Endocrine Abstracts

Introduction: Hirsutism is the presence of excess terminal hair in women with a male pattern. Most cases of hirsutism are secondary to other disease but some of cases are idiopathic. The most accepted hypothesis for the development of hirsutism is increased 5-α reductase activity in skin. Based on this hypothesis, we have launched this study to evaluate the effects of Finasteride cream (a 5-α reductase inhibitor) on idiopathic hirsutism.Methods...

The effect of gonadectomy and gonadal hormone replacement on the adrenal cortex activity was studied in the adult male sand rat Psammomys obesus, a diurnal gerbillid rodent living in Beni-Abbes area, in the Algerian Sahara desert (30°7 N, 2°10 W). Animals freshly captured were orchiectomized during the breeding season and some animals received testosterone oenanthate (75 μg per 40 μl olive’s oil) twice a day during 7 days, 3 weeks after gonadect...

Introduction: It is known that many patients with adrenal incidentaloma display altered glucose tolerance. However, to our knowledge, we have no reports of the frequency of adrenal tumor in Japanese type 2 diabetic patients. We investigated the frequency of adrenal tumor in these patients.Subjects: We evaluated the presence of adrenal tumor in 245 Japanese type 2 diabetic patients (mean age 60.8±13.4 years). The patients who were diagnosed malignant...

The pseudo-Cushing states (PCS) include several clinical conditions such as obesity, polycystic ovary syndrome, depression and alcoholism, characterized by physical features and abnormalities of hypothalamus–pituitary–adrenal axis similar to Cushing’s syndrome (CS). The differential diagnosis between CS and PCS is often complicated and requires several hormonal tests. The aim of this study is to evaluate the diagnostic accuracy of the cortisol response to the or...

Background: Mitotane, 1,1-dichloro-2-(o chlorophenyl) -2- (p-chloro phenyl) ethane (o,p′-DDD) is a compound which represents the effective agent in the treatment of the adrenocortical carcinoma (ACC), able to block cortisol synthesis. Nevertheless the biological mechanism induced by this treatment in this cancer remains unknown. Recently, there has been a strong interest in applying proteomics to foster a better understanding of disease proces...

Introduction: The mutation of SDHB gene is associated with familial pheochromocytoma-paraganglioma syndrome (PPS). SDHB gene is located in locus 1p23–25 and encodes a subunit B of succinate dehydrogenase, which plays a key role in the respiratory chain and Krebs cycle.Pheochromocytoma in PPS usually produces norepinephrin. Even long term remission do not exclude relapse of the disease.We present a case of bilateral adrenal phe...

Objective: There is evidence that current replacement regimens fail to restore well-being in patients with adrenal insufficiency (AI). No data is available on the effect of different therapeutical regimes (hydrocortisone, prednisolone, cortisone acetate) on the quality of life in these patients.Methods: About 883 patients with adrenal insufficiency were contacted, 526 patients participated (60%) and received a disease specific questionnaire and three sta...

Objective: There is evidence that current replacement regimens fail to restore well-being in patients with adrenal insufficiency. No data is available on the effect of twice or thrice daily administration of hydrocortisone on the quality of life in these patients.Methods: About 883 patients with adrenal insufficiency were contacted, 526 patients participated (60%) and received a disease specific questionnaire and three standardized questionnaires (SF36, ...

Background: The renin-angiotensin-aldosterone-system (RAAS) is a major regulator of blood pressure, however, there are no studies available addressing its characterization in a large clinical setting. Therefore, the aim of the present study was to describe the relationship between parameters of the RAAS and actual blood pressure results in a large cohort of patients with and without essential hypertension.Methods: We investigated 3253 patients (ages 63.2...

The aim of the study was to investigate the effect of different coagulants and storage conditions on the stability of ACTH in plasma using the LIAISON-ACTH-Chemiluminescence Immunoassay.Design and methods: Sequential human blood samples were collected from healthy volunteers (n=83) between 8 and 10 pm into EDTA collection tubes (Sarstedt) and EDTA plus aprotinin tubes (Vacuette, Greiner Labortechnik), respectively. After collection the blood sampl...

Worldwide numerous active individuals take phosphodiesterase type 5 inhibitors (PDE-5i), furthermore, to our knowledge, the effects of these drugs on hormone secretion has not been adequately investigated. In particular, considering that a) PDE-5i influence NO bioavailability, b) NO is one of the mediators of the hypothalamus–pituitary–adrenal (HPA) axis response to stress, and, c) physical exercise-related stress activate HPA axis, we investigated whether PDE-5i inf...

Background: The development of a vascular supply is a critical factor in the growth and metastatic spread of malignant tumors. The recognition of the vascular endothelial growth factor (VEGF) pathway as a key regulator of angiogenesis has led to a considerable efforts to exploit its potential for therapy in oncology. Endocrine gland-derived (EG-VEGF) has been recently identified as an endothelial cell mitogen, predominantly expressed in steroidogenic tissues; it represents a n...

Context: The prevalence of NCAH among Turkish women with hirsutism has not been established so far.Objective: To evaluate the prevalences of 21-hydroxylase (21-OHD) and 11-β hydroxylase deficiencies by ACTH stimulation test among hirsute women.Patients and methods: The study population consisted of 285 premenopousal women, aged 16–46 years (mean: 23.2±0.3). All were hirsute and hyperandrogenic. Androgen secreting tum...

Introduction: We present the case of coincidence of pheochromocytoma and aderenocortical carcinoma at the same adrenal gland in patient with neurofibromatosis. That kind of tumors coincidence origin from different blastodermic layers is extremely rare.It is broadly known that pheochromocytoma is rare neoplasm, occurs in 0.1% of hypertensive individuals. Pheochromocytoma may occur sporadically or in certain familial syndromes, including multiple endocrine...

The aim of the present study was to evaluate and compare the response of 17 OHP to ACTH stimulation in patients with various types of adrenal incidentalomas and to examine the occurence of germline CYP21 mutation in these patients.Subjects and methods: Forty patients (27 females, 13 males) with unilateral and bilateral masses were screened for five most common mutations of the CYP21 in peripheral blood DNA samples. A hormonal evaluation, i.e. baseline pl...

Background: Several criteria (i.e., cortisol supprimibility after 1 mg overnight dexamethasone suppression test -F-dex-, low ACTH levels, high 24 h urinary free cortisol levels -UFC-, high midnight serum cortisol levels) have been used for defining SH. Nevertheless, a real gold standard combination of tests is lacking. Recently midnight salivary cortisol (MSC) has been described as a sensitive marker for the diagnosis of overt hypercortisolism, while the role of MSC in the dia...

Background: Incidental discovery of an adrenal mass (AM) presents a common finding in patients with a history of extraadrenal malignant tumour. Discerning malignancy in AM is based on radiology (Rx) and scintigraphic (Sx) criteria, and finally fine-needle aspiration biopsy (FNA) of the tissue.Objective: Determine the concordance of Rx and Sx techniques in patients with an AM and previous oncologic history.Materials and methods: We ...

Introduction: There are contradictory results concerning bone mineral density status in adult patients with congenital adrenal hyperplasia. To resolve this issue, we hypothesized that there could be a correlation between BMD and a total cumulative glucocorticoid dose from the diagnosis in early infancy to adulthood. We then conducted a retrospective in a referral centers for CAH. Thirty-eight adult patients (28 women, 10 men, aged 16–39 years) suffering from CAH and treat...

Introduction: Angiogenesis plays a major role in cancer growth and metastasis. Differences in angiogenesis and the balance of angiogenic growth factors and inhibitors may play a role in determining the observed variations in tumor behaviour. VEGF overexpression in adrenocortical carcinomas (AC) has been recently shown. Moreover a new steroidogenic specific tissue angiogenic factor (EG-VEGF) has been described, and its role is presently unknown in adrenal tumors. Previous evide...

21-hydroxylase deficiency is by far (>90%) the most common cause of congenital adrenal hyperplasia (CAH). Undiagnosed and untreated 21-hydoxylase deficiency bears the risk of salt loss, adrenal insufficiency and sex misassignment, therefore early diagnosis is very important. The most common way to identify children affected by the enzyme defect is the measurement of blood levels of adrenal hormones and precursor steroids, which is an invasive method and may lead to inaccur...

Objectives: Alterations in glucocorticoid (GC) metabolism may contribute to the development of obesity and insulin resistance. We aimed to study the role of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) in human adiposity, paying special attention to the association between altered GC metabolism and insulin sensitivity.Design: In 24-h urine samples of 72 extremely obese (mean BMI 45.5±1.1 kg/m2), but otherwise healthy patie...

Context: The polycystic ovarian syndrome (PCOS) is characterized by hyperandrogenism and associated with obesity and impaired glucose metabolism. Despite the high prevalence of PCOS and the considerable clinical impact, the precise interplay between metabolism and hyperandrogenemia is not entirely clear. We therefore aimed to analyse the relation between circulating free fatty acids (FFAs) and androgen metabolism in vivo in women.Design and partic...

Introduction: Free fatty acids (FFAs) affect pituitary function. While no effect of FFAs on ACTH and cortisol seems to exist in men, data in women are somewhat controversial. Therefore, we aimed to assess the effect of an acute increase of circulating FFA levels induced by the infusion of a lipid-heparin infusion on ACTH and cortisol secretion in healthy young women.Methods: Following a 10-h overnight fast 13 healthy female volunteers were investigated i...

Background/objectives: The aim of the study was to assess association between diabetes mellitus (DM) and arterial hypertension (AH) in patients with adrenal incidentaloma.Design and methods: One hundred and eleven consecutive patients with incidentally discovered adrenal tumours were included in the study. OGTT was done and 24 h urinary catecholamines were measured. Aldosterone and plasma renine activity (PRA) were determined, and 1 mg dexametasone test ...

Within the adrenal gland, chromaffin cells and their progenitors are exposed to a wide variety of growth factors and hormones, including adrenal androgens such as DHEA. The DHEA producing-zona reticularis of the adrenal cortex is in close proximity to the neural crest-derived catecholamine-producing chromaffin cells of the medulla, enabling strong paracrine interactions. In vivo studies in humans revealed that congenital adrenal hyperplasia due to 21-hydroxylase ...

Glucocorticoid receptor (GR) gene polymorphisms have been associated with interindividual variations in glucocorticoid sensitivity in healthy individuals.Aim: Aim of this study was to investigate whether there was an association with sensitivity to glucocorticoids and bone mineral density in HPA axis disorders.Methods: We analyzed 3 polymorphisms of the GR gene (Bcl1, N363S, ER22/23EK) in 185 subjects: 52 patients with Cushing&#146...

Objectives: Oxidative stress is of critical importance in the pathogenesis of endocrinopathies. Since cholesterol serves as a major source of steroid hormone synthesis we investigated the effect of hypochlorite-modified low density lipoprotein (LDL) on aldosterone and cortisol release from human adrenocortical NCI-H295R cells.Methods: Native LDL obtained from healthy volunteers was oxidized to varying degrees by sodium hypochlorite. The resulting modifie...

According to recent studies, primary aldosteronism is considered to be responsible for almost 10% of all cases of arterial hypertension. The genetic background of this common disease, however, has been elucidated only for the rare familial types whereas in the large majority of sporadic cases it still remains unclear. In an attempt to define novel genetic mechanisms of hyperaldosteronism we utilized a random mutagenesis screen after treatment with the alkylating agent N...

Introduction: Late night salivary cortisol appears to be promising as a simple stress-free screening test for Cushing’s syndrome (CS). But there is no consensus on the cut-off value because of the lack of availability larger studies and of standardization of assays. The normal reference ranges are assay-dependent and should be validated for each laboratory.Objective: The purpose of this study was to evaluate the usefulness of late-night salivary cor...

Clinically silent adrenal masses discovered by abdominal imaging procedures performed for non-adrenal disorders, i.e. adrenal incidentalomas, have become a common finding in clinical practice and they represent a clinical concern because of the risk not only of malignancy but also of subclinical hormonal hypersecretion (SCS) that represents a new risk factor for cardiovascular diseases and/or osteoporosis. We studied 73 patients (39F, 34M; mean±S.E.M.: 61.6...

The adrenal incidentalomas have become a common clinical problem. In the vast majority of cases these masses are non- secreting adrenocrotical adenomas. However, some may show minor endocrine abnormalities with a subclinical hyperfunction or represent malignancies.Objectives: The aim of the study was to analyze and follow-up of incidentalomas and to establish the risk factors for mass enlargement and/or hormonal disturbances.Materi...

Objective: To verify whether tissue Doppler imaging (TDI) could contribute to a better understanding of the natural history of cardiomyopathy in active Cushing’s disease (CD), through its enhanced sensitivity to diastolic dysfunction, and identifying preliminary regional signs of systolic dysfunction, before the appearance of clinical symptoms of cardiac pathologies.Methods: Eleven women with newly diagnosed CD, and 15 control cases, purposely match...

Background: Classic 21-hydroxylase deficiency, due to severe mutations in CYP21B gene, is an uncommon disease (1/ 150 000). Salt-wasting form accounts for 75% of the cases and turns up with gluco- and mineralocorticoid deficiency as well as feminine hermaphroditism. Although wide psycho-social repercussion especially in women is known, the rarity of the disease and losses in follow-up may lead to a scarce clinical experience. We present 3 adult patients with CAH- SW followed r...

Background: In experimental studies, a high fluid intake and a corresponding high urine volume have been shown to increase renal excretion rates of urinary free cortisol (UFF) and cortisone (UFE) in adults. We aimed to examine whether 24-h urinary steroid excretion rates are also affected by urine volume in children.Methods: In 24-h urine samples of 100 prepubertal and 100 pubertal healthy children UFF, UFE, tetrahydrocortisol, 5α-tetrahydrocortisol...

Background: In patients with hypercortisolism, who are frequently obese, the prevalence of urolithiasis is increased and urinary excretion rates of calcium (Ca), oxalate (Ox), and uric acid (UA) are regularly elevated. In the present study, we examined whether these lithogenic factors are already associated with dietary intakes, body fat, and cortisol metabolites in free-living children.Methods: In 24-h urine samples of healthy children (150 boys, 150 gi...

In overt or subclinical ACTH-independant Cushing’s syndrome (CS), aberrant adrenal receptors may control cortisol secretion.We systematically studied the 20 patients with adrenal incidentaloma screened in our department for illegitimate adrenal receptors between 2000 and 2006. We investigated plasma cortisol level during successive stimulation tests performed while dexamethasone was given orally every 8 h (upright posture, meal, hypothalamic hormone...

Objective: Hypokalemic Conn’s syndrome is a rare disease with a prevalence of 0.5% in unselected hypertensive populations. However, recent studies indicate a higher prevalence of a milder variant of Conn’s syndrome, reaching 10% in some studies. Long term outcome and health care costs of hypo- and normokalemic variants are largely unknown. The National Conn’s Registry is an initiative to create a national database of sufficient epidemiological strength to invest...

Objective: Pheochromocytoma is a rare disease with an incidence of 2–6 per million, and a prevalence of 0.1–0.6% in patients with hypertension. Pheochromocytoma may occur sporadically or as part of hereditary syndrome. According to the latest studies, among patients with non-syndromic pheochromocytoma, up to 24% of tumors may be inherited. However, genetic testing was not generally performed until recently. There is still a debate which pheochromocytoma patient shoul...

Background: Subclinical Cushing’s syndrome (SCS) due to incidentally discovered adrenal adenomas (AI) has been associated with increased prevalence of hypertension, obesity, and impaired glucose tolerance which are established risk factors for cardiovascular morbidity. Although functional and morphological (structural) changes of endothelium have been correlated with cardiovascular morbidity this has not been looked into detail in patients with adrenal incidentalomas....

Recent studies indicating that normokaliemic primary aldosteronism (PA) is a more frequent cause of hypertension than previously expected led to an increased interest in biochemical screening strategies. We investigated biochemical diagnostic strategies used in different academic centres for patients documented in the German National Conn’s Registry. Data from 7 centres in 5 cities have been entered into a database by trained personnel. For analysis, results from 522 pati...

Autoimmune destruction of the adrenocortical cells is the most frequent form of Addi-son’s disease, however modern imaging methods make possible to discover bilateral neoplastic laesions resulting in adrenal insufficiency more frequently than about twenty years ago. In our group of 315 patients with Addison’s disease we diagnosed metastatic infiltrations of the adrenals in 18 cases and lymphoma of both adrenals in four cases (in sum 7%). Typical clinical signs, bioch...

Detailed information on adrenal function in autoimmune Type 1 diabetes with onset in adult age is still missing. This work compared diabetics with low response (LR) to diabetics with normal response (NR) to low dose ACTH test and control group (C).Thirty-two diabetics were investigated; LR (n=16), NR (n=16), age 44±10 years (mean±S.D.), age at diagnosis 28.5±10 years, disease duration 15±8 years, BMI 24.5&...

Many studies have shown insulin resistance (IR) in majority of patients with adrenal incidentaloma. The euglycaemic hyperinsulinaemic glucose clamp technique is still considered as ‘golden standard’ for evaluation of insuline sensitivity. These methods are also complicated, labor-intensive procedure better for small research studies. Today, several surrogate indexes for insulin sensitivity were introduced such as: HOMA, QUIQI or G/IR. Some studies showed that QUIQI h...

Background: The diagnosis of hyperaldosteronism is hindered by the absence of a well-defined gold-standard. CYP11B2 (aldosterone synthase) belongs to the steroid-metabolizing enzymes catalyzing the last step of the aldosterone synthesis. To establish a molecular marker for aldosterone-producing adenomas, we compared the expression in various adrenal tumors.Methods: Tissue from 20 aldosterone-producing adenomas (APA), 12 hyperplasias associated with hyper...

Objective: Primary aldosteronism (PA) is associated with vascular end organ damage. We evaluated the newly established German Conn’s Register for evidence of renal impairment and compared the data with renal function from hypertensive subjects from an epidemiologic cohort.Methods: The registry was founded in 2006 and has at present 7 participating centres in 5 locations. Data are entered in a central electronic database. Up to July 2007 555 patients...

Retinoid-X-receptor (RXR) and retinoic acid receptor (RAR) are transcription factors; each expresses in α, β and γ isoforms. Whereas RAR plays roles in growth and differentiation, RXR regulates lipids homeostasis. Specifically, RXRβ mediates intracellular control of cholesterol levels. RXR is activated by 9-cis-retinoic acid (9-cis-RA), cervonic acid, docosapentaenoic acid, adrenic acid and arachidonic acid. The present investigation was aimed...

Recent molecular studies suggest a role of ectopic G protein coupled receptors in primary aldosteronism (PA). The clinical relevance of these findings is not known. We therefore combined expression profiling and a clinical testing of hormone responsiveness in patients with primary aldosteronism. Sixteen tissues from aldosterone producing adenomas and 6 normal adrenal glands were subjected to a quantitative PCR for determination of mRNA expression levels of AT2R, GIPR, MC2R, Gn...

Osteoprotegerin (OPG) has been identified as a decoy receptor that inhibits osteoclast differentiation and recently as a paracrine regulator of vascular calcification. OPG is suppressed by glucocorticoid administration. In this study, we evaluated OPG and bone metabolism in Cushing’s syndrome (CS) before and after surgical treatment. Twenty-nine patients with CS (26 women and 3 men, mean age: 40.7–2.8 years) and 27 age and sex-matched controls have been studied for b...

Plasma aldosterone concentration (PAC) to active renin concentration (ARC) ratio (ARR) is an established screening tool for primary aldosteronism. Previously we provided reliable cut-offs measuring PAC by a radioimmunoassay (RIA; Byk&DiaSorin) und ARC by an established immunoluminometric assay (Nichols Institute Diagnostics). Since the latter one is not longer available, we aimed to establish cut-offs for currently available assays.One hundred seven ...

Object: In Addison’s disease hydrocortisone or cortisone have so far been used at doses of 30–37.5 mg/day, respectively, though several studies showed that cortisol normal production is about 5.7 mg/m2 (20–25 mg/day of hydrocortisone or cortisone, respectively). Differently from secondary hypoadrenalism, scanty data exist in patients with Addison’s disease on role of conventional glucocorticoid replacement and metabolic and cardiovascular outcome...

The A-ZIP/F-1 transgenic mouse is a model of lipoatrophic diabetes with severe insulin resistance, hyperglycemia and hyperlipidemia. Recently, a regulatory role of adipose tissue on adrenal gland function and blood pressure has been suggested. To further explore the importance of adipose tissue in the regulation of adrenal function and blood pressure, we studied this mouse model of lipodystrophy. A-ZIP/F-1 mice exhibit significantly elevated systolic and diastolic blood pressu...

In this study we compared plasma adiponectin levels between patients with non-functional adrenal incidentaloma and subclinical Cushing’s syndrome. Our aims were to determine whether there was any difference of plasma adiponectin levels, any relation between cardiovasculer risk factors and to investigate the importance of adiponectin levels in subclinical Cushing’s syndrome patients according to non-functional adrenal incidentaloma patients. The patients referred from...

Background: Hormonal studies have detected subtle abnormalities of the hypothalamic–pituitary–adrenal (HPA) axis due to autonomous cortisol secretion, in a percentage of patients with adrenal incidentalomas, a condition termed as subclinical Cushing’s syndrome. The diagnostic criteria and the clinical significance of this condition are still controversial and consequently there is uncertainty for its management. Data defining the natural course of these tumors, ...

Background: Abrupt catecholamine release may cause paroxysmal attacks in patients with pheochromocytoma, and is associated with major hemodynamic changes during adrenalectomy. We investigated whether preoperative paroxysmal attacks are associated with further intraoperative adverse hemodynamic changes during adrenalectomy for pheochromocytoma.Material and methods: From 1994 to 2006, 88 patients underwent laparoscopic adrenalectomy for pheochromocytoma. I...

Adrenal crisis (AC) is a rare but life-threatening complication in chronic adrenal failure. Here we evaluated frequency, causes and potential risk factors of AC in a large sample of patients with primary AI (PAI) or secondary AI (SAI).In a cross-sectional study 883 patients with AI were contacted by mail. 526 patients agreed to participate and received a disease specific questionnaire. Diagnoses and co-morbidities were verified by review of medical recor...

Sepsis and septic shock remain a major health concern worldwide, and an intact adrenal cortex glucocorticoid (GC) stress response, is critical for organism to survive. Recently, we and others have shown that adrenal gland expresses members of toll-like receptors (TLRs) family which are known to sense pathogens and induce inflammatory response. Data performed on TLRs deficient mice clearly demonstrate a critical involvement of these receptors in immune-neuroendocrine bidirectio...

Primary aldosteronism (PA) has a prevalence of about ten percent in a hypertensive population and is an important risk factor for cardiovascular disease. The aldosterone to renin concentration ratio (ARR) is an established diagnostic tool in the screening for PA. However, hormonal determinations are time-consuming and expensive. Therefore, we studied the value of the sodium to urinary sodium to potassium to urinary potassium (SUSPUP) ratio in 37 patients with PA, in 34 hyperte...

Chromaffin cells from adrenal medulla are the main source of epinephrine and norepinephrine hormones which are known to mediate so called fight-or-flight response to multiple environmental stress conditions. Chromaffin cells together with sympathetic neurons share the same sympathoadrenal cell lineage, but in contrast to neurons they maintain their proliferation during whole life span. However, little is known about chromaffin cells regeneration in an adult adrenal medulla.</p...

The mechanisms that lead to tumor formation of and aldosterone secretion by zona glomerulosa cells in primary aldosteronism are not known. Recently, endothelial cell-derived factors have been characterized that control the release of aldosterone by adrenocortical cells. In addition, we started to characterize the regulation of CITED2, a CBP/p300 interacting transactivator with ED-rich tail 2. Earlier, it was shown in mice that absence of CITED2 leads to adrenal agenesis. Since...

Illicit expression of membrane receptors for circulating regulatory factors, such as GIP and LH receptors, has been well documented in ACTH-independent macronodular adrenal hyperplasias (AIMAHs) causing Cushing’s syndrome. In addition, we have observed an abnormal expression of serotonin, arginine vasopressin and ACTH in a subpopulation of steroidogenic cells in two AIMAH tissues. The aim of the present study was: (i) to investigate the presence of ACTH by immunohistochem...

A 48-year-old woman was referred for ACTH-independent Cushing’s syndrome associated with a left adrenal tumor. Contrasting with hypercortisolism-related hypertension and hypokalemia, renin and aldosterone levels were paradoxically increased. The tumor was surgically removed and pathological examination of the tissue established the diagnosis of corticosurrenaloma. Fragments of the tumor were obtained for in situ hybridization, immunohistochemical and cell incubatio...