Ioannis Androulakis

High prevalence of autonomous cortisol and aldosterone secretion from adrenal adenomas

Objectives  Previous studies based on standard endocrine testing have shown a variable incidence of autonomous cortisol secretion (ACS) or autonomous aldosterone secretion (AAS) in patients with single adrenal adenomas (SAA). We tested whether the use of appropriate controls and modification of standard testing, aiming at eliminating interference from endogenous ACTH, reveals previously undetected subtle ACS and AAS by SAA.

The clinical significance of adrenal incidentalomas

Eur J Clin Invest 2011; 41 (5): 552–560

PROGRESS IN ALDOSTERONISM: A review of the prevalence of primary aldosteronism in pre-hypertension and hypertension

Primary aldosteronism (PA) secondary to excessive and/or autonomous aldosterone secretion from the renin-angiotensin system accounts for ∼10% of cases of hypertension and is primarily caused by bilateral adrenal hyperplasia (BAH) or aldosterone-producing adenomas (APAs). Although the diagnosis has traditionally been supported by low serum potassium levels, normokalaemic and even normotensive forms of PA have been identified expanding further the clinical phenotype. Moreover, recent evidence has shown that serum aldosterone correlates with increased blood pressure (BP) in the general population and even moderately raised aldosterone levels are linked to increased cardiovascular morbidity and mortality. In addition, aldosterone antagonists are effective in BP control even in patients without evidence of dysregulated aldosterone secretion. These findings indicate a higher prevalence of aldosterone excess among hypertensive patients than previously considered that could be attributed to disease heterogeneity, aldosterone level fluctuations related to an ACTH effect or inadequate sensitivity of current diagnostic means to identify apparent aldosterone excess. In addition, functioning aberrant receptors expressed in the adrenal tissue have been found in a subset of PA cases that could also be related to its pathogenesis. Recently a number of specific genetic alterations, mainly involving ion homeostasis across the membrane of zona glomerulosa, have been detected in ∼50% of patients with APAs. Although specific genotype/phenotype correlations have not been clearly identified, differential expression of these genetic alterations could also account for the wide clinical phenotype, variations in disease prevalence and performance of diagnostic tests. In the present review, we critically analyse the current means used to diagnose PA along with the role that ACTH, aberrant receptor expression and genetic alterations may exert, and provide evidence for an increased prevalence of aldosterone dysregulation in patients with essential hypertension and pre-hypertension.

High prevalence of autonomous aldosterone secretion among patients with essential hypertension

Eur J Clin Invest 2011; 41 (11): 1227–1236

Polycystic ovaries and the polycystic ovary syndrome phenotype in women with active acromegaly

Background  Previous retrospective studies have suggested that women with acromegaly may present with menstrual irregularity and symptoms/signs of hyperandogenism, a phenotype similar to that of the polycystic ovary syndrome (PCOS).

Stress-induced Aldosterone Hyper-Secretion in a Substantial Subset of Patients With Essential Hypertension

CONTEXT Aldosterone (ALD) secretion is regulated mainly by angiotensin II, K(+), and adrenocorticotropic hormone (ACTH). Mineralocorticoid receptor antagonists (MRAs) have effectively been used for the treatment of patients with hypertension who do not have primary aldosteronism (PA). OBJECTIVE We tested whether chronic stress-related ACTH-mediated ALD hypersecretion and/or zona glomerulosa hypersensitivity could be implicated in the pathogenesis of essential hypertension (ESHT). PATIENTS AND METHODS One hundred thirteen hypertensives without PA and 61 normotensive controls underwent an ultralow-dose (0.03-μg) ACTH stimulation and a treadmill test. Patients with ALD hyper-response according to the cutoffs obtained from controls received treatment with MRAs and underwent genomic DNA testing for the presence of the CYP11B1/CYP11B2 chimeric gene and KCNJ5 gene mutations. A control group of 22 patients with simple ESHT received treatment with MRAs. RESULTS Based on the cutoffs of ALD and aldosterone-to-renin ratio (ARR) post-ACTH stimulation obtained from controls, 30 patients (27%) exhibited an ALD but not cortisol (F) hyper-response (HYPER group). This group had no difference in basal ACTH/renin (REN) concentrations compared with controls and the 83 patients with hypertension (73%) without an ALD hyper-response to ACTH stimulation. Patients in the HYPER group demonstrated significantly higher ALD concentrations, ARR, and ALD/ACTH ratio (AAR) in the treadmill test. Treatment with MRAs alone produced normalization of blood pressure in these patients whereas patients with hypertension with neither PA nor ALD hyper-response to ACTH stimulation who served as a control group failed to lower blood pressure. Also, two novel germline heterozygous KCNJ5 mutations were detected in the HYPER group. CONCLUSIONS A number of patients with hypertension without PA show ACTH-dependent ALD hyper-secretion and benefit from treatment with MRAs. This could be related to chronic stress via ACTH hyper secretion and/or gene-mutations increasing the zona glomerulosa responsiveness to excitatory stimuli.

Hepatic steatosis in young lean insulin resistant women with polycystic ovary syndrome

OBJECTIVE To investigate the presence of nonalcoholic fatty liver disease (NAFLD) in young lean women with polycystic ovary syndrome (PCOS) and insulin resistance (IR). DESIGN Case control study. SETTING Women with PCOS and healthy controls in a metabolic day ward. PATIENT(S) Seventeen young lean women with PCOS and 17 matched controls were studied prospectively. INTERVENTION(S) Fasting blood and a glucose tolerance test. Ovarian and liver ultrasonography, and computed tomography (CT) of the liver (women with PCOS only). MAIN OUTCOME MEASURE(S) Anthropometric variables, biochemical and hormonal parameters, and several IR indices were determined. Hepatic lipid content was assessed with ultrasonography and CT of the liver. RESULT(S) Women with PCOS had higher androgen levels, and the IR indices, glucose and insulin area under the curve, QUICKI, MATSUDA, and HOMA, compared to controls. In addition to IR, women with PCOS had normal aminotransferase levels, and higher, although within the normal range, alkaline phosphatase levels compared with controls. Women with PCOS had no evidence of NAFLD by either ultrasonography or CT of the liver. CONCLUSION(S) Young lean women with PCOS and IR do not have evidence of NAFLD. Because of the presence of IR, follow-up is required to determine whether they are at risk of developing NAFLD.

Visceral adiposity index (VAI) is related to the severity of anovulation and other clinical features in women with polycystic ovary syndrome

The clinical phenotype of polycystic ovary syndrome (PCOS) includes reproductive and hormonal aberrations. Visceral adiposity index (VAI) is an indicator which could connect hyperandrogenism and anovulation. The objective was to evaluate the relationship between VAI, menstrual disorders and hormonal, biochemical and ultrasound parameters in women with PCOS.

Cough affects Quality of Life in asthmatic children aged 8-14 more than other asthma symptoms

BACKGROUND Asthma may influence childrens health-related quality of life (QoL) differently by various symptoms, at different severity. The primary aim of this study was to evaluate the QoL in children with asthma and describe the impact of each asthma symptom on the childs well-being at different severity levels. MATERIAL AND METHODS Two hundred randomly selected children and one of their parents who consulted an outpatient asthma clinic, participated in the study. Qol was assessed with DISABKIDS-Smiley measure for children aged 4-7 years and with DISABKIDS DCGM-37 and Asthma Module for children 8-14 year old. RESULTS Most of the children suffered from mild or moderate persistent asthma. Children with uncontrolled asthma stated lower QoL compared to partly controlled or controlled in both age groups (p < 0.05 in all domains). Cough appeared to affect QoL of 8-14 year olds more than other symptoms, especially in girls. In younger children, sex (boys, p = 0.039), age (p = 0.045), proxy sex (father, p = 0.048), frequency of doctor visits (4-6 months, p = 0.001), use of beta-2 agonists (p = 0.007) and fathers smoking habits (p = 0.015) were associated with the QoL of coughing children but no correlation between cough and QoL was detected. In the 8-14 year age group coughers reported lower QoL compared to their counterparts; moreover, cough was found to affect QoL more than other symptoms (p < 0.05 in all domains). CONCLUSIONS Cough has a direct effect on asthmatic childrens QoL but there is still an obvious need for research to reveal all the determinats of this effect.

The functional status of incidentally discovered bilateral adrenal lesions

Objective  To investigate autonomous cortisol and aldosterone secretion and insulin resistance (IR) indices, in patients with incidentally discovered bilateral adrenal lesions (BA).