Abstract 008: Novel Pathological Diagnosis Between Aldosterone Producing Adenoma And Idiopathic Hyperaldosteronism

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Fumitoshi Satoh ◽  
Yoshikiyo Ono ◽  
Ryo Morimoto ◽  
Masataka Kudo ◽  
Yoshitsugu Iwakura ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Monoclonal Antibodies ◽  
Tumor Size ◽  
Zona Glomerulosa ◽  
Maximum Diameter ◽  
Steroidogenic Enzymes ◽  
The Status ◽  
Aldosterone Producing Adenoma ◽  
Idiopathic Hyperaldosteronism ◽  
Tumor Area

The expressions of steroidogenic enzymes to produce aldosterone like CYP11B1, CYP11B2, 3BHSD1 and 3BHSD2 remain to be clarified to confirm pathological subclassification between aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA). Furthermore, we examined the correlation between APA tumor size and the status of intratumoral steroidogenic enzymes involved in aldosterone biosynthesis using immunohistochemistry. Surgically proven forty APA patients and ten IHA patients were retrospectively studied. Multi-detector computed tomography, AVS, and laparoscopic adrenalectomy were performed in all of the patients studied. The tumor area of APA at the maximum diameter of the sections was precisely measured by ImageJ software. The status of steroidogenic enzymes was immunohistochemically analyzed using monoclonal antibodies for CYP11B1, CYP11B2, 3BHSD1 and 3BHSD2, and the findings were evaluated according to the H-score system, based on both the number of immunopositive cells and relative immunointensity. Adrenal masses were not detected by computed tomography in 20 APA patients.In all of 10 IHA patients, hyperplastic zona glomerulosa was accompanied by an expression of HSD3B1. In contrast, tumor cells in all 40 APA patients were not immunopositive to HSD3B1, but strongly and dominanty expressed HSD3B2. Perhaps, due to compensatory responses to excess aldosterone, APA had an adjacent zona glomerulosa whose immunoreactivities to HSD3B1 and HSD3B2 were profoundly reduced in all 40 APA patients. Maximum tumor area obtained in the specimens was significantly correlated with preoperative plasma aldosterone concentration, urinary aldosterone excretion, the H-score of CYP11B1, and was inversely correlated with the H-score of CYP11B2. These results demonstrated that small adenomas could produce sufficient aldosterone to cause clinically overt primary aldosteronism because of the significantly higher CYP11B2 expression per tumor area. Monoclonal antibodies against HSD3B1 and HSD3B2 could be useful for immunohistochemical differentiation between APA and IHA. In addition, the relatively higher CYP11B2 expression per area in smaller APA could clinically cause PA despite their CT-undetectable tumor size.

scholarly journals Analysis of Unilateral Adrenal Hyperplasia with Primary Aldosteronism from the Aspect of Messenger Ribonucleic Acid Expression for Steroidogenic Enzymes: A Comparative Study with Adrenal Cortices Adhering to Aldosterone-Producing Adenoma

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 999-1006 ◽  
Author(s):  
Kazuto Shigematsu ◽  
Kioko Kawai ◽  
Junji Irie ◽  
Hideki Sakai ◽  
Osamu Nakashima ◽  
...  
Keyword(s):  
Primary Aldosteronism ◽  
Zona Glomerulosa ◽  
Adrenal Hyperplasia ◽  
Steroidogenic Enzymes ◽  
Unilateral Adrenalectomy ◽  
Messenger Ribonucleic Acid ◽  
Unilateral Adrenal Hyperplasia ◽  
Aldosterone Production ◽  
Long Term Follow Up ◽  
Aldosterone Producing Adenoma

Unilateral adrenal hyperplasia with primary aldosteronism is very rare and shows similar endocrine features to aldosterone-producing adenoma and bilateral adrenal hyperplasia. In this study, the mRNA expression of steroidogenic enzymes in unilateral adrenal hyperplasia was examined by in situ hybridization. We found subcapsular micronodules composed of spironolactone body-containing cells, which showed intense expression for 3β-hydroxysteroid dehydrogenase, 11β-hydroxylase, 18-hydroxylase, and 21-hydroxylase but not 17α-hydroxylase, indicating aldosterone production. This expression pattern was the same as that in unilateral multiple adrenocortical micronodules, reported recently. Additionally, it was noted that a nodule with active aldosterone production was closely adjacent to one showing intense 17α-hydroxylase expression. In the adrenal cortices adhering to aldosterone-producing adenoma, the majority of hyperplastic zona glomerulosa and hyperplastic nodules demonstrated a decreased steroidogenic activity. However, minute nodules indicative of active aldosterone production were found at high frequency. These results suggest that the subcapsular micronodules observed might be the root of aldosterone-producing adenoma. Furthermore, we emphasize the need for long-term follow-up after unilateral adrenalectomy or enucleation of the adenoma because of the possibility that buds with autonomous aldosterone production may still be present in the contralateral or remaining adrenal tissue.

scholarly journals Aldosterone-Producing Adenoma: Does a Larger Tumor Secrete More Apparent Cortisol?

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A76-A77
Author(s):  
Felicity Xu ◽  
Shumin Yang ◽  
Wenwen He ◽  
Qifu Li
Keyword(s):  
Tumor Size ◽  
Cushing Syndrome ◽  
Cell Types ◽  
Maximum Diameter ◽  
Tumor Diameter ◽  
Cortisol Secretion ◽  
Score System ◽  
Great Heterogeneity ◽  
Suppression Test ◽  
Aldosterone Producing Adenoma

Abstract Previous studies revealed that aldosterone-producing adenoma(APA) had a potential for excess co-secretion of cortisol. APA was considered to be composed of heterozygous cell types, including cortisol producing cells(expression of CYP11B1) and aldosterone-producing cells(expression of CYP11B2). The proportion of two cell types and the expression of two steroid synthases showed great heterogeneity in APAs, which may lead to differences in cortisol secretion. However, the hypothesis has not been tested. Therefore, we examined the correlation between tumor size and the ability to autonomously secrete cortisol of APA from the perspective of steroid hormones and immunohistochemistry. 165 patients with surgically proven APA were retrospectively studied. Patients with apparent excess cortisol co-secretion were excluded, which was confirmed by an overnight 1 mg dexamethasone suppression test(1mg-DST). Immunohistochemical staining was performed in 88 tumor specimens and CYP11B2-negative APAs were excluded. The expression of the steroidogenic enzymes was immunohistochemically analyzed, and semi-quantified according to the McCarty H-score system. All APA cases were classified into 2 groups according to the median(15mm) of maximum diameter detected by histological examination: the smaller(n=102) and larger group(n=63). 24am cortisol[78.7(47.7–121.5) VS. 54.6(33.6–81.4) nmol/l, p =0.002] and cortisol after 1mg-DST[28.8(19.1–40.9) VS. 24.1(16.8–30.7) nmol/l, p =0.024] were significantly higher in the larger APA group. The larger APA group had a higher H score of CYP11B1 (p=0.028) and a lower H score of CYP11B2 (p=0.036). Both 24pm cortisol (r =0.2424, p =0.0058)and cortisol after 1mg-DST(r =0.2476, p =0.042)were positively correlated with tumor diameter. The tumor diameter was positively correlated with the H score of CYP11B1 (p=0.0328) and inversely with the H score of CYP11B2(p=0.0285). We tentatively used a new ratio B1 index, calculated by H score of CYP11B1 divided by the sum of H score of CYP11B2 and CYP11B1, to represent the relative expression intensity of CYP11B1 in tumor specimens. B1 index had a stronger correlation with tumor diameter (r =0.3134,p=0.0041). Cortisol after 1mg-DST increased linearly with the tertiles of tumor diameter(p for trend<0.0001). These results suggested that APA without clinically overt cortisol secretion might have a higher proportion of cells expressing CYP11B1 to produce more cortisol with the increasing of tumor size, even developing to overt Cushing syndrome.

The Capacity of a Specific Anti-Streptococcus Mutans Monoclonal Antibodies Test to Identify the Diabetic Patients with Increased Risk of Periodontal Disease

2017 ◽  
Vol 68 (11) ◽  
pp. 2556-2559
Author(s):  
Mona Ionas ◽  
Sebastian Ioan Cernusca Mitariu ◽  
Adela Dancila ◽  
Tiberiu Horatiu Ionas ◽  
Raluca Monica Comaneanu ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Periodontal Disease ◽  
Streptococcus Mutans ◽  
Mutans Streptococci ◽  
Diabetic Patients ◽  
A Value ◽  
Salivary Level ◽  
Increased Risk ◽  
The Status

By means of a specific anti-Streptococcus mutans monoclonal antibodies test we want to identify the diabetic patients which have an increased risk to develop the periodontal disease. The highest percentage, of 88.1% of all patients included in this study represents the subjects with a level greater than 500,000 cfu / mL of streptococcus mutans. The Kruskal-Wallis test reveals a value of p = 0.283 resulted from the status of diabetes in patients and the level of streptococcus mutans in saliva. In conclusion, the status of diabetes in patients seems not to influence the salivary level of mutans streptococci determined with the method used in our study.

Antibody Therapy for the Control of Viral Diseases: An Update

2019 ◽  
Vol 20 (13) ◽  
pp. 1108-1121 ◽  
Author(s):  
Miriam Dibo ◽  
Eduardo C. Battocchio ◽  
Lucas M. dos Santos Souza ◽  
Matheus D. Veloso da Silva ◽  
Bruna K. Banin-Hirata ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Viral Antigen ◽  
Viral Infections ◽  
Antibody Therapy ◽  
Therapeutic Strategies ◽  
Viral Diseases ◽  
Specific Antibodies ◽  
The Status ◽  
Epidemiological Impact

The epidemiological impact of viral diseases, combined with the emergence and reemergence of some viruses, and the difficulties in identifying effective therapies, have encouraged several studies to develop new therapeutic strategies for viral infections. In this context, the use of immunotherapy for the treatment of viral diseases is increasing. One of the strategies of immunotherapy is the use of antibodies, particularly the monoclonal antibodies (mAbs) and multi-specific antibodies, which bind directly to the viral antigen and bring about activation of the immune system. With current advancements in science and technology, several such antibodies are being tested, and some are already approved and are undergoing clinical trials. The present work aims to review the status of mAb development for the treatment of viral diseases.

scholarly journals Aortic dissection during transoesophageal echocardiography: a case report

2020 ◽  
Author(s):  
Rin Hoshina ◽  
Hideyuki Kishima ◽  
Takanao Mine ◽  
Masaharu Ishihara
Keyword(s):  
Computed Tomography ◽  
Coronary Artery ◽  
Aortic Dissection ◽  
Right Coronary Artery ◽  
Bypass Graft ◽  
Transoesophageal Echocardiography ◽  
Ascending Aorta ◽  
Maximum Diameter ◽  
Abnormal Finding ◽  
The Right

Abstract Background Transoesophageal echocardiography (TOE) is a safe and useful tool. In our case, we are presenting a rare case of a patient with aortic dissection during TOE procedure. Case summary A 79-year-old woman was referred to our hospital for recurrent paroxysmal atrial fibrillation (AF) with palpitation. Pre-procedural cardiac computed tomography (CT) showed slight dilated ascending aorta (maximum diameter: 40 mm). We decided to perform catheter ablation (CA) for AF, and recommended TOE before the CA because she had a CHADS2 score of 4. On the day before the CA, TOE was performed. Her physical examinations at the time of TOE procedure were unremarkable. At 3 min after probe insertion, there was no abnormal finding of the ascending aorta. At 5 min after the insertion, TOE showed ascending aortic dissection without pericardial effusion. After waking, she had severe back pain and underwent a contrast-enhanced CT. Computed tomography demonstrated Stanford type A aortic dissection extending from the aortic root to the bifurcation of common iliac arteries, and tight stenosis in the right coronary artery (maximum diameter; 49 mm). The patient underwent a replacement of the ascending aorta, and a coronary artery bypass graft surgery for the right coronary artery. Discussion Transoesophageal echocardiography would have to be performed under sufficient sedation with continuous blood pressure monitoring in patients who have risk factors of aortic dissection. The risk–benefit of TOE must be considered before a decision is made. Depending on the situation, another modality instead of TOE might be required.

scholarly journals Isolated iliac artery aneurysm in association with congenital pelvic kidney treated with iliac branch device: case report

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Guilherme Centofanti ◽  
Kenji Nishinari ◽  
Bruna De Fina ◽  
Rafael Noronha Cavalcante ◽  
Mariana Krutman ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Iliac Artery ◽  
Computed Tomography Angiography ◽  
Common Iliac Artery ◽  
Artery Aneurysm ◽  
Maximum Diameter ◽  
Pelvic Kidney ◽  
Iliac Artery Aneurysm ◽  
Left Common Iliac Artery ◽  
Common Iliac Artery Aneurysm

Abstract Background Association of abdominal aortic aneurysm with congenital pelvic kidney is rare and association with isolated iliac artery aneurysm is not yet described in the literature. Case presentation We present a case of successful repair of an isolated common iliac artery aneurysm associated with a congenital pelvic kidney treated by an endovascular technique. A 75-year-old man was referred for the treatment of an asymptomatic left common iliac artery aneurysm. A computed tomography angiography revealed an isolated left common iliac artery aneurysm and a left pelvic kidney. The maximum diameter of the aneurysm was 32 mm. The congenital pelvic kidney was supplied by three small superior polar arteries that emerged from the proximal non-aneurysmal portion of the common iliac artery and the main artery that arose from the left internal iliac artery. The aneurysm exclusion was accomplished by using an iliac branch device (Gore Excluder Iliac Branch, Flagstaff, AZ). The 1 and 6 months computed tomography angiography after the procedure demonstrated complete exclusion of the aneurysm and preservation of all renal arteries. Conclusion Treating patients with an association of iliac artery aneurysms and pelvic kidneys can be a challenge due the variable arterial anatomy. The use of iliac branch device is a safe and effective alternative in selected cases.

scholarly journals Isolation of Human Adrenocortical Aldosterone-Producing Cells by a Novel Immunomagnetic Beads Method

Endocrinology ◽  
2010 ◽  
Vol 151 (3) ◽  
pp. 1375-1380 ◽  
Author(s):  
Brasilina Caroccia ◽  
Ambrogio Fassina ◽  
Teresa Maria Seccia ◽  
Chiara Recarti ◽  
Lucia Petrelli ◽  
...  
Keyword(s):  
Magnetic Beads ◽  
Zona Glomerulosa ◽  
Multiple Features ◽  
Pheochromocytoma Cells ◽  
Expression Studies ◽  
Neural Cell Adhesion ◽  
Multiple Characteristics ◽  
Normal Human ◽  
Aldosterone Producing Adenoma ◽  
Gene Expression Studies

We detected intense CD56 immunostaining in the zona glomerulosa (ZG) and medulla of the normal human adrenal gland and therefore identified CD56, the neural cell adhesion molecule, as a membrane antigen specific for the ZG, aldosterone-producing adenoma (APA), and chromaffin cells. The APA and pheochromocytoma cells, which are histogenetically derived from the ZG and medulla, respectively, also showed intense CD56 immunostaining. Based on these findings we developed a strategy for isolating cells from the ZG and APA using CD56 immunobinding to magnetic beads. Morphology, gene expression studies, and aldosterone measurement confirmed that CD56 positive (+) cells were ZG and APA cells. Analysis of CD56+ cells under light and phase contrast microscopy evidenced that these cells formed clumps, as the ZG cells usually do; with electron microscopy they showed multiple features typical of a steroidogenic phenotype. Expression levels of the CD56 and the aldosterone synthase (CYP11B2) gene were markedly higher in CD56+ cells than CD56− cells (+1600 and +2100% increase, respectively). Moreover, aldosterone secretion was higher (+1380%) from CD56+ cells than from CD56− cells. Hence, this novel methodology allows isolation of a pure population of ZG and APA cells exhibiting multiple characteristics of the aldosterone-producing cells.

Abstract 057: Cellular and Genetic Causes of Idiopathic Hyperaldosteronism

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Kei Omata ◽  
Fumitoshi Satoh ◽  
Ryo Morimoto ◽  
Sadayoshi Ito ◽  
Yuto Yamazaki ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Median Number ◽  
Zona Glomerulosa ◽  
Potential Contribution ◽  
Unilateral Adrenalectomy ◽  
Aldosterone Synthase ◽  
Formalin Fixed Paraffin Embedded ◽  
Idiopathic Hyperaldosteronism

Background: Primary aldosteronism (PA) affects ~10% of hypertensive patients and has unilateral and bilateral forms (30%:70%). Unilateral PA is caused by aldosterone-producing adenomas (APA), which express CYP11B2 (aldosterone synthase) and frequently harbor somatic mutations in aldosterone regulating genes ( KCNJ5>>CACNA1D ). We recently demonstrated that adrenals from normotensive patients present with pockets of cell expressing aldosterone synthase (CYP11B2). These aldosterone-producing foci (APF) have somatic gene mutations similar to those found in APA ( CACNA1D >> KCNJ5 ). Bilateral PA, which is typically treated by mineralocorticoid receptor (MR) blockade rather than surgery, is termed idiopathic hyperaldosteronism (IHA). Its pathobiology is largely unknown but has been thought to be due to zona glomerulosa (ZG) hyperplasia. Methods: We studied 11 IHA patients (7 males, 4 females) who had unilateral adrenalectomy. Immunohistochemistry for CYP11B2 and next generation sequencing (NGS) targeting genes found in APA were performed on formalin fixed paraffin embedded adrenal tissue. Results were compared to previously described cohorts of 53 age-matched normotensive patients (29 males, 24 females) which were evaluated similarly. Results: CYP11B2 expression was absent from intervening ZG cells in 8/11 (73%) IHA adrenals, but all adrenals harbored at least one APF. The median number and size of APF per case were significantly larger in IHA than normotensive controls (6.1 vs 0 APF/cm 2 of adrenal cortex and 0.25 vs. 0.16 mm 2 , respectively; p<0.0001 and p<0.006). In this IHA cohort, NGS identified CACNA1D and KCNJ5 somatic mutations in 44/71 (62%) and 1/71 (1%) of APF, respectively. Interpretations. Diffuse CYP11B2 expression in adrenal ZG cells was only observed in 3/11 IHA cases, arguing against ZG hyperplasia as the major underlying pathobiology. Rather, we demonstrated increased and enlarged APF in IHA adrenals compared to normotensive controls, supporting potential contribution to the clinical manifestations of hyperaldosteronism. The frequent occurrence of aldosterone-dysregulating CACNA1D somatic mutations in APF support CACNA1D as a potential therapeutic target in IHA to complement current MR blockade approaches.

Nodule Size Effect on Diagnostic Performance of Ultrasonography and Computed Tomography for Papillary Thyroid Carcinoma

2019 ◽  
Vol 15 (5) ◽  
pp. 489-495
Author(s):  
Jia-wei LI ◽  
Cai Chang ◽  
Jia-ying Chen ◽  
Zhao-ting Shi ◽  
Min Chen
Keyword(s):  
Computed Tomography ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Maximum Diameter ◽  
Pairwise Comparisons ◽  
Papillary Thyroid ◽  
Nodule Size ◽  
Significant Difference ◽  
The Us ◽  
Group D

Background: To compare the abilities of ultrasonography (US) and Computed Tomography (CT) to identify calcifications and to predict probability of malignancy for Papillary Thyroid Carcinoma (PTC) and Papillary Thyroid Microcarcinoma (PTMC). Methods: We reviewed 1008 cases of PTC/PTMC with calcifications reported by pre-operative US, CT, or post-operative pathology. The size of the thyroid nodule was obtained from the US report and the maximum diameter (d) was documented. According to the nodule size (d), the PTC and PTMC groups were each divided into two subgroups, as follows: large PTC group (d ≥ 2 cm), small PTC group (1 cm < d < 2 cm), large PTMC group (0.6 cm ≤ d ≤ 1 cm), and small PTMC group (d < 0.6 cm). Results: In the 1008 patients, the ratio of females to males was 2.29 and the mean age was 40.9 years (standard deviation: 11.7 years). Of the 1008 records, 92.8% were found to have calcifications according to the US report, while 50.4% showed calcifications according to the CT report. This difference between US and CT reports was statistically significant (p < 0.0005). The percentages of US reports showing calcifications were similar for all four PTC and PTMC subgroups (93.7%, 94.3%, 92.1%, and 85.1%, respectively; p = 0.052), while the percentages of CT reports showing calcifications were significantly different among the PTC and PTMC subgroups (62.3%, 52.2%, 45.4%, and 31.3%, respectively; p < 0.0005). As for the prediction of malignancy, US was superior to CT in all four subgroups (large PTC group: 97.1% vs. 54.1%, small PTC group: 94.8% vs. 42.9%, large PTMC group: 97.2% vs. 32.0%, small PTMC group: 95.5% vs. 14.9%; p < 0.0005 for all pairwise comparisons). No significant difference was observed in terms of the ability of US to predict the malignancy of PTC versus PTMC (p = 0.31), while CT showed significant superiority in diagnosing PTC versus PTMC (p < 0.0005). The predictive value of CT for PTC declined as the nodule size decreased (p < 0.05 for all pairwise comparisons). Conclusion: Our results showed that US detected calcifications and predicted the malignancy of all nodule sizes of thyroid papillary carcinoma equally well, while the performance of CT declined with the reduction of nodule size.

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