Background Primary hyperaldosteronism may be caused by an aldosterone-producing adenoma (APA), which is correctable by unilateral adrenalectomy or by idiopathic adrenal hyperplasia, a bilateral ...disease without any indication for surgery. This study sought to assess the prevalence and the results of surgery in unilateral adrenal hyperplasia (UAH). Methods The study included 35 patients who underwent unilateral adrenalectomy because of primary hyperaldosteronism after unequivocal successful lateralization by adrenal venous sampling. Demographics, biochemical evaluation, and blood pressure were assessed pre- and postoperatively. Pathology was categorized as APA (isolated adenoma), nodular (multiple micromacronodules), and diffuse UAH (gland thickening without nodules). Results Pathology revealed 9 APAs and 23 nodular and 3 diffuse UAHs. Patients with APAs and UAHs were statistically similar regarding demographics and preoperative blood pressure levels. Bilateral adrenal involvement was evident at imaging in 10 patients (11% in APA versus 35% in UAH, P = NS). After surgery, biochemical cure of the disease was achieved in all patients; blood pressure levels normalized in 66.6% of patients and ameliorated in 22.2% in APA versus 34.6% and 50% in patients with UAH ( P = NS). At a long-term follow-up, only 1 patient with nodular UAH experienced a biochemical recurrence of disease. Conclusion UAH is not rare, sharing the same features of APA. When disease lateralization is confirmed by adrenal venous sampling, unilateral adrenalectomy achieves excellent long-term results.
Background Laparoscopic adrenalectomy has become the gold standard for removing adrenal masses, but several authors still debate the role of laparoscopic adrenalectomy in pheochromocytoma. The ...purpose of this study was to evaluate the short- and long-term outcomes of laparoscopic versus open adrenalectomy for pheochromocytomas and to compare the feasibility and safety of laparoscopic adrenalectomy for neoplasms that are smaller than 6 cm versus those that are larger than 6 cm. Methods From January 1990 to December 2005, the same team in our department carried out 221 adrenalectomies in 211 patients. A total of 64 of these patients underwent 71 adrenalectomies for pheochromocytoma, 24 patients (37%) had open adrenalectomy, and 40 patients (63%) had laparoscopic adrenalectomy. Sex, age, side and size of lesion, operating time, duration of hospital stay, need for intensive care, intraoperative blood pressure variations, blood loss, postoperative analgesia, return to oral nutrition, and complications were compared among groups. Results An advantage of laparoscopic adrenalectomy over open adrenalectomy was observed in mean operating time, hospital stay, need for intensive care, intraoperative hypertension, intraoperative blood loss, postoperative analgesia, and return to oral nutrition ( P ≤ .035 in all). The analysis of tumor size (≤6 vs >6 cm) in laparoscopic adrenalectomy showed that none of the variables differed significantly, except for intraoperative blood loss, which was greater for the larger neoplasms ( P = .007). Conclusions Laparoscopic adrenalectomy, when performed by experienced laparoscopic surgeons, is preferable to open adrenalectomy for the majority of pheochromocytomas, and as long as there is no evidence of invasion of surrounding structures, tumor size does not appear to have a profound effect on surgical outcome.
Autoantibodies to the angiotensin II type 1 receptor (AT1R) have been reported in patients with primary aldosteronism, including aldosterone producing adenoma (APA) and idiopathic adrenal hyperplasia ...(IAH). Sera from 25 primary aldosteronism subjects (12 with IAH and 13 with APA) and 15 normotensive control subjects were assayed for AT1R autoantibodies by enzyme-linked immunosorbent assay and an AT1R-transfected cell-based bioassay. Nine of 12 IAH subjects (75%) and six of 13 APA subjects (46%) were positive for AT1R autoantibodies in the bioactivity assay. The mean AT1R autoantibody activity for the IAH and APA subjects was significantly greater than controls (P < .001 and P < .01, respectively), and this in vitro activity was suppressed by the AT1R blocker losartan. None of the controls had significant AT1R autoantibody activity. Enzyme-linked immunosorbent assay values were less sensitive but were positive in some subjects with IAH and APA. The mean arterial pressure of these primary aldosteronism subjects correlated modestly with AT1R autoantibody activity. These data confirm the presence of active AT1R autoantibodies in a high percentage of subjects with primary aldosteronism irrespective of their underlying etiology. These observations have both pathophysiological and clinical implications.
Primary Aldosteronism (PA) is characterized by inappropriate aldosterone production partially autonomous of the renin-angiotensin system. Since the ARR ratio was introduced a much higher prevalence ...of this disease is recognized. PA could be the most common identifiable, specifically treatable and potentially curable form of hypertension so the need of a clinical practice guideline on primary aldosteronism becomes mandatory. Recently the Endocrine Society USA published clinical practice guidelines for the diagnosis and treatment of patients with primary hyperaldosteronism. Systematic reviews of available evidence were used to formulate the key treatment and prevention recommendations. Actually the Endocrine Society consensus is the most used guidelines in diagnosis and treatment of hyperaldosteronism. However, there remains a few unresolved issues, which unfortunately require more of a detour guide and cannot be easily addressed by a straight forward guideline.
Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus ...criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism and apply these criteria to an international cohort to analyse the frequency of remission and identify preoperative determinants of successful outcome.
The Primary Aldosteronism Surgical Outcome (PASO) study was an international project to develop consensus criteria for outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism. An international panel of 31 experts from 28 centres, including six endocrine surgeons, used the Delphi method to reach consensus. We then retrospectively analysed follow-up data from prospective cohorts for outcome assessment of patients diagnosed with unilateral primary aldosteronism by adrenal venous sampling who had undergone a total adrenalectomy, consecutively included from 12 referral centres in nine countries. On the basis of standardised criteria, we determined the proportions of patients achieving complete, partial, or absent clinical and biochemical success in accordance with the consensus. We then used logistic regression analyses to identify preoperative factors associated with clinical and biochemical outcomes.
Consensus was reached for criteria for six outcomes (complete, partial, and absent success of clinical and biochemical outcomes) based on blood pressure, use of antihypertensive drugs, plasma potassium and aldosterone concentrations, and plasma renin concentrations or activities. Consensus was also reached for two recommendations for the timing of follow-up assessment. For the international cohort analysis, we analysed clinical data from 705 patients recruited between 1994 and 2015, of whom 699 also had biochemical data. Complete clinical success was achieved in 259 (37%) of 705 patients, with a wide variance (range 17-62), and partial clinical success in an additional 334 (47%, range 35-66); complete biochemical success was seen in 656 (94%, 83-100) of 699 patients. Female patients had a higher likelihood of complete clinical success (odds ratio OR 2·25, 95% CI 1·40-3·62; p=0·001) and clinical benefit (complete plus partial clinical success; OR 2·89, 1·49-5·59; p=0·002) than male patients. Younger patients had a higher likelihood of complete clinical success (OR 0·95 per extra year, 0·93-0·98; p<0·001) and clinical benefit (OR 0·95 per extra year, 0·92-0·98; p=0·004). Higher levels of preoperative medication were associated with lower levels of complete clinical success (OR 0·80 per unit increase, 0·70-0·90; p<0·001).
These standardised outcome criteria are relevant for the assessment of the success of surgical treatment in individual patients and will allow the comparison of outcome data in future studies. The variable baseline clinical characteristics of our international cohort contributed to wide variation in clinical outcomes. Most patients derive clinical benefit from adrenalectomy, with younger patients and female patients more likely to have a favourable surgical outcome. Screening for primary aldosteronism should nonetheless be done in every individual fulfilling US Endocrine Society guideline criteria because biochemical success without clinical success is by itself clinically important and older women and men can also derive post-operative clinical benefit.
European Research Council; European Union's Horizon 2020; Else Kröner-Fresenius Stiftung; Netherlands Organisation for Health Research and Development-Medical Sciences; Japanese Ministry of Health, Labour and Welfare; Ministry of Health, Slovenia; US National Institutes of Health; and CONICYT-FONDECYT (Chile).
The syndrome of apparent mineralocorticoid excess (AME) is a heritable form of hypertension due to an inborn error of cortisol metabolism and is characterized by hypokalemia and low renin levels ...despite subnormal or normal levels of aldosterone and other known mineralocorticoids. The syndrome is attributable to congenital deficiency of the enzyme 11β-hydroxydehydrogenase (11β-HSD), which converts cortisol (F) to biologically inactive cortisone. This results in a prolonged half-life of F, which acts at the kidney level as a potent mineralocorticoid (MC). In fact, both F and aldosterone have similar affinities in vitro for type I MC receptor (MR), and 11β-HSD activity protects the MR in vivo from the higher circulating levels of F. The biochemical marker of this disorder is an increased ratio of tetrahydrocortisol (THF) + allo-THF/tetrahydrocortisone (THE) in the urine, which has been found in more than 20 patients described to date, together with evidence of a more general defect in steroid ring A reduction. Only a few cases (the so-called type II form) described in Italy differ from the classic form having a normal
THF
THE
ratio, but in both forms the ratio of free urinary
F
E
has recently been found to be similarly high. Dexamethasone is the treatment of choice but is often inadequate in long term control of high blood pressure. Acquired forms of AME are those consequent on abuse of licorice or carbenoxolone, which both inhibit 11β-HSD; the latter also inhibits the reverse 11-oxoreductase reaction leading to somewhat different abnormalities of urinary cortisol/cortisone. So far, two isoenzymes of 11β-HSD have been purified and cloned; 11β-HSD type 1 is NADP-dependent, abundant in liver, lung, and testis, and catalyzes both 11β-dehydrogenation and 11β-oxoreduction; no mutation in its gene was detected in patients with AME. A second NAD-dependent isoenzyme is present in kidney and placenta and catalyzes dehydrogenation only. Very recently (1995) two groups have independently demonstrated the presence of mutations in its gene, located in chromosome 16q22. New and co-workers found a point mutation in exon 6 of two affected siblings of an Iranian family, while White and co-workers in parallel studies showed point mutations or small deletions in both alleles in nine unrelated patients; importantly, expression studies showed minimal or absent activity for almost all the mutant sequences. No definite mutations have been so far identified in patients with AME type II. AME is thus the third single gene cause of human hypertension to be described, after glucocorticoid remediable aldosteronism in 1992 and Liddle's syndrome in 1994.
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