Hormonal prostate cancer therapies and cardiovascular disease: a systematic review.

Therapeutic intervention for prostate cancer mostly relies on eliminating circulating androgen or antagonizing its effect at the cellular level. As the use of endocrine therapies grows, an under-reported incidence of cardiovascular toxicities occurs in prostate cancer patients. In this review, we summarize data of clinical studies, investigating the cardiovascular and metabolic alterations associated with the use of old and new endocrine drugs (gonadotropin-releasing hormone [GnRH] agonists and antagonists, androgen receptor inhibitors, 17α-hydroxylase/c-17,20-lyase [CYP17] inhibitor) in prostate cancer. To date, studies looking for links between cardiovascular complications and hormone-mediated therapies in prostate cancer have reached conflicting results. Several confounding factors, such as age of patients and related cardiovascular liability, other comorbidities, and use of concomitant drugs, have to be carefully evaluated in future clinical trials. Further research is needed given the continuous advancements being made in prostate cancer treatment.

Safety and efficacy of bariatric surgery in Mexico: A detailed analysis of 500 surgeries performed at a high-volume center. / Seguridad y eficacia de la cirugía bariátrica en México: análisis detallado de 500 cirugías en un centro de alto volumen.

INTRODUCTION AND OBJECTIVES: Bariatric surgery is the best method for treating obesity and its comorbidities. Our aim was to provide a detailed analysis of the perioperative outcomes in Mexican patients that underwent surgery at a high-volume hospital center. MATERIALS AND METHODS: A retrospective study was conducted on all the patients that underwent bariatric surgery at a single hospital center within a time frame of 4 and one-half years. Demographics, the perioperative variables, complications (early and late), weight loss, failure, and type 2 diabetes mellitus remission were all analyzed. RESULTS: Five hundred patients were included in the study, 83.2% of whom were women. Mean patient age was 38.8 years and BMI was 44.1kg/m2. The most common comorbidities were high blood pressure, dyslipidemia, and diabetes. Laparoscopic gastric bypass surgery was performed in 85.8% of the patients, sleeve gastrectomy in 13%, and revision surgeries in 1%. There were 9.8% early complications and 12.2% late ones, with no deaths. Overall weight loss as the excess weight loss percentage at 12 and 24 months was 76.9 and 77.6%. The greatest weight loss at 12 months was seen in the patients that underwent laparoscopic gastric bypass. A total of 11.4% of the patients had treatment failure. In the patients with type 2 diabetes mellitus, 68.7% presented with complete disease remission and 9.3% with partial remission. There was improvement in 21.8% of the cases. CONCLUSIONS: In our experience at a high-volume hospital center, bariatric surgery is safe and effective, based on the low number of adverse effects and consequent weight loss and type 2 diabetes mellitus control. Long-term studies with a larger number of patients are needed to determine the final impact of those procedures.

Anti-TNF-α therapy reduces retinol-binding protein 4 serum levels in non-diabetic patients with psoriasis: a 6-month prospective study.

BACKGROUND: Retinol-binding protein-4 (RBP4), an adipokine considered as an emerging cardiometabolic risk factor, is increased in patients with moderate-to-severe psoriasis. OBJECTIVE: In this study, we aimed to establish the effect of anti-TNF-α therapy on RBP4 levels in patients with moderate-to-severe psoriasis. We also assessed if RBP4 levels correlate with metabolic syndrome features and disease severity in these patients. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with adalimumab. Patients with kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of treatment (time 0) and at month 6. RESULTS: Twenty-nine patients were assessed. Statistically significant reduction (P = 0.0001) of RBP4 levels was observed after 6 months of therapy (RBP4 at time 0: 55.7 ± 21.4 µg/mL, vs. 35.6 ± 29.9 µg/mL at month 6). No significant correlation between basal RBP4 levels and metabolic syndrome features or disease severity was found. Nevertheless, although RBP4 levels did not correlate with insulin resistance, a negative and significant correlation between RBP4 levels obtained after 6 months of adalimumab therapy and other metabolic syndrome features such as abdominal perimeter and body mass index were observed. At that time, a negative and significant correlation between RBP4 levels and disease activity scores and ultrasensitive CRP levels was also disclosed. CONCLUSION: Our results support an influence of the anti-TNF-α blockade on RBP4 serum levels. This finding is of potential relevance due to increased risk of cardiovascular disease in patients with psoriasis.

Cutaneous vasculitis associated with severe bacterial infections. A study of 27 patients from a series of 766 cutaneous vasculitis.

OBJECTIVES: To assess the clinical spectrum of severe bacterial infections presenting as cutaneous vasculitis (CV) in a defined population. METHODS: Unselected series of 766 patients with CV diagnosed at a single university referral center. RESULTS: An underlying severe bacterial infection was diagnosed in 27 (22 men/5 women; mean age ± standard deviation [SD]: 53 ± 18 years) of 766 cases presenting with CV (3.5%). These infections were: pneumonia (n=8), endocarditis (n=6), meningitis (n=4), intra-abdominal infections (n=3), septic arthritis (n=2), septicaemia (n=2), septic bursitis (n=1), and urinary tract infection (n=1). All the patients were admitted for suspected CV. The median delay from admission to the diagnosis of infection was 4 days. A typical palpable purpura without relevant visceral vasculitic involvement was the main clinical manifestation. Patients with severe bacterial infections were older, with male predominance, had more frequently fever, constitutional symptoms, focal infectious features, and leukocytosis with left shift and anaemia than the remaining patients with CV. Although antibiotics were prescribed in all the patients, seven also required the use of low-dose corticosteroids to achieve complete resolution of the cutaneous lesions. Most patients experienced full recovery but two of them underwent prosthetic cardiac valve replacement, and another two died due to infection-related complications. CONCLUSIONS: CV may be the presenting manifestation of a severe underlying bacterial infection. Physicians should keep in mind this fact to make an early diagnosis of infection and, consequently, prevent life-threatening complications.

Relationship of leptin with adiposity and inflammation and resistin with disease severity in psoriatic patients undergoing anti-TNF-alpha therapy.

BACKGROUND: Altered secretion patterns of proinflammatory adipokines may influence the increased risk of cardiovascular mortality observed in patients with chronic inflammatory diseases. OBJECTIVE: To determine whether two adipokines, leptin and resistin, correlate with metabolic syndrome features and disease severity in psoriatic patients who underwent anti-TNF-α therapy. METHODS: Prospective study of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α- adalimumab. Patients with kidney disease, hypertension or body mass index ≥35 Kg/m(2) were excluded. Metabolic and clinical evaluation was performed at the onset of anti-TNF-α treatment and at month 6. RESULTS: Twenty-nine patients were assessed. A correlation between adiposity and leptin was observed (waist circumference and leptin levels after 6 months of therapy: r = 0.43; P = 0.030). Leptin concentration also correlated with blood pressure before adalimumab onset (systolic: r = 0.48; P = 0.013 and diastolic blood pressure: r = 0.50; P = 0.010 ). A marginally significant negative correlation between insulin sensitivity (QUICKI) and leptin levels was also observed. CRP levels correlated with leptin prior to the onset of adalimumab (r = 0.45; P = 0.020) and with resistin both before (r = 0.45; P = 0.020) and after 6 months of therapy (r = 0.55; P = 0.004). A positive association between parameters of disease activity such as BSA (r = 0.60; P = 0.001) and PASI (r = 0.63; P = 0.001) prior to the onset of adalimumab therapy and resistin concentrations was also disclosed. No significant changes in leptin and resistin concentrations following the 6-month treatment with adalimumab were seen. CONCLUSION: In patients with moderate-to-severe psoriasis leptin correlates with metabolic syndrome features and inflammation whereas resistin correlate with inflammation and disease severity.

Applicability of the 2006 European League Against Rheumatism (EULAR) criteria for the classification of Henoch-Schönlein purpura. An analysis based on 766 patients with cutaneous vasculitis.

OBJECTIVES: In 2006 the European League Against Rheumatism (EULAR) proposed new classification criteria for Henoch-Schönlein purpura (HSP). We aimed to establish the applicability of these criteria in patients with primary cutaneous vasculitis (CV). We also compared these criteria with previously established classification criteria for HSP. METHODS: A series of 766 (346 women/420 men; mean age 34 years) consecutive unselected patients with CV was assessed. One hundred and twenty-four of them with secondary CV or with CV associated with other well defined entities were excluded from the analysis. The 2006 EULAR criteria for HSP were tested in the remaining 642 patients with primary CV. Two sets of criteria for HSP were used for comparisons: a) the 1990 American College of Rheumatology (ACR-1990), and b) the ACR modified criteria proposed by Michel et al. in 1992 (Michel-1992). RESULTS: 451 (70.2%) of 642 patients were classified as having HSP according to the EULAR-2006 criteria, 405 (63.1%) using the ACR-1990 criteria, and 392 (61.1%) by the Michel-1992 criteria. However, only 336 patients (52.3%) met at the same time the EULAR-2006 and the ACR-1990 criteria, and only 229 patients (35.7%) fulfilled both the EULAR-2006 and Michel-1992 criteria. It is noteworthy that only 276 (43%) patients met the three set of criteria. Children fulfilled all the sets of criteria more commonly than adults (215 [66.6%] of 323 vs. 61 [19%] of 319, respectively; p<0.0001). CONCLUSIONS: According to our results, the EULAR-2006 criteria show low concordance with previous sets of classification criteria used for HSP.

Anti-TNF-α therapy improves insulin sensitivity in non-diabetic patients with psoriasis: a 6-month prospective study.

OBJECTIVE: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular death. Several studies have shown a beneficial effect of anti-TNF-α therapy on the mechanisms associated with accelerated atherogenesis in patients with inflammatory arthritis, including an improvement of insulin sensitivity. In this study, we aimed to determine for the first time whether the anti-TNF-α monoclonal antibody adalimumab may improve insulin sensitivity in non-diabetic patients with psoriasis. METHODS: Prospective study on a series of consecutive non-diabetic patients with moderate to severe psoriasis seen at the Dermatology Division of Hospital Universitario Marques de Valdecilla (Northern Spain) who completed 6 months of therapy with adalimumab (80 mg at week 0 followed by 40 mg every other week, starting 1 week after the initial dose). Patients with chronic kidney disease, hypertension or body mass index ≥ 35 kg/m(2) were excluded. Metabolic and clinical evaluation including assessment of insulin sensitivity using the Quantitative Insulin Sensitivity Check Index (QUICKI) was performed at the onset of the treatment (time 0) and at month 6. RESULTS: Twenty-nine patients (52% women; 38.6 ± 10.7 years) with moderate to severe psoriasis [body surface area (BSA) 37.9 ± 16.3%], Psoriasis Area and Severity Index [(PASI) 18.9 ± 7.8] were assessed. Statistically significant improvement (P=0.008) of insulin sensitivity was observed after 6 months of adalimumab therapy (QUICKI at time 0: 0.35 ± 0.04 vs. 0.37 ± 0.04 at month 6). Significant improvement of erythrocyte sedimentation rate, ultrasensitive C-reactive protein, BSA, PASI, Nail Psoriasis Severity Index, physician global assessment and psoriatic arthritis screening and evaluation questionnaire was also observed at month 6 (P < 0.05 for each variable). CONCLUSION: Our results support a beneficial effect of the anti-TNF-α blockade on the mechanisms associated with accelerated atherogenesis in patients with psoriasis.

Non-infectious aortitis: a report of 32 cases from a single tertiary centre in a 4-year period and literature review.

OBJECTIVES: Non-infectious aortitis often presents with non-specific symptoms leading to inappropriate diagnostic delay. We intend to describe the clinical spectrum and outcome of patients with aortitis diagnosed at a single centre. METHODS: We reviewed the clinical charts of patients diagnosed with non-infectious aortitis between January 2010 and December 2013 at the Rheumatology Division from a 1.000-bed tertiary teaching hospital from Northern Spain. The diagnosis of aortitis was usually based on FDG-PET-CT scan, and also occasionally on CT or MRI angiography or helical CT-scan. RESULTS: During the period of assessment 32 patients (22 women and 10 men; mean age 68 years [range, 45-87]) were diagnosed with aortitis. The median interval from the onset of symptoms to the diagnosis was 21 months. FDG-PET CT scan was the most common tool used for the diagnosis of aortitis. The underlying conditions were the following: giant cell arteritis (n=13 cases); isolated polymyalgia rheumatica (PMR) (n=11); Sjögren's syndrome (n=2), Takayasu arteritis (n= 1); sarcoidosis (n=1), ulcerative colitis (n=1), psoriatic arthritis (n=1), and large-vessel vasculitis that also involved the aorta (n=2). The most common clinical manifestations at diagnosis were: PMR features, often with atypical clinical presentation (n=23 patients, 72%); diffuse lower limb pain (n=16 patients, 50%); constitutional symptoms (n=12 patients, 37%), inflammatory low back pain (n=9 patients, 28%) and fever (n=7 patients, 22%). Acute phase reactants were increased in most cases (median erythrocyte sedimentation rate 46 mm/1st hour, and a median serum C-reactive protein 1.5 mg/dL). CONCLUSIONS: Aortitis is not an uncommon condition. The diagnosis is often delayed. Atypical PMR features, unexplained low back or limb pain, constitutional symptoms along with increased acute phase reactants should be considered 'red flags' to suspect the presence of aortitis.

Interleukin-6 as a predictor of cardiovascular events in troponin-negative non-ST elevation acute coronary syndrome patients.

AIM: Risk stratification in acute coronary syndrome without ST-segment elevation (NSTE-ACS) and troponin-negative remains a challenge. We evaluated the value of interleukin-6 (IL-6) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prognosis assessment of low-moderate risk NSTE-ACS and troponin-negative, and whether these biomarkers could improve the predictive performance of the established thrombolysis in myocardial infarction (TIMI) risk score. METHODS: A total of 212 low-moderate risk patients with NSTE-ACS and troponin-negative were prospectively studied. Clinical follow up at 6 months was performed for adverse endpoints. RESULTS: A total of 28 patients (13.5%) presented adverse clinical events. Those with adverse clinical events were associated with higher levels of IL-6 [8.58 (5.13-20.95) ng/l vs. 6.12 (4.16-9.14) ng/l, p = 0.043] and NT-proBNP [275.3 (108.6-548.2) ng/l vs. 126.8 (55.97-430.20) ng/l, p = 0.046]. In moderate risk group, we observed a higher event rate in patients with troponin-negative but elevated levels of IL-6 (p = 0.024). Only elevated IL-6 (> 12.40 ng/l) was an independent predictor of adverse outcomes [hazard ratios: 3.62, 95% confidence interval (CI) 1.69-7.75, p = 0.001]. The addition of IL-6 and history of ischaemic heart disease (IHD) to TIMI risk score significantly improved both the discrimination (integrated discrimination improvement, p = 0.003) and reclassification (Clinical Net reclassification improvement, p = 0.010) of the model for adverse events. CONCLUSIONS: Interleukin-6 is an independent predictor of adverse events in low-moderate risk patients with NSTE-ACS and troponin-negative. Its use identifies a higher risk population in moderate-risk patients. This provides together with history of IHD a better discrimination and reclassification beyond that achieved with clinical risk variables from TIMI risk score in these patients.

Single-nucleotide polymorphisms at the 9p21.3 genomic region not associated with the risk of cardiovascular disease in patients with rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic polygenic inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular disease (CVD). In this study, we evaluated the potential association of 9p21.3 single-nucleotide polymorphisms (SNPs) - previously linked to coronary artery disease - and CVD risk in 2001 Spanish RA patients genotyped for 9p21.3 SNPs using TaqMan™ assays. Carotid intima media thickness (cIMT) and presence of carotid plaques were also analyzed. Cox regression model did not disclose significant differences between patients who experienced CVD and those who did not. Neither association was found between cIMT or carotid plaques and SNPs allele distribution. In conclusion, results do not support a role of rs10116277 or rs1537375 SNPs in CVD risk in Spanish RA patients.

No evidence of association between functional polymorphisms located within IL6R and IL6ST genes and Henoch-Schönlein purpura.

Henoch-Schönlein purpura (HSP) is the most common type of primary small-sized blood vessel vasculitis in children and an uncommon condition in adults. Interleukin (IL)-6 is a proinflammatory cytokine whose effect is controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/gp130) is the signal-transducing subunit of the IL-6R. Two hundred and eighty five Spanish HSP patients and 877 sex and ethnically matched controls were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional polymorphisms. No significant differences in the genotype and allele frequencies between HSP patients and controls were observed. Moreover, there were no differences between HSP patients according to the age at disease onset, presence of nephritis or gastrointestinal manifestations. Our results do not confirm association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with HSP.

[Revascularization of total renal artery occlusion by angioplasty and stent placement]. / Revascularización eficaz de obstrucción total de arterial renal mediante angioplastia y colocación de Stent.

Revascularization of renal artery stenosis for the treatment of hypertension is an established procedure. In selected clinical scenarios, successful revascularization procedures may preserve or restore renal function. We present a 66-year-old man with secundary hypertension and deteriorating renal function caused by bilateral atherosclerotic renal artery disease (complete obstruction of the left renal artery and subocclusive stenosis of the right) in which blood pressure was successfully controlled and renal function improved and maintained steady after bilateral percutaneus transluminal angioplasty and renal artery stenting.

Revascularización eficaz de obstrucción total de arterial renal mediante angioplastia y colocación de Stent / Revascularization of total renal artery occlusion by angioplasty and stent placement

La revascularización de la estenosis de la arteria renal para el tratamiento de la hipertensión es un procedimiento ya admitido. En escenarios clínicos seleccionados, el éxito del procedimiento de revascularización puede mantener o restaurar la función renal. Presentamos el caso clínico de un paciente varón de 66 años con hipertensión arterial secundaria y deterioro de función renal causada por arteriosclerosis bilateral de las arterias renal (obstrucción completa de la arteria renal izquierda y estenosis suboclusiva de la derecha) en el cual la presión arterial fue controlada con éxito y la función renal mejoró después de una angioplastia transluminal percutánea bilateral y colocación de sendos stents de arterias renales

Revascularization of renal artery stenosis for the treatment of hypertension is an established procedure. In selected clinical scenarios, successful revascularization procedures may preserve or restore renal function. We present a 66-year-old man with secundary hypertension and deteriorating renal function caused by bilateral atherosclerotic renal artery disease (complete obstruction of the left renal artery and subocclusive stenosis of the right) in which blood pressure was successfully controlled and renal function improved and maintained steady after bilateral percutaneus transluminal angioplasty and renal artery stenting

Tumour markers in serum, bronchoalveolar lavage and biopsy cytosol in lung carcinoma: what environment lends the optimum diagnostic yield?

BACKGROUND: The aim of this study was to assess the diagnostic yield of the tumour markers carbohydrate antigen (CA 125), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC) and specific tissue polypeptide antigen (TPS) in serum, bronchoalveolar lavage (BAL) and biopsy cytosol in a group of patients with bronchogenic carcinoma. METHODS: Serum, BAL and biopsy cytosol samples were collected in a group of 85 patients with benign or malignant pulmonary diseases. After appropriate processing, tumour markers were determined by enzyme immunoassay. The diagnostic yields (sensitivity, specificity and accuracy) in each environment (serum, BAL or biopsy) were obtained by using "ROC" curves. RESULTS: Determined individually, CA 125, NSE and SCC show the greatest diagnostic accuracy in cytosol. CEA and TPS do so in BAL. CEA is the most relevant marker in serum and BAL, and CA 125 in cytosol. When the different tumour markers are associated, they offer better overall yields for all except TPS. CONCLUSIONS: For the factors evaluated in this study, determination of CEA in BAL was clinically the most useful marker in comparison with serum and cytosol determinations, although the latter may also be helpful in certain situations. Although there is no specific tumour marker for lung cancer, the combination of several can be used to monitor most patients with lung cancer.

DNA aneuploidy, S-phase fraction and nuclear p53 positivity in non-small cell lung carcinoma.

OBJECTIVES: Surgical resection currently offers the best option for managing non-small cell lung carcinoma (NSCLC) but its efficiency is limited by subsequent tumor recurrence. We evaluated whether flow cytometric study and the p53 gene staining pattern may be useful in this respect. DESIGN AND METHODS: We took biopsy samples of 40 patients with operable NSCLC to study the frequency of aneuploidy, proliferative activity, and alterations in the p53 tumor suppressor gene and compared them with clinicopathological parameters such as age, gender, smoking, histological type, tumor size, and degree of differentiation. To study DNA content, the nuclei were analyzed by flow cytometry using a FACS flow cytometer (Becton-Dickinson) equipped with an argon ion laser, with a propidium iodide excitation of 488 nm. We used the immunohistochemical technique for p53 analysis in samples of paraffin-embedded tissue corresponding to the same patients from whom fresh tissue was taken. RESULTS: Nuclear p53 staining was detected in 66.7% of the samples; 69.4% of the cases revealed aneuploid DNA histograms and 59% presented with an S phase fraction of more than 12%. Comparison with clinicopathological parameters showed that p53 protein was associated significantly with histological classification (p = 0.04), gender (p = 0.01), and smoking (p = 0.04). CONCLUSIONS: Immunodetection of p53 overexpression and DNA ploidy in the bronchial epithelium may be a useful tool in any future multifactorial analysis in such tumors for identifying previous lesions that may progress to malignancy.

Tumor markers in lung cancer: does the method of obtaining the cut-off point and reference population influence diagnostic yield?

OBJECTIVES: The aim of this study was to evaluate the clinical usefulness of the tumor markers CA125, CEA, NSE, SCC, and TPS in a group of patients with lung cancer. We estimated the influence of the method for choosing the cut-off point and of considering as a reference population either healthy controls or patients with some form of non-neoplastic pulmonary disease (NNPD). DESIGN AND METHODS: The tumor markers were determined using enzyme immunoassay techniques, and their diagnostic yield was evaluated using ROC curves and their correlation with the percentages between false and true positives. The diagnostic parameters of the tumor markers are presented in 116 patients with lung cancer and compared with a group of 25 healthy controls and another group of 80 patients with some form of NNPD. We determined on the one hand the cut-off points resulting from the best sensitivity-specificity balance in the ROC curves and on the other those resulting from considering a specificity of 95%. With the two cut-offs we studied the different diagnostic parameters: sensitivity, specificity and accuracy or area below the ROC curve. RESULTS: Optimum diagnostic yield is obtained when we choose the cut-off point determined by the best balance of sensitivity and specificity in the ROC curves and take a healthy population as a reference group. The cut-off values for CA125, CEA, NSE, SCC, and TPS were 24 U/mL, 2.8 ng/mL, 9.8 ng/mL, 1.6 ng/mL, and 67.8 U/L, respectively. CONCLUSIONS: Our results suggest that in future studies on tumor markers, a group of healthy subjects should be used as a reference population and ROC curves should be used to obtain the optimum cut-offs.

Adrenal insufficiency occurring during septic shock: incidence, outcome, and relationship to peripheral cytokine levels.

PURPOSE: In patients with septic shock, to (1) determine the incidence of adrenal insufficiency (AI), (2) observe the effects of glucocorticoid therapy on outcome in those with impaired adrenal function, and (3) investigate a possible correlation between adrenal function and peripheral cytokine levels. PATIENTS AND METHODS: Twenty-one patients admitted to the medical and surgical intensive care unit with septic shock and 11 healthy volunteers were studied. Cortisol, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels were measured before and after infusion of low (1 microgram) and standard doses (250 micrograms) of adrenocorticotropic hormone (ACTH) within 24 hours of the diagnosis of septic shock. Patients with subnormal adrenal responses to ACTH were treated with stress doses of steroids. Hormone, cytokine, and survival data in patients with normal response were compared to those with subnormal adrenal function. RESULTS: Five patients (23.8%) exhibited AI by ACTH stimulation testing. Three of them received steroid supplementation with rapid improvement in hemodynamic parameters. Autopsies of 2 patients with AI revealed intact adrenal cortices. Sixteen patients had adequate adrenal responses (AAR) to the standard-dose ACTH infusion. TNF-alpha levels were inversely correlated with mean arterial pressure (MAP) (r = -.52, P = 0.038) in AAR but not AI. There was no difference in mean peripheral TNF-alpha levels between AAR and AI. There was no correlation between TNF-alpha levels and mortality or adrenal function in those with septic shock. A trend toward lower IL-6 levels in AI suggests a link between reduced IL-6 levels and understimulation of the pituitary-adrenal axis in this group. Mortality in patients with AI was 80% at 4 weeks as compared with 43.8% in the group with normal adrenal response. CONCLUSIONS: Adrenal hyporesponsiveness is a feature of septic shock in some patients. Its etiology is probably complex. Steroid supplementation appeared to improve short-term survival when AI occurred, although these patients' overall mortality was worse than that of patients with septic shock and AAR. The standard-dose (250 micrograms) rapid ACTH infusion test was adequate for detecting AI. Adrenal insufficiency should be suspected in patients with septic shock who do not respond to conventional treatment. Performing the ACTH infusion test and initiating a trial of stress doses of glucocorticoids pending the results is a reasonable strategy in this situation.