Endocrine Abstracts

Background: Previous research show that autoimmune adrenal insufficiency develops gradually over time and inexorably results in a total inability to produce adrenal steroids. However, growing evidence suggest that a few patients preserve some steroid producing capacity.Aim: To explore the frequency of residual cortisol production and possible clinical consequences in patients with autoimmune Addison´s disease (AAD).Material an...

Introduction: Ovarian adrenal rest tumors (OARTs), in contrast with testicular adrenal rest tumors, are very rare. Up to date, 13 cases were reported in the literature; all treated surgically.Aim: We describe a case of a young female with uncontrolled classical congenital adrenal hyperplasia (CCAH), presenting with bilateral OARTs, successfully treated with steroid replacement.Methods: Data on clinical history and biochemical work-...

Introduction: Adrenocortical carcinoma (ACC) is an aggressive tumour with unsatisfactory treatment options in advanced disease. Activation of epithelial to mesenchymal transition (EMT) has been described as causative of metastatic spread in human cancers. New drugs were developed targeting EMT with a focus on FGF/FGFR signalling. We here asked whether EMT is relevant in ACC.Methods: We analysed 6 normal adrenal glands (NAG), 40 adrenocortical adenomas (A...

Congenital adrenal hyperplasia (CAH) is usually caused by the mutations of steroid 21-hydroxylase gene (CYP21A2). CYP21A2 resides in RCCX copy number variation (CNV), and the genomic structure of RCCX CNV creates difficulties in the genetic testing of CAH. An RCCX CNV allele on one chromosome can carry CYP21A2 in various numbers. Homozygous deletion of complete CYP21A2 results in most severe form of CAH, whereas an additional and intact ...

Background: The human cytochrome P450 (CYP) 2W1 is involved in the metabolism of several endogenous substrates, including lysophospholipids and fatty acids. Using a polyclonal antibody, we previously demonstrated a high CYP2W1 immunoreactivity in adrenocortical tumors, particularly in those secreting steroids. The aim of the study was to better elucidate the relationship between CYP2W1 and steroid secretion in adrenocortical carcinoma (ACC) H295R cell line and in a larger seri...

Introduction: Primary bilateral macronodular adrenal hyperplasia (PBMAH) are benign adrenocortical disease responsible for benign tumors and cortisol autonomous secretion. There is a broad spectrum of clinical, imaging and hormonal presentations. Aberrant membrane receptor expression is frequent, the most characteristic example being the food dependent Cushing syndrome due to ectopic expression of the GIP receptor (GIP-R). In 20 to 25 % of these patients, inactivating heterozy...

The angiotensin II (AngII) hormone exerts a number of biological effects through the type 1 angiotensin II receptor (AT1R). One of the main targets of AngII are vascular smooth muscle cells, their stimulation activates many signaling pathways and results in gene expression changes.Affymetrix Gene Chip experiments were performed to analyze the effects of AngII stimulation on gene expression. For the determinations, aortic thoracic aorta from young male Wi...

Congenital adrenal hyperplasia (CAH) summarizes a group of genetic disorders of enzymes involved in cortisol biosynthesis. The most common causes detrimental mutations in the steroidogenic cytochrome P450 enzyme 21-hydroxylase (CYP21A2). Patients are dependent on a lifelong oral cortisol replacement therapy to ensure survival but quality of life is often reduced and co-morbidities are substantially increased. Also, the administered supraphysiological glucocorticoid dosescannot...

Introduction: Chronic hypercortisolemia during Cushing Syndrome (CS) determines significant changes in the plasticity and function of metabolic tissues like visceral adipose tissue (VAT). Persistence of alterations in VAT function after CS remission is under debate, as data of clinical studies is not consistent due to confounder factors and limited availability of VAT. Animal model of reversible CS presents long-term alterations on VAT after remission. We investigate VAT alter...

Background: Several evidences suggested that conventional glucocorticoids (CGCs) used as replacement treatment in adrenal insufficiency (AI) are inadequate to mimic physiological cortisol circadian rhythm (CCR), and that CCR disruption, represented by non-physiological pattern of peaks and troughs and elevated evening GC levels, might be responsible for the increased metabolic and, consequently, cardiovascular risk. It has been demonstrated that once daily dual-release-hydroco...

Introduction: It is well documented that adrenal tumor tissue is responsive to human chorionic gonadotropin (hCG) as well as to luteinizing hormone (LH) with both hormones sharing a similar physiological role and a mutual receptor.Objective: The objective of our study was to assess the adrenal steroid response to acute, exogenous hCG stimulation in patients with adrenal incidenatalomas (AI) and for the first time, in a healthy control group.<p class=...

Introduction: PBMAH is a rare but heterogeneous disease, characterized by multiple benign adrenal macronodules with variable levels of cortisol excess. In 2013, our team discovered germline heterozygous inactivating mutations of ARMC5, acting as a tumor suppressor gene. ARMC5 mutation rate is 50% in patients with PBMAH treated by adrenalectomy for severe hypercortisolism, 80% in familial cases and 20% in sporadic cases according to the current literature. The...

Background: Chronic glucocorticoids excess leads to morphological and functional cardiac alterations, a substrate for arrhythmias. Autonomous cortisol secretion (ACS) from adrenal incidentalomas is a model of chronic endogenous hypercortisolism, leading to severe cardiovascular diseases.Aim: To investigate prevalence and incidence of atrial fibrillation in a large cohort of patients with adrenal incidentalomas and ACS.Methods: Afte...

Background: LC-MS/MS is recommended for accurately measuring circulating steroids. However, laboratories using LC-MS/MS adopt various pre-analytical and analytical strategies, and little is known about comparability of results. Whether different blood derivatives impact LC-MS/MS measurements is unclear, and the benefit of unifying the calibration system among laboratories was not tested.Aim: Comparisons of LC-MS/MS measurements of circulating aldosterone...

In heart failure with reduced ejection fraction, catabolic mechanisms have a strong negative impact on mortality and morbidity. The relationship between anabolic hormonal deficiency and heart failure with preserved ejection fraction (HFpEF) has still been poorly investigated. On the other hand, oxidative stress is recognized as a player in the pathogenesis of HFpEF. Therefore, we performed a cohort study in HFpEF in order to: 1) define the multi-hormonal deficiency prevalence ...

Introduction: The management of patients with adrenal incidentaloma (AI) and possible subclinical hypercortisolism (SH) is debated. This randomized study was aimed to evaluate the effects of adrenalectomy on arterial hypertension (AH).Methods: We consecutively evaluated 590 AI patients (referred to 3 Italian Centres between 06/2016 and 12/2019). Among these, 134 patients showed a possible SH (i.e. 1 mg DST between 1.8 and 5 µg/dl). Based on the excl...

Relacorilant is a highly selective glucocorticoid receptor modulator that antagonizes the effects of excess cortisol while showing no significant affinity for the mineralocorticoid and progesterone receptors. In a Phase 2 study in patients with endogenous hypercortisolism, relacorilant demonstrated improvements in glycemic and hypertension control with no treatment-related hypokalemia or antiprogesterone effects. An international, multicenter, Phase 3 clinical trial, using ran...

Background: Autoimmune destruction is the most common aetiology of primary adrenal insufficiency (PAI) in Europe and north America. In contrast, tuberculosis is a common cause of PAI in developing countries. More recently, adrenal histoplasmosis (AH) is being increasingly reported from IndiaAims: To study the aetiology, clinical presentation and mortality in adults with PAI who were diagnosed between 2006-2019 and to determine the changes in aetiology si...

Objective: Aldosterone-producing adenomas (APA) are a major cause of primary aldosteronism. Somatic mutations explain the excess aldosterone production in the majority of patients with APA with mutations in KCNJ5 encoding a potassium channel the most prevalent in most reported populations. Mechanisms driving cell proliferation are largely undefined.Design and method: Quantitative transcriptome analysis using RNA-seq was used to identify differen...

Adrenocortical carcinoma (ACC) is an aggressive cancer, with, in its advanced stages, a median 5-year survival rate of less than 15%. ACC is rare in humans, but in dogs the incidence is at least 100 times higher. Because these dogs receive medical care, have an intact immune system, and have inter-individual and intratumoral heterogeneity, the dog is a unique spontaneous animal model to study new treatment options for ACC. However, to determine similarity of canine and human A...

Background: Women with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have a poor Quality of Life (QoL) compared to the general population and are less satisfied with their body appearance. Data indicates that psychosocial determinants such as good professional and general support could be associated with an improved QoL. Since there is only little data available that has been deduced from samples of small size this effect should be further examined....

Introduction: Aging is associated with the pathogenesis of many endocrinological disorders, especially for functioning adrenocortical disorders. In addition, mitochondria DNA abnormalities have been reported to be correlated with aging through ROS which eventually resulted in cell senescence. We previously reported that cortisol-producing adenomas (CPA) expressed more abundant cell senescent markers including p16 and p21, compared to other hormone-producing adenomas. However, ...

Background: Autonomous cortisol secretion (ACS) in patients with adrenal incidentalomas (AI) has been associated with increased mortality in previous small studies. Our aim was to evaluate if ACS is a risk factor for mortality in a large population of patients with AI.Methods: Consecutive patients examined for adrenal adenomas, found as AI, without catecholamine or aldosterone hypersecretion between 2005 and 2015 were included and followed for up to 14 y...

Real life experience of 8 people with adrenal insufficiency using subcutaneous hydrocortisone infusion in continuous and pulsatile regimens recruited through hydrocortisone pump support groupBackground: Subcutaneous hydrocortisone (HC) infusion using continuous (CSHI) and pulsatile (PSHI) regimes are treatment options for adrenal insufficiency. It is an off-labelled treatment in UK for patients with adrenal insufficiency (AI).Both ...

Insulin resistance and obesity are a global health problem and directly linked to macrophage-driven inflammation of the adipose tissue. Glucocorticoid therapy, used to treat inflammatory conditions, increases adiposity and insulin resistance. It is unknown however, whether anti-inflammatory actions of glucocorticoids at physiological levels can have beneficial effects on adipose tissue inflammation, potentially limiting insulin resistance. Using a macrophage specific deletion ...

Introduction: Pheochromocytomasand paragangliomas are tumors derived from chromaffin cells which result from mutations of at least six different genes as autosomal dominant disorders.Aim: To evaluate the existence of correlations between genetic alterations and clinical data in 16 patients with pheochromocytomas and/or paragangliomas.Methods: From 2007 to 2009, 13 patients with pheochromocytoma [3 men, medium age 39 years (14&#8211...

Introduction: Peritoneal implantation of benign pheochromocytomas – also known as pheochromocytomatosis – is a rare event caused by tumour rupture during surgical intervention. In our tertiary referral centre, we managed over two hundred patients with adrenal pheochromocytoma in the past 27 years. Now we report on the two cases diagnosed and followed with pheochromocytomatosis.Case 1: A 33-year-old man presenting with paroxysmal hypertension ...

Background: The recent ESE-ENSAT guidelines on adrenocortical carcinoma (ACC) indicated new treatment options for patients with “high risk for recurrence” as one of the major research topics for the field. However, since almost no data were available on the use of cytotoxic drugs in an adjuvant setting, no clear recommendation could be given. Here we report our experience with adjuvant platin-based therapy since 2002 at the University of Würzburg and MD Anders...

Introduction: Adrenocortical carcinoma (ACC) is a rare entity, usually associated with a poor prognosis. There are still many areas of uncertainty regarding its approach.Methods: A Portuguese ACC register was established in 2020, including information from 24 endocrine centres. Kaplan-Meier was used to calculate overall survival and recurrence; log- rank test to assess survival and progression free survival (PFS) differences between groups; cox-regressio...

Introduction: Excess glucocorticoid (GC) activity has been implicated in the pathophysiology of multiple cancer types. For instance, approximately half of adrenocortical carcinoma (ACC) patients exhibit excess GC (GC+). This provides a unique opportunity to study correlates of GC activity, such as a possible suppression of tumor immune response and immune checkpoint inhibitor (ICI) efficacy due to the broad immunosuppressive effects of GC. ACC multi-omics data can be used ...

Background: Adrenocortical carcinomas (ACC) are rare malignant tumours, with a quoted incidence of 0.7–2.0 cases/million habitants/year, with ectopic ACC being exceptionally rate. Diagnosis is based on clinical and biological assessment supplemented by imaging. Patients commonly present with features secondary to steroid excess, but around 15% of patients are diagnosed incidentally.Case report: A 54-year old lady, presented to clinic for assessment...

Background: Adrenocortical oncocytoma is a veryrare adrenal tumor type, usually nonfunctioning and benign. Neurofibromatosistype 1 (NF1) is an autosomal dominant disease caused by mutations of the NF1 gene encoding neurofibromin, a tumor supressor gene that acts by activating a RAS GTP-ase which negatively regulates RAS activity. NF 1 is usually associated with pheocromocytoma, rarely with adrenal carcinoma, and no association with adrenal oncocytoma has been reported.<p c...

Background: Adrenocortical carcinoma (ACC) is a rare cancer that originates from the cortex of the adrenal gland. Although its exact etiology is not clear, it has been found to be associated with some hereditary cancer syndromes. Sometimes patients present with hormonal excess symptoms (virilization, Cushing’s syndrome) or local symptoms consistent with an abdominal mass. In ACC, computed tomography (CT) and magnetic resonance imaging (MRI) are preferred imaging modaliti...

Background: Cushing’s syndrome is a rare condition in pregnancy, because infertility is one of the main features of this pathology. Association between pregnancy and cortisol excess involves a high rate of mortality and morbidity for mother and fetus. Hypertension, preeclampsia, diabetes, miscarriage, preterm delivery or sudden intrauterine death can occur. We describe a case of a pregnancy in a patient with a history of Cushing’s Syndrome, diagnosed during the pre...

Introduction: Steroid 11β-hydroxylase deficiency (11-OHD) is the second most common causeof congenital adrenal hyperplasia (CAH),characterized by the overproduction of adrenal androgens and deoxycorticosterone (DOC).It usually presents with virilization of the female fetus, precocious puberty in male infants and hypertension with or without hypokalemia in both genders. Because of high levels of mineralocorticoids, patients rarely present with salt wasting (SW). We herein ...

Introduction: The analysis of the signaling pathways involved in vascular calcification is difficult due largely to the limitation in obtaining vascular tissue samples. Therefore, the use of bioinformatics tools for the identification of potential biomarkers associated with vascular calcification is an advantage for the advancement in the knowledge of the molecular pathways involved in this pathology.Objective: Increase understanding of the molecular mec...

Background: Replacing physiological cortisol levels is important for the long-term health of patients with adrenal insufficiency and congenital adrenal hyperplasia (CAH). Modified-release formulations of hydrocortisone are one strategy being used to replace the cortisol circadian rhythm in adult patients but there is no data in children. Physiologically based pharmacokinetic (PBPK) modelling is a valuable tool for paediatric drug development1; however, there are no ...

Introduction: Cushing’s syndrome (CS) secondary to ectopic adrenocorticotrophic hormone (ACTH)–producing prostate cancer is rare with less than 30 cases reported. We report a case of Cushing’s syndrome secondary to prostate adenocarcinoma with recurrent hypokalemia, sepsis and rapid disease progression. A 61-year-old man presented in January 2019 with 3-week history of lower limb swelling and weakness. Past medical history is significant for metastatic prosta...

Background and Aims: Higher cortisol levels are associated with cardiovascular mortality in the elderly resulting from potential angiostatic effects of glucocorticoids (GCs). These features are replicated in patients with endogenous GCs excess (Cushing’s syndrome) as well as with exogenous hypercortisolism due to excessive pharmacological GCs usage. Both groups present the augmented cardiovascular disease event rate. GCs may also adversely influence remodeling after myoc...

Most of adrenal incidentalomas (AI) are nonfunctional, although some of those demonstrate an autonomous subtle cortisol hypersecretion that could lead to increased risk for osteoporosis. Several polymorphisms of glucocorticoid receptor (GR) gene have been found to alter glucocorticoid tissue sensitivity. The aim of this study was toinvestigate whether subclinical hypercortisolism (SH) and BclI variant of the GR gene have an impact on bone mineral density (BMD) in wome...

Introduction: Adrenocortical carcinoma (ACC) is a rare malignant tumor with heterogeneous prognosis. The median overall survival of all ACC patients is about 3-4 years. Complete surgical resection provides the only cure [Fassnacht M, et al., 2018]. In cases of advanced ACC, therapeutic options are limited. No effective second-line therapies are recommended for patients with disease progression to EDP chemotherapy scheme and Mitotane. It is essential to study alternative drugs,...

Background: The adrenocortical carcinoma (ACC) is a rare malignancy with poor outcomes and overall survival of less than 40%. Different prognostic factors were evaluated in patients with ACC. We analyzed overall survival (OS) and recurrence-free survival (RFS) in patients with ACC depending on Ki-67 and ENSAT staging.Methods: We performed a retrospective study on 62 ACC patients treated at the Croatian Referral Center for adrenal gland disorders from 200...

Background: Previous studies have shown an association between low CYP11B2 DNA methylation levels and high CYP11B2 mRNA levels in aldosterone-producing adenoma (APA), suggesting that epigenetic mechanisms play a pivotal role for regulating CYP11B2 function in primary aldosteronism. It has been proposed that aldosterone-producing cell clusters (APCCs) may become a source of autonomous aldosterone production when evolving into APA.Aim: Our aim was to deter...

Background: Patients with Cushing’s Syndrome (CS) suffer from a variety of neuropsychiatric and cognitive problems. Following remission, some, but not all of these symptoms resolve. Recent cross-sectional studies in patients with CS show persistent structural and functional brain abnormalities. However, longitudinal studies using magnetic resonance imaging, and a detailed neurocognitive assessment, performed before and after treatment, are not available.<p class="abs...

Our previous data showed that histological markers of the X-zone in mice adrenal (fetal zone in human adrenal) were still present in adult males and postpartum SF1/SOCS3 KO females. This change led to a distinct distribution of lipid droplets along the adrenal cortex and a blunted ACTH-induced corticosterone secretion in SF1/SOCS3 KO mice. Here we have examined the morphological and functional adrenals of SF1/SOCS3KO male mice adrenals at 3, 8 and 15 weeks through histochemica...

Introduction: Congenital adrenal hyperplasia (CAH) is an autosomal recessively inherited disorder resulting from the mutations of one of Seven genes involved in adrenal steroidogenesis. The consequent enzyme defects lead to defects of varying severity of steroid biosynthesis. Patients require lifelong substitution treatment and endocrine care.Objectives: One of the many consequences of CAH is reduced fertility. The aim of this study was to investigate th...

Objective: Aldosterone production can be regulated by adrenocorticotrophic hormone (ACTH) which normally controls cortisol secretion. Some cases of aldosterone-producing adenoma (APA) display features which may suggest increased sensitivity to the stimulatory effects of ACTH. The aim of this study was to investigate if there is any relationship between the hypothalamic--pituitary-adrenocortical (HPA) axis activity and the characteristics of APAs.Methods:...

Background: Low plasma aldosterone after adrenalectomy due to aldosterone-producing adenoma (APA) and postoperative hypoaldosteronism recovery have been well described. However, prospective time course comparing simultaneously aldosterone and renin levels is still lacking.Aim: We prospectively studied clinical and biochemical findings emphasizing aldosterone and renin levels, in a cohort of patients with APA who underwent adrenalectomy in a single tertia...

Background: The relationship between obesity, metabolic traits and adrenal incidentaloma (AI) in clinical studies have been discussed mainly in one direction: as the consequences of mild autonomous cortisol secretion in autonomous cortisol secreting AI (ACS) and as possible consequences of minimal hormonal secretion not detectable by current diagnostic methods in non-functioning (NF) AI. However, the observed anabolic and mitogenic effects of insulin on adrenal cortex from pre...

Background: Primary aldosteronism (PA) is the most frequent form of secondary hypertension, with a high prevalence in resistant hypertension (RH), a condition of insufficient blood pressure (BP) control despite a 3-drug based treatment at full dose, including a diuretic. The prevalence of PAin refractory hypertension (ReH), a condition of persistently elevated BP values despite therapy with 5 drugs, is not known.Objective: To investigate the prevalence o...

Isolated acquired hypoaldosteronism (HA) is considered to be a cause of hypovolemic hyponatremia (HH) with urinary sodium loss (UNaL) and hyperkalemia/upper-limit serum potassium (SK). However, some authors question the presentation of hyponatremia of these characteristics in the absence of Addison’s disease (AD).We present a series of patients with HA. Methods: Aretrospective study of 70 cases of HH with UNaL (UNa > 25 mmol/l) and SK ≥ 5 mmol/l or in...

Background: For patients in an adrenal crisis, the timely administration of parenteral hydrocortisone can be life-saving. Data from the Addison’s Disease Self-Help Group found that a large proportion of adrenal crises occur out of hospital, with many patients relying on the emergency services for initial parenteral hydrocortisone administration. Despite regular patient education (including parenteral hydrocortisone self-administration) and recommendations to wear steroid...

Background: Adrenal incidentalomas (AI) are common and reported at frequencies of 2-10% at CT-scans of the abdomen. It is established that the number of diagnosed and investigated cases of AI have increased over the last decades. This increase is closely related to the development of modern radiology. General access of CT scanners with higher performance have led to an improved capacity and consequently more performed investigations. Other contributing factors are improved ima...

Background: Multiple sclerosis (MS) is a chronic inflammatory autoimmune and neurodegenerative disease of the central nervous system typically affecting young adults. Autonomic dysfunction is commonly detected in patients with multiple sclerosis. Lower response of sympathoadrenal system to various stressors is mainly connected with more developed disease. However, data evaluating sympathoadrenal system function in early MS are limited. Present study investigates stress respons...

Introduction: The majority of adrenocortical carcinomas (ACC) autonomously produce steroids. However, urinary steroid profile of patients with ACC revealed that these tumors secrete and release predominantly intermediate metabolites. This steroid secretion pattern could be attributed to the undifferentiated status of the tumor cells expressing an incomplete pattern of enzymes involved in the steroidogenic cascade.Aims: Our study aim was to analyze the ex...

Introduction: Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD CAH) is a rare genetic disorder resulting in impaired cortisol biosynthesis, increased steroid precursors, and excess androgen production. Inhibition of adrenocorticotropic hormone (ACTH) release via antagonism of the corticotropin-releasing factor-1 (CRF1) receptor could reduce adrenal androgen production, thereby reducing the amount of exogenous glucocorticoids required for androgen ...

Introduction: Primary hyperaldosteronism (PHA) is the most common hormonal cause of secondary hypertensionconnected with substantially higher cardiovascular morbidity and mortality than essential hypertension (EH). The association between aldosterone excess in PHA and mutations in KCNJ5 and CACNA1D genes has been previously described and the possible relation with gene polymorphisms was to consider. The present study is to assess possible association between polymorphisms of i...

Introduction: Systemic sclerosis (SSc) is a connective tissue disorder with higher prevalence in females which is characterized by vascular damage, pulmonary hypertension, inflammation and progressive fibrosis of skin and other internal organs such as lung. In the skin it has been shown that dermal adipose tissue atrophy and microangiopathy drive fibrosis development, however which is the underlying mechanism and whether this mechanism is responsible for the female prevalence ...

Aim: The introduction of modern pheochromocytoma anesthetic management in a specialized endocrinology center with using of the algorithm of SPOHM.Materials and methods: The implementation of pheochromocytoma anesthetic management in 65 women during surgical intervention by video assistant laparoscopic adrenalectomy. All patients were used an algorithm of SPOHM: preoperative tableted hypotensive therapy before admission (outpatients); preoperative infusio...

Introduction: Catecholamine-secreting tumours derived from the adrenal medulla and the nodes of the autonomic nervous system are known as pheochromocytomas or paragangliomas, respectively. Although their clinical manifestations are similar, their differentiation is important from an epidemiological and prognostic point of view and their possibility of being associated with genetic syndromes.Case report: We present a case of a 16 year old patient, with no...

Introduction: Pheochromocytoma is a rare catecholamine secreting neuroendocrine tumor. We describe a rare case of Tako – Tsubo cardiomyopathy as first manifestation of pheochromocytoma, which later developed into PMC.Case report: A 39-year-old woman, with no history of arterial hypertension, was admitted to the emergency room with acute headache, severe chest pain radiating to the back, nausea and vomiting. At presentation, patient was in cardiores...

Introduction: The Short Synachten Test (SST) is the gold standard test for assessing adrenal insufficiency, however these can be time and resource consuming. Improved cortisol assays (Scottish consensus) currently advise a cut-off of 430 nmol/l at 30 minutes . However, there is no clarity about the optimum baseline cortisol level and recommendations range varies from 300–500 nmol/l.The aim of this study was to establish a single baseline cortisol c...

Background: Primary hyperaldosteronism (PHA) is the most frequent type of endocrine hypertension with a prevalence that is continuously rising. Following the introduction of diagnostic tests that consider both the adrenocorticotropic hormone effect andrenin–angiotensin–aldosterone system (RAAS), the post-dexamethasone saline infusion test (D-SIT) and the overnight dexamethasone, captopril, valsartan test (DCVT) using pharmaceutical RAAS blockade, a higher prevalenc...

Introduction: Adrenal vein sampling (AVS) is a gold standard in the assessment of the cause of primary aldosteronism (PA). It is technically demanding procedure having the high rate of failure, even in expert centres. Our study aimed to investigatewhether the data on aldosterone and cortisol concentration from successfully cannulated adrenal vein could determine the subtype of PA in certain patients with partially successful AVS.Materials and methods: Th...

Context: Patients with adrenal insufficiency (AI) have excess mortality and morbidity, mainly due to cardiovascular diseases. The mechanisms for this is unclear.Objective: To assess cardiovascular structure and function in AI patients on conventional replacement therapy and after switching to once-daily, modified-release hydrocortisone (OD-HC).Methods: The analysis included 17 adult AI patients (11 with primary AI, 7 with secondary...

Introduction: Endocrine Society guideline indications for screening (EGS) of hypertensive patients for hyperaldosteronism are not universally followed in clinical Endocrinology. We present a series of patients with hyperaldosteronism, diagnosed following strict EGS compliance.Methods: Retrospective. Following compliance with EGS in all patients attended in a general Endocrinology outpatient clinic, 70 hypertensive patients were diagnosed with hyperaldost...

Introduction: Primary aldosteronism (PA) is the most common cause of endocrine hypertension. In recent studies, increased prevalence of hyperparathyroidism (HP) has been observed in PA patients. However, the prevalence of HP in overt or milder forms of PA has not been evaluated yet.Objectives: To estimate the prevalence of HP in patients with PA (overt and milder forms) and investigate the effect of treatment (eplerenone or surgery) on PTH secretion....

Introduction: Primary aldosteronism (PA) causes 15–25% of cases of drug-resistant hypertension (RBP). Adrenal vein sampling (AVS) is considered the gold standard for diagnosis of aldosterone aberrant secretion origin. The distinction between unilateral and bilateral disease dictates the targeted therapeutic approach, with surgery for aldosterone producing adenomas and medical therapy for patients with bilateral hyperplasia. As AVS is an invasive, not well standardized pr...

Background: The pulsatile endogenous cortisol secretion is crucial for ultradian rhythmicity in blood and this rhythmicity triggers pulses of gene signaling in tissues. Disturbances in cortisol pulsatility can lead to cognitive, metabolic and cardiovascular dysfunction, and could explain why patients with primary adrenal insufficiency on conventional glucocorticoid replacement have reduced quality of life, increased mortality and are at risk of cardiovascular complications. Pu...

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) is encoded by the CYP21A2 gene. The CYP21A2 gene is partially overlapped by the TNXB gene encoding an extracellular matrix protein called Tenascin-X. Deficiency of Tenascin X can cause the Ehlers-Danlos Syndrome (EDS). Deletions of CYP21A2 extending into TNXB rarely cause CAH combined with EDS. CAH associated with mild hypermobility form of EDS due to TNXB haploinsufficiency caused by heterozygous mutation h...

Background: Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by impaired cortisol synthesis, requiring life-long glucocorticoid (GC) replacement therapy. Given the detrimental systemic effects of GCs in the long term, the aim of our study was to assess whether CAH patients have increased metabolic and cardiovascular alterations compared with age-matched controls.Materials and methods: For this cross-sectional...

Introduction: The prevalence of adrenal incidentalomas (AI) and renal cysts increase with age. Depending on the study population age and sex, on average, both are prevalent with about 8 to 10% in subjects older than 50 years of age.Aim: We aimed to investigate the co-occurrence of AI and simple renal cysts.Methods: Our study included 970 subjects, 494 with AI – all evaluated in single centre, and 476 control group (CG) patien...

Background: The burden and management of Addison’s disease (AD) in Africa have not been well documented. We aimed to identify specific disease characteristics, patient demographics and patterns of clinical management in established AD in Africa, hypothesizing that deficiencies in diagnosis and management exist.Methods: An on-line survey of a large pool of medical practitioners’ experience from Africa and Middle East, relating to AD was conduc...

Introduction: Anti-phospholipid syndrome is characterised by the presence of arterial or venous thrombosis, it is autoimmune in nature and manifests as a systemic disease. Adrenal vein haemorrhagic infarction which is a sequel of adrenal vein thrombosis ultimately leads to loss of adrenal function, it is one of the presentations of anti-phospholipid syndrome especially with catastrophic type. In one analysis adrenal involvement was reported in only 13% of the reported cases of...

Introduction: Primary adrenal insufficiency (PAI) is a rare disease with a prevalence of 82–144 cases/milion. The etiology of PAI is represented primarily by autoimmune adrenalitis, followed by tuberculosis and less common by fungal infections, HIV, hemorrage in adrenal glands, certain drugs and by some genetic disorders such as Triple A syndrome (AAA), Adrenoleukodystrophy (ALD), congenital adrenal hypoplasia, congenital adrenal hyperplasia, etc.C...

Introduction: Primary retroperitoneal bronchogenic cysts are rarely seen. Bronchogenic cysts are mostly benign which originate from the remnants of the primitive foregut during the embryonic development.These lesions can be seen near or inside any organ that originates from the embryonic foregut. Bronchogenic cysts are most often found in the thoracic cavity, especially in the mediastinum. Except this many distant sites, such as abdomen, retroperitoneum,...

Introduction: Primary aldosteronism (PHA), also known as primary hyperaldosteronism or Conn’s syndrome, refers to the excess production of the hormone aldosterone from the adrenal glands.Study objectives: To show clinical, biochemical, and morphological data of 09 patients with primary hyperaldosteronism as well as the therapeutic choice for each patientMehtods: it is aretrospective and descriptive study of 09 cases with prim...

A 49-year-old man who has diabetes mellitus and alcoholic cirrhosis presented to the emergency department due to left upper quadrant abdominal pain and left back soreness for three days. He received sclerotherapy and endoscopic band ligation twice for gastric varices few months prior to admission. On physical examination, he had rebound tenderness at left upper abdomen. The computed tomography (CT) of abdomen revealed diffusely enlarged left adrenal gland with rim-enhanced mul...

Primary adrenal cysts are a relatively rare form of lesions with incidence of 0.06% in general population and higher prevalence in women (female-to-male ratio 2.3:1). Adrenal endothelial cysts are the most common form of adrenal cysts subtypes (45%) and they usually present with abdominal or flank pain, or nonspecific symptoms . Adrenocortical carcinomas are a rare condition as well, with an incidence of 1–2 per million per year. The typical clinical presentation may inc...

Introduction: Patients with clinical clues suggesting the possible presence of secondary hypertension should undergo a more extensive evaluation, because in this case some of these disorders can be cured, leading to partial or complete normalization of the blood pressure.Case description: We report a case of a 43-year-old man, who suffered for years of hypertension despite concurrent use of adequate doses of three antihypertensive agents from different c...

Background: The prevalence of adrenal incidentalomas has increased. The malignancy is determined by radiographic appearance and, secondly, by the size. Adenomas manifest a low attenuation on computed tomography (CT) (<10 Hounsfield Units(HU)).The cut-off point of 10 HU has been proposed to discriminate benign and malignant lesions.Objective: To determine if the cut-off point of 10 HU is useful in clinical practice to discriminate benign and malignant...

We present a 41 years old lady who presented with non specifc symptoms- lethargy, general myalgia, memory impairment. She also complained of hot flushes, sweats and had a brief episode of panic attacks hence was commence on Sertraline by the GP. She has a past medical history of appendicectomy. Her mother had lymphoma and mother died from lung cancer. She is a smoker, however is teetotal. She has 3 children and works in a laundry. She was initially referred to the haematologis...

Adrenocortical carcinoma (ACC) is a rare malignancy with heterogeneous but dismal prognosis and despite numerous efforts to improve patient care, effective treatment options are still lacking. ACC in vitro research faces for decades one major obstacle - the unavailability of different ACC cell line models. Here, we present a newly established human ACC cell line that was directly transferred to and now proliferates in cell culture. JIL-O cell line was derived from a p...

Introduction: Adrenocortical cancer is a rare malignant tumour with a poor prognosis. The incidence is 0.7–2.0/million/year.Objectives: The aim of this study was to characterise the clinicopathological features and prognostic factors of a large cohort of patients with adrenocortical cancer diagnosed between 1974–2019.Patients and Methods: The study included eighty patients (22 men and 58 women) with histologically confi...

Introduction: Adrenocortical carcinoma (ACC)is a rare disease with an unfavourable prognosis. Complete surgical resection of the tumour provides the only chance for long-term cure. The aim of this study was to compare long term outcomes in patients with ACC referred to surgery in an expert adrenal centre (EC) versus nonspecialised centres (NSC).Materials and methods: This retrospective study included 48 patients with ACC, ENSAT stage I-III. All of study ...

Introduction: Glucocroticoids (GCs) which are routinely used in the treatment of Acute Lymphocytic Leukemia (ALL), found recently to be beneficial in a subset of AML patients resistant to chemotherapy, by promoting leukemia cells apoptosis. Current studies indicate that vitamin D (VitD) deficiency is highly prevalent among AML patients, posing vitamin D as a therapeutic supplementation. Our previous study demonstrated that VitD exerts inhibitory effect on Dexamethasone-induced...

Introduction: Prolonged exposure to stress has a modifying effect on activity of hypothalamo-pituitary-adrenal (HPA) axis. This is a protective adaptation aimed to diminish potential deleterious effects of chronic hypercortisolism, and to diminish effects of acute exposure to heterotypic forms of stress. Our aim was to analyze modes of cortisol response to acute physical stress in groups of different stress categories and sex.Subjects and methods: Study ...

Introduction: Despite the fact that CS is widely employed, further investigation on the topic of the physiology vis a vis this type of delivery is required, especially regardingstress related hormonal response during this practice. The aim of this study is to provide data regarding stress related hormonal response during Vaginal Delivery (VD) and elective CS evaluating levels of Cortisol, Interleukin 6 (IL-6), Growth Hormone (GH) and Insulin-like Growth Factor 1 (IGF-1).<p...

Liquorice is a sweetener found in many food products, soft drinks, snacks and herbal medicines. Liquorice ingestion is an uncommon cause of AME or pseudohyperaldosteronisim. The mechanism involves the inhibition of 11-beta-hydroxysteroid dehydrogenase type-2 by the active ingredient called glycyrrhizin, which leads to the uninhibited activation of mineralocorticoid receptors by cortisol. Confectionary products that contain liquorice are readily available in the European Union....

Introduction: The defecatory strain in constipated people can raise the blood pressure and occasionally trigger cardiovascular events.Methods: Review of the patient’s clinical records and the relevant literature.Results: Clinical Case: A 53-year old woman with history of breast surgery for adenocarcinoma and chronical constipation had severe resistant hypertension in the previous three years; she had hypertensive crises with ...

Introduction: Composite pheochromocytoma is a rare tumor composed histologically of pheochromocytoma and other neurogenic tumor components such as neuroblastoma, ganglioneuroblastoma, ganglioneuroma, peripheral nerve sheath tumor, or other types of neuroendocrine carcinoma. The frequency of composite adrenal tumors reportedly ranges from <3% of all adrenal gland neoplasms to 1–9% of pheochromocytomas. The clinicopathological diagnosis of composite pheochromocytoma is...

We describe a case of cystic pheochromocytoma (PCC) with negative biochemical evaluation, diagnosed on the basis of hypertensive crises during operative management and histopathologic findings. A 57-year-old woman complained of several episodes of stabbing right upper abdominal pain accompanied by tachycardia, headache, lack of breath, elevated blood pressure and vomiting in the preceding three years. At presentation, blood investigations were significant only for mildly eleva...

Introduction: Neurofibromatosis type 1 is a disease caused by mutations in the tumor suppressor gene NF1.Although pheochromocytoma is a rare manifestation in these patients (~0.1–5.7%), the incidence is significantly higher than that of the general population.Results (case description): A 50 years old female patient had a clinical diagnosis of neurofibromatosis type 1 since she was 5 years old. She received follow-up in ...

Background: PA is a frequent cause (5–13%) of secondary hypertension (HT), yet diagnostic work-up of PA remains challenging.Aim: To describe the characteristics of a series of hypertensive patients diagnosed with PA compared to those with negative biochemical screening (aldosterone-to-renin ratio/ARR)Methods: Clinical, hormonal and imaging evaluation.Results: We have screened for PA 34 patients diagnose...

Introduction: Management of patientswith congenital adrenal hyperplasia (CAH) is a challenge to find a right balance of glucocorticoid doses and long-term consequences of overtreatment isassociated with increased risk of cardiometabolic disorders.The aim of our study was to evaluate body mass index (BMI), body composition, blood pressure (BP) and insulin sensitivity in children and youth with CAH in comparison with healthy control subjects.<p class="...

Objective: The saline infusion test (SIT) is a standard confirmatory test for primary aldosteronism (PA) and based on impaired aldosterone suppression in PA compared to essential hypertension (EH). In the past, aldosterone was quantified using immunoassays (IA). Due to the more widespread use of liquid chromatography tandem mass spectrometry (LC-MS/MS) in clinical routine, we aimed at a method-specific aldosterone threshold for the diagnosis of PA during SIT and explored the d...

Objective: Clinical and histopathological assessment of a consecutive series of Munich patients operated between 2016 and 2018 for unilateral primary aldosteronism (PA).Background: Unilateral PA is the most common surgically curable form of hypertension mainly caused by an aldosterone-producing adenomas (APA). Somatic mutations in KCNJ5, CACNA1D, ATP1A1 or ATP2B3drive the aldosterone excess in the majority of APAs. Genetic variants in <...

Introduction: The majority of adrenal neoplasms are benign while adrenocortical carcinomas (ACC) are rare with poor prognosis. Previous studies indicated that estrogens play important role in the etiology and progression of adrenocortical tumors. Estrogens exert genomic activities trough the estrogen-receptor (ER) subtypes α and β, while the non-genomic effects are mediated by membrane-bound-G-protein-coupled-ER-30 (GPR30). Although estrogens induce cancer cell ...

Background: Primary aldosteronism constitutes the most common form of hormonal hypertension. However, it is often mistreated and widely underdiagnosed. Despite the great progress in laboratory technics of adrenal diseases, in the field of primary aldosteronism there is still a need for novel biomarkers that would clarify the diagnosis in equivocal cases. Adropin is a newly discovered protein that may play a role in glucose metabolism and the development of cardiovascular disea...

Aim: A cohort of adrenal incidentalomas which had radiological or histological characteristics in keeping with an adrenal adenoma was analysed in terms of the radiological and functional characteristics.Methods: A retrospective cross-sectional analysis of a cohort of adrenal adenomas was carried out. Lesions were followed up for a median of 8.2months (IQR 1.4–34.6). In the majority of patients (69.95%), the diagnosis of a benign adrenal adenoma was...

Introduction: Cushing’s syndrome denotes pathologic hypercortisolism as a result of excessive adrenocorticotropic hormone (ACTH) production or autonomous adrenal production of cortisol according to the ACTH levels. However, 30% of the patients with CS have ACTH levels in the ‘grey zone’ (5–20 pg/ml), thereby posing a challenge in establishing the aetiological diagnosis.Case presentation: A 20-year-old woman presented to our depart...

Introduction: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease affecting up to 30% of the population in western countries. Previous studies have demonstrated that increased glucocorticoid levels play an important role in the development of obesity, hyperglycemia, dyslipidemia, insulin resistance, as well as NAFLD. However, the effects of glucocorticoid substitution on the liver in patients with primary or secondary adrenal insufficiency have been rare...

Purpose: To evaluate differences in the prevalence of autonomous cortisol secretion (ACS) and related comorbidities between patients with unilateral and bilateral adrenal incidentalomas (AI).Methods: Seven Spanish institutions participated in this institutional review board-approved retrospective study for patients with AI. 342 patients with one or more AI ≥ 1 cm evaluated by participating physicians between 2001 and 2019 were subject to inclusion....

Context: Adrenal incidentalomas (AI) can be found in 3–10% of the general population. The vast majority of them (70%) represents nonfunctioning adrenal incidentalomas (NFAI). Although several comorbidities have been studied in patients with autonomous cortisol secretion (ACS) there are limited data for those with NFAI.Aim: To study metabolic disorders frequency in patients with AI and especially NFAI.Design: Retrospective stu...

Background: The high prevalence of chronic disease urges for new ways of working with our patients as active members of the health care team to better design processes for ongoing supportive treatment. Our Division of Endocrinology & Metabolism at the University of Alberta prioritized the need to improve care for those living with adrenal insufficiency (AI). We have worked with AI patient partners to address learning needs and priorities of our patients, their caregivers, ...

Background: Topical corticosteroids (TCs) are widely used as depigmenting agents alone or in combination with other fairness creams. However, its use may cause secondary adrenocortical insufficiency.Objective: The aim of the present study is to evaluate the relationship between practice of whitening creams (Topical Corticosteroids) and serum cortisol level in a sample of healthy females at Ain- shams University hospital.Methods: We...

Congenital adrenal hyperplasia (CAH) refers to an autosomal recessive condition due to 21 hydroxylase (21OHD) deficiency, is characterized by impaired biosynthesis of glucocorticoid and mineralocorticoid. The consequent increase in the ACTH leads to bilateral adrenocortical hyperplasia and hyperandrogenism. Nonclassic CAH (NCCAH) manifests with a less severe clinic that presents later in life with the sympthoms of excessive androgen production. Clinical features include premat...

Introduction: Betablockers are not a first-line antihypertensive therapy, although they have specific cardiological indications. The use of betablockers, especially the non-selective ones, may be associated with paradoxical hypertension, due to unopposed alpha-adrenergic peripheral vasoconstriction.Methods: Review of the patient’s Clinical Record and of the relevant literature.Results: Clinical Case: A 66 year old woman was r...

Introduction: Phaeochromocytomas are mostly benign tumours with origin from chromaffin tissue of adrenal glands, whereas paragangliomas aretumours located along the sympathetic or/and the parasympathetic chain. Generally they are quite rare neoplasms with ability of producing, storing and secreting of catecholamines. Predominatingly they are sporadic, but in some cases they may develop in progress of particular genetic syndromes, such as multiple endocrine neoplasia type 2 (ME...

Introduction: Pheochromocytoma is a functional catecholamine producing tumor that originates from adrenal chromaffin cells and is an extremely rare cause of ectopic Cushing syndrome. We report clinical case of adrenal incidentaloma with the evidence of both pheochromocytoma and sub-clinical Cushing’s syndrome.Observation: A fifty-two year-old female patient was referred to our institution because of an incidentally discovered right adrenal mass. Al...

Introduction: Severe haemorrhage from an adenoma is rare and potentially fatal. We report an unusual case of idiopathic unilateral severe adrenal haemorrhage from a non-functioning adrenal adenoma which was incidentally discovered 12 years earlier.Case Presentation: A 59-year-old female was admitted to the hospital for a severe sudden onset of abdominal pain associated with vomiting. About 12 years ago, she was found incidentally to have a left adrenal a...

Introduction: Extrapulmonary manifestations of tuberculosis can cause a diverse range of atypical presentations, depending on the system involved. Involvement of lymph nodes, pleura, central nervous system and bone are some of the organs that are well-described in the literature. This leads to a diverse range of presentations which can misguide diagnosis unless there is a high index of suspicion. Endocrinological manifestations are rare, but can occur uponhaematogenous dissemi...

The classic episodic triad of headache, sweating and palpitations facilitates the diagnosis of phaeochromocytoma. The absence of these symptoms can lead to misdiagnosis in patients with uncommon symptoms attributable to phaeochromocytoma. We present such a case.Case report: A 64 year old man was referred to endocrinology having been coincidentally found to have a right adrenal mass with features of a phaeochromocytoma. He was asymptomatic and engaged in ...

Introduction: The introduction of immunotherapy with checkpoint inhibitors for oncologic diseases has improved the survival and quality of life of our patients; however, these therapies are frequently associated with autoimmune endocrine disease.Methods: Revision of the patient’s clinical record and the related literature.Results: Clinical Case : An 88-year old woman was referred to our Endocrinology Clinic because of a PET i...

Introduction: Primary aldosteronism is characterized by hypertension and accounts for about 10% of hypertensive patients. Post-operative hypoaldosteronism is well documented in cases within the past 3 years of unilateral adrenalectomy for aldosterone-producing adenomas.Case report: We present the case of a 46-year-old patient with a 10-year history of hypertension and hypokalaemia (1.9 mmol/l) with normal renal function. Serum aldosterone was high with l...

Introduction: Adrenocortical carcinoma (ACC) is a rare and aggressive tumor, with a poor prognosis and median survival of 3–4 years. Complete surgical resection is the only possibility of cure. The rate of post-surgical recurrence is high, so adjuvant treatment with mitotane plays a key role.Objectives: To evaluate predictive factors of response to adjuvant treatment with mitotane in monotherapy in patients that underwent surgical resection of ACC....

Introduction: Adrenocortical carcinoma is a rare endocrine disease characterized by an aggressive behaviour with a poor prognosis. Clinical experience, even with a little number of patients, has enhanced knowledge about this malignancy, in most cases challenging.Objective: Characterization of patients with adrenocortical carcinoma followed at the endocrine department of a hospital centre, between 1991 and 2019.Methods: Retrospectiv...

Purpose: To analyze CT signs and parameters of vascularization of pulmonary neuroendocrine tumours (PNT) and their relationship with the development of ACTH ectopic syndrome.Materials and methods: 23 patients with PNT were evaluated with contrast-enhanced MDCT. Arterial and venous phases were obtained at 10 and 35 seconds after the attenuation of 200 HU at the descending aorta, a delayed phase was at 6–8 min after the start of injection of contrast...

Objective: To identify the radiological characteristics of adrenal abnormalities as reported on CT abdomen;To identify functional characteristics of adrenal incidentalomas; To identify 12 month outcomes of adrenal incidentalomas1500 consecutive unselected computerised Tomograms(CT abdomen) done for non-adrenal indication, reviewed for adrenal abnormalities to identify, the incidence size, radiological density, those with abnormalities underwent endocrine...

A 17-year-old woman was hospitalized emergently after suffering sudden palpitations and losing consciousness. On admittance she was in a state of shock, with a pulse rate of 140/min and systolic blood pressure of 70 mmHg. Echocardiography revealed a diffuse wall hypokinesis with decreased left ventricular ejection fraction. Acute heart failure was diagnosed. Coronary angiography, LV imaging, and myocardial biopsy suggested fulminant Takotsubo cardiomyopathy due to catecholamin...

Melatonin inhibits vascular smooth muscle cell proliferation and apoptosis through upregulation of Sestrin2Excessive vascular smooth muscle cell (VSMC) proliferation contributes to the development of atherosclerosis and restenosis. On the other hand, apoptosis of VSMCs accelerates plaque rupture in the atherosclerotic vessels. Therefore, a strategy that regulates both VSMC proliferation and apoptosis is essential for the development of new pharmacologica...