Endocrine Abstracts

Adrenocortical carcinoma (ACC) is a rare and highly aggressive endocrine neoplasm, with limited therapeutic option. Activating β-catenin somatic mutations are observed in ACC and associated with a poor outcome. Activation of the Wnt/β-catenin signaling pathway seems to play a major role in ACC aggressiveness, and might be a promising therapeutic target. The H295 cell line derived from an ACC harbors an activating β-catenin mutation. We herein assess the in vi...

Background: Although primary aldosteronism (PA) is the common cause of hypertension subjected to surgery, methods of pathological confirmation of aldosterone overproduction have not been established. Aim of the study was to investigate immunohistochemically the expression of CYP11B2 in the adrenal tissue of PA.Methods: Twenty five patients with PA including 20 patients with aldosterone-producing adenoma (APA) and 5 patients without APA (non-APA) were stu...

Introduction: For defining SH in AI patients at least 2 altered criteria among serum cortisol after 1 mg dexamethasone test (1 mgDST), ACTH levels, 24 h urinary free cortisol (UFC) and midnight serum cortisol levels are generally required. Midnight salivary cortisol (MSC), a sensitive and easy-to-perform marker of overt hypercortisolism, appears to be of limited utility in these patients. Data on the role of salivary cortisol using LC-MS/MS, the gold standard procedure for ste...

CAH has been described to be associated to infertility and semen abnormalities in 40–70% of adult male patients, because of hypogonodotropic hypogonadism, consequent to the increased levels of sex steroids, but mostly because of the frequent presence of testicular adrenal rest tumors. The aim of the current study was to evaluate semen parameters and hormonal setting in a subset of men with CAH. Fourteen patients with classical CAH due to 21-HD (six with simple virilizing,...

Introduction: Defects in the pseudogene, CYP21A1P, can be transferred to the functional CYP21A2 gene by recombination and account for approximately 95% of CYP21A2 mutations, leading to CAH-21OHD. We conducted a comprehensive genetic analysis to assess whether Multiplex Ligation dependent Probes Amplification (MLPA) could substitute southern blotting with radioactive probes without compromising reliability of the diagnosis.Patients and Methods: We studied...

Objective: An adrenal incidentaloma is discovered in about 3–4% of patients undergoing radiological examination (CT/MRI) of the abdominal region. Current diagnostic algorithms for differentiating between benign and malignant lesions largely depend on imaging studies, which lack in specificity. This often leads to extended radiological follow-up of benign lesions, which is time-consuming, expensive and carries a health risk. It was recently suggested that urinary steroid p...

Cyclical Cushing’s syndrome is typically detected by collecting sequential daily early morning urine (EMU) samples for cortisol to creatinine ratio over a 28 day period. More recently nocturnal salivary cortisol (NSC) measurement has been shown to be a sensitive means of screening for Cushing’s syndrome. The Endocrine Society have suggested that NSC may be used to assess patients for cyclical Cushing’s however there is limited evidence that it correlates with th...

Background: Zebrafish is emerging as a comprehensive model system in endocrinology. Zebrafish synthesise steroid hormones in the interrenal (counterpart of the mammalian adrenal), gonad and brain. Data on steroidogenic pathways is patchy and steroidogenic enzymes in zebrafish have not been well characterised. Human 17α-hydroxylase (hCYP17A1) facilitates two conversion steps, 17α-hydroxylase and 17,20-lyase reactions in the adrenal and gonad. Two zCyp17a (zCyp17a1; zC...

Background: Cytochrome P450 side-chain cleavage enzyme (CYP11A1) catalyses the first and rate-limiting step of steroidogenesis. CYP11A1 firstly converts cholesterol into 22R-hydroxycholesterol, which relies on mitochondrial steroidogenic acute regulatory protein (StAR)-mediated cholesterol import. Two further StAR-independent CYP11A1 reactions facilitate pregnenolone biosynthesis. CYP11A1 deficiency is rare and manifests with adrenal insufficiency (AI), and, in 46,XY individua...

Background: Novel treatment options are required for patients with adrenocortical carcinomas (ACCs). mTOR-inhibitors are anti-neoplastic drugs that target the mTOR-pathway.Aim: To describe the expression of the mTOR-pathway in normal and pathological adrenocortical tissues.Methods: We evaluated mRNA expression levels of mTOR, S6K and 4EBP1 in 10 normal adrenals (NA), 11 adrenal hyperplasias (AH), 19 adrenal adenomas (ACA) and 26 AC...

Introduction: The diagnosis of Cushing’s Syndrome (CS) and in particular cyclic CS can be complicated. Standard screening tests for CS are the measurement of cortisol in 24-hours urine collections and in midnight saliva. In case of cyclic CS, results of these tests can be normal in between periods of hypercortisolism. The development of a method to measure cortisol in scalp hair provides the opportunity to investigate historical cortisol levels of months to years ago, wit...

Introduction: Autonomous aldosterone secretion (AAS) is present in approximately 10% of hypertensives. Adrenal incidentalomas (AI) can be found in up to 19% of hypertensive individuals. However, data on the incidence of AAS in hypertensive patients with AI is scarce. Our aim was to evaluate the adrenal aldosterone secretory profile in patients with adrenal adenomas with and without arterial hypertension.Patients and methods: We investigated 72 normotensi...

Introduction: Adrenal insufficiency, or relative insufficiency, might partly explain increased mortality rates in nephroblastoma and neuroblastoma survivors after unilateral adrenalectomy. Aim of this study was to assess adrenal function and its metabolic effects after unilateral adrenalectomy.Patients and Methods: Cross-sectional study with a socio-demographically similar control group, conducted between October 2009-March 2011 at the Erasmus University...

Objective: The major diagnostic problem in primary aldosteronism is the differentiation between bilateral hyperplasia and aldosterone producing adenoma which is essential for further treatment. Adrenal vein sampling is regarded as the current gold standard, however it is an invasive, highly examiner-dependent method. Molecular imaging targeting the aldosterone synthase (CYP11B2) which is expressed specifically in aldosterone producing adrenal tissue may be an useful alternativ...

Neuroendocrine balance of the hypothalamo-pituitary-adrenal axis (HPA) is a critical component in the control of metabolic homeostasis, and its dysregulation can contribute to severe pathologies, like obesity, where the HPA is significantly altered at the central and systemic levels. Somatostatin and cortistatin have been shown to reduce circulating ACTH and glucocorticoid-levels in rodents and humans in vivo. However, to date, no studies have thoroughly investigated and compa...

Introduction: We present a case of probable cyclical Cushing’s syndrome (CS) masquerading as polycystic ovarian syndrome (PCOS) which went undetected for almost a decade. Our case highlights the subtleties and complexities of interpreting diagnostic tests in patients with cyclical endogenous hypercorticolism.Case: A 33-year old female with presumed PCOS presented with a seven year history of persistent hirsutism and acne. However there was no menstr...

Context: Unilateral adrenalectomy is the therapy of first choice in aldosterone producing adenoma (APA). Improvement of blood pressure (BP) and hypokalemia is achieved in the majority of patients. Because of hypoaldosteronism, hyperkalemia can develop in the postoperative course. Our aim was to analyze the frequency of hyperkalemia, to determine the cause of hypoaldosteronism and to assess the influence of preoperative mineralocorticoid antagonist (MRA) therapy at our center.<...

Aberrant and upregulated eutopic receptors have been identified in vitro in patients with primary aldosteronism (PA). We previously identified an exaggerated aldosterone response to synacthen in patients with PA versus healthy controls. In this study we aimed to evaluate whether the synacthen test differentiates between patients with PA and essential hypertension (EH).The 250mcg intramuscular synacthen test was performed after 30 minutes recumbenc...

Women with CAH have decreased fertility and sexual activity because of psychological aspects and genital status. The aim of this study was to evaluate sexual function and psychological attitudes in 18 women with CAH due to 21-HD (12 with non-classical, four with salt-wasting and two with simple virilizing CAH; 20–48 yrs) under standard treatment, and 18 age-matched healthy women. Sexual function was evaluated by a validated Female Sexual Function Index (FSFI) questionnair...

In patients with primary aldosteronism (PA), adrenal vein sampling (AVS) is considered the gold standard to distinguish between unilateral and bilateral disease, while diagnostic imaging tests (CT/MRI) are often inconclusive for the diagnosis of PA. To date agreement is lacking on the best criteria indicating successful cannulation and lateralization. Aim of the study was to evaluate the impact of different diagnostic criteria for the successful cannulation and lateralization ...

Primary aldosteronism (PA) is the most common cause of secondary hypertension. Although decline in renal function especially that experienced after adrenalectomy (ADX) has been demonstrated, details of the mechanism remain to be elucidated. Aim of the study was to investigate the factors predicting renal outcome after ADX in PA. Twenty patients with PA and four patients with non-functioning adrenal tumor (NFT) as control were studied. eGFR, serum potassium, plasma aldosterone ...

Introduction: Carcinoma of the adrenal cortex (ACC) is a rare disease with an estimated incidence of 1–2 per 1 million population. Optimal treatment of ACC is multidisciplinary and has complex aspects such as adrenal surgery, adjuvant therapy with mitotane and cytotoxic chemotherapy in advanced stages. The Dutch Adrenal Network (DAN), a collaboration between all university centers and Máxima Medical Center, was founded with the objective of improving patient care and...

Introduction: Adrenal incidentalomas (AIs) are increasingly detected due to the widespread use of abdominal imaging for diagnostic purposes. AIs are usually benign non-functioning adenomas but few prospective studies exist regarding their evolution.The aim of this study was to investigate the morphological and hormonal changes of AIs in a cohort of patients with long-term follow-up.Materials and methods: This was a prospective obse...

Effects of sugar cane extract (SCE) on the adrenal corticosterone and progesterone secretion in male rats were investigated using an in vitro cell culture system. Three-week old male rats were fed SCE free diet or 2.16% SCE diet for 7 weeks. After 7 weeks of treatment, animals were decapitated, and adrenal cells were cultured in the absence or presence of rat ACTH (10–15 to 10-10 M) for 4 hours. Body and adrenal gland weight, plasma concentration of ACTH, corticost...

Objective: The prevalence of primary aldosteronism (PA) occures in approximately 5–10% of patients with hypertension. Aldosterone induces fluid retention and a variety of angiopathy. We investigated the course of hypertension and renal function in the post-treatment period.Methods: Nine patients with PA were performed adrenalectomy and 21 patients were administered medications including mineralocorticoid receptor brocker. Blood pressure, serum potas...

The management of nonfunctioning adrenal masses is controversial. The size is usually the only criterion for surgical treatment. The objective was to study the progression of the tumor size and the follow-up of several cardiovascular risk parameters in patients with nonsurgical nonfunctioning adrenal masses.Retrospective longitudinal observational study of 24 patients (54.2% men) with nonfunctioning adenomas followed for five years without surgical treat...

The Nonclassical Congenital Adrenal Hyperplasia (NCCAH) is an autosomal recessive disorder. The importance of the diagnosis in fertile women relies in its therapeutic implications, genetic counseling and antenatal care during pregnancy. Diagnosis is established by the presence of basal 17-OH-progesterone (17-OHP) levels ≧6 ng/ml or stimulated after ACTH test ≧15 ng/ml. Basal values between 2-6 ng/ml or stimulated between 10–15 ng/ml would require further con...

Introduction: Mesenchymal bone marrow cells (BMCs) contain pluripotent progenitor cells, which differentiate into multiple lineages. In a previous study, we reported that adenovirus-mediated forced expression of steroidogenic factor-1/adrenal 4 binding protein (SF-1/Ad4BP), an essential nuclear receptor for steroidogenesis, could transform human BMCs into steroidogenic cells, suggesting a possibility of cell transplantation therapy in patients with steroid deficiency. In this ...

ACTH-independent macronodular hyperplasia (AIMAH) affects both adrenals, and familial forms are reported, suggesting a genetic origin. Rare mutations have been reported in several genes, including Gs alpha (GNAS), Phosphodiesterase 11A (PDE11A), Fumarate Hydratase (FH), and the Glucocorticoids receptor (GR).Objective: To assess the prevalence known genes mutations, and identify new candidate genes in AIMAH.Design and methods: Germl...

Introduction: Unilateral aldosterone hypersecretion can be adequately treated based on the localization by adrenal venous sampling. However, bilateral aldosterone producing adenoma or primary aldosteronism with preclinical Cushing syndrome cannot be treated with simple unilateral adrenalectomy. Diagnosis of intra-adrenal localization of aldosterone hypersecretion is necessary for surgical treatment of these types of primary aldosteronism.Method: From 200...

The effects of glucocorticoids are mediated by the glucocorticoid receptors (GR) and some single nucleotide polymorphisms (SNPs) have been associated to enhanced sensitivity (N363S, BclI) or reduced sensitivity (ER22/23EK) to glucocorticoids.Aim of the present study was: 1) to assess the frequency of N363S, BclI and ER22/23EK in 46 patients with Cushing’s syndrome (CS) and 73 patients with adrenal incidentaloma (AI) compared to 186 healthy subjects;...

Primary Aldosteronism (PA) is the most frequent cause of endocrine hypertension. Three forms of familial hyperaldosteronism (FH) have been described, named FH-I to -III. Recently, a mutation of KCNJ5 has been shown to be associated with FH-III, whereas the cause of FH-II is still unknown. In this study we searched for mutations in KCNJ5 in 46 patients from 21 families with FH, in which FH-I was excluded. We identified a new germline G151E mutation in two PA affected subjects f...

Primary aldosteronism (PA) is the most major cause of secondary hypertension, with its prevalence ranging from 3 to 20% of the hypertensive patients. Although guideline for diagnosis of PA has been established by the Endocrine Society, details of its applicability remain to be elucidated. In this study, we investigated the applicability of each step of the guideline in hypertensive patients by the multi-center collaborative study of National Hospital Organization (NHO) in Japa...

Introduction: The genetic mechanisms underlying adrenocortical tumor development are still largely unknown. We used high-resolution single nucleotide polymorphism (SNP) microarrays to detect copy number alterations (CNAs) and copy neutral losses of heterozygosity (cnLOH) in cortisol-secreting adrenocortical adenomas (ACAs). We focused on microalterations aiming to discover new candidate genes involved in early tumorigenesis and/or autonomous cortisol secretion.<p class="ab...

Background: The human adrenal cortex is composed of 3 distinct zones: the zona glomerulosa (ZG), the zona fasciculata (ZF), and the zona reticularis (ZR). Steroidogenic enzymes are expressed in a zone-specific manner. The promoters of CYP11B1 and CYP11B2 possess a number of target sites for DNA methylation that is closely associated with gene silencing.Methods and Materials: Adrenals from 5 autopsy subjects were assessed for immunohistrochemically define...

Introduction: Primary aldosteronism (PA) is one of the common diseases, and aldosterone-producing adenoma (APA) is a surgically curable type, which is usually treated by unilateral total adrenalectomy. We had recently developed a new method of supper-selective ACTH-stimulated adrenal venous sampling (SS-ACTH-AVS) for exactly detecting the main lesion(s) of hyperaldosteronemia. Then we attempted to partially remove the unilateral lesion of hyperaldosteronism detected by SS-ACTH...

Depolarisation of adrenal zona glomerulosa cells is a pivotal event for the secretion of aldosterone. Potassium channels like TASK1 and TASK3 are highly expressed in the adrenal cortex and determine the membrane voltage. Deletion of TASK3 K+ channels in mice caused a severe age-dependent hyperaldosteronism. The aim of this study was to identify the mechanisms underlying this phenotype.Neonatal TASK3-/- mice (ko) showed higher plasma aldosteron...

Kisspeptins are the product of the KiSS-1 gene, a metastasis suppressor gene, and play important physiological roles in the hypothalamo-pituitary gonadal axis and reproduction. It was reported that kisspeptin-10 stimulated the aldosterone synthesis in H295R human adrenal cancer cells (Nakamura et al., 2007). However, expression of kisspeptin and its receptor has not been studied in tumor tissues of adrenocortical tumors. The aim of the present study was therefore to clarify ex...

Introduction: Cushing’s Syndrome (CS) has been associated with bone mass abnormalities and with an increased risk of osteoporotic fractures.Objective: Evaluate the effect of treatment on the 10-year probability of fracture predicted by FRAX® and on the overall bone profile, in patients with CS.Patients and Methods: We evaluated 36 patients (6 M, 30 F, 12 post-menopausal, mean-age 43.6±13.5), 22 with Cushin...

Adrenocortical tumors (ACT) include benign and malignant tumors. Adrenocortical carcinomas (ACC) are highly malignant neoplasms with a poor prognosis, but their genetic alterations to date identified are limited. Laboratory studies on ACT have revealed a wide variety of signaling pathways involved in these tumors, among these Wnt/β-catenin signaling pathway and Ras/Raf/MEK/ERK pathway resulted often disregulated. Another important factor in many signaling pathways is the ...

Introduction: Tumour cachexia-anorexia syndrome (CAS) is a complex disorder characterized by progressive nutritional and metabolic alterations that lead to loss of muscle and adipose tissue observed in advanced-stage cancer. CAS indicates unfavourable prognosis, regardless of cancer type. Under the influence of permanent aggression, we have evaluated the effects of the cancer cachexia development on the hypothalamic-pituitary-adrenal (HPA) axis.Methods: ...

Context: The biological diagnosis of adrenal disorders is currently based on the quantitation of serum steroids using automated immunoassays. These direct assays often lack the required accuracy and precision and interlaboratory surveys show that performance characteristics of MSMS are far better than those of automated immunoassays.Method: After liquid chromatography of serum extracts, steroids were quantified on Waters QuattroPremier mass-spectrometer ...

Unsuspected adrenal masses, or incidentalomas, are increasingly found with the widespread use of thoracic and abdominal imaging. These masses may be hormonally active or nonfunctional and benign or malignant. Clinicians must determine the nature of the mass to decide what treatment, if any, is needed.In our 17 year experience, we observed 232 patients (158 females, 74 males aged 22-91, mean age 69) affected with monolateral incidentaloma. 58 of them (25%...

Introduction: Primary aldosteronism (PA) is the most frequent curable form of hypertension. Hypokalemia is a late symptom of PA. Consequently, PA often is not diagnosed for many years. Our aim was to identify clinical and laboratory parameters in a large cohort of PA patients obtained during their first assessment.Methods: 96 consecutive patients prospectively studied since 2008 at the German Conn’s Registry Center in Munich were eligible for this s...

Introduction: Several previous studies showed a reduced quality of life (QoL) in patients with Addison`s disease, but only few data on the potential influencing factors are available so far.Methods: We determined current QoL in 200 patients with Addison`s disease using AddiQoL-36, a questionnaire developed in collaboration with the European consortium Euradrenal. Furthermore, data about symptoms, diagnosis and medication were collected by questionnaires ...

Background: Adrenocortical carcinomas (ACC) are rare tumors with an incidence of 1–2 per million. Although rare, it is an aggressive endocrine cancer with poor prognosis. As of today there is no reliable diagnostic biomarker to distinguish benign tumors from malignant tumors. Global changes in DNA methylation and DNA promoter hypermethylation are important events in tumorigenesis. Promoter hypermethylation can cause silencing of tumour suppressor genes or lead to abnormal...

Diagnosis of primary aldosteronism (PA) is made by screening, confirmation testing and subtype diagnosis (CT scan and adrenal vein sampling, AVS). However, some tests are costly and unavailable in most hospitals. We evaluated the role of serum 18-hydroxycorticosterone (s18OHB) and urinary and serum 18-hydroxycortisol (u and s18OHF) and 18-oxocortisol (u and s18oxoF) in the diagnosis of PA and its subtypes, aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (...

Objective: To identify miRNAs predictors of poor prognosis in adrenocortical cancer.Methods: Using microarrays, we evaluated the expression of 728 human miRNAs in six adenomas (ACAs) and twelve carcinomas (ACCs). The ACC group was composed of two subgroups A and B consisting of six recurrent (subgroup A) and six non-recurrent tumors (subgroup B). These two distinct subgroups have been characterized recently (de Reynies et al, 2009) on the basis of distin...

Primary Aldosteronism (PA) is the most frequent cause of secondary hypertension and patients display an increased prevalence of cardiovascular events compared to essential hypertensives. To date, three familial forms of PA have been described and termed, familial hyperaldosteronism types I, II and III (FH-I to -III). The aim of this study was to investigate the prevalence and clinical characteristics of the three forms of FH in a large population of PA patients. Three hundred ...

Patients with adrenal insufficiency need adjustment of the hydrocortisone (HC) dose during an intercurrent illness. Current recommendation to double the daily HC dose at each occasion does not consider the non-linear dose proportionality in bioavailability i.e. doubling the dose gives less than 100% increase in exposure. We have developed an intercurrent illness dose regimen for a once daily dual release HC tablet using population pharmacokinetic (POPPK) modeling.<p class=...

Introduction: Left ventricular hypertrophy (LVH) is associated with increased morbidity and mortality. LVH defined by ECG (ECG-LVH) has been evaluated using standard voltage criteria by Sokolow and Lyon (SL-LVH) and more recently using the Cornell product criteria (CP-LVH). Evaluation of CP-LVH is beneficial in hypertensive patients: however, in patients with primary aldosteronism (PA) whose incidence of cardiovascular events is higher than essential hypertension (EHT), there ...

Cushing’s disease, i.e. cortisol excess due to an ACTH-secreting pituitary adenoma, is a rare disorder with considerable morbidity and mortality. Current therapeutic strategies include pituitary surgery, radiation, adrenalectomy and medical treatment with steroidogenesis inhibitors, as drugs aimed at the pituitary adenoma are as yet under investigation. Experimental data showed that retinoic acid restrains ACTH secretion by tumoral corticotrophes thus we decided to evalua...

We have previously reported the following metabolic abnormalities were common in 203 adult patients with CAH: obesity (41%), hypercholesterolemia (46%), insulin resistance (29%), osteopenia (40%) and osteoporosis (7%) (Arlt et al. JCEM 2010 95 5110–21). The CAH patients were taking different glucocorticoid therapies at various doses (n=196): hydrocortisone (n=25 M, 26 W), prednisolone (n=21M,67W), dexamethasone (n=15M,22W) or comb...

Background: Adrenal crisis (AC) is a life-threatening complication in patients with congenital adrenal hyperplasia due to classical 21-hydroxylase deficiency (21-OHD). AC was defined as an acute state of health impairment which required i.v. glucocorticoid administration and hospital admission. No data on AC over life-time in 21-OHD is available.Study design: In a retrospective study AC was studied following two approaches: a) questionnaire-based: 122 ad...

We investigated whether urinary cortisol metabolites could help to diagnose patients with cortisol oversecretion either with benign adrenal or corticotroph tumours.Liquid chromatography tandem mass spectrometric assay (LC-MSMS) of cortisol (F)m, cortisone, tetra-hydrocortisol (THF), allo-THF, tetra-hydrocortisone (THE), α-cortol, β-cortol, α-cortolone, α-cortolone and internal standard 6-α-methylprednisolone were assayed after de...

In order to prove that different sound-waves trigger different human hormones release by the way of their vibratile impact on the bodies, we exposed 30 testers (heterogeneous for gender, age and lifestyle) to different frequencies of noisy sound-waves (not melodic and rhythmic music). We organized three sessions in different days and with different waves frequencies: 1st at 40–115 Hz, 2nd at 8200–8500 Hz, 3rd with mixed radio-waves.Blood cortis...

Context: Differentiating Cushing’s disease (CD) from pseudo-Cushing’s syndrome (PCS) is one of the most challenging problems since no biological test is yet perfect. Almost 30 years ago our group demonstrated the interest of 4 mg i.v. dexamethasone suppressing test (DST) to differentiate obese patients to CD.Objective: To reevaluate the diagnostic accuracy of the 4 mg i.v. DST in carefully selected patients with PCS and CD.<p class="abstext...

Introduction: Patients with adrenal adenomas appear to exhibit an appreciable prevalence of autonomous aldosterone secretion (AAS). Our aim was to evaluate the anti-hypertensive effect of targeted therapy with mineralocorticoid receptor (MR) antagonists in AAS patients.Patients and methods: We studied 60 hypertensive patients, 21 males and 39 females, harboring an adrenal adenoma with AAS. All patients were receiving combination of anti-hypertensive trea...

Subclinical Cushing’s syndrome (SCS) is a status of altered hypothalamo-pituitary-adrenal (HPA)-axis secretion in the absence of the classical signs or symptoms of overt cortisol excess. Among the various tests used for the diagnosis of SCS, the 1-mg dexamethasone test (DST) is the most used. Alprazolam (ALP), a benzodiazepine activating GABAergic receptors, possesses clear centrally-mediated inhibitory effects on ACTH and cortisol secretion in normal subjects, while it d...

Similarly as in autoimmune Addison’s disease (AAD), diagnosed in about 80% of primary adrenal insufficiency, idiopathic isolated secondary adrenal insufficiency (ISAI) seems to have an autoimmune origin.Within the last 35 years we have registered in our Department 325 patients with ISAI (F/M ratio 10.9) aged 17–87 years. In comparison, we have in our registry 241 patients with AAD, collected within over 40 years. The diagnosis of ISAI was based...

Introduction: Patients with adrenal incidentalomas (AI) and subclinical hypercortisolism (SH) are thought to have increased incidence of cardiovascular risk factors, including diabetes mellitus (DM) and hypertension. Data regarding dyslipidemia are scarce. The aim of this study is to evaluate the possible influence of SH on lipid pattern in relation to the presence/absence of DM.Methods and design: 276 AI patients were enrolled (168 F, 108 M), 55 with di...

Background: Studies across the world have unveiled different prevalence of primary aldosteronism (PA) in distinct geographical areas and human races. However, owing to disparities in methodology and recruitment, the true incidence is still open. Especially information in Asian resistant hypertension is rare, so we determined to investigate the prevalence of PA in this population.Methods: We launched a large-scale, hospital-based national survey and enrol...

Objective: The aim of this study was to determine genetic, anthropometric and metabolic features in an unselected population of adult Norwegian patients with classical 21-hydroxylase deficiency (21OHD).Patients,Methods, and design: Sixty-four 21OHD-patients participated (23 men, 41 women; mean age 40.3 (range 19–72) in a cross-sectional study including DNA sequencing of the CYP21A1P-CYP21A2 locus, anthropometric measurements i...

The 1-mg overnight dexamethasone suppression test (DST) is a screening test for endogenous Cushing’s syndrome (CS). The principle is that dexamethasone (D) will suppress ACTH and cortisol (C) secretion in healthy individuals, but not in CS. We have studied the associations between D and C concentrations in patients without CS after 1-mg DST.Methods: On suspicion of CS, 59 patients received 1-mg D at 23 p.m. and next day at 8 a.m. blood was drawn for...

Exogenous corticotropin-releasing factor (CRF) induces an increase in glucocorticoid production and also may protect the gastric mucosa against stress-induced injury. However, it remained unknown whether glucocorticoids released in response to CRF injection contribute to the gastroprotective effect of CRF. In the present study we investigated whether exogenous CRF may protect the gastric mucosa against gastric injury through involvement of glucocorticoids and, consequently, th...

BACKGROUND: The determination of Night Salivary Cortisol (NSC) is a useful survey in the screening for hypercortilosism. Study data about its usefulness, even when different methods of dosage are used, are anyway scarce.OBJECTIVE: To compare the diagnostic performance in the NSC dosage of the chemiluminescence method (CLIA) and of mass spectrometry (LC-MS/MS).METHODS: Saliva samples were taken at 11:00 pm in 36 healthy volunteers a...

Objective: The main physiological function of the renin-angiotensin-aldosterone system (RAAS) is the regulation of water and salt homeostasis as well as arterial blood pressure. In addition, the RAAS is proposed to be involved in the pathophysiology of several diseases like hypertension, vascular remodelling, atherosclerosis, insulin resistance and type 2 diabetes mellitus. In a cohort study in north-east Germany, we investigated the association of plasma renin- (PRC) or plasm...

Background: In case of inoperable disease or tumor recurrence, there are only a few medical treatment options for patients with adrenocortical carcinoma (ACC). The oral alkylating drug Temozolomide (TMZ) shows efficacy in a subset of patients with melanoma, glioblastoma or pancreatic neurendocrine tumours. Response to TMZ seems determined by the tumoral expression level of the DNA repair enzyme O(6)-Methylguanine-DNA methyltransferase (MGMT).Aims: To eva...

Background: Adrenal vein sampling (AVS) is the gold standard test for identification of unilateral primary aldosteronism (PA) which is curable by surgery, but is a difficult procedure with low success rates. Rapid cortisol assays during AVS improved AVS success rates.Methods: We have developed a gold nanoparticles based immunochromatographic quick cortisol assay (QCA) in which cortisol concentration could be measured both quantitatively and semi-quantita...

Background: Data on the prevalence of primary aldosteronism (PA) in subjects with resistant hypertension (inadequate pressure control with three full-dose drugs, including a diuretic) are scanty and it is not known if PA is associated with a more severe vascular damage.Aim: To determine the prevalence of PA in patients with resistant hypertension and define the possible association with early cardiovascular damage.Methods: Seventy ...

Background/Aim: Classic 21-hydroxylase deficiency (21HD) presents some traits of the metabolic syndrome.Aim: To investigate early metabolic alterations in lipid and adipokine profile together with markers of subclinical inflammation in children and young adults with classic 21HD, which could predict early atherogenesis.Patients und Methods: Thirty nine patients with classic 21HD (4–30 years); 39 age-, sex- and BMI-matched heal...

Adrenal incidentalomas (AI) are a common finding in patients studied by abdominal imaging and approximately 9–17% is found bilaterally. So far, the potential role of hypothalomo-pituitary adrenal (HPA) axis dysregulation in the pathogenesis of AI, especially of those found bilaterally, has not been addressed. The DEXA-CRH test has been previously used to detect dysregulation of the HPA axis; herein, it was used to assess ACTH and cortisol responses in a large group of pat...

Background: Idiopathic primary hyperaldosteronism (IHA) is the subtype of primary aldosteronism (PA) in which lateralization of the mineralocorticoid hypersecretion cannot be demonstrated. Scanty data are available on the clinical history of IHA: a couple of brief reports suggest a remission of aldosterone hypersecretion after years of treatment with mineralocorticoid receptor blocking agents.Aim of this study was to check the persistence/remission of al...

Context: Recent studies showed a high prevalence of anxiety and depressive symptoms in patients with primary hyperaldosteronism (PA). A cross-sectional analysis suggested only minor improvement following adrenalectomy (ADX) and mineralocorticoidreceptor antagonist (MRA) therapy.Objective: Our aim was to determine the course of anxiety and depression in untreated patients.Design: We investigated 15 patients with PA at time of diagno...

Introduction: There is no published data on dispensed drug pattern in patients with Autoimmune Addison’s disease (AAD). Sweden has excellent condition for research in this area, with high-quality population based registers. Among them is the Swedish Prescribed Drug Register (SPDR) that contains information about dispensed prescribed drugs. By linking registry data, we aimed at accurately estimate the prevalence and incidence of AAD, the prevalence of common concomitant au...

There is no consensus on the best dosing regimen for glucocorticoid replacement therapy. The general intention is to individualize according to the clinical response and use the lowest possible maintenance dose without risking adrenal crisis.Aim: To survey patients with adrenal insufficiency (AI) on their glucocorticoid replacement therapy dosing regimen.Method: Patients (children and adults) were recruited via patient organization...

Primary aldosteronism (PA) is a major cause of secondary hypertension. Among PA, the diagnosis of an aldosterone-producing adenoma (APA) is critical because an APA can be cured surgically. Adrenal venous sampling (AVS) is the golden standard test in the diagnosis of an APA, but is available only in specialized medical centers. Meanwhile, aldosterone secretion of an APA is reported to be more sensitive to ACTH than that of idiopathic hyperaldosteronism (IHA) or essential hypert...

Introduction: There are limited prospective safety data on glucocorticoid replacement. The aim of this study was to assess the safety and efficacy during long term treatment using a once-daily oral dual-release hydrocortisone in patients with adrenal insufficiency (AI).Methods: This is an open, multi-centre study in 71 patients with AI. Most patients were recruited from a previous controlled trial (n=53) where they had received the dual-release th...

This study aimed at searching for malignancy in a group of 2300 patients with incidentally found adrenal tumours (1688 women and 612 men aged 11-87 years) registered at our Department of Endocrinology. The methods of investigation included clinical and imaging studies, hormonal assays and pathomorphological examinations in the patients treated by surgery. In 168 patients, aged 11 to 81 years, adrenocortical cancer was diagnosed ranging in diameter from 2.5 to 25.0 cm. In 7 pat...

Background: Mitotane (o,p’DDD) is the reference therapy for adrenocortical carcinoma (ACC) and should undergo metabolization in o,p’DDE and o,p’DDA to exert its anti-proliferative activity. We have previously shown that there is a link between RRM1 gene expression and o,p’DDD activity in an adjuvant setting. Aim of this study was to assess whether RRM1 gene expression is correlated to the bioavailability and cytotoxic activity of o,p’DDD and its metabo...

Introduction: The improvement in imaging techniques has increased the number of incidentally discovered adrenal lesions. Current clinical recommendations are based on the NIH consensus statement (2002) and include: CT at 6,12 and 24 months plus annual hormone evaluation for 4 years.The aim of this study was to describe the results of the application of the current guidelines in a cohort of consecutive patients whose initial diagnosis was non-functioning ...

Background: There is uncertainty as to whether glucocorticoid receptor (GCR) polymorphisms play a role in the development of glucocorticoid-related side-effects in individuals receiving hydrocortisone replacement for Addison’s disease.Method: One-hundred-and-forty-seven Addison’s patients were age, gender, ethnicity and body mass index (BMI) matched with 147 control subjects. Genotyping was performed using polymerase chain reaction (PCR) for th...

The adrenal function of children is investigated similarly to adults’ using at rest (basal) and after testing serum cortisol concentration ((F)). di Iorgi et al. (JCEM 95:2132) showed a good diagnostic accuracy of glucagon testing investigating (F) increase. We retrospectively addressed the relevance of using, in children with short stature tested for GH deficiency, 1/ the normal reference range of our assay for basal (F) and 2/ the threshold provided by di Iorgi et al. o...

Adrenal masses are among the most prevalent human tumors and are frequently detected unexpectedly by imaging studies performed for reasons unrelated to suspect of adrenal diseases.Subclinical hypercortisolism (SH) is the most frequent endocrine dysfunction detected in patients with adrenal incidentalomas (AI), accounting from five to 20% of all cases depending on inclusion criteria. one mg overnight dexamethasone suppression test (one mg DST) should be t...

Objective: To evaluate the outcome of preoperative therapy with ketoconazole (KTZ) and/or metyrapone (MTP), in previously untreated CS patients who later underwent surgery.Design and methods: A total of 62 CS patients (85% ACTH-dependent), who have been treated with steroidogenesis inhibitors prior to surgery in our centre between 1983 and 2010, were retrospectively studied. T0 and t1 defined visit at baseline and at the end of medical treatment, respect...

Cushing’s syndrome results from exposure to excess glucocorticoids. Ectopic Cushings is endogenous ACTH dependant form of Cushing’s associated with markedly raised ACTH and cortisol levels. This leads to an impaired immune response, setting the stage for occurrence of opportunistic infections. Nocardia is a gram positive bacterial infection caused by aerobic actinomycetes in genus Nocardia. We report a series of patients diagnosed with ectopic Cushings, with growth o...

Background data: Laparoscopic adrenalectomy has became in the last decade “gold standard” for treating of adrenal tumors with diameters smaller than six cm. In addition, one should note than larger tumors or potentially malignant tumors can now also be removed laparoscopically, with virtually no complication.Objective: The authors evaluate the effectiveness of laparoscopic adrenalectomy for a large adrenal tumors.Methods:...

It is well known that primary aldosteronism (PA) is frequently associated with metabolic syndrome. Among possible pathogenic mechanisms, adiponectine gene variants may play a role in the development of metabolic complications especially type two diabetes.Aim of this study was to assess the presence of two single nucleotide polymorphisms of the adiponectin gene (G276T and T45G) in patients with PA and determine their relation to metabolic parameters.<...

Introduction: It has been reported that primary aldosteronism(PA) is often associated with subclinical Cushing syndrome (SCS). In the present study, we investigated the frequency of SCS in subjects with PA.Method: Subjects included consecutive patients (n=43) who were diagnosed as PA between 2003 and 2011 in our institute. They were screened by plasma renin activity (PRA (ng/ml/h)) plasma aldosterone concentration (PAC (pg/mL)) ratio (ARR) above 2...

Introduction: Recent publications regarding primary aldosteronism (PA) have challenged the concept of PA being a rare disease. In 2007 a standardized protocol for diagnosing and treating PA was introduced in Iceland for patients suspected of having PA. Data from the Icelandic Heart Association suggests that 35–40% of the adult population (age 46–67) have hypertension. The aim of this study was to gather information about PA as a cause of hypertension at the referral ...

A genome-wide association study indicated a correlation between a locus at 5q32 and high aldosterone to renin ratio in subjects from KORA F4 survey. As we considered the genes in this locus for their potential relevance for the etiology of primary aldosteronism, we observed significantly higher expression of one of them, SLC26A2, in mouse adrenal glands, even though the gene’s function in the adrenal was not reported in the literature. Using the human adrenocortical cell ...

Background: Due to improvements in diagnosis capabilities, there has been a recent increase in adrenal tumors, that are incidentally discovered in patients, who underwent examination by sonography (S), computed tomography (CT) and magnetic resonance imaging (MRI) The aim of this study was to define the usefulness of contrast-enhanced three-dimensional sonography in the diagnosis of nonfunctioning adrenal incidentalomas.Patients and methods<p class="a...

The growing incidence of adrenal incidentaloma needs new methods of assessment of their function, especially for cases with subclinical hyperfunction. The bilateral adrenal incidentalomas in patients with subclinical Cushing syndrome (SCS) often need only unilateral surgery, but if their diameters and phenotypes are similar, coming to decision about side of adrenalectomy may be difficult. Another problem generate tumors suspected of subclinical aldosterone hypersecretion: the ...

It has been well known the primary aldosteronism (PA) is the most common endocrine hypertension, and it is accounted approximately 10% of all hypertensive patients. It is always challenging for physicians which tests we should select for the confirmatory tests for the patients with aldosterone-renin retio (ARR) positive. We analyzed our 83 PA patients for the sensitivity of each confirmatory test.We screened those PA suspicious patients by ARR and we con...

Background: Aldosterone to renin ratio (ARR) is the gold standard for screening of primary aldosteronism (PA). However, the lower value of ARR cannot rule out the possibility of PA. In this study, we evaluated the change of plasma aldosterone concentration (PAC) in ACTH stimulation among hypertensive patients and explored whether it improved the sensitivity of ARR for detecting PA.Method: Eighty-five patients with hypertension with plasma renin activity ...

Introduction: Assessment of the RAAS has been recently granted a much greater role in the evaluation of patients with arterial hypertension (AH). There is no single test efficient in selection of patients for second-step etiological investigation.Methods: 198 consecutive patients- 119 women (60%) and 79 men (40%)- hospitalized in years 2009-2011 at the Clinical Department of Endocrinology UMB as to diagnose PA. In each patient PRA and PAC (basic and afte...

Background: Cushing’s syndrome is a disease that presents with clear symptoms and causes considerable harm to the body if left untreated, yet often remains undiagnosed for prolonged periods of time. Face-classification software might recognize typical changes of the face and thus aid in diagnosing the disease early as we have previously shown in the classification of acromegaly.Methods: Using a regular compact digital camera, we took frontal and sid...

Background: Cushing disease CD is a rare disorder, caused by an (ACTH) producing tumor. Transsphenoidal pituitary surgery (TSS) remains the treatment of choice for CD. Fewer information is available on the long-term outcome in the group of patients harboring ACTH-secreting adenoma. The aims of this study were to analyze our 20-year experience with surgical treatment in Cushing’s disease and to examine whether remission rate is related with size tumors.<p class="abstex...

Introduction: Cushing’s disease is the most frequent cause of hypercortisolism. Although the classical form is easy to diagnose, nonspecific features raise differential diagnosis problems. Severe forms are associated with high mortality, but subclinical hypercortisolism also has significant morbidity.Patients and methods: Retrospective study of Cushing’s disease evolution in 14 patients, diagnosed between 2000 and 2011 (11 women, 3 men, age at ...

Introduction: The association between autoimmune diseases, including systemic lupus erythematosus (SLE), and endogenous hypercortisolism is rare. The latter is usually misinterpreted as iatrogenic in the case of patients taking exogenous systemic corticosteroid therapy. The excess endogenous glucocorticoids may play an important role in suppressing autoimmune activity. Similarly, the abrupt resolution of endogenous hypercortisolism may lead to a rebound worsening of autoimmuni...

Cushing disease is defined by signs and simptoms of hypercortisolism due to augmented ACTH secretion from pituitary origin. It is very rare in pediatric age, with general incidence around 13 cases/1 000 000 persons/year.Case description: S.G.N, male, 14.5 years old, was brought for medical attention due to weight gain and weakness in the last 4 months. At physical examination, he presented with moon face, cervical acanthosis nigricans, hypertrichosis and...

Adrenocortical carcinoma (ACC) is a rare tumor with poor prognosis due to its highly malignant phenotype and lack of effective treatment options.The etiology of ACC is still unknown. To better understand the pathogenesis of this type of tumor and to determine differentially abundant proteins and candidate biomarkers for adrenal cancer diagnosis and prognosis, we used a novel approach based on two-dimensional differential gel electrophoresis (2D-DIGE). Pr...

Introduction: The role of glucocorticoids in the regulation of GH secretion is not well defined. Hypercortisolism inhibits GH secretion, but also hypocortisolism is correlated with impaired GH response to dynamic tests. This study was aimed to evaluate the GH reserve after GHRH+arginine test in patients with Addison’s disease (AD) and in operated patients with Cushing’s disease (CD).Design: Twelve AD patients (6M, 6F, aged 52±3.4 years, BM...

Purpose: The aim of this study was to evaluate the functional status and growth rates of adrenal incidentalomas, diagnosed at our center between 2005 through 2010.Methods: The computer and archive records of 113 patients, diagnosed as adrenal incidentalomas and followed-up at our center, were retrospectively analysed.Results: A total of 113 patients (133 tumors, 80 women (%70.8) and 33 men (% 29.2), ranged in age between 27 and 77 ...

Primary hyperaldosteronism is a common cause of secondary hypertension. Distinguishing between the two subtypes (unilateral aldosterone-producing adenoma and bilateral idiopathic hyperaldosteronism) is crucial for patient’s management. Adrenal venous sampling is an important method for evaluation of the condition, but selective successful right adrenal venous sampling is often reported to be a difficult procedure. A retrospective review of 51 cases suffering from primary ...

Background: Measurement of serum cortisol levels can be useful in the diagnosis of conditions of both adrenal insufficiency and excess. Several methods are available for the measurement of the cortisol levels and immunoassays are commonly used in routine laboratories. The aim of our study was therefore to compare four different automated immunoassays for measurement of cortisol in serum.Methods: Serum samples of seventy two healthy volunteers were used f...

Introduction: Exogenous Cushing’s syndrome is a challenging diagnosis in non-compliant patients or in cases with difficult anamnesis, while the access to self medication is relatively open.Aim: We present a young female case presenting with tertiary adrenal insufficiency.Case report: S.C., 40 years old has progressively weight gain of 30 kilos since the last year. The Body Mass Index is 40 kg/m2, with androgen redis...

Introduction: Non-Hodgkin’s lymphoma is an AIDS defining malignancy. However, a primary adrenal lymphoma as a presenting feature of HIV infection has not been previously reported.Case Report: A 66-year-old male presented with a short history of severe fatigue, weight loss, dizziness and nausea. Baseline blood results revealed normal biochemistry with mild normocytic anaemia, neutropaenia with lymphopaenia and the short synacthen test demonstrated in...

Cushing’s disease is the main cause of endogenous hypercortisolism. Comorbidities increase morbidity and mortality and the treatment is fundamentally surgical. Patients may use drugs to lower hypercortisolism as pre-surgical preparation and post-surgical treatment when cure is not reached.Objective: Evaluate the benefits and collateral effects of ketoconazole in Cushing’s disease.Methods: In 22 patients with Cushing’...

Introduction: Optimal glucocorticoid (GC) replacement in patients with adrenal insufficiency (AI) is desirable for the prevention of long-term side effects of GC. Both hyperglycemia and hypoglycemia are the risk of atherosclerosis. For the determination of optimal GC replacement method in patients with AI, we tested a utility of continuous glucose monitoring (CGM).Subjects and methods: Three patients with primary or secondary AI were examined. Case 1, 50...

Seventy six-year-old man was referred to our hospital for examination of hypertension and hypokalemia. His blood pressure was uncontrolled although he was taking amlodipine besilate, spironolacton and candesartan. In addition, he suffered from atrial fibrillation and chronic heart failure. His serum potassium was low (2.8 mmol/l) and bilateral adrenal glands were found swelling. Hence, we investigated him thoroughly on the suspicion for primary aldosteronism.<p class="abst...

Introduction: Adrenal lesions occur in more than 10% of the general population. Most are benign, but 2.5% are metastatic disease to the adrenal from tumors such melanoma, renal, breast, colon and lung carcinoma. Adrenal metastatic disease is usually asymptomatic and diagnosed in the extension study or the primary tumor. However it is unusual as a presentation of an endocrine tumor or like the first manifestation of metastatic disease.We present two patie...

Adrenal masses are common incidental radiological findings. It has been estimated that as many as 10–20% of patients with essential hypertension may suffer from undiagnosed primary aldosteronism (PA). In patients who have both adrenal incidentaloma, which the functioning one must be identified. We report a case where an unilateral PA was detected on 18F-fluorodexoyglucose (FDG)-positron emission tomography (PET), and comfirmed by adrenal venous sampling.<p ...