A 25-year-old lady presented with hypertensive encephalopathy. She also had chronic refractory hypertension for the past 7 years. Workup revealed persistent hypokalaemia with metabolic alkalosis suggesting hyperaldosteronism. Hyperaldosteronic states such as renal artery stenosis, Conn's syndrome and Liddle's syndrome were ruled out. Her plasma renin activity was high. Contrast-enhanced CT of the abdomen showed a 1.9×2 cm heterogeneously enhancing lesion in the anterior aspect of the right kidney suggesting a possibility of reninoma. The benign tumour was resected by a nephron-sparing surgery. Histopathology suggested a juxtaglomerular cell tumour. Anti-hypertensive drugs were completely withdrawn postoperatively.

A 56-year-old woman with a history of paraplegia and chronic pain due to neuromyelitis optica (Devic's syndrome) was admitted to a spinal cord injury unit for management of a sacral decubitus ulcer. During the hospitalization, she required emergency transfer to the intensive care unit (ICU) because of progressive deterioration of respiratory muscle function, severe respiratory acidosis, obtundation and hypotension. Upon transfer to the ICU, arterial blood gas revealed severe acute-on-chronic respiratory acidosis (pH 7.00, PCO2 120 mm Hg, PO2 211 mm Hg). The patient was immediately intubated and mechanically ventilated. Intravenous fluid boluses of normal saline (10.5 L in about 24 h) and vasopressors were started with rapid correction of hypotension. In addition, she was given hydrocortisone. Within 40 min of initiation of mechanical ventilation, there was improvement in acute respiratory acidosis. Sixteen hours later, however, the patient developed life-threatening hypokalemia (K(+) of 2.1 mEq/L) and hypomagnesemia (Mg of 1.4 mg/dL). Despite aggressive potassium supplementation, hypokalemia continued to worsen over the next several hours (K(+) of 1.7 mEq/L). Urine studies revealed renal potassium wasting. We reason that the recalcitrant life-threatening hypokalemia was caused by several mechanisms including total body potassium depletion (chronic respiratory acidosis), a shift of potassium from the extracellular to intracellular space (rapid correction of respiratory acidosis with mechanical ventilation), increased sodium delivery to the distal nephron (normal saline resuscitation), hyperaldosteronism (secondary to hypotension plus administration of hydrocortisone) and hypomagnesemia. We conclude that rapid correction of respiratory acidosis, especially in the setting of hypotension, can lead to life-threatening hypokalemia. Serum potassium levels must be monitored closely in these patients, as failure to do so can lead to potentially lethal consequences.

Endocrine diseases have been associated with cardiovascular events. Both altered coagulation and fibrinolysis markers and thrombotic disorders have been described in several endocrine diseases. This review summarizes the evidence on the influence of thyroid diseases, cortisol excess and deficiency, pheochromocytoma, hyperparathyroidism, hyperaldosteronism, hyperprolactinemia, and growth hormone excess and deficiency; on parameters of hemostasis; and on arterial and venous thrombotic events. All these endocrine diseases do have, or may have, influence either on hemostasis or on the risk of thrombotic events. Future studies are needed to establish the clinical relevance of these associations.

BACKGROUND:

To date, the available non-invasive remedies for primary aldosteronism are not satisfactory in clinical practice. The phosphoinositide 3-kinase (PI3Ks)/protein kinase B (PKB or AKT)/mammalian target of rapamycin (mTOR) signaling pathway is essential for tumorigenesis and metastasis in many types of human tumors, including renal cancer, adrenal carcinoma and pheochromocytoma. The possibility that this pathway is also necessary for the pathogenesis of primary aldosteronism has not yet been explored. To answer this question, we investigated the activity of the PI3K/AKT/mTOR signaling pathway in normal adrenal glands (NAGs), primary aldosteronism (PA) patients and NCI-H295R cells.

METHOD

OLOGY

PRINCIPAL FINDINGS:

Between January 2005 and December 2011, we retrospectively reviewed the records of 45 patients with PA. We compared clinical characteristics (age, gender and biochemical data) and the expression of phospho-AKT (p-AKT), phospho-mTOR (p-mTOR), phospho-S6 (p-S6) and vascular endothelial growth factor (VEGF) by immunohistochemical staining and western blotting, analyzing 30 aldosterone-producing adenomas (APAs), 15 idiopathic hyperaldosteronism (IHA) tissues and 12 NAGs following nephrectomy for renal tumors (control group). Compared with the control group, most of the PA patients presented with polydipsia, polyuria, resistant hypertension, profound hypokalemia, hyperaldosteronemia and decreased plasma renin activity. Compared with normal zona glomerulosa, the levels of p-AKT, p-mTOR, p-S6 and VEGF were significantly upregulated in APA and IHA. No significant differences were found between APA and IHA in the expression of these proteins. Additionally, positive correlations existed between the plasma aldosterone levels and the expression of p-AKT and p-mTOR. In vitro studies showed that mTOR inhibitor rapamycin could inhibit cell proliferation in NCI-H295R cells in a dose- and time-dependent manner. Furthermore, this inhibitor also decreased aldosterone secretion.

CONCLUSIONS:

Our data suggest that the PI3K/AKT/mTOR signaling pathway, which was overactivated in APA and IHA compared with normal zona glomerulosa, may mediate aldosterone hypersecretion and participate in the development of PA.

Incidentally detected adrenal masses occur frequently especially in the elderly. This is due to technical advances as well as to widespread use of radiologic imaging performed for other reasons. After discovery of an adrenal mass two major questions arise: firstly, is the lesion malignant and, secondly, is it hormonally active? Malignancy is only very rarely the cause for incidental adrenal masses. However, in patients with a history of malignant disease these are suspicious for metastases. Imaging may help distinguish adrenal masses in terms of size and signal characteristics. About 10 - 15 % of adrenal incidentalomas are hormonally active. Clinically significant are an overproduction of catecholamines, aldosterone and cortisol. Hormonal evaluation should be considered according to the clinical context: screening for hyperaldosteronism is recommended if hypertension is present and screening for cortisol-excess should be performed in patients with typical clinical signs. In contrast, a pheochromocytoma should be ruled out in almost all patients with adrenal incidentaloma. Often only a combination of different tests can prove hormone-excess. These tests are influenced by a variety of factors and should therefore be interpreted with caution.

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. The aldosterone to renin ratio (ARR) is the gold standard for screening, but variability between biochemical methods used remains of concern. The aim of the study was to analyze center-specific features of biochemical diagnostic strategies prior to the 2008 consensus within the German Conn's Registry. The study was designed as a retrospective study in 5 tertiary care hospitals. Patients analyzed for PA between 1990 and 2006 were studied. Characteristics of the assays used to determine ARR during establishing the diagnosis of PA were analyzed in the retrospective part of the German Conn's Registry. Eighty-six out of 484 documented ARR values had to be excluded from further evaluations because the laboratory or the assays were unknown. In the remaining 398 patients ARR was determined using 10 different assay combinations in the centers (aldosterone plus plasma renin activity or concentration). Considerable differences were seen between the mean concentrations for aldosterone (p<0.0001), renin concentration (p<0.001), and renin activity (p=0.009) for the different assays. The differences between the absolute concentrations measured by the different assays also had significant impact upon the resulting mean ratios. If published cutoff values are applied, the use of different commercial assays to determine the ARR in clinical routine results in major differences in positive screening rates. This heterogeneity affects sensitivity and specificity of screening for PA. Our data emphasize the importance of standardized screening procedures, which must include standardization of biochemical methods.

Aldosterone plays a major role in regulating sodium and potassium homeostasis, and blood pressure. More recently aldosterone has emerged as a key hormone in mediating end organ damage. In extreme cases, dysregulated aldosterone production leads to primary aldosteronism, the most common form of secondary hypertension. However, even within the physiological range, high levels of aldosterone are associated with an increased risk of developing hypertension over time. Primary aldosteronism represents the most common and curable form of hypertension, with a prevalence that increases with the severity of hypertension. Although genetic causes underlying glucocorticoid remediable aldosteronism, one of the three Mendelian forms of primary aldosteronism, were established some time ago, somatic and inherited mutations in the potassium channel GIRK4 have only recently been implicated in the formation of aldosterone producing adenoma and in familial hyperaldosteronism type 3. Moreover, recent findings have identified somatic mutations in two additional genes, involved in maintaining intracellular ionic homeostasis and cell membrane potential, in a subset of aldosterone producing adenoma.This review summarizes our current knowledge on the genetic determinants that contribute to variations in plasma aldosterone and renin levels in the general population, and the genetics of familial and sporadic primary aldosteronism. Various animal models that have significantly improved our understanding of the pathophysiology of excess aldosterone production will also be discussed. Finally, we will outline the cardiovascular, renal and metabolic consequences of mineralocorticoid excess beyond blood pressure regulation.

Cardiovascular (CV) complications such as myocardial infarction, heart failure, stroke and renal failure are related to both the degree and the duration of blood pressure (BP) increase. Resistant hypertension (RH) is associated with a higher risk of CV complications and a higher prevalence of target organ damage (TOD). The relationship between CV disease and TOD can be bidirectional. Elevated BP in RH may cause CV structural and functional alterations, and the development or persistence of left ventricular hypertrophy, aortic stiffness, atherosclerotic plaques, microvascular disease and renal dysfunction, may render hypertension more difficult to control. Specifically, RH is related to several conditions, including obesity, sleep apnea, diabetes, metabolic syndrome and hyperaldosteronism, characterized by an overexpression of humoral and hormonal factors that are involved in the development and maintenance of TOD. Optimal therapeutic strategies, including pharmacological treatment and innovative invasive methodologies, have been shown to achieve adequate BP control and induce the regression of TOD, thereby potentially improving patient prognosis.Hypertension Research advance online publication, 18 April 2013; doi:10.1038/hr.2013.30.

Rhabdomyolysis presenting with severe hypokalemia as the first manifestation of primary hyperaldosteronism is extremely rare.Two middle-aged Chinese females were admitted to our emergency department for muscular weakness and limb pain, and both have the history of early onset hypertension. Laboratory test showed elevated creatinine phosphokinase (4, 907 and 8, 531 IU/L) and extremely low serum potassium (1.38 mmol/L and 1.98 mmol/L). Rhabdomyolysis and severe hypokalemia were established as first diagnosis. Hypokalemic rhabdomyolysis was confirmed after nervous system disorders, autoimmune diseases and trauma were excluded. Adrenal computerized tomography scan and postural stimulation test revealed aldosterone-producing adenomas. They both received laparoscopic adrenalectomy and were stable at the 2-year follow-up visit.The two cases remind physicians to bear in mind the risk of hypokalemia-induced rhabdomyolysis among patients with primary hyperaldosteronism.

PURPOSE:

Percutaneous ablation of functioning adrenal adenomas has been an alternative to videolaparoscopic treatment. This study aimed to evaluate the feasibility, safety and efficacy of radiofrequency ablation (RFA) in the treatment of functioning adrenal tumors using a computed tomography (CT)-guided percutaneous technique as demonstrated by our experience and the literature.

METHODS:

Eleven adult patients (mean age 46 years) with a diagnosis of functioning adrenal adenoma underwent CT-guided RFA between October 2011 and August 2012. All RFA procedures were performed using a needle electrode with a single lateral filament and the RITA(®) 1500X radiofrequency generator. The RFA protocol consisted of two cycles of 5 min each with 1-min interval, with no additional ablation cycles. Contrast-enhanced CT scans were obtained and analyzed for immediate treatment success and possible complications.

RESULTS:

Maximum tumor dimension ranged from 1.2 to 3.4 cm. The mean procedure time was 74 min, and length of hospital stay ranged from 0.9 to 3.2 days (mean 1.8 days). One patient had residual pneumothorax and one patient had neuritis involving the T10 dermatome. Of 11 patients, 10 recovered from their condition. Only one patient remained with hyperaldosteronism, but with reduced anti-hypertensive medication.

CONCLUSIONS:

CT-guided percutaneous RFA was a safe and effective treatment for functioning adrenal adenomas, with short hospital length of stay and low complication rate.