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Aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion are reported in an increasing number of patients. Five aldosterone-producing adenomas from patients with primary aldosteronism and subclinical hypercortisolism were examined. The aims of our study were: (1) to analyze pathological features and immunohistochemical expression of CYP11B1 (11β-hydroxylase) and CYP11B2 (aldosterone synthase) in these tumors; (2) to investigate somatic mutations involved in adrenal steroid hypersecretion and/or tumor growth. Archival micro-dissected paraffin-embedded slides from tumor specimens were used for histological and molecular studies. Immunohistochemistry was performed using monoclonal anti-CYP11B1 and anti-CYP11B2 antibodies. Cellular composition was determined by examining for known features of zona fasciculata and zona glomerulosa, and immunoreactivity for CYP11B1 and CYP11B2 by McCarty H-score. Spot regions for mutations in KCNJ5, ATP1A1, ATP2B3, CACNA1D, PRKACA, and CTNNB1gene sequences were evaluated. Four APAs showed a predominant (≥50%) zona fasciculata-like cell pattern: one tumor had CYP11B1 H-score = 150, no detectable CYP11B2 expression, and harbored a PRKACAp.Leu206Arg mutation (that we have reported previously elsewhere), one had no CYP11B1 expression, CYP11B2 H-score = 40, and no mutations; the remaining two adenomas had high CYP11B1 H-score (160 and 240, respectively) and low CYP11B2 H-score (30 and 15, respectively), with the latter harboring a CTNNB1p.Ser45Phe activating mutation. One of five aldosterone-producing adenomas had a predominant zona glomerulosa-like pattern, CYP11B1 H-score = 15, CYP11B2 H-score = 180, and no mutations. The majority of aldosterone-producing adenomas with concurrent subclinical cortisol hypersecretion were composed mainly of zona fasciculata-like cells, while CYP11B1 and CYP11B2 immunostaining demonstrated clear heterogeneity. In a subset of cases, different somatic mutations may be involved in hormone excess and tumor formation.

L’aldosterone ha un ruolo fisiologico ben riconosciuto nella regolazione dell’omeostasi idrosalina. Più recentemente è stato definito un suo ruolo fisiopatologico nel danno cardiovascolare attraverso complessi meccanismi di regolazione e risposte biologiche/cliniche. Sono state descritte azioni dirette infiammatorie, profibrotiche e di danno endoteliale a livello di cuore e vasi, e vi sono evidenze di effetti cardiovascolari mediati da meccanismi metabolici e dal sistema nervoso centrale. Studi su modelli animali e nell’uomo hanno dimostrato il ruolo protettivo degli antagonisti del recettore mineralcorticoide sulle complicanze cardio-metaboliche.

Although unilateral primary aldosteronism is the most common surgically correctable cause of hypertension, no standard criteria exist to classify surgical outcomes. We aimed to create consensus criteria for clinical and biochemical outcomes and follow-up of adrenalectomy for unilateral primary aldosteronism and apply these criteria to an international cohort to analyse the frequency of remission and identify preoperative determinants of successful outcome.

To differentiate the impact of insulin levels/resistance per se from that of excess weight on blood pressure (BP) daily changes, we evaluated, using 24-h ambulatory blood pressure monitoring (ABPM), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a cohort of young normotensive patients affected by polycystic ovary syndrome (PCOS). A cross-sectional study was performed. Fifty-four patients were studied according to (a) insulinemic state: 32 hyperinsulinemic and/or insulin-resistant (h-INS) and 22 normoinsulinemic (n-INS) patients; and (b) body mass index (BMI): 22 obese (BMI > 30) and 32 lean (18.0 < BMI < 24.9) patients. Each subject’s SBP and DBP and heart rate (HR) were measured by ABPM. Supine and upright plasma renin activity (PRA), and aldosterone levels were also assayed. Patients in the h-INS group showed higher 24-h, daytime, and nighttime diastolic blood pressure (DBP), higher nighttime systolic blood pressure (SBP) levels, as well as an increased 24-h, daytime and nighttime HR, compared to both obese and lean patients in the n-INS group. In relation to BMI, only 24-h, daytime, and nighttime DBP were higher in obese than in lean patients. At variance, when both h-INS and obesity were considered, 24-h SBP and DBP were higher in h-INS obese subjects than in the other groups. In multivariate analysis, insulin (max peak), area under the curve of insulin and insulin sensitivity index was independently associated with SBP. (1) Within a normotensive range, hyperinsulinemia and/or insulin resistance influence daily BP variation more than obesity does, suggesting a pivotal role of insulin on BP control in PCOS; (2) altered insulinemic state and ABPM-derived higher nighttime BP and HR may represent early markers to identify PCOS subjects prone to high cardiovascular risk.

Cushing’s syndrome (CS) is associated with cardiovascular disease. The impact of the hemodynamic load on left ventricular mass (LVM) in patients with CS is not well known. In fact, the effects of 24-h blood pressure (BP) load and BP circadian rhythm on cardiac structure and function have not been studied. Aim of the present study has thus been to assess the presence of cardiac remodeling in patients with newly diagnosed CS, combining evaluation of cardiac remodeling and assessment of BP burden derived by 24-h ambulatory blood pressure monitoring (ABPM). 25 patients (4 M, 21 F) with CS underwent echocardiography in order to assess cardiac morphology and geometry (relative wall thickness—RWT). As controls, 25 subjects similar for demographic characteristics and 24-h BP were used. CS Patients were similar to controls by age, sex, mean 24-h BP, and body mass index. There was a significant increase in left ventricular mass (LVM; 44.4 ± 14.7 vs. 36.9 ± 10 g/m2.7, p= 0.03) and a significant increase in RWT (0.46 ± 0.07 vs. 0.41 ± 0.08, p= 0.02) in CS patients compared to controls. The prevalence of CS patients with pressure non-dipping profile was greater than that of controls (56 vs. 16 %, p< 0.05), with no significant association with LVM or geometry. 24-h urinary cortisol was not associated with LVM (r= 0.1, p= 0.5) or RWT (r= 0.02, p= 0.89) in the CS group. In conclusion, LVM and the concentric pattern of the left ventricle are relatively independent from 24-h BP load and profile (dipping/non-dipping) in CS patients.

Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation.

Cushing’s syndrome is associated with high cardiovascular morbility and mortality. Blood pressure (BP) variability within a 24-h period is increasingly recognized as an independent predictor of cardiovascular risk. The aim of our study was to investigate the short-term BP variability indices in Cushing’s syndrome. Twenty-five patients with Cushing’s syndrome (mean age 49 ± 13 years, 4 males; 21 Cushing’s disease and 4 adrenal adenoma patients) underwent 24-h ambulatory BP monitoring (ABPM) and evaluation of cardiovascular risk factors. Cushing patients were divided into 8 normotensive (NOR-CUSH) and 17 hypertensive (HYP-CUSH) patients and were compared with 20 normotensive (NOR-CTR) and 20 hypertensive (HYP-CTR) age-, sex-, and BMI-matched control subjects. Short-term BP variability was derived from ABPM and calculated as the following: (1) standard deviation (SD) of 24-h, daytime, and nighttime BP; (2) 24-h weighted SD of BP; and (3) average real variability (ARV), i.e., the average of the absolute differences between consecutive BP measurements over 24 h. In comparison with controls, patients with Cushing’s syndrome, either normotensive or hypertensive, had higher 24-h and daytime SD of BP, as well as higher 24-h weighted SD and ARV of BP (P= 0.03 to P< 0.0001). No difference in metabolic parameters was observed between NOR-CTR and NOR-CUSH or between HYP-CTR and HYP-CUSH subgroups. ABPM-derived short-term BP variability is increased in Cushing’s syndrome, independent of BP elevation. It may represent an additional cardiovascular risk factor in this disease. The role of excess cortisol in BP variability has to be further clarified.

The aim of the study was to assess the age-specific, sex-specific, and region-specific average sodium and potassium intake and its association with anthropometric characteristics in a sample of the Italian adult hypertensive population.

The aim of the study was to evaluate patients with Cushing’s syndrome the coronary flow reserve (CFR), an index of coronary microvascular function. Fifteen newly diagnosed patients with Cushing’s syndrome (1 male/14 females; mean age 45 ± 11 years), were selected for having no clinical evidence of ischemic heart disease. Twelve patients had pituitary-dependent Cushing’s disease and three had an adrenal adenoma. Fifteen subjects matched for age, sex, and major cardiovascular risk factors were used as controls. Coronary flow velocity in the left anterior descending coronary artery was investigated by transthoracic Doppler echocardiography at rest and during adenosine infusion. CFR was obtained as the ratio hyperemic/resting diastolic flow velocity. A reduced coronary reserve (hyperemic/resting ratio =2.5) was found in 5/15 Cushing patients and 4/15 controls. In all patients with abnormal CFR, epicardial coronary stenosis was excluded by multi-slice computed tomographic coronary angiography. CFR was inversely related to urinary cortisol in patients with endogenous hypercortisolism (Spearman’s rho = -0.57, P= 0.03), while no correlation was found in controls. Coronary microvascular function, as assessed by CFR, is pathologically reduced in a considerable number of patients with Cushing’s syndrome without clinical symptoms of ischemic heart disease and in the absence of epicardial coronary artery lesions, as well as in controls matched for cardiovascular risk factors. The presence of comorbidities can explain this early coronary abnormality in both patients and controls. Whether urinary cortisol may be a predictor of coronary microvascular function in the setting of patients with Cushing’s syndrome, needs further investigation.The aim of the study was to evaluate patients with Cushing’s syndrome the coronary flow reserve (CFR), an index of coronary microvascular function. Fifteen newly diagnosed patients with Cushing’s syndrome (1 male/14 females; mean age 45 ± 11 years), were selected for having no clinical evidence of ischemic heart disease. Twelve patients had pituitary-dependent Cushing’s disease and three had an adrenal adenoma. Fifteen subjects matched for age, sex, and major cardiovascular risk factors were used as controls. Coronary flow velocity in the left anterior descending coronary artery was investigated by transthoracic Doppler echocardiography at rest and during adenosine infusion. CFR was obtained as the ratio hyperemic/resting diastolic flow velocity. A reduced coronary reserve (hyperemic/resting ratio =2.5) was found in 5/15 Cushing patients and 4/15 controls. In all patients with abnormal CFR, epicardial coronary stenosis was excluded by multi-slice computed tomographic coronary angiography. CFR was inversely related to urinary cortisol in patients with endogenous hypercortisolism (Spearman’s rho = -0.57, P= 0.03), while no correlation was found in controls. Coronary microvascular function, as assessed by CFR, is pathologically reduced in a considerable number of patients with Cushing’s syndrome without clinical symptoms of ischemic heart disease and in the absence of epicardial coronary artery lesions, as well as in controls matched for cardiovascular risk factors. The presence of comorbidities can explain this early coronary abnormality in both patients and controls. Whether urinary cortisol may be a predictor of coronary microvascular function in the setting of patients with Cushing’s syndrome, needs further investigation.

Symptomatic primary hyperparathyroidism (PHPT) is associated with increased cardiovascular mortality. However, data on the association between asymptomatic PHPT and cardiovascular risk are lacking. We assessed coronary flow reserve (CFR) as a marker of coronary microvascular function in asymptomatic PHPT of recent onset.

Primary aldosteronism is the most frequent cause of secondary hypertension and is responsible for an increased risk of cardiometabolic complications. A concomitant subtle cortisol hyperproduction could enhance cardiovascular risk. We prospectively estimated the occurrence of subclinical hypercortisolism in primary aldosteronism patients.

The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is multifactorial, and the presence of insulin resistance is recognized as the pathophysiological hallmark of this condition. Arterial hypertension is referred as an insulin-resistant state, and insulin resistance may substantially contribute to the cardiovascular risk in this disorder. We examined the inter-relationship between insulin sensitivity, adiponectin levels, and NAFLD in hypertensive patients with different circadian blood pressure profiles.

Objectives: Nonalcoholic fatty liver disease (NAFLD) is a major cause of liver-related morbidity and is frequently associated with obesity and metabolic syndrome. The recently discovered hormone adiponectin is produced by adipose tissue, and low plasma adiponectin is considered a key factor in the development of the insulin resistance underlying metabolic syndrome. Animal studies suggest that adiponectin may protect against non-alcoholic steatohepatitis, but direct evidence in humans is lacking. We therefore conducted this study to assess the relationship between plasma adiponectin and nonalcoholic fatty liver disease to explore its role in the pathogenesis of this disease.Design and methods: We measured plasma adiponectin and anthropometric, biochemical, hormonal and metabolic correlates in a group of 17 NAFLD patients with diagnosis confirmed by biopsy, and 20 controls with comparable age, body-mass index and sex. Furthermore we compared plasma adiponectin in patients with simple steatosis and steatohepatitis.Results: Plasma adiponectin was significantly lower in NAFLD patients than controls (5.93±0.45 vs 15.67±1.60 ng/ml). Moreover, NAFLD patients were significantly more insulin resistant while having similar serum leptin. Adiponectin was similar in simple steatosis and in steatohepatitis (6.16±0.78 vs 5.69±0.49 ng/ml). An inverse correlation was observed between adiponectin and homeostatic model assessment (HOMA) of insulin resistance (P= 0.008), while adiponectin did not correlate with serum transaminases and lipid values.Conclusions: These data support a role for low circulating adiponectin in the pathogenesis of NAFLD and confirm the strict association between reduced adiponectin production by adipose tissue, NAFLD and insulin resistance.

Clinically silent adrenal masses discovered by imaging studies performed for unrelated reasons, i.e. adrenal incidentalomas, have become a rather common finding in clinical practice. However, only limited studies of incidence, prevalence, and natural history of adrenal incidentalomas are available. A comprehensive review of the literature shows the prevalence of adrenal incidentalomas to be 2.3% at autopsy and 0.5-2% at abdominal computed tomography scan. Most lesions are adrenocortical adenomas at histology, whereas the prevalence of adrenocortical carcinomas is relatively low. The risk of malignancy over time for masses defined as benign at diagnosis is estimated at about 1/1000, even though 5-25% of masses increase in size during follow-up. Hyperfunction develops in about 1.7% of cases and the risk is higher in patients with lesions larger than 3 cm. Cortisol hypersecretion is the most likely disorder that may ensue, and it remains subclinical in about two-thirds of cases. The lack of controlled studies precludes making specific management recommendations. Large perspective controlled studies to define the epidemiology, natural history, and possible associated morbidity of adrenal incidentalomas and their impact on the quality of life of patients are needed.

To detect the association of single polymorphisms of the renin–angiotensin–aldosterone system (RAAS), or different combinations thereof, with hypertension.

Background: Scarce data are available on the influence of psychological aspects on 24-hour ambulatory blood pressure patterns either in normotensive or hypertensive subjects. This study was designed to evaluate the relationship between psychological profile and changes in daytime/nighttime blood pressure rhythm. Methods:Nocturnal dipping was defined as the night/day ratio of ambulatory mean systolic and/or diastolic blood pressure ≤0.87. Three-hundred and two outpatients (M/F = 174/128; mean age = 49.8 years, SD = 13.6; range, 16–80 years)underwent 24-hour ambulatory blood pressure monitoring. They were administered a self-rating scale, the Psychosocial Index, as an indicator of stress, psychological distress, sleep disturbances, well-being, abnormal illness behavior and quality of life. There were 242 patients taking antihypertensive medication (146 adequately controlled and 96 not controlled) and 60 who were drug free (33 never-treated hypertensive and 27 normotensive subjects). Patients were divided according to the presence (n = 125) or absence (n = 177) of night blood pressure dipping. The two groups were compared using analysis of covariance, with age as a covariate. Results:Dippers had lower (p < 0.001) nocturnal systolic and diastolic blood pressure than nondippers, and higher (p < 0.05) daytime diastolic blood pressure. Patients with nocturnal blood pressure decline had a markedly higher (p < 0.001) level of stress than nondippers. When the sample was divided according to the presence or absence of hypertension, only subjects with normalblood pressure showed nocturnal dipping associated with increased stressful life circumstances. Conclusions:Our findings indicate that dippers experience stressful life circumstances, both in terms of life events and chronic stress. Thissuggests that stress-reducing techniques may be particularly helpful in the setting of hypertension characterized by nighttime blood pressure dipping.

During the past 30 years, there have been advances in understanding of the pathogenesis of Cushing's syndrome and in differential diagnosis of its various forms. Improved diagnostic tests and procedures have increased the ability to recognise even mild hypercortisolism and have provided the means to obtain an accurate diagnosis. Despite these advances, the occurrence of unusual clinical presentations and laboratory shortcomings may produce diagnostic problems and challenge clinical intuition. This article reviews recent pathogenic views, new tests, and new diagnostic problems in the evaluation of Cushing's syndrome. Atypical clinical presentations of hypercortisolism and some laboratory shortcomings that may confuse the diagnosis of Cushing's syndrome are also reported.

AbstractMajor depression is a common, life-threatening complication of Cushing’s syndrome, with no significant differences between pituitary-dependent and -independent forms. Little is known about the clinical correlates of depression; in particular, whether patients with Cushing’s disease and major depression show some clinical features that are distinctive compared to those who are not depressed. The occurrence of major depression according to DSM-IV criteria was ascertained in 162 patients with pituitary-dependent Cushing disease. Major depression occurred in 88 of the patients (54%). It was significantly associated with older age, female sex, higher pretreatment urinary cortisol levels, relatively more severe clinical condition, and absence of pituitary adenoma. Patients with Cushing’s disease and depression appeared to suffer from a more severe form of illness, both in terms of cortisol production and clinical presentation, compared to those who were not depressed. Because of these connections, the presence of depression is an important clinical feature that should not be neglected. The findings in this study may have implications for a better understanding of the pathophysiological role of depression associated with medical illness.

A juxtaglomerular cell tumor (JGCT) was found in a 40 year old woman. For 5 years she had mild hypertension, responding to classical anti-hypertensive treatment, then she became severely hypertensive. Two renal angiographies and a CT scan were reported as normal. A second CT scan and third selective renal angiography were diagnostic, associated with lateralization of renin in renal vein measurement. Light, electron microscopy and immunohistochemistry of the resected tumor confirmed the diagnosis of renin-secreting juxtaglomerular cell tumor of the kidney.

Contradictory findings have been reported about a possible causal relationship of life stress to Graves' disease. We evaluated this issue by investigating the occurrence of stressful life events in the year before the first signs of disease onset, using methods that have been found to be valid and reliable in psychosomatic research. Seventy consecutive patients with Graves' disease and a control group of 70 healthy subjects, matched for sociodemographic variables, were studied. Paykel's Interview for Recent Life Events (a semistructured research interview covering 64 life events) was administered to patients, not during the acute phase of illness but while on remission, by antithyroid drug treatment. Patients with Graves' disease reported significantly more life events compared to controls (p<0.001). They also had more independent events (p<0.001) and events that had an objective negative impact (p <0.001) according to an independent rater, unaware whether the events had occurred in patients or controls. All categories of events were found to be significantly more frequent in patients suffering from Graves' disease than in controls. By rigorous methods (inclusion of patients with Graves' disease only, careful dating of the onset of symptoms, accurate event definition, delay of the interview upon disease remission, use of a blind rater for judging independence and objective negative impact), our results support the concept of an excess of life events in Graves' disease. Stressful life events may affect the regulatory mechanisms of immune function in a number of ways. Within the extreme complexity of the phenomena implicated in the pathogenesis of autoimmune thyroid hyperfunction, our findings emphasize the role of emotional stress.

Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin-angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10−5, but not 10−8and 10−6mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10−5mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10−5mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone-secreting cells.

Patients with glucocorticoid–remediable aldosteronism (GRA) from 12 kindreds possess chimaeric gene duplications arising from unequal crossing–over, fusing regulatory sequences of steroid 11β–hydroxylase to coding sequences of aldosterone synthase. These chimaeric genes are specific for GRA and explain the biochemistry, physiology and genetics of this form of hypertension. Sites of crossing over range from intron 2 to intron 4. Most mutations have arisen independently from either sister or non–sister chromatid exchange between these genes, which are only 45 kilobases apart. The possibility of a susceptibility allele for GRA of Irish origin is suggested. These findings indicate the utility of a direct genetic test for this disorder.

The adrenal gland of various mammalian species has been shown to contain all the components of a functional renin-angiotensin system. We investigated the existence of this local system in human adrenal tissues surgically obtained. Eight normal adrenals (cortex and medulla) and 6 aldosterone-producing adenomas (aldosteronomas) were examined. Minced tissues were superfused over 270 min, and 15-min fractions were collected. In the perfusates, active renin was measured by immunoradiometric assay with human anti-renin monoclonal antibodies; immunoreactive angiotensin II/III and aldosterone were measured by radioimmunoassay. Adrenal tissues, either normal or pathological, were found concomitantly to release renin, angiotensin II/III and aldosterone. The pattern of this spontaneous release exhibited a pulsatile character. The total amount of renin and angiotensin II/III secreted during superfusion clearly exceeded the tissue content (determined by extraction). Addition of the angiotensin-converting enzyme inhibitor quinaprilat (4×10−5mol/l) in the superfusion caused a concomitant decrease of angiotensin II/III and aldosterone secretion by 3 normal tissues, and no change in 2 aldosteronomas. These data provide evidence that the human adrenal gland in vitro generates and releases both renin and angiotensin II/III, and support the hypothesis that locally formed angiotensin II/III may play a role as a paracrine regulator of physiological aldosterone secretion.

In view of a potential clinical use, we assessed the antiproliferative effect of paclitaxel on the human steroid-secreting NCI-H295 adrenocarcinoma cell line. By MTT, paclitaxel induced a dose-dependent inhibition of cell proliferation, with IC50 lower than blood levels of the drug achieved in patients treated for other malignancies. Cell exposure to paclitaxel for 24 h at the different IC50s produced a dose-responsive increase in DNA fragmentation, morphologically confirmed by electron microscopy. A time-dependent decrease in aldosterone, cortisol and testosterone was observed. Paclitaxel is an effective antiproliferative agent in this human adrenocortical carcinoma cell line. Apoptosis induced by the drug is involved in neoplastic cell death. A potential role of the drug in the treatment of patients with adrenocortical cancer could be considered.

The aim of this study was to assess the cardiovascular and hormonal responses to 1-desamino-8,D-arginine vasopressin (DDAVP) in hypertensive patients before and after non-selective β-blockade. We infused DDAVP at 400 ng/kg body weight for 10 min in nine subjects with mild essential hypertension before and 14 days after administration of nadolol at 80 mg/day. Blood pressure and heart rate were recorded, and blood was drawn at 0, 30 and 60 min for measurement of plasma renin activity, aldosterone, cortisol, noradrenaline, adrenaline and dopamine. Before the administration of nadolol, DDAVP induced a significant decrease in blood pressure, and significant increases in the heart rate, plasma renin activity, cortisol and noradrenaline; there were no changes in adrenaline or dopamine. After the administration of nadolol, baseline noradrenaline was significantly increased, while cortisol, adrenaline and dopamine remained unchanged. A second infusion of DDAVP did not significantly alter dopamine, heart rate, noradrenaline, adrenaline or dopamine, but plasma renin activity, aldosterone and cortisol still showed a significant increase. The blunted hypotensive effect of DDAVP after the administration of nadolol may be aspecific, due to lower basal blood pressure levels, or may indicate a mechanism of action common to both drugs. A similar post-DDAVP increase before and after β-blockade suggests that the drug has a direct effect on the renin-secretory apparatus. An indirect effect, mediated by changes in intrarenal haemodynamics or by other factors with renin-stimulating activity, e.g. tissue plasminogen activator, can also be hypothesized.

Acta Endocrinologica (Copenh) 1991;125:319-30The legends of Figs. 4 and 5 were incorrect. The figures and their correct legends are reproduced here.

A case of primary aldosteronism is presented in which computed tomography showed bilateral adrenal tumors. Adrenal scintigraphy during dexamethasone suppression revealed bilateral radiotracer uptake, with markedly predominant visualization of the left side. The left adrenal gland was removed, and an aldosterone-producing adenoma was confirmed by histologic examination. Fifteen months after surgery, serum potassium and plasma aldosterone were normal, and a marked decrease of blood pressure was observed, indicating that the right adrenal tumor was a benign nonfunctioning mass. Unilateral adrenalectomy on the side of the scintigraphically predominant lesion reversed the clinical syndrome of primary aldosteronism. © American Journal of Hypertension, Ltd. Am J Hypertens 1997;10:476–478

The effect of a surgical cure of hypercortisolism on hypertension in 54 patients with Cushing’s syndrome was assessed. The correlation between preoperative duration of hypertension and posttreatment blood pressure was significant (P < .01). Restoration of normal cortisol was associated with blood pressure normalization in 39 out of 54 cases. Duration of hypertension of patients with normalized blood pressure was significantly shorter than that of patients with persistent hypertension post-operatively (P < .0001). Duration of hypertension, ie, long-lasting exposure to increased cortisol, appears to be the determinant of persistent hypertension following successful surgery in Cushing’s syndrome. Am J Hypertens 1996;9:77–80