Characteristics of preoperative steroid profiles and glucose metabolism in patients with primary aldosteronism developing adrenal insufficiency after adrenalectomy.
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ABSTRACT:
SUBMITTER: Wang X
PROVIDER: S-EPMC8160266 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Unilateral primary aldosteronism (PA) is the most common surgically curable form of hypertension that must be accurately differentiated from bilateral PA for therapeutic management (surgical versus medical). Adrenalectomy results in biochemical cure (complete biochemical success) in almost all patients diagnosed with unilateral PA; the remaining patients with partial or absent biochemical success comprise those with persisting aldosteronism who were misdiagnosed as unilateral PA preoperatively. To identify determinants of postsurgical biochemical outcomes, we compared the adrenal histopathology and the peripheral venous steroid profiles of patients with partial and absent or complete biochemical success after adrenalectomy for unilateral PA. A large multicenter cohort of adrenals from patients with absent and partial biochemical success (n=43) displayed a higher prevalence of hyperplasia (49% versus 21%; P=0.004) and a lower prevalence of solitary functional adenoma (44% versus 79%; P<0.001) compared with adrenals from age- and sex-matched patients with PA with complete biochemical success (n=52). We measured the peripheral plasma steroid concentrations in a subgroup of these patients (n=43) and in a group of patients with bilateral PA (n=27). Steroid profiling was associated with histopathologic phenotypes (solitary functional adenoma, hyperplasia, and aldosterone-producing cell clusters) and classified patients according to biochemical outcome or diagnosis of bilateral PA. If validated, peripheral venous steroid profiling may be a useful tool to guide the decision to perform surgery based on expectations of biochemical outcome after the procedure.
| S-EPMC6202235 | biostudies-literature
Project description:Introduction and importanceAdrenal insufficiency (AI) is common after adrenalectomy for Primary Adrenal Cushing's syndrome (PACS), due to the inhibition of the Hypothalamic-Pituitary-Adrenal Axis (HPAA) by the functioning adrenal mass. The treatment of post-surgical AI is based mainly on glucocorticoid supplementation therapy. To date, however, there is no known predicting factor of the duration of supplementation therapy in patients treated with laparoscopic adrenalectomy for PACS.Case presentationWe report the case of a 22-year-old Caucasian female who presented with dyspnea, osteoporosis, vertebral collapses and fractures of the pelvis. The diagnosis of ACTH-independent Cushing's syndrome was provided. Abdominal MRI revealed a left adrenal mass suggestive for adrenal adenoma, highly suggestive for PACS. The patient underwent left laparoscopic adrenalectomy. After surgery, glucorticoid supplementation therapy was started. More than A-year steroid replacement therapy was necessary before the patient completely recovered the function of the HPAA. During this period the patient was strictly followed up in order to adjust pharmacologic treatment, thus allowing to investigate the possible causes of such a slow and hard recover of the contralateral adrenal gland function.ConclusionAI is common after adrenalectomy for PACS due to HPAA suppression. The duration of steroid replacement therapy may be vary depending on patient's characteristics and may be uncommonly long, as in our case. We concluded the not only cortisol and ACTH level, but also radiological findings, such as the size of the mass, its functional activity as well as the hypotrophy or atrophy of the contralateral adrenal gland may be predictive of the duration of the steroid therapy. These factors, if correctly studied before surgery, may be of help in tailoring the postoperative management of the patients after adrenalectomy.
| S-EPMC9142400 | biostudies-literature
Project description:BackgroundAdrenal venous sampling (AVS) is performed to distinguish the subtype of primary aldosteronism (PA). The clinical implication of contralateral suppression (CS; aldosterone/cortisolnondominant<aldosterone/cortisolperipheral) at AVS remains unclear. We aimed to investigate the clinical significance of CS and its impact on postoperative outcomes after unilateral adrenalectomy.MethodsIn this retrospective observational multi-center study, we analyzed PA patients who underwent both successful adrenocorticotropin hormone-stimulated AVS and unilateral adrenalectomy. Successful cannulation was defined as the selectivity index (cortisoladrenal/cortisolperipheral) ≥3. Clinical and biochemical outcomes after unilateral adrenalectomy were evaluated based on the international Primary Aldosteronism Surgical Outcome consensus.ResultsAmong 263 patients analyzed, 247 had CS (93.9%). Patients with CS had lower serum potassium levels, higher plasma aldosterone concentration, higher aldosterone-to-renin ratio (ARR), and larger adenoma size than those without CS. Those with CS showed significantly higher lateralization index than those without CS (P<0.001). Although postoperative blood pressure and ARR significantly decreased in those with CS, clinical and biochemical outcomes were comparable in both groups. When the cut-off value of age was determined using receiver operating characteristic (ROC) analysis, patients aged ≥50 years old with contralateral suppression index (CSI; the ratio between aldosterone/cortisolnondominant and aldosterone/cortisolperipheral) ≤0.26 had greater odds ratio (6.43; 95% confidence interval, 1.30 to 31.69) of incident chronic kidney disease than those aged <50 years with CSI >0.26 after adjusting for other factors.ConclusionCS may not predict postoperative clinical and biochemical outcomes in subjects with unilateral aldosterone excess, but it is associated with postsurgical deterioration of renal function in subjects over 50 years with CSI ≤0.26.
| S-EPMC8419620 | biostudies-literature
Project description:ImportanceIn addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects.ObjectiveTo evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism.Design, setting, and participantsA cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded.Main outcomes and measuresClinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery.ResultsOn the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P < .001) and 3 (15) mm Hg (P = .04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P < .001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater.Conclusions and relevanceIn this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.
| S-EPMC6484800 | biostudies-literature
Project description:Aldosterone- and cortisol-coproducing adrenal adenoma (A/CPA) cases have been observed in patients with primary aldosteronism (PA). This study investigated the incidence, clinical characteristics, and molecular biological features of patients with A/CPAs. We retrospectively identified 22 A/CPA patients from 555 PA patients who visited the Chinese People's Liberation Army General Hospital between 2004 and 2015. Analysis of clinical parameters revealed that patients with A/CPAs had larger tumors than those with pure APAs (P < 0.05). Moreover, they had higher proportions of cardiovascular complications, glucose intolerance/diabetes, and osteopenia/osteoporosis compared to the pure APA patients (P < 0.001). In the molecular biological findings, quantitative real-time PCR analysis revealed similar CYP11B1 and CYP17A1 mRNA expressions in resected A/CPA specimens and in pure APA specimens. Western blot and immunochemical analyses showed CYP11B1, CYP11B2, and CYP17A1 expressions in both A/CPAs and pure APAs. Seventeen cases with KCNJ5 mutations were detected among the 22 A/CPA DNA samples, but no PRKACA or other causative mutations were observed. Each patient improved following adrenalectomy. In conclusion, A/CPAs were not rare among PA patients. These patients associated with high incidences of cardiovascular events and metabolic disorders. Screening for excess cortisol secretion is necessary for PA patients.
| S-EPMC5889857 | biostudies-literature
Project description:The underlying cause of resistant hypertension after adrenalectomy for primary hyperaldosteronism remains controversial. The objective of this study was to identify preoperative factors predictive of resistant hypertension in patients after undergoing retroperitoneoscopic adrenalectomy. Between 2003 and 2009, 124 patients with unilateral aldosterone-producing adenoma or unilateral adrenal hyperplasia underwent retroperitoneoscopic adrenalectomy at our institution. Clinical and biochemical data were reviewed retrospectively at baseline and after a median follow-up time of 59.2 ± 37.2 months. Adrenalectomy cured hypertension in 68 patients (54.8%) and 43 (34.8%) had persistent hypertension that was much easier to control after surgery, whereas 13 patients (10.4%) had continued hypertension and poor blood pressure control. Multivariate regression analysis revealed that the main determinants of postoperative cure were duration of hypertension less than 5 years [odds ratio (OR): 6.515, 95% confidence interval (CI) 2.278-10.293), number of antihypertensive medications ≤2 (OR: 2.939, 95% CI 1.254-5.235), preoperative response to spironolactone (OR: 3.405, 95% CI 1.681-6.985), the TT genotype of the CYP11B2 gene (344 C/T) (OR: 2.765, 95% CI 1.221-4.986), and the presence of adenoma rather than hyperplasia (OR: 5.274, 95% CI 2.150-8.141). The main determinants of surgical cure or control of hypertension in patients with primary hyperaldosteronism were duration of hypertension, number of antihypertensive medications, preoperative response to spironolactone, the presence of adenoma, and CYP11B2 (344 C/T) genotype. Consideration of these factors may help in the evaluation of patients for surgery and for the identification of patients with continued postoperative hypertension that may require more long-term monitoring and treatment.
| S-EPMC3723202 | biostudies-literature
Project description:Primary adrenal insufficiency is life threatening and can present alone or in combination with other comorbidities. Here, we have described a primary adrenal insufficiency syndrome and steroid-resistant nephrotic syndrome caused by loss-of-function mutations in sphingosine-1-phosphate lyase (SGPL1). SGPL1 executes the final decisive step of the sphingolipid breakdown pathway, mediating the irreversible cleavage of the lipid-signaling molecule sphingosine-1-phosphate (S1P). Mutations in other upstream components of the pathway lead to harmful accumulation of lysosomal sphingolipid species, which are associated with a series of conditions known as the sphingolipidoses. In this work, we have identified 4 different homozygous mutations, c.665G>A (p.R222Q), c.1633_1635delTTC (p.F545del), c.261+1G>A (p.S65Rfs*6), and c.7dupA (p.S3Kfs*11), in 5 families with the condition. In total, 8 patients were investigated, some of whom also manifested other features, including ichthyosis, primary hypothyroidism, neurological symptoms, and cryptorchidism. Sgpl1-/- mice recapitulated the main characteristics of the human disease with abnormal adrenal and renal morphology. Sgpl1-/- mice displayed disrupted adrenocortical zonation and defective expression of steroidogenic enzymes as well as renal histology in keeping with a glomerular phenotype. In summary, we have identified SGPL1 mutations in humans that perhaps represent a distinct multisystemic disorder of sphingolipid metabolism.
| S-EPMC5330744 | biostudies-literature
Project description:BackgroundThe prevalence of diabetes mellitus (DM) was higher in primary aldosteronism (PA) patients. We aimed to evaluate the outcome of DM after adrenalectomy and determine the factors associated with that in PA patients.MethodsPA patients with DM (PA + DM patients) who received adrenalectomy were recruited into the study. The patients were classified into 3 groups based on their DM conditions after treatment, including "remission", "improved" and "unchanged" groups. Univariate and multivariate logistic regression analysis was conducted to uncover the preoperative factors affecting the outcome of DM after adrenalectomy.ResultsA total of 54 PA + DM patients received adrenalectomy. After adrenalectomy, 16.7%, 33.3% and 50.0% of patients were classified into the "remission", "improved" and "unchanged" groups, respectively. The factors negatively associated with remission or improvement from DM after adrenalectomy were longer duration of hypertension (P = 0.029). Higher concentration of urinary magnesium (P = 0.031) and higher 24 h urinary potassium (P = 0.049) were factors negatively associated with the "remission" from DM after adrenalectomy.ConclusionsAdrenalectomy was beneficial for the remission and improvement from DM in the half of PA patients with DM. Longer duration of hypertension, higher concentration of urinary magnesium and higher 24 h urinary potassium may prevent the remission and improvement from DM after adrenalectomy in PA patients. Examination of urinary electrolyte could be considered in PA patients with DM for predicting the outcome of DM after adrenalectomy.
| S-EPMC9793683 | biostudies-literature
Project description:The adrenal glands are the primary source of mineralocorticoids, glucocorticoids, and the so-called adrenal androgens. Under physiological conditions, cortisol and adrenal androgen synthesis are controlled primarily by ACTH. Although it is well established that ACTH can stimulate steroidogenesis in the human adrenal gland, the effect of ACTH on overall production of different classes of steroid hormones has not been defined. In this study, we examined the effect of ACTH on the production of 23 steroid hormones in adult adrenal primary cultures and 20 steroids in the adrenal cell line, H295R. Liquid chromatography/tandem mass spectrometry analysis revealed that, in primary adrenal cell cultures, cortisol and corticosterone were the two most abundant steroid hormones produced with or without ACTH treatment (48? h). Cortisol production responded the most to ACTH treatment, with a 64-fold increase. Interestingly, the production of two androgens, androstenedione and 11?-hydroxyandrostenedione (11OHA), that were also produced in large amounts under basal conditions significantly increased after ACTH incubation. In H295R cells, 11-deoxycortisol and androstenedione were the major products under basal conditions. Treatment with forskolin increased the percentage of 11?-hydroxylated products, including cortisol and 11OHA. This study illustrates that adrenal cells respond to ACTH through the secretion of a variety of steroid hormones, thus supporting the role of adrenal cells as a source of both corticosteroids and androgens.
| S-EPMC3774117 | biostudies-literature
Project description:Primary aldosteronism (PA) is the most common cause of endocrine hypertension. Unilateral PA can be cured using unilateral adrenalectomy (Adx). PA surgery outcome (PASO) criteria, which include clinical and biochemical outcomes, have been proposed to evaluate PA cure after Adx. However, clinical outcomes are often inconsistent with biochemical outcomes. In addition, although confirmatory tests are included as endpoints of biochemical outcomes in the PASO criteria, their clinical usefulness has not yet been established. We evaluated clinical parameters and confirmatory test results before and after Adx in 16 patients with PA and assessed the usefulness of the confirmatory tests. The following were the clinical outcomes after Adx: 37.5% complete success, 62.5% partial success, and 0% absent success. The ratio of biochemical complete success was as follows: 69% aldosterone/renin ratio and basal plasma aldosterone concentration, 19% as assessed by the captopril challenge test, 47% as assessed by the saline infusion test, 30% as assessed by the furosemide upright test, and 100% urine aldosterone. Of these, biochemical complete success was judged in four cases by aldosterone/renin ratio and basal plasma aldosterone concentration, one case by captopril challenge test, five cases by saline infusion test, and one case by furosemide upright test. Although clinical outcomes and urine aldosterone levels improved after Adx, confirmatory tests failed to improve in some cases. The current criteria are not considered useful for biochemical evaluation after Adx. To determine whether additional treatment with mineralocorticoid receptor antagonists is required, more accurate biochemical criteria should be established after Adx.
| S-EPMC10232090 | biostudies-literature