Bruno Allolio

Adrenal Venous Sampling Evaluation of the German Conn's Registry

In patients with primary aldosteronism, adrenal venous sampling is helpful to distinguish between unilateral and bilateral adrenal diseases. However, the procedure is technically challenging, and selective bilateral catheterization often fails. The aim of this analysis was to evaluate success rate in a retrospective analysis and compare data with procedures done prospectively after introduction of measures designed to improve rates of successful cannulation. Patients were derived from a cross-sectional study involving 5 German centers (German Conns registry). In the retrospective phase, 569 patients with primary aldosteronism were registered between 1990 and 2007, of whom 230 received adrenal venous sampling. In 200 patients there were sufficient data to evaluate the procedure. In 2008 and 2009, primary aldosteronism was diagnosed in 156 patients, and adrenal venous sampling was done in 106 and evaluated prospectively. Retrospective evaluation revealed that 31% were bilaterally selective when a selectivity index (cortisol adrenal vein/cortisol inferior vena cava) of ≥2.0 was applied. Centers completing <20 procedures had success rates between 8% and 10%. Overall success rate increased in the prospective phase from 31% to 61%. Retrospective data demonstrated the pitfalls of performing adrenal venous sampling. Even in specialized centers, success rates were poor. Marked improvements could be observed in the prospective phase. Selected centers that implemented specific measures to increase accuracy, such as rapid-cortisol-assay and introduction of standard operating procedures, reached success rates of >70%. These data demonstrate the importance of throughput, expertise, and various potentially beneficial measures to improve adrenal vein sampling.

Effectiveness of eplerenone or spironolactone treatment in preserving renal function in primary aldosteronism.

OBJECTIVEnPrimary aldosteronism (PA) has deleterious effects on kidney function independent of blood pressure levels. Up to now, data on effectiveness of different PA therapies regarding renal function are scarce.nnnDESIGN AND METHODSnThis prospective multi-center study included 29 patients with newly diagnosed PA evaluated before and 1 year after treatment initiation, and a second cohort including 119 patients who were evaluated 5.3 and 6.8 years after treatment initiation. Glomerular filtration rate (GFR), spot urine albumin excretion/urinary creatinine (UAE/Ucrea) ratio, biochemical parameters, and 24-h blood pressure were measured. In a larger cross-sectional cohort, renal function was evaluated depending on the type of treatment (adrenalectomy (ADX; n=86); spironolactone (n=65); and eplerenone (n=18)).nnnRESULTSnGFR and UAE/Ucrea ratio significantly decreased in newly diagnosed PA patients after treatment initiation. In the second cohort, GFR and UAE/Ucrea ratio did not change during study period, and blood pressure was well controlled. In the larger cross-sectional cohort, no differences were seen in GFR and UAE/Ucrea ratio between PA patients on different treatment regimens. However, eplerenone treatment showed lower potassium levels and higher number of required antihypertensive medications.nnnCONCLUSIONSnRenal dysfunction with elevated albuminuria was seen in PA patients and was reversible after treatment initiation. Medical therapies with spironolactone or eplerenone seem to be as effective as ADX regarding renal function and blood pressure; however, sufficient daily doses need to be given.

Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn's Registry

DESIGNnAbnormalities in glucose homeostasis have been described in patients with primary aldosteronism (PA) but most studies show inconsistent results. Therefore, we aimed to compare the prevalence of type 2 diabetes mellitus and metabolic syndrome (MetS) in newly diagnosed PA patients to a matched control cohort of the background population.nnnMETHODSnIn total, 305 PA patients of the prospective German Conns Registry were compared to the population-based Study of Health In Pomerania (SHIP1; n=2454). A 1:1 match regarding sex, age, and BMI resulted in 269 matched pairs regarding type 2 diabetes and 183 matched pairs regarding MetS. Of the total, 153 PA patients underwent oral glucose tolerance testing (OGTT) at diagnosis and 38 PA patients were reevaluated at follow-up.nnnRESULTSnType 2 diabetes and MetS were significantly more frequent in PA patients than in the control population (17.2% vs 10.4%, P=0.03; 56.8% vs 44.8%, P=0.02 respectively). Also, HbA1c levels were higher in PA patients than in controls (P<0.01). Of the total, 35.3% of non-diabetic PA patients showed an abnormal OGTT (¼ newly diagnosed type 2 diabetes and ¾ impaired glucose tolerance). PA patients with an abnormal OGTT at baseline presented with significantly improved 2u200ah OGTT glucose (P=0.01) at follow-up. We detected a negative correlation between 2u200ah OGTT glucose levels and serum potassium (P<0.01).nnnCONCLUSIONSnType 2 diabetes and MetS are more prevalent in patients with PA than in controls matched for sex, age, BMI, and blood pressure. This may explain in part the increased cardiovascular disease morbidity and mortality in PA patients.

Epidemiology of Adrenocortical Carcinoma

It is generally accepted that adrenocortical carcinoma (ACC) is a rare disease. However, valid data on the exact incidence and prevalence of ACC are lacking. Adrenal masses are among the most frequent tumors in humans. The vast majority of these tumors are nowadays found incidentally, and the prevalence of these adrenal incidentalomas is estimated as at least 3% in a population over the age of 50 years and increases to as much as 10% in the elderly [1–5]. However, it is well established that about 80% of these incidentally detected adrenal masses represent hormonally inactive adrenal adenomas and only a small minority are ACCs [2, 4, 6]. Data obtained from the National Cancer Institute Survey from the early 1970s estimated an incidence of 1–2 per million population per year, leading to 0.2% of cancer deaths in the United States [7]. A more recent analysis of the SEER database, including data from 12 US states, indicated an annual age-adjusted incidence of 0.72 per million [8, 9]. However, data from the German ACC Registry suggest that the incidence is >1 per million (Fassnacht & Allolio, unpublished data) and may be even higher.

High JAG1 expression in adrenocortical carcinomas is associated with better prognosis

Fig. 5 Impact of JAG1 protein expression on overall survival (A, n=126) and disease free survival (B, n=45) in patients with ACC. Interestingly, high JAG1 expression was significantly associated with a longer overall and disease free survival (Fig 5A and B). At multivariate analysis including the ENSAT stage, JAG1 maintained its independent impact on overall survival (P=0.007, HR=0.64, 25%CI: 0.46-0.89). 1Cristina L. Ronchi, 1Silviu Sbiera, 1Sonja Steinhauer, 2Vanessa Scott-Wild, 1Martin Fassnacht, 1Bruno Allolio