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Adrenal masses are frequently incidentally identified from cross-sectional imaging studies, which are performed for other reasons. The intensity of the approach to the patient with such a mass is tailored to the clinical situation, ranging from a quick evaluation to a detailed work-up. In all cases, the three components of the evaluation are clinical assessment, review of the images, and biochemical testing with the goal of ruling out malignancy and identifying hormonally active lesions. This article incorporates recent information to produce a logical, systematic assessment of these patients with risk stratification and proportionate follow-up., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Nonclassic apparent mineralocorticoid excess (NC-AME) is proposed as a novel clinical condition with a mild phenotypic spectrum that ranges from normotension to severe hypertension. This condition is mainly characterized by a high serum cortisol to cortisone ratio (F/E) and concomitant low cortisone (E), however further metabolic changes in NC-AME have not been studied. A cross-sectional study was performed in a primary-care cohort of 396 Chilean subjects, which were classified in two groups: NC-AME (n = 28) and healthy controls (n = 27). A discovery study based in untargeted metabolomics assay in serum samples from both groups was performed by UPLC-Q-TOF/MS. Global metabolomic variations were assayed by principal component analysis and further compared by orthogonal partial least-squares discriminant analysis (OPLS-DA). NC-AME subjects exhibited higher values of blood pressure, fractional excretion of potassium, and lower plasma renin activity and urinary sodium to potassium ratio. Metabolomic analyses showed 36 differentially regulated metabolites between NC-AME and control subjects. A ROC curve analyses identified eight metabolites with high discriminatory capacity between NC-AME and control subjects. Moreover, gamma-L-glutamyl-L-methionine sulfoxide and 5-sulfoxymethylfurfural, exhibited significant association with cortisone, which are potential biomarkers of NC-AME, however further assays should elucidate its biological role in setup and progression of this phenotype., (© 2021. The Author(s).)

Background: This study aimed to investigate the characteristics and extent of glycometabolism impairment in patients with adrenal diseases, including Cushing syndrome, primary aldosteronism, pheochromocytoma, and nonfunctional adrenal incidentaloma., Methods: This study enrolled thirty-two patients with adrenal diseases as adrenal disease groups and eight healthy individuals as healthy controls. Blood glucose levels were indicated by glucose concentration in interstitial fluid, which was documented using flash glucose monitoring system. According to flash glucose monitoring system data, parameters representing general blood glucose alterations, within-day and day-to-day glucose variability, and glucose-target-rate were calculated. Furthermore, blood glucose levels at nocturnal, fasting, and postprandial periods were analyzed. Besides, islet β-cell function and insulin resistance were assessed., Results: Analysis of flash glucose monitoring system-related parameters indicated impaired glycometabolism in patients with adrenal diseases compared with that of healthy controls at general blood glucose, within-day and day-to-day glucose variability, and glucose-target-rate levels. Furthermore, the dynamic glucose monitoring data revealed that significantly affected blood glucose levels compared with that of healthy controls were observed at postprandial periods in the Cushing syndrome and primary aldosteronism groups; at nocturnal, fasting and postprandial periods in the pheochromocytoma group. Significant insulin resistance and abnormal β-cell function were observed in the Cushing syndrome group compared with that in healthy controls., Conclusion: Adrenal diseases can negatively affect glucose metabolism. Patients diagnosed with adrenal diseases should receive timely and appropriate treatment to avoid adverse cardiovascular events linked to hyperglycemia and insulin resistance., (Copyright © 2020 Han, Cao, Zhao, Yang, Yin, Shen, Zhang, Gao, Ren, Liang, Yang, Zhang and Liu.)

Adrenal steroidogenesis is a robust process, involving a series of enzymatic reactions that facilitate conversion of cholesterol into biologically active steroid hormones under the stimulation of angiotensin II, adrenocorticotropic hormone and other regulators. The biosynthesis of mineralocorticoids, glucocorticoids, and adrenal-derived androgens occur in separate adrenocortical zones as a result of the segregated expression of steroidogenic enzymes and cofactors. This mini review provides the principles of adrenal steroidogenesis, including the classic and under-appreciated 11-oxygenated androgen pathways. Several adrenal diseases result from dysregulated adrenal steroid synthesis. Herein, we review growing evidence that adrenal diseases exhibit characteristic modifications from normal adrenal steroid pathways that provide opportunities for the discovery of biomarker steroids that would improve diagnosis and monitoring of adrenal disorders., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: During follow-up in cancer patients, adrenal lesions are frequently found by computer tomography imaging. In these patients, the frequency of subclinical Cushing's syndrome (SCS) has not been fully explored. The aim of the present study was to investigate the presence of SCS in cancer patients with adrenal lesions in comparison to patients with true adrenal incidentalomas., Design: We studied 95 patients with adrenal lesions: 57 patients (group A, 20 males and 37 females) had a history of extra-adrenal malignancy and adrenal lesions were discovered during staging of the primary cancer, and 38 patients (group B, 6 males and 32 females) had adrenal incidentalomas. The two groups had similar BMI. All patients had unenhanced HU < 10 in computed tomography to ensure low risk of adrenal metastatic disease. Patients' morning plasma cortisol levels and ACTH were measured. An overnight 1 mg dexamethasone suppression test (ODST) was performed in all participants; in case of abnormal results, 24-h urine cortisol and the low-dose dexamethasone suppression test were additionally conducted. The cutoffs of morning cortisol values used for ODST were 1.8 and 5 μg/dl., Results: When the cutoff of 1.8 μg/dl for suppressed morning cortisol was used, 42.1% of group A and 39.5% of group B had abnormal results (p = 0.95). By using the threshold of 5 μg/dl after ODST, 5.3% of group A and 13.2% of group B did not have suppressed cortisol levels with the 1 mg ODST (p = 0.18). The main factors found to influence suppressed cortisol levels after ODST in both groups were BMI and size of the adrenal lesion., Conclusions: Patients with extra-adrenal malignancies and adrenal lesions had similar rates of subclinical hypercortisolemia compared to patients with true adrenal incidentalomas.

Background: Adrenal hemorrhage (AH) is a rare condition that can lead to acute adrenal insufficiency and may be fatal. The risk factors of AH include focal adrenal lesion, abdominal trauma and anticoagulation therapy. The clinical manifestation of AH varies widely; the symptoms may be related to adrenal insufficiency or may reflect multiple organ failure. However, in many cases, the course of AH is asymptomatic., Objectives: The study is a retrospective analysis of 23 cases of AH, whose aim is to discuss the etiology and the management of selected patients, as well as a literature review., Material and Methods: The paper presents a retrospective analysis of 23 patients with AH confirmed by radiological and/or pathological examination. Epidemiological data, the results of laboratory tests, and radiological and pathological examinations were included in the analysis., Results: The risk factors of AH were not established in 13 patients, 5 patients had experienced a trauma prior to AH diagnosis, 1 patient was diagnosed with sepsis, 2 patients had concomitant neoplastic disease, and in 2 patients, 2 risk factors were present. Among patients who required emergency admission, 5 patients were hospitalized due to acute abdominal pain, 1 patient due to sepsis and 1 patient due to symptoms of active endocrinopathy. In the remaining patients, diagnostic procedures were prompted by the detection of adrenal incidentaloma (AI). A total of 40% of patients underwent surgical treatment due to the magnitude of AH or clinical and laboratory evidence of overt endocrinopathy. In the remaining patients, conservative treatment and further observation was recommended. In 34.8% of these patients, follow-up examinations revealed a gradual regression., Conclusions: It seems that there is a need to distinguish patients with AH who do not require surgical intervention. Follow-up radiological examination is necessary to reassess the lesion. The patients in whom shrinkage of the tumor can be observed are likely not to require surgical treatment.

An emerging branch of research is examining the linkage between Vitamin D and nonskeletal disorders, including endocrine diseases. In this regard, a still little studied aspect concerns the involvement of vitamin D in adrenal gland disorders. Adrenal gland disorders, which might be theoretically affected by vitamin D unbalance, include adrenal insufficiency, Cushing's syndrome, adrenocortical tumors and hyperaldosteronism. In this review, we provide an updated document, which tries to collect and discuss the limited evidence to be found in the literature about the relationship between vitamin D and adrenal disorders. We conclude that there is insufficient evidence proving a causal relationship between vitamin D levels and adrenal disorders. Evidence coming from cross-sectional clinical studies can hardly clarify what comes first between vitamin D unbalance and adrenal disease. On the other hand, longitudinal studies monitoring the levels of vitamin D in patients with adrenal disorders or, conversely, the possible development of adrenal pathologies in subjects affected by impaired vitamin D levels would be able to elucidate this still unclear issue.

The present report describes 6 cases of adrenal venous sampling (AVS) in patients who underwent computed tomography (CT) during arteriography because cannulation of right adrenal veins was otherwise difficult. CT was performed during arteriography to obtain information on the location and direction of the right adrenal vein. Two right adrenal veins were visualized in 1 case. The right central adrenal vein was not visualized in 1 case owing to an injury from a previous unsuccessful AVS procedure, but the right renal capsular vein was well visualized. CT during arteriography could contribute to a high AVS success rate., (Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.)

The diagnosis and management of adrenal diseases hinge upon accurate determination of hormone concentrations in blood and other body fluids. The advent of immunoassays for various steroid hormones has enabled the remarkable progress in adrenal disease over the last several decades, with some limitation. Sequential immunoassay of single analytes is a tedious process, which requires aliquots for each assay. In many complex adrenal diseases, including adrenal cancer and congenital adrenal hyperplasia, the patterns or ratios of multiple steroids rather than the value of any one steroid is more relevant. Although gas chromatography/mass spectrometry of urinary steroid metabolites has been employed to profile steroid production, throughput is slow, and availability is sparse. Recent generations of liquid chromatography-tandem mass spectrometry instruments (LC-MS/MS) provide the throughput and sensitivity required to measure many steroids simultaneously using small samples for commercial and research uses. Even in the best hands, however, LC-MS/MS suffers from limitations and requires diligent attention to detail during method development and implementation. This article reviews the theory, instrumentation principles and terminology, and practical application of mass spectrometry to clinical adrenal disorders., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: To evaluate the prevalence of antibodies to 21-hydroxylase (anti-21[OH]), a marker of autoimmune adrenal disease, in a cohort of patients with primary Sjögren's syndrome (SS) and to investigate whether the presence of anti-21(OH) correlates with clinical, serologic, and salivary gland features of the disease., Methods: Sera from 63 consecutive patients with primary SS, 32 patients with autoimmune thyroid disease (AITD), and 20 healthy controls were obtained and anti-21(OH) levels were determined by radioimmunoassay. Clinical, serologic, and histopathologic features were recorded, and a short Synacthen test was used to assess adrenal function reserve. Seven available minor salivary gland (MSG) tissue specimens from patients in the primary SS cohort were also assessed for interferon-α (IFNα), BAFF, and interleukin-21 (IL-21) cytokine transcripts, which are all implicated in B cell activation., Results: Anti-21(OH) positivity was detected in 17.5% and 28.1% of primary SS and AITD patients, respectively, and in none of the healthy controls. While no evidence of adrenal insufficiency was detected in any of the patients studied, a blunted rate of increase in cortisol levels was observed in patients with detectable serum autoantibodies against 21(OH), compared to their anti-21(OH)-negative counterparts. A strong correlation between the serum titer of anti-21(OH) antibodies and expression of IFNα, BAFF, and IL-21 messenger RNA in MSG tissues was also detected., Conclusion: Adrenal autoimmunity occurs in almost 20% of patients with primary SS in association with markers of B cell activation. Although the presence of adrenal autoantibodies was not associated with adrenal insufficiency in the present study, there was a blunted adrenal response, suggesting the need for further followup and monitoring of adrenal function in patients with primary SS who are positive for the autoantibodies., (Copyright © 2012 by the American College of Rheumatology.)

Background and Aim: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T(30)) the low-dose 1-µg short synacthen test (LD-SST); and (ii) the prognostic value of SFC and STC., Methods: Consecutive, hemodynamically stable, cirrhotic patients (34 Child-Pugh class A, 29B, and 32C) underwent the LD-SST. Patients were followed for at least 12 months to assess non-transplant-related mortality., Results: Child-Pugh class C patients had significantly higher basal levels of SFC than Child-Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T(0) STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver-operator curve analysis, the area-under-the-curve values were 0.67 for T(30) SFC (0.51-0.79), 0.81 for Child-Pugh score (0.70-0.88), and 0.79 for albumin level (0.63-0.88). During the follow-up period, 16 patients with high T(30) SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T(30) SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T(30) SFC, log-rank test). Albeit not statistically significant, the risk of death for patients with T(30) SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin., Conclusions: One-year, non-transplant-related mortality is high among patients with T(30) levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

The clinical presentation of adrenal hemorrhage varies, depending on the extent of hemorrhage as well as the amount of adrenal cortex involved by the hemorrhage. We report here a case of neonatal adrenal hemorrhage revealed by late onset of neonatal jaundice. This adrenal hemorrhage most probably resulted from shoulder dystocia. The aim of this work was to focus on the fact that jaundice can be caused by adrenal hemorrhage and to emphasize the crucial importance of abdominal ultrasound in cases of persistent jaundice., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aberrant receptors have been implicated in the pathogenesis of several types of adrenal tumours. So far the presence of aberrant receptors has been investigated in patients with massively enlarged adrenals due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) and unilateral adrenal adenomas associated with overt or subclinical Cushing's syndrome. The likelihood of aberrant responses in patients presenting with bilateral adrenal incidentalomas (BI) presenting as discrete solitary bilateral adenomas has not been thoroughly addressed. This is an observational cross-sectional prospective study conducted in a secondary/tertiary care centre. We studied 33 patients; 28 with incidentally discovered bilateral discrete adrenal adenomas and five with massive bilateral adrenal macronodular hyperplasia. We probed responses to physiological stimuli, namely upright posture and meal; in a subgroup of menopausal women the presence of aberrant gonadotropin receptors was assessed by the LHRH test. Abnormal responses obtained in tests performed with no dexamethasone suppression were always repeated and confirmed under dexamethasone suppression. Aberrant cortisol responses were confirmed in 10 patients; 9 to posture, 1 to meal (along with a positive response to posture) and 1 to LHRH tests. Patients who responded to any test compared to those who tested negative had larger adenomas, higher post-LDDST and midnight cortisol and a trend for lower ACTH levels. Patients without subclinical hypercortisolism (SH) did not respond to any test while 50% of patients with SH had an aberrant response (P = 0.002). A greater prevalence of aberrant responses was noted in patients with bilateral macronodular hyperplasia compared to those with solitary bilateral adenomas (80 vs. 21.4%, P = 0.02). Aberrant cortisol responses, primarily to posture testing, are present in a substantial proportion of patients with bilateral adrenal incidentalomas. Such cortisol responses are observed only in patients with subclinical hypercortisolism and especially in those patients with larger adrenal lesions.

Background: Hypothalamic-pituitary-adrenal axis suppression (HPAS) in asthmatic children treated with inhaled corticosteroids (ICS), with or without nasal steroids (NS), may be more common than previously thought. Only dynamic testing will identify children at risk of adrenal crisis. It is impractical to test all asthmatic children for HPAS with a gold standard adrenal function test, i.e. the metyrapone or insulin tolerance test., Objective: To determine which clinical or biochemical parameter is the most useful screening test for HPAS in asthmatic children., Methods: Twenty-six asthmatic children, 5-18 yr old, on ICS ± NS, not treated with oral or topical steroids in the preceding year were recruited. Height, weight, height velocity, weight velocity and a change in systolic blood pressure from the recumbent to the standing position (ΔSBP) were recorded. Early-morning urine for urinary free cortisol (UFC) and urinary cortisol metabolites (UCM) was collected. UFC was analysed by both a chemiluminescent assay and gas chromatography/mass spectrometry (GC-MS). Morning serum cortisol and adrenocorticotropic hormone (ACTH) levels were measured. The overnight metyrapone test was performed if the fasting morning serum cortisol was >83 nmol/l. HPAS was diagnosed if the ACTH failed to rise >100 pg/ml after metyrapone. Spearman correlation coefficients (r) were calculated between the post-metyrapone ACTH and each variable. A receiver-operating characteristics (ROC) curve was drawn for the most promising test, and the diagnostic performance was calculated., Results: All clinical and biochemical parameters investigated were weakly and non-significantly correlated with the post-metyrapone ACTH, except for the morning serum ACTH (r = 0.68; p <0.001). The best discrimination between those who have and those who do not have HPAS is a morning serum ACTH level of 11.7 pg/ml. This corresponds to a sensitivity of 0.89 (0.57-0.98), a specificity of 0.77 (0.53-0.90), a positive predictive value of 0.67 (0.39-0.87), a negative predictive value of 0.93 (0.69-0.99), an accuracy of 0.81 (0.61-0.94), a positive likelihood ratio of 3.78 (1.68-9.49) and a negative likelihood ratio of 0.15 (0.03-0.60)., Conclusions: The morning serum ACTH level was found to be the most useful screening test to detect HPAS in this sample of children receiving ICS ± NS. A larger study should be undertaken to refine the diagnostic precision of the morning serum ACTH level., (© 2011 John Wiley & Sons A/S.)

Background: Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC)., Methods: This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30)., Results: Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306)., Conclusions: Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.

Background: The long-term effects of perinatal growth and corticosteroid exposure on adrenal steroid concentrations in adults born very preterm are uncertain., Objectives: To examine the effect of birth weight, early postnatal growth, and pre- and postnatal corticosteroid administration on serum adrenal steroids in 19-year-old subjects born very preterm., Design and Methods: Subjects born before 32 weeks of gestation in The Netherlands participating in the Project on Preterm and Small for Gestational Age Infants (POPS) were investigated at 19 years of age. Serum cortisol, DHEA sulfate (DHEAS), and androstenedione (Adione) concentrations were measured in 393 out of 676 eligible subjects, compared with controls, and associated with perinatal growth and pre- and postnatal corticosteroids administration using multiple linear regression analyses., Results: Serum DHEAS and Adione in men and women were higher than in controls. In the multiple regression analyses, birth weight SDS showed a statistically significant negative association with serum DHEAS concentrations in women (β: -0.865, 95% confidence interval (CI): -1.254 to -0.476) and in men (β: -0.758, 95% CI: -1.247 to -0.268) and with serum Adione concentrations in women (β: -0.337, 95% CI: -0.593 to -0.082). Early postnatal weight gain showed no association with any of measured adrenal markers. In women, serum Adione was associated with postnatal dexamethasone exposure (β: 0.932, 95% CI: 0.022 - 1.843)., Conclusions: Young adults born very preterm show elevated adrenal androgens, particularly when born small for gestational age. Postnatal corticosteroid administration is positively associated with serum Adione in young women.

Background: In patients with primary hyperaldosteronism, distinguishing between unilateral and bilateral adrenal hypersecretion is critical in assessing treatment options. Adrenal venous sampling (AVS) has been advocated by some to be the gold standard for localization of the responsible lesion, but there remains a lack of consensus for the criteria and the standardization of technique., Study Design: We performed a retrospective study of 114 patients with a biochemical diagnosis of primary hyperaldosteronism who all underwent CT scan and AVS before and after corticotropin (ACTH) stimulation. Univariate and multivariate analyses were performed to determine what factors were associated with AVS lateralization, and which AVS values were the most accurate criteria for lateralization., Results: Eighty-five patients underwent surgery at our institution for unilateral hyperaldosteronism. Of the 57 patients who demonstrated unilateral abnormalities on CT, AVS localized to the contralateral side in 5 patients and revealed bilateral hyperplasia in 6 patients. Of the 52 patients who showed bilateral disease on CT scan, 43 lateralized with AVS. The most accurate criterion on AVS for lateralization was the post-ACTH stimulation value. Factors associated with AVS lateralization included a low renin value, high plasma aldosterone-to plasma-renin ratio, and adrenal mass > or = 3 cm on CT scan., Conclusions: Because 50% of patients would have been inappropriately managed based on CT scan findings, patients with biochemical evidence of primary hyperaldosteronism and considering adrenalectomy should have AVS. The most accurate measurement for AVS lateralization was the post-ACTH stimulation value. Although several factors predict successful AVS lateralization, none are accurate enough to perform AVS selectively., (Copyright © 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

Context: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare and heterogeneous condition characterized by abnormal steroid production. Cortisol secretion can be regulated by aberrant hormone receptors., Objective: A large series of patients with AIMAH were evaluated to provide information on the prevalence and profile of aberrant regulations, in relation with the functional status., Design and Patients: Thirty-two consecutive patients with AIMAH were prospectively studied: 10 had a Cushing's syndrome (CS), and 22 had a subclinical CS (SCS)., Methods: A baseline endocrine evaluation was followed by an in vivo protocol in search of aberrant cortisol responses (seven provocative tests). An acute inhibition test with the somatostatin analog octreotide was also performed., Results: At least one aberrant cortisol response was identified in 28 of 32 (87%) patients. The overall prevalence of aberrant responses was independent of the functional status. Responses to the upright posture and to metoclopramide were frequently observed (67 and 56% respectively). A glucagon response was frequently observed in the SCS group (58%). A cortisol inhibition by octreotide was specifically found in the three CS patients who positively responded to the mixed meal, and was observed also in 12 of 13 (92%) patients with SCS., Conclusions: Cortisol responses indicative of aberrant receptor expression were highly prevalent in AIMAH. Thorough phenotyping of AIMAH may help uncover the underlying pathophysiology.

B-, H- and L-catepsine-like activity regarding Na-benzoyl-D,L-arginine-4-nitroanilide, L-leucine-4-nitroanilide and azocasein was studied in the blood plasma of patients with different diseases of thyroid, parathyroid and adrenal glands. It has been shown that the high H- catepsine-like activity confirming the activation of blood catepsin H secretion accompanied by the tissue growth under any pathology took place in the blood plasma of patients with all the above diseases. High B- catepsine-like activity in the blood plasma of patients with thyroid diseases was exceptionally fixed under the nodular forms of thyroid pathology, while the character of changes in L catepsine-like activity under these diseases was not so natural. In diaseses of the adrenal glands the changes in the B- and L-catepsine-like activity were only shown in the blood plasma of patients with cerebral layer tumors but not the gland cortex: B-catepsine-like activity increased in the blood plasma of patients with benign or malignant tumors, and L-catepsine-like activity decreased under benign tumor from chromaffin tissue. The established picture of changes in enzymatic activity in the blood plasma of patients does not allow to think that the determination of blood B- and L- catepsine-like activity can be recommended for obtaining additional information at diagnosis thyroid diseases.

Objective: The clinical symptoms of non-classic adrenal hyperplasia (NCAH) are the same as those in patients with polycystic ovary syndrome (PCOS). The aim of our study was to compare conventional corticoid treatment of NCAH with the effect of combined oral contraception (COC) administration (used in treatment of PCOS) on clinical and laboratory parameters of NCAH., Design: A prospective clinical study, cross-over design., Material and Methods: Since 1999 from 298 hyperandrogenic women, eight patients having 21-hydroxylase deficient NCAH have been identified. They were divided equally into two groups according to the order of application treatment modality (hydrocortison vs. COC). Effect of treatment of both modalities on clinical symptoms (hirsutism - FG score, acne, menstrual cycle) and laboratory parameters (testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulphate, sex hormone binding globulin (SHBG)) were evaluated., Results: We observed the decrease of plasma androgens in both groups, which did not differ significantly. Significant increase of SHBG (i.e. decrease of free androgens) was, however, documented in each period with COC administration. Not surprisingly, improvement of the most frequent clinical symptom of NCAH in our study group, oligomenorrhea, was also more apparent in COC. Hirsutism was only a minor problem in our group that did not allow to evaluate treatment effect of both the modalities, Conclusion: Our results indicate that ovarian suppression by COC administration can effectively suppress androgen production and improve the most frequent clinical symptom (irregular cycle) in patients with NCAH, so can be successfully used for the treatment at least under basal conditions. Whether corticosteroid substitution can be limited to patients with inadequate response to COC on plasma androgen levels or with signs of adrenal insufficiency requires further data.

Introduction: Neoangiogenesis appears to be an important event in tumour invasion and in the formation of metastases in many endocrine-related human cancers. Vascular endothelial growth factor (VEGF) is a glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells and acts through VEGF receptors. The aim of the study was to evaluate the plasma blood concentrations of VEGF, sVEGFR1, and sVEGFR2 in patients with benign and malignant adrenal tumours treated by surgery., Material and Methods: We studied the blood before surgery of 41 patients with adrenal cortex tumours and 10 normal subjects without hormonal or CT/USG pathology of the adrenal glands (controls). We studied the blood after adrenalectomy of 16 patients with tumours of the adrenal cortex., Results: Concentrations of VEGF, sVEGFR1 and sVEGFR2 in blood plasma before as well as 30 days after surgery were evaluated by ELISA. VEGF blood concentrations before surgery did not differ in the patients with the cortical tumours as compared to the controls. After surgery VEGF concentrations decreased among the patients, taken in total, with adrenal cortex tumours and cortical adenomas. Before surgery sVEGFR1 blood concentrations were increased in the patients with Conn's syndrome only in comparison with the controls. After surgery, sVEGFR1 concentrations decreased significantly in the group with cortical adenomas only. Before and after surgery sVEGFR2 blood concentrations did not differ between the groups of patients studied and the controls., Conclusions: Peripheral blood concentrations of VEGF and its receptors cannot be clinically valuable markers that discriminate between benign and malignant adrenocortical tumours before and after adrenalectomy.

Objective: Salivary cortisol in the assessment of glucocorticoid related disorders. DESIGN-METHODS: Serum and salivary cortisol were measured in 189 patients (22 Cushing's syndrome, 67 pseudo-Cushing, 11 Addison's disease, 89 controls) at 8:00 and 24:00 h., Results: Serum and salivary cortisol correlated in the whole study population (r=0.62, p=0.000). Morning serum and saliva cortisol in Addison's disease were lower than in controls (6.74+/-1.69 vs 22.58+/-1.78 microg/dL, and 0.15+/-0.25 vs 0.67+/-0.12 microg/dL) (p<0.001). Morning serum cortisol was similar in controls and patients with Cushing's syndrome or pseudo-Cushing (22.58+/-1.78 vs 13.96+/-6.02 vs 16.13+/-1.69 microg/dL). Morning serum and salivary cortisol at 8:00 had the same sensitivity to distinguish patients with Addison's disease from healthy controls. 24:00 am serum cortisol in controls (2.61+/-0.20 microg/dL) was lower than in the pseudo-Cushing group (6.53+/-0.77 microg/dL, p<0.001) and in Cushing's syndrome (10.90+/-2.36 microg/dL, p=0.003). 24:00 am salivary cortisol in controls (0.0025+/-0.001 microg/dL) was lower than in patients with Cushing's syndrome (0.58+/-0.11 microg/dL, p<0.001) and those higher than in patient with pseudo-Cushing (0.10+/-0.06 microg/dL, p=0.001). Both salivary cortisol and serum cortisol presented high specificity (82% and 100%) to detect Cushing's syndrome but salivary cortisol higher sensitivity (saliva 88% and serum 50%)., Conclusion: Morning salivary cortisol is as good as serum as screening test for patients with Addison's disease and nighttime salivary cortisol is more adequate than serum in the screening of Cushing's syndrome.

Incidentally discovered adrenal masses are diagnosed with increasing frequency, especially among patients with hypertension. Thus, a reliable screening test for primary hyperaldosteronism (PA) is essential to avoid unnecessary diagnostic procedures to this population. The aim of the present study is the evaluation of aldosterone to renin ratio (ARR), using plasma renin concentration, in the diagnostic algorithm of patients with adrenal incidentaloma. A total of 123 individuals were studied: 17 patients with proven PA (age 55.5 +/- 1.4 years), 27 patients with nonfunctioning adrenal incidentaloma (age 60.3 +/- 1.8 years, 14 hypertensives and 13 normotensives) and 79 control subjects (age 58.7 +/- 1.4 years, 27 hypertensives and 52 normotensives). A receiver operating characteristic (ROC) analysis disclosed that an ARR > or =32 combines a sensitivity of 100% with a specificity of 96.2% for the diagnosis of PA. No difference in AlphaRR between hypertensive and normotensive individuals harbouring an adrenal incidentaloma and hypertensive and normotensive controls was found. Patients with adrenal incidentalomas with subtle glucocorticoid hypersecretion demonstrated similar ARR compared to patients with normal cortisol secretion. In conclusion, ARR is reliable for the exclusion of PA in patients with adrenal incidentalomas. Furthermore, subtle aldosterone hypersecretion, as indicated by increased ARR, in patients with adrenal incidentalomas is not associated with the presence of hypertension or subtle glucocorticoid hypersecretion.

Context: Cortisol is an important catabolic hormone, but little is known about the metabolic effects of acute cortisol deficiency., Objective: The objective of the study was to test whether clinical symptoms of weight loss, fatigue, and hypoglycemia could be explained by altered energy expenditure, protein metabolism, and insulin sensitivity during cortisol withdrawal in adrenocortical failure., Design, Participants, and Intervention: We studied seven women after 24-h cortisol withdrawal and during replacement control during a 3-h basal period and a 3-h glucose clamp., Results: Cortisol withdrawal generated cortisol levels close to zero, a 10% decrease in basal energy expenditure, increased TSH and T(3) levels, and increased glucose oxidation. Whole-body glucose and phenylalanine turnover were unaltered, but forearm phenylalanine turnover was increased. During the clamp glucose, infusion rates rose by 70%, glucose oxidation rates increased, and endogenous glucose production decreased. Urinary urea excretion decreased by 40% over the 6-h study period., Conclusions: Cortisol withdrawal increased insulin sensitivity in terms of increased glucose oxidation and decreased endogenous glucose production; this may induce hypoglycemia in adrenocortical failure. Energy expenditure and urea loss decreased, indicating that weight and muscle loss in Addison's disease is caused by other mechanisms, such as decreased appetite. Increased muscle protein breakdown may amplify the loss of muscle protein.

Background: Measuring plasma adrenocorticotropic hormone (ACTH) is a key step in the differential diagnosis of hypothalamic-pituitary-adrenal disorders., Methods: The recently developed electrochemiluminescence Elecsys ACTH immunoassay (Roche Diagnostics, Mannheim, Germany) was evaluated at six clinical laboratories on the Modular E170 and/or the Elecsys 2010 (Roche Diagnostics) immunoanalysers., Results: The within-run and between-run imprecision was

Objective: The use of an intravenous catheter with a rest period has been recommended to avoid false-positive results for hyperprolactinaemia and false-negative results for hypocortisolaemia. We tested the relevance of this recommendation., Design: Plasma cortisol and prolactin levels were determined before (T-15) and after a 15-min rest period (T0) in 119 patients, 38 males (M) and 81 females (F). 52 of the 119 patients were known (K; 30 females and 22 males) and 67 unknown (UK; 49 females and 18 males) to the unit., Results: Prolactin was lower after rest in women (12.3+/-22.7 ng/l vs 11.7+/-22.5 ng/ml, P=0.03), but not in men (6.2+/-4.5 ng/ml at T-15 vs 5.8+/-3.2 ng/ml at T0, P=0.09), in the UK subgroup (10.6+/-20.7 ng/ml at T-15 vs 10.1+/-20.9 ng/ml at T0, P=0.06) and in the K subgroup (10.1+/-16.7 ng/ml at T-15 vs 9.7+/-15.8 ng/ml at T0, P=0.08). None of the patients with prolactin levels higher than 20 ng/ml at T-15 diminished its prolactin value below this cut-off value. Plasma cortisol levels were lower after rest in women (17.9+/-5.9 microg/dl at T-15 vs 16.5+/-6.1 microg/dl at T0, P<0.0001), in the UK subgroup (18+/-6.1 microg/dl at T-15 vs 16.6+/-6.4 microg/dl at T0, P=0.0003) but not in men (18+/-4.4 microg/dl at T-15 vs 17.5+/-5.8 microg/dl at T0, P=0.47) and in the K subgroup (17.8+/-4.6 microg/dl at T-15 vs 17+/-5.4 microg/dl at T0, P=0.13). At T0, 3.3% and 15% of patients presented values below the cut-off value of 10 microg/dl (276 nmol/l) and 17 microg/dl (470 nmol/l), respectively., Conclusion: These results don't justify intravenous catheterisation with a rest period for plasma prolactin determination in contrast with plasma cortisol determination.

There are limited data regarding the role of vascular endothelial growth factor (VEGF) in arterial hypertension. The aim of the present study was to determine some markers of vascular function, including VEGF, active renin and prostaglandin E2 (PGE2) in patients with endocrine hypertension. The study comprised: 30 patients with primary aldosteronism; 32 patients with active Cushing's syndrome; 19 patients with pheochromocytoma; 22 patients with essential hypertension and 24 healthy volunteers. VEGF was significantly elevated in all groups of patients as compared to the controls. VEGF levels in patients with Cushing's syndrome were significantly higher than those in patients with essential hypertension and primary aldosteronism. We did not find significant differences in VEGF levels between patients with Conn adenomas and idiopathic aldosteronism as well as between patients with Cushing's disease and Cushing's syndrome. PGE2 levels were not significantly different among the groups. Active renin was significantly the lowest in patients with primary aldosteronism and significantly the highest in those with pheochromocytoma compared to controls. The level of active renin in patients with primary aldosteronism was significantly lower than in patients with Cushing's syndrome and pheochromocytoma. In conclusion, VEGF levels were significantly elevated in patients with endocrine hypertension due to glucocorticoid, mineralocorticoid and/or catecholamine excess. The highest VEGF levels were detected in patients with Cushing's syndrome. The latter is associated with accelerated development of atherosclerosis and increased cardiovascular risk. VEGF might contribute to the cardiovascular risk in this disease. This effect was not likely to be PGE2 mediated.

Background: There may be a link among stress, adrenal medullary activation, and the development of hypertension. Obesity is characterized by sympathetic activation and predisposes to hypertension, but may be associated with low or normal adrenal medullary activity. We hypothesized that plasma epinephrine (E) levels and adrenal medullary responsiveness to mental stress are lower in overweight than in lean borderline hypertensive subjects., Methods: We compared groups of lean (n = 62) and overweight (n = 29) borderline hypertensive young men as well as lean (n = 36) and overweight (n = 7) normotensive young men from the same population. Plasma catecholamines and heart rate (HR) were measured at rest during a hyperinsulinemic glucose clamp and during mental arithmetic-induced stress., Results: Plasma norepinephrine (NE) and E, HR, and responses to stress were increased in borderline hypertensive subjects. Our results showed that NE was increased only in lean borderline hypertensive subjects at rest, but in overweight subjects as well during stress, with DeltaNE being similar in lean and overweight subjects. We found that E was higher in lean than in overweight borderline hypertensive subjects at rest and during stress (both P <.001), as were DeltaE and DeltaHR (both P <.05). Independent of BP status, body mass index was negatively related to E during stress (P <.01) and waist circumference negatively related to resting E (P <.001) and DeltaHR (P =.02)., Conclusions: Sympathetic neural activity and responsiveness are increased in borderline hypertensive young men, but measures of overweight are independently related to lower plasma E and HR responses. We suggest that adrenal medullary activation in borderline hypertension mainly characterizes lean subjects.

Once considered rare, primary aldosteronism (PAL) is now regarded as the commonest potentially curable and specifically treatable form of hypertension. At Greenslopes Hospital Hypertension Unit (GHHU), the decision in 1991 to screen all (and not just hypokalemic or resistant) hypertensives by aldosterone/renin ratio (ARR) testing led to a 10-fold increase in detection rate of PAL and four-fold increase in removal rate of aldosterone-producing adenomas (APAs). The GHHU/Princess Alexandra Hospital Hypertension Unit PAL series stands at 977 patients and 250 APAs removed with hypertension cured in 50-60% (remainder improved). Reliable detection requires that interfering medications are withdrawn (or their effects considered) before ARR measurement, and reliable methods (such as fludrocortisone suppression testing) to confirm PAL. Adrenal venous sampling is the only dependable way to differentiate APA from bilateral adrenal hyperplasia. Genetic testing has facilitated detection of glucocorticoid-remediable, familial PAL. Identification of mutations causing the more common familial variety described by GHHU in 1991 should further aid in detection of PAL.

We are reporting a child with congenital panhypopituitarism, in whom deficient fetal steroidogenesis was suspected prenatally because of undetectable estriol levels measured in the maternal triple-marker screen. No fetal abnormalities were detected by ultrasonography. Amniocentesis demonstrated a normal 46,XX karyotype. Measurement of maternal urinary steroids failed to show elevation in the excretion of the major precursor for estriol, 16 alpha-hydroxydehydroepiandrosterone, indicating that the fetus did not have steroid sulfatase deficiency (placental sulfatase deficiency), the most common genetic cause of extremely low estriol. The steroid analysis excluded other rare single gene defects, including aromatase deficiency and 17 alpha-hydroxylase deficiency. We therefore suspected that the cause of low estriol in this fetus was adrenal insufficiency. Postnatal evaluation was consistent with panhypopituitarism, characterized by deficiency of all anterior pituitary hormones. Because this screen is now offered to more than half the pregnant women in the United States, reports of low estriol levels have become increasingly common. Therefore, it is essential that physicians be familiar with the various etiologies, perform the appropriate antenatal evaluation to determine the specific cause, and closely monitor both mother and child ante- and postnatally.

Cystatin C is a low-molecular endogenous inhibitor of cysteic proteinases. Sets for immune-enzyme assay of cystatin C in human blood serum (KRKK, Slovenia) were made used of in the case study. The concentration of cystatin C (CCC) in blood serum was found to be higher in cases of certain hemoblastoses (Non-Hodgkin's disease, lymphogranulomatosis and multiple myeloma), with the highest concentration of the inhibitor being observed in patients with resistance to the conducted polychemotherapy and a poor prognostication. The treatment of Non-Hodgkin's disease and of lymphogranulomatosis brought about a normalized CCC in blood serum. It was suggested that CCC in blood serum reflects a nature of tumor growth and, obviously, it can be a criterion in assessing the therapy efficiency. The concentration of alpha 1-proteinases inhibitor remained unchanged before and after treatment.

We report a case of Cushing's syndrome due to ACTH-independent macro-nodular adrenal hyperplasia (AIMAH). The patient, a 51-year-old man, had been suffering from poorly controlled arterial hypertension for the previous 6 years and he complained of progressive weight gain, gynecomastia and impotence. Physical examination revealed classic cushingoid features. Endocrine basal assessment showed increased urinary free cortisol (264-600 micrograms/24 hr). Urinary steroid profile showed an increase of total 17-hydroxycorticosteroids (17-OHCS: 23 mg/24 hr), with a threefold increase of tetrahydrocortisol (THF:9.66 mg/24 hr) and of tetrahydrocorticosterone (THB: 1.35 mg/24 hr). Tetrahydrodesossicortisol was only slightly elevated (THS:0.67 mg/24 hr) and tetrahydrodesossicorticosterone was at the inferior limit of the normal range (THDOC: 0.03 mg/24 hr). Total 17-ketosteroids were decreased (17-KS: 3 mg/24 hr). Plasma cortisol level was elevated and without circadian rhythm (26-29 micrograms/dl in the morning, 26-28 micrograms/dl at 24:00 h). DHEAs and free testosterone levels were significantly reduced (106 ng/dl and 3.9 pg/ml respectively). ACTH was undetectable and unresponsive to CRH. Both dexamethasone and octreotide failed to suppress plasma cortisol levels. Abdomen computed tomography scan demonstrated bilaterally enlarged multinodular adrenal glands. Cerebral magnetic resonance revealed no alteration of the pituitary gland. The patient underwent bilateral adrenalectomy. On macroscopic examination, adrenal glands were occupied by multiple yellow nodules and their compressive weight was 190 g, with left adrenal heavier than the right one (120 g and 70 g respectively). Histologically, nodular lesions were predominantly composed of large clear cells, with small foci of "hybrid" cells and adipose tissue metaplasia. Reticularis zone was atrophic. In the immediate post-operatory course pulmonary embolism occurred, despite prophylaxis with low molecular weight heparin. After having recovered from this complication, the patient showed progressive regression of cushingoid status. The findings of increased THF/THS and THB/THDOC ratios were in agreement with a relative hyperfunction of 11-beta-hydroxylase "in vivo", which might have contributed to the hypercortisolism, in addition to the marked increase of secernent adrenal mass.

Immunochromatography has shown that human NOV (NOVH), a member of the CCN (CTGF/CYR61/NOV) family, forms a physiological complex with fibulin-1 in blood. We developed an enzyme immunoassay specific for NOVH and showed for the first time that the concentration of NOVH differs in each of these biological fluids. The normal concentration of NOVH circulating in the blood is 350-400 ng/ml, but this concentration varies with age. By using sera from patients with adrenal gland diseases we found that in vivo ACTH or glucocorticoids are not responsible for the high concentration of NOVH in this endocrine gland. However, the NOVH concentration was significantly modified in malignant adrenocortical tumors, but not in benign adrenocortical tumors. The concentration of NOVH was significantly decreased in patients suffering from astrocytomas or multiple sclerosis, two diseases of the nervous system. Thus, NOVH is a potentially useful marker for the diagnosis of these diseases.

The non-obese diabetic (NOD) mouse is a model of spontaneous type-1 diabetes used in the field of diabetes research. This study looked at the adrenal glands of NOD and control mice both indirectly in vivo for hormone secretion, and directly in vitro for histological examination. Adrenal glands were taken from NOD mice, of both sexes, at different ages and corticosterone and adrenocorticotropic hormone (ACTH) plasma levels evaluated by radioimmunoassay. There was evidence of lymphocytic infiltration of the adrenal glands, which however, was not accompanied by changes in corticosterone levels. There was a reduction in ACTH levels with age (R2 = 0.98). Mice from other strains (TFW, CBA and Balb/c) showed no lymphocytic infiltration in the adrenal glands and had lower levels of corticosterone than NOD mice of similar ages, but the differences were not significant. In conclusion, since the NOD mouse shows histological signs of adrenalitis, thyroiditis, sialitis and parathyroiditis, this animal can be regarded as a model to investigate mechanisms involved in diffuse lymphocytic infiltration of peripheral endocrine glands (polyendocrine autoimmunity). In addition, if diabetes in the NOD mouse is the result of a polyendocrine disorder rather than a process specific for diabetes, then this finding may have implications for attempts to prevent type-1 diabetes in humans.

Objective: The adrenal gland is the endocrine organ most commonly involved in patients infected with human immunodeficiency virus (HIV). It is important to recognize patients with adrenal insufficiency, because this disorder may be fatal if untreated. The incidence of adrenal insufficiency in critically ill HIV-infected patients is unclear, partly because different criteria are used to diagnose adrenal insufficiency. To help clarify the incidence of adrenal insufficiency in HIV-infected critically ill patients, we compared the incidence based on the stress cortisol concentration, low-dose corticotropin stimulation test, and high-dose corticotropin stimulation test., Setting: Medical intensive care unit., Patients: Twenty-eight critically ill patients with HIV, mean age 43 +/- 9 years; 20 were male; 54% died., Interventions: We performed a 1-microg (low-dose adrenocorticotropic hormone; LD-ACTH) and 249 microg (high-dose; HD-ACTH) corticotropin stimulation test in HIV-infected critically ill patients not receiving corticosteroids. According to results of the stress serum cortisol concentration and LD-ACTH and HD-ACTH tests, patients were classified as having adrenal insufficiency or as normal. The results of newly revised diagnostic criteria for adrenal insufficiency (i.e., stress cortisol concentration and cortisol response to LD-ACTH <25 microg/dL) were compared with the traditional criteria (i.e., stress cortisol level and response to HD-ACTH <18 microg/dL). In addition, the associations between adrenal insufficiency and the CD4 count, human cytomegalovirus antigenemia, and other risk factors for adrenal insufficiency were determined., Measurements and Main Results: When we used a stress cortisol concentration <18 microg/dL as the sole diagnostic threshold for diagnosis of adrenal insufficiency, 50% (14 of 28) of patients had adrenal insufficiency. The incidence was 75% (21 of 28) when we used a diagnostic threshold of <25 microg/dL for the stress cortisol concentration. When we used both the stress cortisol concentration and LD-ACTH test with a diagnostic cortisol threshold concentration <18 microg/dL, 21% (six of 28) had adrenal insufficiency. The incidence was 46% (13 of 28) when we used a cortisol diagnostic threshold concentration of <25 microg/dL. When we used both the stress cortisol concentration and the HD-ACTH stimulation test with a diagnostic cortisol threshold of <18 microg/dL, 7% (two of 28) had adrenal insufficiency. The incidence of adrenal insufficiency was 21% (six of 28) with a cortisol diagnostic threshold value of <25 microg/dL. Human cytomegalovirus antigenemia was the only variable assessed that was associated with adrenal insufficiency., Conclusion: There is a high incidence of adrenal insufficiency in critically ill HIV-infected patients that varies with the criteria used to diagnose adrenal insufficiency. The LD-ACTH stimulation test is more sensitive than the high-dose test for diagnosing adrenal insufficiency in this population. Because of the high incidence of inadequate adrenal function, all critically ill HIV-infected patients should undergo an evaluation for adrenal insufficiency with the stress cortisol concentration and LD-ACTH stimulation tests.

Background: The short synacthen test (SST) is the gold standard investigation for the evaluation of adrenal insufficiency and is also frequently used for the evaluation of the hypothalamic-pituitary-adrenal (HPA) axis. The 0900-h serum cortisol concentration has also been evaluated as an indication of cortisol reserve, and a result > 450 nmol/L is highly suggestive of a normal serum cortisol response to the insulin tolerance test, while no patient with a 0900-h serum cortisol < 100 nmol/L had a sufficient response. The aim of this study was to determine if the number of inappropriate SSTs could be reduced if a 0900-h serum total cortisol was done prior to the dynamic function test., Method: Two hundred and ten SSTs were performed at 0900 h and the response at 30 min evaluated., Results: Of the 210 SST, 151 (71%) demonstrated a maximum response at 30 min of serum cortisol > 550 nmol/L. All the patients with a 0900-h serum cortisol > 500 nmol/L had an adequate response ( > 550 nmol/L), while no patient with a 0900-h serum cortisol of < 100 nmol/L had an adequate SST response. Twenty one per cent of patients were shown to have had an unnecessary invasive procedure., Conclusion: We conclude that the SST is of little added value in patients with a 0900-h serum cortisol of less than 100 nmol/L or more than 500 nmol/L and it should be included in the appropriate protocols for endocrine investigation.

Objective: To characterize the clinical course of adrenal hemorrhage (AH) by using a systematic review of the presentation, associated conditions, and outcomes in patients with AH seen at our institution between 1972 and 1997 (a 25-year period)., Patients and Methods: A computer search of recorded dismissal diagnoses identified 204 patients with a diagnosis of AH, but only 141 fulfilled our study criteria. Their records were analyzed systematically by presentation, bilateral or unilateral hemorrhage, corticosteroid treatment, and survival., Results: AH is a heterogeneous entity that occurs in the postoperative period, in the antiphospholipid-antibody syndrome, in heparin-associated thrombocytopenia, or in the setting of severe physical stress and multiorgan failure. Standard laboratory evaluation is not helpful in establishing the diagnosis. Of the 141 cases of AH, 78 were bilateral, and 63 were unilateral. Corticosteroid treatment in situations of severe stress or sepsis had little effect on outcome (9% vs. 6% survival with and without corticosteroid treatment, respectively). This is in sharp contrast to AH occurring postoperatively (100% vs. 17% survival with or without treatment, respectively) or in the antiphospholipid-antibody syndrome (73% vs. 0% survival, respectively)., Conclusions: A high index of suspicion is required to make a timely diagnosis of AH. Fever and hypotension in the appropriate clinical setting necessitate further investigation. Although the diagnosis of AH is infrequently made while the patient is alive, appropriate imaging techniques are useful for establishing a timely diagnosis. In severe physical stress or sepsis, AH may be a marker of severe, preterminal physiologic stress and poor outcome.

Introduction: Endocrine alterations associated with chronic renal failure have been reviewed recently. Some of these alterations are of clinical relevance. The aim of this study was to investigate the effect of renal transplantation on the endocrine system of the adrenal gland of the transplant recipients., Methods: The serum angiotensin-converting enzyme (SACE), plasma renin (PR) and plasma aldosterone (PA) were examined in 30 patients before and after renal allotransplantation. Additionally measured parameters were blood pressure, serum creatinine, potassium, sodium, the duration of dialysis and immunosuppressive medication., Results: Six weeks after renal transplantation, serum creatinine decreased from 820.07 +/- 172.01 to 138.12 +/- 67.54 micromol/l. In the same period, serum potassium decreased from 5.42 +/- 0.89 to 4.17 +/- 0.42 mmol/l. PA and PR decreased from 1,150.84 +/- 976.06 to 233.52 +/- 217.07 micromol/l, and from 121.07 +/- 100.12 to 26.16 +/- 10.86 microU/ml, respectively. SACE decreased from 0.21 +/- 0.21 to 0.13 +/- 0.11 micromol/l. No significant correlation was seen with blood pressure, serum sodium, the duration of dialysis and immunosuppressive drugs. Additionally, 2 patients with acute renal graft dysfunction showed significant increases in PR and PA. After successful treatment both levels declined very quickly to prerejection levels. Patients after binephrectomy show no elevation in PR (5-47 microU/ml) or PA (21-416 micromol/l) neither before nor after renal transplantation., Conclusions: We conclude that renal transplantation has profound effects on the recipient's renin-angiotensin-aldosterone system. Because of the rapid depression after renal transplantation, it does not appear to be involved in the pathogenesis of post transplantation hypertension but may reflect a role for repair processes after renal allotransplantation., (Copyright 2001 S. Karger AG, Basel.)

By means of ultra and cytochemical study the catecholamine inserts in erythrocytes look like dark lumps and beads the size and quantity of which being directly proportional to the sympathetic adrenaline system functional state. Under the conditions of catecholamine shortage the inserts reducing to fragments occurs and under catecholamine growth the increase in inserts size takes place. In both cases the erythrocyte structure disorder has been observed. Cytochemical method of catecholamine detection in erythrocytes also allows simultaneously to determine the erythrocyte morphological state.

The short ACTH test is used in evaluating the hypothalamo-pituitary-adrenal axis (HPA-axis) in preterm neonates after dexamethasone treatment. This test mainly examines primary adrenal suppression but is also used as a method to test secondary adrenal insufficiency because long-term deprivation of ACTH causes atrophy of the adrenal cortex. The CRH test, on the other hand, directly examines the function of the pituitary. We tested 18 infants in the neonatal intensive care unit with both the ACTH test and the CRH test to determine which of these two tests more reliably demonstrates HPA-axis suppression. One patient had normal responses both in the ACTH test and in the CRH test when the limit of 360 nmol/L was used as a sign of proper cortisol secretion. In four cases the patients' cortisol secretion would have been regarded as normal by the low-dose ACTH test, whereas the CRH test did not show an adequate cortisol response. In conclusion, the ACTH test did not reliably indicate HPA-axis suppression after a short (<2 weeks) course of dexamethasone therapy in this study. Therefore, whether the infant is or will be under acute stress after short glucocorticoid treatment, ensuring adequate cortisol secretion with the CRH test should be considered.

A low plasma ACTH response to insulin-induced hypoglycemia and an exaggerated and delayed plasma ACTH response to CRH stimulation have been considered as an indicator of hypothalamic hypopituitarism. We report a case of hypothalamic adrenal insufficiency which manifested normal ACTH response to insulin-induced hypoglycemia. This case provides important information to categorize hypothalamic adrenal insufficiency caused by abnormal regulation of CRH release.

Adrenomedullin was originally discovered in human pheochromocytoma but is now known to be widely distributed in various organs. Adrenomedullin is a potent vasodilatator peptide that exerts major effects on cardiovascular function. Plasma adrenomedullin concentration is increased in patients with cardiovascular disease such as hypertension, congestive heart failure, myocardial infarction, renal failure and other diseases. The present review summarizes the recent advances on adrenomedullin research and demonstrates that adrenomedullin is one of the important vasoactive peptides involved in the physiology and pathophysiology of cardiovascular system.