Approach to the Patient with an Incidental Adrenal Mass.

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.

Assessment of Glycometabolism Impairment and Glucose Variability Using Flash Glucose Monitoring System in Patients With Adrenal Diseases.

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 ß-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 ß-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.

Patients with extra-adrenal malignancies and adrenal lesions have similar rates of subclinical hypercortisolism compared with patients with true adrenal incidentalomas.

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.

Adrenal hemorrhage: A single center experience and literature review.

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.

Adrenal disorders: Is there Any role for vitamin D?

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.

Mass spectrometry theory and application to adrenal diseases.

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.

Brief report: adrenal autoimmunity in primary Sjögren's syndrome.

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.

Hypothalamic-pituitary-adrenal axis suppression in asthmatic children on inhaled and nasal corticosteroids: is the early-morning serum adrenocorticotropic hormone (ACTH) a useful screening test?

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.

Aberrant cortisol responses to physiological stimuli in patients presenting with bilateral adrenal incidentalomas.

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.

Associations among systemic blood pressure, microalbuminuria and albuminuria in dogs affected with pituitary- and adrenal-dependent hyperadrenocorticism.

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.

Consequences of adrenal venous sampling in primary hyperaldosteronism and predictors of unilateral adrenal disease.

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.

[B-, H- and L-cathepsin-like activity in blood plasma of patients with diseases of the thyroid, parathyroid and adrenal glands].

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.

Peripheral blood concentrations of vascular endothelial growth factor and its soluble receptors (R1 and R2) in patients with adrenal cortex tumours treated by surgery.

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.

The aldosterone to renin ratio in the evaluation of patients with incidentally detected adrenal masses.

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.

The use of intravenous catheterisation with a rest period is useful for determination of plasma cortisol levels but not plasma prolactin levels.

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.

Multicenter evaluation of a rapid electrochemiluminescent adrenocorticotropic hormone (ACTH) immunoassay.

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

Primary aldosteronism--careful investigation is essential and rewarding.

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.

Vascular endothelial growth factor (VEGF), prostaglandin E2(PGE2) and active renin in hypertension of adrenal origin.

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.

Congenital hypopituitarism as a cause of undetectable estriol levels in the maternal triple-marker screen.

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.