Primary Hyperaldosteronism: When to Suspect It and How to Confirm Its Diagnosis

The definition of primary hyperaldosteronism (PA) has shifted, as progress has been made in understanding the disease. PA can be produced by unilateral or bilateral cortical adrenal hyperproduction of aldosterone, due to hyperplasia, aldosterone-secreting cell clusters, aldosterone-producing macro or micro adenoma/s, and combinations of the above, or by an aldosterone-producing carcinoma. PA is a highly prevalent disease, affecting close to 10% of the hypertensive population. However, PA is clearly underdiagnosed. The purpose of this review is to address current knowledge of PA’s clinical manifestations, as well as current methods of diagnosis. PA is associated with a higher cardiovascular morbidity and mortality than essential hypertension with similar blood pressure control. Young hypertensive patients, those with a first-degree relative with PA or ictus, and/or those with apnea/hypopnea syndrome, moderate/severe/resistant hypertension, adrenal incidentaloma, and/or hypokalemia should be screened for PA. PA can induce atrial fibrillation (AF), and those patients should also be screened for PA. We propose the use of the Captopril challenge test (CCT), oral salt loading, or intravenous salt loading for PA diagnosis, given their availability in the majority of hospital centers. CCT could be first-line, since it is safe and easy to perform.

Diagnostic Dilemmas: A Multi-Institutional Retrospective Analysis of Adrenal Incidentaloma Pathology Based on Radiographic Size

Introduction/Background Adrenal incidentalomas (AIs) are masses >1 cm found incidentally during radiographic imaging. They are present in up to 4.4% of patients undergoing CT scan, and incidence is increasing with usage and sensitivity of cross-sectional imaging. Most result in diagnosis of adrenal cortical adenoma, questioning guidelines recommending removal of all AIs with negative functional workup. This retrospective study analyzes histological outcome based on size of non-functional adrenal masses. Material and Methods 10 years of data was analyzed from two academic institutions. Exclusion criteria included patients with positive functional workups, those who underwent adrenalectomy during nephrectomy, <18 years, and incomplete records. AI radiologic and histologic size, histologic outcome, laterality, imaging modality, gender, and age were collected. T-test was used for comparison of continuous variables, and the two-sided Fisher’s exact or chi-square test were used to determine differences for categorical variables. Univariate analysis of each independent variable was performed using simple logistic regression. Results 73 adrenalectomies met the above inclusion criteria. 60 were detected on CT scan, 12 on MRI, and one on ultrasound. Eight of 73 cases resulted in malignant pathology, 3 of which were adrenocortical carcinoma (ACC). Each ACC measured >6 cm, with mean radiologic and pathologic sizes of 11.2 cm and 11.3 cm. Both radiologic and pathologic size were significant predictors of malignancy (p=0.008 and 0.011). Conclusions Our results question the generally-accepted 4 cm cutoff for excision of metabolically-silent AIs. They suggest a 6 cm threshold would suffice to avoid removal of benign lesions while maintaining sensitivity for ACC.

Adrenal incidentaloma: prevalence and referral patterns from routine practice in a large UK university teaching hospital

Context Adrenal incidentalomas are increasingly being identified during unrelated imaging. Unlike AI clinical management, data on referral patterns in routine practice are lacking. Objective To identify factors associated with AI referral Design We linked data from imaging reports and outpatient bookings from a large UK teaching hospital. We examined; (i) AI prevalence and (ii) pattern of referral to endocrinology, stratified by age, imaging modality, scan anatomical site, requesting clinical specialty and temporal trends. Patients Utilising key radiology phrases to identify scans reporting potential AI, we identified 4,097 individuals from 479,945 scan reports (2015-19). Main Outcome Measures Prevalence of AI and referral rates Results Overall, AI lesions were identified in 1.2% of scans. They were more prevalent in abdomen CT and MRI scans (3.0% and 0.6%, respectively). Scans performed increased 7.7% year-on-year from 2015-19, with a more pronounced rise in the number with AI lesions (14.7% pa). Only 394/4097 patients (9.6%) had a documented endocrinology referral code within 90 days, with medical (11.8%) more likely to refer than surgical (7.2%) specialties (p&lt;0.001). Despite prevalence increasing with age, older patients were less likely to be referred (p&lt;0.001). Conclusions While overall AI prevalence appeared low, scan numbers are large and rising; the number with identified AI are increasing still further. The poor AI referral rates, even in centres such as ours where dedicated AI multi-disciplinary team meetings and digital management systems are used, highlights the need for new streamlined, clinically-effective systems and processes to appropriately manage the AI workload.

A case report on asymptomatic and biochemically silent pheochromocytoma in adrenal incidentaloma

Pheochromocytoma are rare tumours originating from the chromaffin tissue. The clinical manifestations are variable and are not specific as pheochromocytoma and often imitate other diseases. The diagnosis is established by measurement of catecholamines and their metabolites in urine or plasma and by radiographic studies for localisation. Surgical removal of the tumour is the preferred treatment. 45 years old female presented with adrenal incidentaloma of about 6.1×6.2×5.4 cm well defined heterogenous lesion with internal cystic areas seen in right adrenal region abutting upper pole of right kidney. Biochemical investigations for adrenal hormones including plasma aldosterones, cortisols, plasma metanephrines, 24 hrs urinary metanephrines and VMA were found to be normal. Proceeded with adrenelectomy and histopathology of the specimen revealed pheochromocytoma as diagnosis. Pheochromocytoma leads to high mortality and morbidity rates if untreated. Fractionised metanephrines and catecholamines in a 24 hrs urine analysis is the preferred biochemical test. In a biochemically silent pheochromocytoma imaging modalities are used to identify and locate the tumour. Adequete alpha and beta blockade should be ensured before tumour removal. Surgery is recommenced irrespective of size and normal biochemical study to prevent complications.

Attenuation Value in Adrenal Incidentalomas: A Longitudinal Study

ContextA tendency to grow has been reported in adrenal incidentalomas. However, long-term data regarding attenuation value, a measure of lipid content, are not available.AimThis study aims to collect radiological data (diameter in mm and attenuation value in Hounsfield units, HU) with computed tomography (CT) in adrenal incidentalomas, in order to compare baseline characteristics with the last follow-up imaging.DesignThis is a longitudinal study which included patients with a new diagnosis of adrenal incidentaloma, evaluated from January 2002 to June 2020.SettingReferral University-Hospital center.PatientsTwo hundred seventy-seven patients with 355 different cortical adenomas (baseline group) were evaluated at the first outpatient visit; the follow-up cohort consists of 181 patients with 234 adenomas (12–175 months after baseline). Inclusion criteria were conservative management and radiological features able to minimize malignancy or risk of progression.Main Outcome MeasureCT modification according to endocrine function: autonomous cortisol secretion (ACS) if cortisol &gt;50 nmol/L after 1-mg dexamethasone test (DST).ResultsAt baseline CT, mean diameter was 18.7 mm and attenuation value was 0.8 HU (higher in ACS, 66 cases &gt;10 HU), without modification in early imaging (12–36 months). The size increased over time (r = 0.289), achieving the largest differences after at least 60 months of follow-up (mean diameter, +2 mm; attenuation value, −4 HU), combined with a reduction in the attenuation value (r = −0.195, especially in patients with ACS). Lipid-poor adenomas (&gt;10 HU) presented a reduced cortisol suppression after 1-mg DST, an increase in size and the largest decrease in attenuation value during follow-up. Univariate analysis confirmed that larger adenomas presented reduced suppression after DST and increase in size during follow-up.ConclusionsGrowth is clinically modest in adrenal incidentaloma: the first follow-up CT 5 years after baseline is a reasonable choice, especially in ACS. Mean density is increased in patients with ACS and overt hypercortisolism. Mean density reduces during follow-up in all adrenal adenomas, suggesting an increase in lipid content, especially in those with ACS.

Presentation and management of pheochromocytomas and paragangliomas: about 40 cases

Background Pheochromocytoma and paraganglioma are rare neuroendocrine tumors of the chromaffin tissue, which may produce catecholamines. The aim of our study was to analyze the clinical and para-clinical aspects as well as the therapeutic and evolutionary aspects of pheocromocytomas and paragangliomas based on a series of 40 cases. Methods Our retrospective population-based research study includes 40 patients. Then, a statistical analysis was carried out using the SPSS software (version21). Results Our study involves 40 patients, including 23 women (57, 5%) and 17 men (42,5%). The mean age at the time of the diagnosis was 43.8 ± 16.8 years. The circumstances of the discovery were mainly characterized by adrenal incidentaloma and hypertension. The biological diagnosis was based on the dosage of urinary metanephrines and plasma-free metanephrines in, respectively, 61.5% and 18% of cases. A computerized tomography scan and/or a magnetic resonance imaging scan could help to locate the tumor in 100% of cases. Our series includes 3 cases of bilateral pheochromocytoma, 3 cases of paragangliomas and 1 case of malignant pheochromocytoma, while a hereditary form was retained in 3 patients. In fact, thirty-two patients were operated; cure was clinically labeled in 100% and biologically in 87.5% of patients. Conclusions The main points for improvement that our study has revealed are; a patient follow-up after surgery, which was not always regular, and an insufficient screening for genetic diseases associated with pheochromocytomas and paragangliomas.

Assessment of Plasma-Free Cortisol Concentrations by LC-MS/MS in Patients with Autonomous Cortisol Secretion

Autonomous cortisol secretion (ACS) of an adrenal incidentaloma (AI) is associated with mild cortisol excess that could result in poor metabolic and cardiovascular outcomes. The biological activity of glucocorticoids depends on the unbound, free fraction. We aimed to evaluate plasma free cortisol (FC) concentrations in patients with ACS in this cross-sectional study. One hundred and ten AI patients in 3 groups; non-functioning (NFA, n=33), possible ACS (n=65), ACS (n=12) were enrolled. Following measurements were conducted: Clinical data and total serum cortisol (TC), plasma corticotrophin (ACTH), serum dehydroepiandrosterone sulfate (DHEA-S), cortisol after 1 mg dexamethasone by both immunoassay and LC-MS/MS (DexF), serum corticosteroid binding globulin (CBG), plasma dexamethasone concentration [DEX] and plasma FC by LC-MS/MS. Patients with ACS featured an unfavorable metabolic profile. Plasma [DEX] and serum CBG levels were similar between groups. Plasma FC was significantly higher in ACS when compared to NFA and possible ACS groups p<0.05 and p<0.01, respectively. In multiple regression analysis DexF (beta=0.402, p<0.001) and CBG (beta=−0.257, p=0.03) remained as the independent predictors of plasma FC while age, sex, BMI, smoking habit, and existing cardiovascular disease did not make a significant contribution to the regression model. In conclusion, the magnitude of cortisol excess in ACS could lead to increased plasma FC concentrations. Further studies in AI patients are needed to demonstrate whether any alterations of cortisol affinity for CBG exist and to establish whether plasma FC concentrations predict the unfavorable metabolic profile in ACS.