Traditional and novel cardiovascular risk factors in non-functioning adrenal adenomas

Background

The majority of the incidentally discovered adrenal masses are non-functioning adrenal adenomas; however data regarding traditional and novel cardiovascular risk predictors in these subjects is lacking. The objective of our study was to investigate the levels of PAI-1, IL-6 and Apelin along with several traditional cardiovascular risk markers in subjects with non-functioning adrenal adenomas.

Methods

38 subjects with non-functioning adrenal adenomas and 30, age, gender and BMI matched healthy controls were enrolled. Participants underwent hormonal evaluation including morning cortisol, adrenocorticotrophic hormone (ACTH), post dexamethasone suppression test (DST) cortisol, dehydroepiandrosterone sulfate (DHEAS) and urinary cortisol. Anthropometric and metabolic parameters, body composition, PAI-1, IL-6 and Apelin were measured.

Results

Subjects with non-functioning adrenal adenomas had significant elevations in systolic blood pressure, mean arterial pressure, waist circumference, uric acid, and post DST cortisol and had significantly reduced levels of DHEAS when compared to BMI matched controls. No significant difference was observed in terms of PAI-1, IL-6 and Apelin between groups. PAI-1 and IL-6 were significantly correlated with mean arterial pressure, BMI, uric acid, total and LDL-cholesterol. Linear regression analysis showed that morning cortisol and Apelin levels independently predicted HOMA levels in subjects with adrenal adenomas.

Conclusion

Subjects with non-functioning adrenal adenomas feature several cardiovascular risk factors even when compared to BMI matched individuals. Subtle cortisol autonomy in adrenal adenomas may be associated with those findings.     

Association of pulse wave velocity and intima‐media thickness with cardiovascular risk factors in young adults

Pulse wave velocity (PWV), a measure of arterial stiffness, and intima‐media thickening (IMT), a measure of early atherosclerosis, are intermediate markers of cardiovascular disease which are predictive of cardiovascular events. Traditionally, both were thought to result from accumulative exposure to traditional cardiovascular risk factors. However, their association with risk factors in young adults in low‐income settings is unknown. We sought to investigate the association between PWV and IMT with traditional cardiovascular risk factors in the Andhra Pradesh Children and Parents Study cohort from Southern India. Male and female adults (N = 1440) aged between 20 and 24 years underwent measures of PWV and IMT. Exposure variables included smoking, body mass index (BMI), mean arterial pressure (MAP), glucose, homeostatic model assessment of insulin resistance (HOMA‐IR), total cholesterol, high‐density lipoprotein cholesterol (HDL‐cholesterol), and triglycerides. Association between outcome and exposure variables was assessed using linear regression analysis. Average values for PWV and IMT were 5.9 ± 0.6 m/s and 0.5 ± 0.1 mm. In univariable analysis, PWV associated with MAP, BMI, smoking, total cholesterol, glucose, and HOMA‐IR and IMT associated with MAP, BMI, tobacco use, and HDL‐cholesterol. In multivariable analysis, PWV remained strongly positively associated with MAP increasing by 0.5 m/s (P < .001) for a 10 mm Hg increase in MAP (R² = .37). In contrast, IMT negatively associated with HDL‐cholesterol (β = ?.10; P = .012, R² = .02). There was weak evidence that PWV and IMT positively associated with BMI. In young adults from Southern India, PWV positively associated with blood pressure and IMT negatively associated with HDL‐cholesterol. This suggests separate etiologies for atherosclerosis and arterial stiffening in young adults.     

Subclinical hypercortisolism and CT appearance in adrenal incidentalomas: a multicenter study from Southern Sweden

Evaluation of subclinical hypercortisolism (SH) in patients with adrenal incidentaloma (AI) including its correlation to size, attenuation at unenhanced computed tomography (CT) and unilateral or bilateral adrenal disease. Nine hospitals in Southern Sweden investigated during 2005-2007 consecutively patients with AI with hormonal and CT examinations according a regional protocol. Two hundred and twenty-eight patients with AI with median size 2.0 cm were included. One mg overnight dexamethasone suppression test (DST) was performed in 223 patients and basal P-ACTH measured in 146 patients. SH was defined as cortisol ≥ 50 nmol/l at DST in combination with basal ACTH <2 pmol/l. In patients with unilateral AI 42% (76/180) had inadequate suppression at DST and 23% (27/115) had SH. The probability for SH and inadequate suppression at DST correlated positively to size and inversely to attenuation at CT. Bilateral AI were found in 43 patients and of these 70% (30/43) had inadequate suppression at DST and 42% (13/31) SH. The patients with SH or inadequate suppression at DST had increased frequency of hypertension which increased further in patients with post-DST cortisol ≥ 140 nmol/l. The applied criterion for SH is useful for initial evaluation of patients with AI. SH is common in patients with AI, particular in bilateral disease. In patients with unilateral AI the probability for SH correlated positively to size and inversely to attenuation at CT. Furthermore, SH and the post-DST cortisol concentration was associated with hypertension.     

Significance of plasma D-dimer in relation to the severity of atherosclerosis among patients evaluated by non-invasive indices of cardio-ankle vascular index and carotid intima-media thickness

The aim of this study is to elucidate the usefulness of plasma D-dimer for the prediction of thrombotic events in highly atherosclerotic patients. The severity of atherosclerosis was measured by non-invasive methods including cardio-ankle vascular index (CAVI) and carotid intima-media thickness (IMT) in 100 patients with atherosclerosis aged 72.1 years on average. CAVI was significantly correlated with the levels of D-dimer, platelet aggregation (Plt Aggre), uric acid (UA), creatinine (Cr), blood urea nitrogen (BUN), and C-reactive protein (CRP), whereas IMT was significantly correlated with the levels of Cr, BUN, and CRP. CAVI and IMT were suitable for stratification of the patients. A comparison of hemostatic markers (D-dimer, fibrinogen and Plt Aggre) between the less sclerotic group (group A; CAVI <8.0 and IMT <1.1 mm, n = 26) and the highly sclerotic group (group B; CAVI >8.0 and IMT >1.1 mm, n = 32) revealed that the incidence of thrombosis was significantly higher in group B (18.8%) than in group A (3.8%) and that D-dimer was significantly higher (p < 0.01, Mann–Whitney U test) in group B (0.48 μg/ml, median) than in group A (0.32 μg/ml, median). Moreover, multiple linear regression analyses of CAVI and IMT indicated that D-dimer and age were significant variables. In conclusion, D-dimer is significantly associated with thrombosis in highly atherosclerotic patients.     

Occult Cushing's syndrome in type-2 diabetes

Subclinical Cushing's syndrome (SCS) caused by adrenal incidentalomas is frequently associated with overweight and insulin resistance. Metabolic syndrome X may therefore be a clue to the presence of CS. However, the incidence of CS in this situation remains unknown. We have conducted a prospective study to evaluate the prevalence of occult CS in overweight, type-2 diabetic patients devoided of specific clinical symptoms of CS. Two hundred overweight, type-2 diabetic patients, consecutively referred for poor metabolic control (HbA(1C) > 8%), were studied as inpatients. A first screening step was performed with the 1-mg overnight dexamethasone suppression test (DST) using a revised criterion for cortisol suppression (60 nmol/liter) to maximize the sensitivity of the procedure. A second confirmatory step of biochemical investigations (midnight plasma cortisol concentration, plasma cortisol circadian rhythm, morning plasma ACTH concentration, 24-h urinary free cortisol, and 4-mg i.v. DST) was performed in patients with impaired 1-mg DST. A third step of imaging studies was performed according to the results of second-step investigations. Fifty-two patients had impaired 1-mg DST. Among these, 47 were further evaluated. Thirty were considered as false positives of the 1-mg DST, whereas 17 displayed at least one additional biological abnormality of the hypothalamic-pituitary-adrenal axis. Definitive occult CS was identified in four patients (2% of the whole series) with Cushing's disease (n = 3) and surgically proven adrenal adenoma (n = 1). Definitive diagnosis remains to be established in seven additional patients (3.5%) with mild occult CS associated with unsuppressed plasma ACTH concentrations and a unilateral adrenal tumor of 10-29 mm in size showing prevalent uptake at radiocholesterol scintigraphy. In conclusion, a relatively high prevalence of occult CS was found in our study. Further studies are needed to evaluate the impact of the cure of occult CS on obesity and diabetes mellitus in these patients. Such studies might provide a rationale for systematic screening of occult CS in this population.     

Hepatitis C virus eradication with direct‐acting antiviral improves insulin resistance

Sustained virological response (SVR) after interferon‐based therapy is associated with improvement of insulin resistance (IR) in HCV‐infected patients. Few data are available in the direct‐acting antivirals (DAAs) era, especially in cirrhotic patients. We prospectively evaluated the long‐term effect of DAAs on IR. Patients treated with DAAs between May 2015 and December 2016 in 3 tertiary care centres were recruited. Patients with diabetes were excluded. Biochemical and virological data were collected at baseline, 12/24/48 weeks (W) after the end of therapy (EOT). Presence of IR was defined by a ‘homeostasis model assessment index for IR’ [HOMA‐IR])> 2.5. Liver fibroscan was performed at baseline, at 24/48W after EOT. Hundred and thirty‐eight patients were enrolled (mean age 58 years, M/F 85/53, GT1 61%, 68.8% cirrhotic). Sixty‐eight patients (94/138) had IR. Patients with IR had significantly higher stiffness than patients without it (23 ± 12 vs 15 ± 8; P < .0001). SVR12 was achieved in 135 (98%) patients, and 124 (90%) patients reached the 48W post‐EOT. At this time point, the percentage of patients with IR significantly decreased to 49% (P = 0,01). HOMA‐IR was significantly lower than baseline (1.8 vs 3; P < .001), and this was related to a significant reduction of insulin level (11.7 ± 6.3 vs 16.4 ± 8.3). High BMI was associated with a significantly lower probability of achieving a non‐IR status at 24W (P = .05) and 48W (P = .03).In conclusion, SVR following DAAs led to a significant reduction of IR, even in patients with cirrhosis. Nevertheless, IR can persist after the achievement of SVR, especially in patients with high BMI.     

Higher morning serum cortisol level predicts increased fibrinogen but not shortened APTT

Background  There is emerging evidence that serum cortisol might be independently associated with prothrombotic activity, suggesting that increased cortisol levels might finally contribute to the pathogenesis of atherosclerotic disorders. Since hypercoagulability is principally sustained by either defective naturally occurring anticoagulant mechanisms or to heightened coagulation factors, most of which are cumulatively explored by the activated partial thromboplastin time (APTT), the present investigation was designed to asses the potential relationship between morning serum cortisol, APTT and fibrinogen in a general population of healthy outpatients. Methods  We performed a retrospective analysis on the database of our Laboratory Information System to retrieve results of morning serum cortisol, APTT and fibrinogen, which were performed on consecutive outpatients referred by general practitioners for routine blood testing over the previous 2 years. Results  Cumulative results for morning serum cortisol, APTT and fibrinogen were retrieved for 302 adults >35 years old (M/F = 61/90; age 49 ± 13 years; range 35–79). A statistically significant increased concentration of fibrinogen was observed in subject with morning serum cortisol values above the upper limit of the reference range (P < 0.001), whereas the concentration of APTT was not significantly different between the two subgroups of subjects with normal and increased morning serum cortisol (P = 0.432). This difference remained statistically significant even after adjusting for age and sex. In multivariable linear regression analysis, the concentration of fibrinogen, but not the value of the APTT, was significantly associated with morning serum cortisol. Conclusions  The results of this retrospective investigation confirm that baseline cortisol levels might predict higher fibrinogen in the general population. This potential biological interrelationship deserves further scrutiny for the potential implications on prediction and prevention of the cardiovascular risk.     

Relationship of a Body Shape Index and Body Roundness Index with carotid atherosclerosis in arterial hypertension

Background and aimsA Body Shape Index (ABSI) and Body Roundness Index (BRI) are two new anthropometric adiposity indices that have shown to be associated better than BMI with adipose abdominal tissue, with the onset of diabetes and the risk of premature death. Little is known about the influence of ABSI and BRI on subclinical vascular damage. The study was aimed to assess the relationship between ABSI and BRI with carotid atherosclerosis damage in subjects with arterial hypertension.Methods and resultsA total of 468 patients with arterial hypertension (30–80 years old) were enrolled; adiposity indices were calculated (BMI, WC, ABSI, BRI) and carotid ultrasonographic examination was performed to detect atherosclerotic damage (IMT or atherosclerotic plaque). BRI, but not ABSI, was higher in subjects with IMT> 0.90 mm in comparison to those with a lower IMT (p < 0.001), whereas patients with carotid plaques showed higher values of ABSI (p = 0.001), as well as of BRI (p = 0.003). Linear regression analysis disclosed significant correlation of IMT with ABSI, BRI and BMI (all p < 0.001). In the multivariate analysis, BRI was independently correlated with cIMT (p = 0.015). On the contrary, ABSI did not show any independent association with cIMT. However, ABSI was strongly associated with carotid plaques in multiple logistic regression analysis after adjustment for potential confounding factors. When BRI or BMI replaced ABSI into the multivariate models, they did not show any independent correlation with carotid plaques.ConclusionsABSI may be proposed as a better correlate of carotid atherosclerosis than the traditional measures of adiposity.     

Arterial wave reflection is associated with severity of extracoronary atherosclerosis in patients with coronary artery disease.

BACKGROUND: Arterial wave reflection is a major determinant of left ventricular function, coronary perfusion and cardiovascular risk. We investigated whether arterial wave reflection may detect atherosclerosis of peripheral arteries in patients with documented coronary artery disease (CAD). METHODS: Radial artery applanation tonometry and pulse wave analysis was performed in 184 patients with documented CAD at coronary angiography; central blood pressures and augmentation index (AI) were measured. Ankle-brachial (ABI) index and intima-media thickness (IMT) were used as indices of atherosclerosis of the lower limbs and the carotid arteries respectively. RESULTS: Patients with abnormal IMT (> 0.7 mm, first tertile) or ABI (< 0.94, first tertile) had higher AI than patients with lower IMT or higher ABI (24 +/- 17 versus 17 +/- 16% and 23 +/- 18 versus 18 +/- 13%, respectively, P < 0.05). In multivariate analysis, increasing AI was associated with age, female gender, heart rate, mean blood pressure, hyperlipidaemia, and use of statins (regression coefficient (beta) = 0.50, beta = 0.15, beta = -0.60, beta = 0.23, beta = 0.16 and beta = -0.14, respectively, P < 0.05). Increasing AI was associated with an adjusted-odds ratio of 1.035 [95% confidence interval (CI), 1.005-1.066], P = 0.02 for an abnormal IMT and of 1.08 (95% CI, 1.024-1.146), P = 0.005 for ABI after adjustment for age, gender, heart rate, height, blood pressure, atherosclerotic risk factors, obesity and medication. No relation was found between AI and Gensini score or for the number of diseased coronary vessels. CONCLUSION: Augmentation index is a marker of extensive extracoronary atherosclerosis in patients with CAD.     

Subclinical atherosclerosis and endothelial dysfunction in young South-Asian patients with systemic lupus erythematosus

Patients with systemic lupus erythematosus (SLE), especially Asian Indians, are at increased risk of developing premature atherosclerosis. To find out the prevalence and predictors of carotid intima-medial thickness (IMT) and brachial artery flow-mediated dilatation (FMD). Endothelial dysfunction was assessed by FMD in brachial artery and IMT was measured in common carotid artery in SLE patients and healthy controls. Sixty SLE patients (mean age 31 ± 9 years) and 38 healthy controls (mean age 34 ± 6 years) were included. The IMT was higher in SLE patients as compared to controls (0.49 ± 0.08 mm vs. 0.39 ± 0.05 mm, p < 0.0001). SLE and damage were independent predictors of abnormal IMT. FMD was impaired in SLE patients compared to controls (9.97% vs. 18.97%, p < 0.00001). None of the classical cardiovascular risk factors were predictors of FMD or abnormal IMT. Indian patients with SLE have higher prevalence of subclinical atherosclerosis and endothelial dysfunction. Presence of damage was associated with abnormal IMT in SLE patients.     

Antecedent longitudinal changes in body mass index are associated with diurnal cortisol curve features: The multi-ethnic study of atherosclerosis

ContextPrior studies have shown a cross-sectional association between body mass index (BMI) and salivary diurnal cortisol profile features (cortisol features); however, to our knowledge prior population-based studies have not examined the longitudinal association of body-mass index (BMI) with cortisol features.ObjectiveTo examine the association of (1) prior annual BMI percent change over 7 years with cortisol features, (2) baseline cortisol features with subsequent change in BMI over 6 years and (3) the association of change in cortisol features with change in BMI over 6 years.DesignLongitudinal study.SettingMulti-Ethnic Study of Atherosclerosis (MESA) Stress I & II Studies (2004–2006 & 2010–2012).Participants1685 ethnically diverse men and women attended either MESA Stress exam (mean age 65 ± 10 years at MESA Stress I; mean age 69 ± 9 years at MESA Stress II).Outcome MeasuresLog-transformed cortisol features including wake-up cortisol, cortisol awakening response, early decline slope (30 min to 2 h post-awakening), late decline slope (2 h post-awakening to bedtime), bedtime, and total area under the curve (AUC) cortisol.ResultsOver 7 years, following multivariable adjustment, (1) a 1% higher prior annual BMI % increase was associated with a 2.9% (95% CI: − 5.0%, − 0.8%) and 3.0% (95% CI: − 4.7%, − 1.4%) lower current wake-up and total AUC cortisol, respectively; (2) there was no significant association between baseline cortisol features and subsequent change in BMI and (3) among participants with BMI ≥ 30 kg/m², flattening of the late decline slope was associated with increases in BMI (every 1-unit increase late decline slope were associated with a 12.9% increase (95%CI: − 1%, 26.8%) in BMI, respectively).ConclusionsWe found a significant association between prior annual BMI % change and cortisol features, but no significant association between baseline cortisol features and subsequent change in BMI. In participants with obesity increases in BMI were associated with less pronounced declined. Collectively, our results suggest that greater adiposity may lead to a blunted diurnal cortisol profile.     

Acute administration of alprazolam, a benzodiazepine activating GABA receptors, inhibits cortisol secretion in patients with subclinical but not overt Cushing’s syndrome

The purpose of this study is to verify whether acute pre-treatment with alprazolam (ALP), a benzodiazepine that inhibits HPA secretion in normal subjects, could better characterize patients with subclinical Cushing’s syndrome (SCS) than the 1-mg dexamethasone test (DST). In 22 patients with SCS, 10 with overt Cushing’s syndrome (CS), 11 with non-functioning adrenal incidentalomas (NF) and 14 normal subjects (NS) we studied the effect of ALP (1 mg, p.o. at 2300 hours) on cortisol levels after 1-mg DST. Cortisol levels (mean ± SEM) after DST were lower (P = 0.012) in SCS (3.9 ± 0.3 μg/dl) than in overt CS (10.4 ± 1.9 μg/dl), while they were higher (P = 0.0005) than in NF (1.1 ± 0.1 μg/dl) and NS (1.5 ± 0.1 μg/dl). After ALP pre-treatment, cortisol levels further decreased (P = 0.004) in SCS (3.0 ± 0.3 μg/dl), but neither in CS (9.3 ± 1.3 μg/dl) nor in NF (1.3 ± 0.1 μg/dl) and in NS (1.3 ± 0.1 μg/dl). In SCS, cortisol levels after ALP + 1-mg DST persisted lower (P = 0.0005) than those in CS, but higher (P = 0.0005) than those in NF and NS. Considering individual cases, ALP pre-treatment reduced cortisol levels <3 and <1.8 μg/dl in 50 and 23 % of SCS patients, respectively. ALP amplifies the cortisol inhibition exerted by 1-mg DST in patients with SCS but not in those with CS. The clinical usefulness of ALP to increase the sensitivity of 1-mg DST to identify true autonomous cortisol release in patients with adrenal incidentalomas as well as to predict different clinical outcomes remains to be clarified.     

Adrenal black adenoma associated with Cushing's syndrome

We report a case of adrenal black adenoma associated with Cushing's syndrome. A 41-yr-old man presented to our hospital with a 6-yr history of severe hypertension and general fatigue, and a 1-mo history of diabetes mellitus. Physical examination disclosed cushing-oid manifestations. His serum cortisol concentrations ranged from 14.0 to 15.4 microg/dL, with an ACTH level <5 pg/mL. Urinary free cortisol level was increased (125 microg/d). Cortisol was not suppressed on the overnight 1 mg oral dexamethasone suppression test (DST), 2-d low-dose DST, and 2-d high-dose DST. Abdominal computed tomography and magnetic resonance imaging studies revealed a solid round tumor approx 3 cm in diameter, located in the left adrenal gland. Left adrenalectomy was performed; the surgical specimen revealed a black ade-noma consisting of compact cells within numerous pigments that seemed to be lipofuscin in nature.     

Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy

Glucocorticoid replacement therapy in patients with adrenal insufficiency (AI), whether primary (Addison's disease) or secondary (due to hypopituitarism), has been established for some 50 years. The current standard treatment regimen involves twice‐ or thrice‐daily dosing with a glucocorticoid, most commonly oral hydrocortisone. Based on previous small‐scale studies and clinical perception, life expectancy with conventional glucocorticoid replacement therapy has been considered normal, with a low incidence of adverse events. Data from the past 10–15 years, however, have shown that morbidity remains high and life expectancy is reduced. The increased morbidity and decreased life expectancy appear to be due to both increased exposure to cortisol and insufficient cortisol coverage during infections and other stress‐related events. This is thought to reflect a failure of treatment to replicate the natural circadian rhythm of cortisol release, together with a failure to identify and deliver individualized cortisol exposure and to manage patients adequately when increased doses are required. The resulting over‐ or under‐treatment may result in Cushing‐like symptoms or adrenal crisis, respectively. This review summarizes the morbidity and mortality seen in patients receiving the current standard of care for AI and suggests areas for improvement in glucocorticoid replacement therapy.     

Cortisol in urine and saliva: relations to the intima media thickness, IMT.

OBJECTIVE: The objective of the study was to analyse the relations between excretion of cortisol in urine and saliva and the intima media thickness (IMT) of the artery carotis communis. DESIGN AND METHODS: In a cross-sectional study, 121 healthy participants completed a comprehensive questionnaire. Additionally, three samples of urine and four samples of saliva were collected in the 24 h before the examination, which included an ultrasound examination of the artery carotis communis, measuring height, weight, hip and waist width, blood pressure after 10 min of rest, and analysis of blood samples for cholesterol, high density lipoprotein (HDL)-cholesterol, and HbA(1c). The highest average of three measurements of IMT immediately before cartosis bulbous from either left or right side was used in the analyses as the dependent variable IMT. RESULTS: Values of cortisol in urine adjusted for creatinine were not related to IMT, but the level of salivary cortisol 1 h after awakening and the reactivity in salivary cortisol the first hour after awakening were significantly associated with IMT in women i.e. high cortisol was associated with low IMT. This result remained significant in multiple regression analysis including age, body mass index (BMI), cholesterol, HbA(1c), and alcohol. CONCLUSION: The reactivity in salivary cortisol the first hour in the morning might be used in research relating to stress, hormonal changes and early atherosclerosis.     

The impact of serum uric acid level on arterial stiffness and carotid atherosclerosis: The Korean Multi-Rural Communities Cohort study

Objective

Serum uric acid level has been found to be associated with a risk factor for cardiovascular diseases. However, the topic has not been explored in the general population, especially in Korea. This study was designed to determine whether serum uric acid is associated with carotid atherosclerosis and arterial stiffness in the Korean Multi-Rural Communities Cohort study.

Methods

A total of 5568 participants from the Korean Multi-Rural Communities Cohort were evaluated for the risk of hyperuricemia in cardiovascular atherosclerosis. Important surrogates for cardiovascular atherosclerosis such as intima–media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were assessed. We evaluated the association between these atherosclerosis indices and serum uric acid level or hyperuricemia through multivariate-adjusted logistic and linear regression analyses.

Results

There was a significant difference of carotid IMT and baPWV between males and females (p < 0.0001, respectively). Both male and female subjects with hyperuricemia showed higher baPWV than subjects without hyperuricemia (p = 0.0004 for males; p = 0.001 for females). Serum uric acid level was positively correlated with baPWV in males (β = 0.0006, p < 0.0001) and in females (β = 0.0001, p = 0.04), whereas no association between serum uric acid and carotid IMT was found in either gender. A linear relationship of baPWV with increasing serum uric acid level was observed in males (p = 0.0005) and in females (p = 0.004).

Conclusion

Serum uric acid level could be considered an important risk factor for arterial stiffness in Korean population, whereas carotid IMT is not associated with serum uric acid in either gender when using data from the Korean Multi-Rural Communities Cohort study.     

Adult-onset asthma is associated with increased carotid atherosclerosis among women in the Atherosclerosis Risk in Communities (ARIC) study

Some studies have suggested that asthma may be a risk factor for coronary heart disease and stroke, particularly in women. Child and adult-onset asthma differ according to inflammatory characteristics and gender distribution. We examined whether childhood-onset and adult-onset asthma were associated with carotid artery intima-media thickness (IMT) in men and women in the Atherosclerosis Risk in Communities (ARIC) study. In unadjusted analyses, the weighted mean far wall IMT thickness for women with history of adult-onset asthma was significantly greater than that of women without history of asthma (0.731 mm versus 0.681 mm; p<0.0001) while IMT for women with history of childhood-onset asthma (IMT=0.684 mm) did not differ substantially from non-asthmatic women. Mean IMT did not differ significantly according to asthma history among men. When the data were fitted to a linear model, the interaction between asthma status and gender was significant (p=0.006). After adjusting for age, race, BMI, smoking status, smoking pack years, diabetes, hypertension, physical activity, education level, and high and low density lipoprotein levels, the mean IMT difference between women with adult-onset asthma and no history of asthma was attenuated but remained significant (0.713 mm versus 0.687 mm, p=0.008). In conclusion, adult-onset asthma but not child-onset asthma is associated with increased carotid atherosclerosis among women but not among men.     

The dynamics of post-operative plasma ACTH values following transsphenoidal surgery for Cushing’s disease

Rapid assessment of adrenal function is critical following transsphenoidal surgery (TSS) for Cushing’s disease (CD) in order to determine surgical efficacy. We hypothesize that there may be a role for ACTH measurement as a rapid indicator of adrenal function. Following surgery for CD, glucocorticoids were withheld and paired plasma ACTH and serum cortisol levels were measured every 6 h. Post-operative hypocortisolemia was defined as serum cortisol <2 mcg/dl or a serum cortisol <5 mcg/dl with the onset of symptoms of adrenal insufficiency within 72 h. We studied 12 subjects, all female, mean age 44.6 years (range 25–55), including 13 surgeries: nine subjects attained hypocortisolemia. Plasma ACTH levels decreased more in subjects with hypocortisolemia (0.9 pg/ml/hr, P = 0.0028) versus those with persistent disease (0 0.2 pg/ml/hr, P = 0.26) within the first 48 h after surgery. In contrast to subjects with persistent disease, all subjects with hypocortisolemia achieved a plasma ACTH <20 pg/ml by 19 h (range 1–19 h). Four of the nine subjects with hypocortisolemia achieved plasma ACTH <20 pg/ml by 13 h and the remaining five subjects by 19 h. Hypocortisolemia occurred between 3-36 h following achievement of a plasma ACTH <20 pg/ml. In CD, a reduction in postoperative plasma ACTH levels differentiates subjects with surgical remission versus subjects with persistent disease. The utility of plasma ACTH measurements in the postoperative management of CD remains to be determined.     

Greater adverse effects of cholesterol and diabetes on carotid intima-media thickness in South Asian Indians: comparison of risk factor-IMT associations in two population-based surveys

Asian Indians appear particularly susceptible to coronary heart disease compared with other ethnic groups. We compared the effects of vascular risk factors on carotid intima–media thickness (IMT) in a population of South Asians from Andhra Pradesh, India with a population of Caucasians from Perth, Australia.Cardiovascular risk factors and ultrasound-assessed carotid IMT were measured in randomly selected adults from two villages in rural India (n = 303) and compared to those for randomly sampled adults from Australia (n = 1111). Regression models with interaction terms were used to compare the strengths of associations between risk factors and carotid IMT, in these two populations. There were stronger associations of cholesterol (p for interaction = 0.009) and diabetes (p = 0.04) with carotid IMT in the Indian compared to the Australian population. Also, while increasing HDL-cholesterol was associated with decreasing carotid IMT in the Australian population the reverse was true for the Indian population (p < 0.001). The associations with IMT of blood pressure, triglycerides, age, HDL to total cholesterol ratio, glucose, BMI, waist, waist to hip ratio and smoking were not different between the populations.Greater adverse effects of total cholesterol and diabetes on atherosclerosis and no protective effect of HDL-cholesterol amongst Asian Indians provide a novel possible explanation for observed excess rates of cardiovascular disease amongst these populations.     

Clinical investigation of a unique type of hypothalamic adrenal insufficiency

Hypothalamic adrenal insufficiency (AI) is a rare but distinct type of AI. The leading cause of hypothalamic AI is a secondary side-effect of exogenous steroid intake, particularly in large amounts and/or long-term periods. The next cause would be the effect of the tumor in the hypothalamic lesions. We show here 9 cases of hypothalamic AI without any disorder on imagings and a history of steroid administration. All patients had general fatigue; 7 patients (77.8%) had a history of hypoglycemia; 5 patients (55.6%) had a history of hypotension. None of the patients had hyponatremia, hyperkalemia, or eosinophilia. Their morning plasma adrenocorticotropic hormone (ACTH) value was low at 8.5 ± 4.2 pg/mL, and serum cortisol value was low at 4.5 ± 1.3 µg/dL. All patients demonstrated normal responses during the corticotropin-releasing hormone loading (CRH) test but inadequate responses during the insulin tolerance test (ITT). After hydrocortisone replacement therapy, their morning plasma ACTH and serum cortisol values were significantly recovered (P < .05). Moreover, more than half of the patients were fine after discontinuing hydrocortisone replacement therapy. These results indicate that this unique type of hypothalamic AI has a curable clinical course making hydrocortisone replacement therapy a novel therapeutic option.