Current recommendations for evaluation of adrenal incidentaloma are likely to result in significant costs, both financial and emotional, due to high false-positive rates. The dose of radiation involved in currently recommended CT scan follow-up confers a risk of fatal cancer that is similar to the risk of the adrenal becoming malignant. This argues for a review of current guidelines.

BackgroundObese individuals who smoke have a 14 year reduction in life expectancy. Both obesity and smoking are independantly associated with increased risk of malignancy. Natural killer cells (NK) are critical mediators of anti-tumour immunity and are compromised in obese patients and smokers. We examined whether NK cell function was differentially affected by cigarette smoke in obese and lean subjects.Methodology and Principal FindingsClinical data and blood were collected from 40 severely obese subjects (BMI>40 kg/m2) and 20 lean healthy subjects. NK cell levels and function were assessed using flow cytometry and cytotoxicity assays. The effect of cigarette smoke on NK cell ability to kill K562 tumour cells was assessed in the presence or absence of the adipokines leptin and adiponectin. NK cell levels were significantly decreased in obese subjects compared to lean controls (7.6 vs 16.6%, p = 0.0008). NK function was also significantly compromised in obese patients (30% +/− 13% vs 42% +/−12%, p = 0.04). Cigarette smoke inhibited NK cell ability to kill tumour cell lines (p<0.0001). NK cells from obese subjects were even more susceptible to the inhibitory effects of smoke compared to lean subjects (33% vs 28%, p = 0.01). Cigarette smoke prevented NK cell activation, as well as perforin and interferon-gamma secretion upon tumour challenge. Adiponectin but not leptin partially reversed the effects of smoke on NK cell function in both obese (p = 0.002) and lean controls (p = 0.01).Conclusions/SignificanceObese subjects have impaired NK cell activity that is more susceptible to the detrimental effects of cigarette smoke compared to lean subjects. This may play a role in the increase of cancer and infection seen in this population. Adiponectin is capable of restoring NK cell activity and may have therapeutic potential for immunity in obese subjects and smokers.

ObjectiveSeveral studies have reported the existence of a subgroup of obese individuals with normal metabolic profiles. It remains unclear what factors are responsible for this phenomenon. We proposed that adipocyte size might be a key factor in the protection of metabolically healthy obese (MHO) individuals from the adverse effects of obesity.SubjectsThirty-five patients undergoing bariatric surgery were classified as MHO (n = 15) or metabolically unhealthy obese (MUO, n = 20) according to cut-off points adapted from the International Diabetes Federation definition of the metabolic syndrome. Median body mass index (BMI) was 48 (range 40–71).ResultsThere was a moderate correlation between omental adipocyte size and subcutaneous adipocyte size (r = 0.59, p<0.05). The MHO group had significantly lower mean omental adipocyte size (80.9±10.9 µm) when compared with metabolically unhealthy patients (100.0±7.6 µm, p<0.0001). Mean subcutaneous adipocyte size was similar between the two groups (104.1±8.5 µm versus 107.9±7.1 µm). Omental, but not subcutaneous adipocyte size, correlated with the degree of insulin resistance as measured by HOMA-IR (r = 0.73, p<0.0005), as well as other metabolic parameters including triglyceride/HDL-cholesterol ratio and HbA1c. Twenty-eight patients consented to liver biopsy. Of these, 46% had steatohepatitis and fibrosis. Fifty percent (including all the MHO patients) had steatosis only. Both omental and subcutaneous adipocyte size were significantly associated with the degree of steatosis (r = 0.66, p<0.0001 and r = 0.63, p<0.005 respectively). However, only omental adipocyte size was an independent predictor of the presence or absence of fibrosis.ConclusionMetabolically healthy individuals are a distinct subgroup of the severely obese. Both subcutaneous and omental adipocyte size correlated positively with the degree of fatty liver, but only omental adipocyte size was related to metabolic health, and possibly progression from hepatic steatosis to fibrosis.

These findings may help explain how cigarette smoking has a detrimental effect in TAO and suggests that IL-1 may be an attractive therapeutic target in TAO.

The term adrenal incidentaloma (AI) is usually defined as an adrenal mass unexpectedly detected through an imaging procedure performed for reasons a priori unrelated to adrenal dysfunction or suspected dysfunction. The preferred approach to their management in terms of diagnosis, follow-up, and treatment remain controversial despite a state-of-the-science conference sponsored by the U.S. National Institutes of Health. Although most experts' recommendations tend to be relatively minor variations of the conference's approach, dissenting voices have been heard. Despite their frequent appearance, the challenge remains to recognize and treat the small percentage of AI that do pose a significant risk, either because of their hormonal activity or because of their malignant histology, while leaving the rest alone. Although the differential diagnosis of an incidentally discovered mass is quite extensive, most AIs are non-secreting cortical adenomas. The noninvasive differentiation of benign and malignant lesions depends upon imaging characteristics, and sometimes radiologic diagnosis can be definitive, but often it is not, Among function lesions, autonomous cortisol production seems to be the most common and may be associated with increased cardiovascular risk and clinical features of the "metabolic syndrome." Follow-up of cases in which a specific diagnosis is not made initially involves assessment for growth and development of hormonal function, but even here, controversy about the extent of evaluation persists.

Objective: Cytokines are likely to play a key pathogenic role in thyroid-associated ophthalmopathy (TAO). Anti-cytokine therapy has been proposed to be a possible treatment for active TAO. We aimed to establish the effects of selected cytokines on intercellular adhesion molecule 1 (ICAM1) expression, glycosaminoglycan (GAG) production and adipogenesis in orbital fibroblasts (OFs) from patients with TAO. Methods: Orbital tissue was taken during surgery from eight patients with TAO and five control subjects. OFs were cultured and ICAM1 expression measured by flow cytometry. GAG production was measured by hyaluronic acid ELISA. OFs were grown in adipogenic media and the degree of adipogenesis quantified. Results: Responses were similar in OFs from patients with and without TAO. Tumour necrosis factor-a (TNFa) and interleukin1 (IL1) (0.1 ng/ml) stimulated ICAM1 expression by eight-to ten-fold. Anticytokine agents inhibited the cytokine-upregulated ICAM1 expression by 90-99% (P!0.01). TNFa and IL1 (0.1 ng/ml) increased hyaluronic acid production by 44 and 95% (P!0.01) respectively. Anti-cytokine agents inhibited these responses by 79-138% (P!0.04). TNFa (0.1 ng/ml) inhibited adipogenesis (K0.013 AU and K1.0; P!0.03) whilst IL1 (0.1 ng/ml) stimulated adipogenesis (C0.05 AU and C5.7; P!0.02) measured by oil-red-O extraction and visual assessment respectively. The anti-IL1 agent inhibited IL1-mediated adipogenesis by 69-106% (P!0.04). Conclusion: TNFa and IL1 stimulate ICAM1 expression and GAG production, but have opposite effects on adipogenesis in OFs in vitro. IL1 promotes adipogenesis and its effects can be blocked by anti-IL1 agents in vitro. These agents may be the anti-cytokine treatment of choice for clinical trials in active TAO. European Journal of Endocrinology 155 395-403

Adipose tissue in MHO individuals had lower levels of Pref-1, a known inhibitor of preadipocyte differentiation, and a more favorable inflammatory profile. These factors may be key to protecting this subgroup of obese individuals from the adverse metabolic profile associated with excess adiposity.

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