analysis, FH-II does not segregate with either the AT1 gene or the CYP11B2 gene, or any other genetic defect in the chromosome 8q21-8qtel region. A genome-wide search is in progress. As has already occurred in FH-I, the elucidation of underlying genetic mutations in FH-II is likely to facilitate early detection, thereby helping to broaden its spectrum and to permit close follow-up and appropriately timed institution of specific therapy, and wider detection among patients with hypertension of potentially curable or specifically treatable forms.
Family Health↗
The neurohormonal natural history of essential hypertension: towards primary or tertiary aldosteronism?
Use of the aldosterone-to-renin ratio has controversially suggested that approximately 10% of hypertensives have primary aldosteronism, and most of these individuals are thought to have idiopathic hyperaldosteronism. The usual renin-angiotensin system control is intact in these individuals and is similar to that in low renin and essential hypertensives, differing only in the degree of sensitivity. There is recent evidence suggesting that hyperaldosteronism relates to aldosterone synthase genetic polymorphism, and also that increased angiotensin II stimulation of the adrenal glands appears to paradoxically upregulate the receptors increasing angiotensin II sensitivity. Taken together, the possibility arises that, in susceptible hypertensives, hyperaldosteronism could be acquired. Indeed, it is well known that renin-driven renovascular hypertension is associated with the development of hyperaldosteronism. Hypothetically, within the wider hypertensive population, these findings set the scene that angiotensin II adrenal sensitivity increases over time until the secretion of aldosterone becomes "autonomous" and hence "tertiary" aldosteronism in a significant proportion of hypertensives.
Aldosterone↗
Laparoscopic partial versus total adrenalectomy for aldosterone producing adenoma.
PURPOSE: Laparoscopic surgery has become a standard method for adrenal treatment. Primary hyperaldosteronism is known to be frequently characterized by multiple adrenal lesions. The indication of laparoscopic partial or total adrenalectomy in patients with aldosterone producing adenoma (APA) remains controversial. We performed the 2 procedures and compared the outcomes of these 2 operations retrospectively. MATERIALS AND METHODS: A total of 92 patients with primary hyperaldosteronism were laparoscopically treated at our institution from 1995 to 2004. A total of 29 patients underwent partial adrenalectomy or enucleation, while unilateral total adrenalectomy was performed in 63. A single pathologist examined the number and histopathological characteristics of APAs. Postoperative median followup was 60.3 and 29.3 months, respectively. RESULTS: Laparoscopic adrenalectomies were successfully performed in each group, although the partial type had fewer ports and shorter operative time. All 63 patients with total adrenalectomy showed recovery from hypertension, suppressed plasma renin activity and high plasma aldosterone. Two of 29 patients with partial adrenalectomy or enucleation still experienced hypertension with high plasma aldosterone. Of the 63 extirpated specimens 17 adrenals (27.0%) demonstrated multiple space occupying lesions along with the main APA. CONCLUSIONS: Primary hyperaldosteronism is highly associated with multiple adrenal space occupying lesions. The risk-to-benefit ratio must be carefully weighed against the potential advantage of partial adrenalectomy. We chose total laparoscopic adrenalectomy in patients with unilateral APA and primary hyperaldosteronism.
Adenoma↗
Plasma aldosterone response to ACTH in primary aldosteronism and in patients with low renin hypertension.
ACTH alpha 1-24 was infused at incremental rates of 12.5-200 mIU/30 min in dexamethasone-suppressed hypertensive patients on a regular sodium diet. The plasma aldosterone response to this stimulus in 8 patients with hyperaldosteronism due to an adrenal aldenoma and 11 with adrenal hyperplasia was significantly greater at all infusion rates (P less than 0.05) when compared with the response in 6 normal subjects on a similar diet. This responsiveness to ACTH in the patients with primary hyperaldosteronism was similar to that of the normal subjects on a low sodium diet. Twelve patients with low renin and 6 patients with normal renin essential hypertension were similarly studied. There was no significant difference in the median aldosterone response between these 2 groups and the normal subjects on a normal diet, but the response was significantly lower compared with that in patients with primary hyperaldosteronism. These data show that patients with hyperaldosteronism from an adrenal adenoma or hyperplasia have a consistent and exaggerated response to ACTH. The hyper-responsiveness is not apparently shared by the majority of patients with low renin essential hypertension and does not support the concept that this group is an intermediate form of primary aldosteronism. Individual patients within this group, however, may have such a response and might be identified by this type of testing.
Adenoma↗
Genetic study of patients with dexamethasone-suppressible aldosteronism without the chimeric CYP11B1/CYP11B2 gene.
Glucocorticoid-remediable aldosteronism is an inherited disorder caused by a chimeric gene duplication between the CYP11B1 (11beta-hydroxylase) and CYP11B2 (aldosterone synthase) genes. The disorder is characterized by hyperaldosteronism and high levels of 18-hydroxycortisol and 18-oxocortisol, which are under ACTH control. The diagnosis of glucocorticoid-remediable aldosteronism had been traditionally made using the dexamethasone suppression test; however, recent studies have shown that several patients with primary aldosteronism and a positive dexamethasone suppression test do not have the chimeric CYP11B1/CYP11B2 gene. The aim of this work was to evaluate whether other genetic alterations exist in CYP11B genes (gene conversion in the coding region of CYP11B1 or in the promoter of CYP11B2) that could explain a positive dexamethasone suppression test and to determine another genetic cause of glucocorticoid-remediable aldosteronism. We also evaluated the role of 18-hydroxycortisol as a specific biochemical marker of glucocorticoid-remediable aldosteronism. We studied eight patients with idiopathic hyperaldosteronism, a positive dexamethasone suppression test, and a negative genetic test for the chimeric gene. In all patients we amplified the CYP11B1 gene by PCR and sequenced exons 3-9 of CYP11B1 and a specific region (-138 to -284) of CYP11B2 promoter. We also measured the levels of 18-hydroxycortisol, and we compared the results with those found in four subjects with the chimeric gene. None of eight cases showed abnormalities in exons 3-9 of CYP11B1, disproving a gene conversion phenomenon. In all patients a fragment of 393 bp corresponding to a specific region of the promoter of CYP11B2 gene was amplified. The sequence of the fragment did not differ from that of the wild-type promoter of the CYP11B2 gene. The 18-hydroxycortisol levels in the eight idiopathic hyperaldosteronism patients and four controls with chimeric gene were 3.9 +/- 2.3 and 21.9 +/- 3.5 nmol/liter, respectively (P < 0.01). In summary, we did not find other genetic alterations or high levels of 18-hydroxycortisol that could explain a positive dexamethasone suppression test in idiopathic hyperaldosteronism. We suggest that the dexamethasone suppression test could lead to an incorrect diagnosis of glucocorticoid-remediable aldosteronism.
Adult↗
Primary aldosteronism in childhood due to primary adrenal hyperplasia.
We present an unusual case of primary aldosteronism in childhood. A 9-year-old boy had hypertension, hypokalemia, hyporeninemia and hyperaldosteronism. Dexamethasone administration decreased plasma aldosterone transiently but failed to correct the hyperaldosteronism, excluding dexamethasone-suppressible hyperaldosteronism. Plasma aldosterone decreased with upright posture and showed a circadian rhythm. Spironolactone treatment normalized blood pressure and serum potassium and lowered aldosterone secretion. During the studies, plasma aldosterone correlated with serum cortisol but not with plasma renin. Preoperative results indicated that this patient presented the functional features of aldosteronoma. Adrenal computed tomography, scintigraphy and left venography were not diagnostic of adrenal lesions. The left adrenal venous sampling showed hypersecretion of aldosterone from the left adrenal gland. The left adrenalectomy revealed micronodular hyperplasia but resulted in a prompt and sustained reversal of hypertension and hyperaldosteronism. These findings suggest that primary aldosteronism in this patient resulted from primary adrenal hyperplasia. Thus, adrenal hyperplasia is a heterogenous group of disorders and carefully selected studies allow prospective selection of appropriate treatment.
Adrenal Hyperplasia, Congenital↗
Aetiological, clinical and metabolic profile of hypokalaemic periodic paralysis in adults: a single-centre experience.
BACKGROUND: Hypokalaemic periodic paralysis constitutes a heterogeneous group of disorders that present with acute muscular weakness. In this analysis, we discuss the aetiological factors that appear to be more common in the Indian population. METHODS: From 1995 to 2001, 31 patients presented with periodic paralysis (mean age 34.5 years, range 11-68 years). Of the 31 patients, 19 were men. The clinical and laboratory data of these patients were analysed. Patients were investigated for possible secondary causes of hypokalaemla. RESULTS: There were 13 patients (42%) with renal tubular acidosis, 13 with primary hyperaldosteronism (42%), 2 each with thyrotoxic periodic paralysis and sporadic periodic paralysis, and I with Gitelman syndrome. Of the 13 patients with renal tubular acidosis, 10 had proximal and 3 distal renal tubular acidosis. Three of these patients with renal tubular acidosis had Sjogren syndrome. The patients diagnosed to have renal tubular acidosis had significantly lower serum bicarbonate (18.7 [14.6] v. 29.6 [5.0] mEq/L; p < 0.05) and higher levels of chloride (107.5 [6.0] v. 99.5 [3.4] mEq/L; p < 0.05) compared with those who had primary hyperaldosteronism, although the potassium values were similar (2.4 [0.65] v. 2.26 [0.48] mEq/L; p = 0.43). All patients with primary hyperaldosteronism had hypertension at presentation and were proven to have adrenal adenomas. CONCLUSION: A significant number of patients in this study had secondary and potentially reversible causes of hypokalaemic periodic paralysis. The common causes were renal tubular acidosis and primary hyperaldosteronism. A detailed work-up for secondary causes should be undertaken in Indian patients with hypokalaemic periodic paralysis.
Acidosis, Renal Tubular↗