Is hypothyroidism a risk factor for non-alcoholic steatohepatitis?

PURPOSE: Thyroid hormones play an important role in the regulation of lipid and carbohydrate metabolism, both of which are affected in patients with non-alcoholic steatohepatitis (NASH). Anecdotally, we have observed that a number of patients with NASH carried a diagnosis of hypothyroidism. However, it is unknown if thyroid dysfunction plays any role in the pathogenesis of NASH. To further investigate this observation, we conducted a case-control study to determine the association between hypothyroidism and NASH. SUBJECTS AND METHODS: Cases were defined as patients with well-documented NASH attending hepatology clinics at Indiana University Hospital from January 1, 1995 to December 31, 2000. Age, gender, race, and body-weight matched individuals seen during the same period in the general medical clinics served as controls. Patients with a previous diagnosis of hypothyroidism who are currently on synthetic T4 replacement were considered to be "hypothyroid". The strength of association was assessed by logistic regression analysis after controlling for the frequency of diabetes mellitus, hyperlipidemia, and hypertension. RESULTS: One hundred seventy-four patients with NASH (cases) and 442 controls were included. The mean age of cohort was 49 +/- 13 years, 59% were female, and 98% were white. The prevalence of hypothyroidism in patients with NASH was 15% was significantly higher than in the controls (7.2%, P < 0.001). By multivariate analysis, the prevalence of hypothyroidism in the NASH group was significantly higher than in control group (OR: 2.3, 95% CI: 1.2-4.2, P = 0.008). CONCLUSION: These data suggest that hypothyroidism is associated with human NASH. Further research is needed to confirm this finding and to understand its implications.     

Is age a risk factor for major pancreatic surgery? An analysis of 300 resections.

BACKGROUND/AIMS: The aim of this study was to analyze if age alone is a risk factor in major pancreatic surgery. METHODOLOGY: From September 1, 1985 to December 31, 1997, 806 patients underwent surgery for malignant and benign diseases of the pancreas in a prospective case control study performed at the Department of Surgery, Johannes Gutenberg University Hospital Mainz. In 228 patients (men: n = 139; women: n = 89; mean age: 61 years; range: 23-83 years) we performed partial (n = 178) or total (n = 50) pancreaticoduodenectomy, which was combined with portal vein resection in 16 cases. Left pancreatic resection was carried out in 72 patients (men: n = 40; women: n = 32; mean age: 65 years; range: 28-86 years). RESULTS: Surgical complications after pancreaticoduodenectomy occurred in 22.1% of patients < or = 70 years and in 30.2% of patients > 70 years, however, less than half of them had severe complications ranging below 50%. General complications developed in 16.1% of patients < or = 70 years and in 27.9% of patients > 70 years (p < 0.001). The mortality rates 30 and 90 days after surgery were 3.2% (< or = 70 years) and 2.3% (> 70 years), and 6.0% (< 70 years) and 6.9% (> 70 years), respectively. Regression analysis showed the following factors to exert an independent influence on mortality: Pre-operative serum bilirubin, the diameter of the pancreatic duct, intra-operative blood loss and the occurrence of surgical and nonsurgical complications. Age did not exert an independent influence on the prognosis of either morbidity or mortality. However, general complications developed significantly more often in elderly patients. After left pancreatic resection surgical complications developed in 29.3% (< or = 70 years) and 21.4% (> 70 years) of patients, however the rate of severe complications was below 10%. General complications occurred in 10.3% (< or = 70 years) and 28.6% (> 70 years) (p < 0.001). Mortality rates 30 and 90 days after operation were 1.7% (< or = 70 years) and 14.2% (> 70 years), and 3.4% (< or = 70 years) and 14.2% (> 70 years) (p = n.s.), respectively. Regression analysis showed the intra-operative blood loss to exert an independent influence on post-operative morbidity and mortality. Age had no independent influence on either morbidity or mortality. CONCLUSIONS: Results obtained by this study show that, although general complications develop significantly more often in elderly patients, age is not an independent risk factor for post-operative mortality after major pancreatic resection. Factors of importance in improving the outcome of this operation include the experience of the surgeon in selecting patients eligible to undergo the procedure, his operative skills in performing major pancreatic resections, as well as better anticipation and management of post-operative complications.     

Is subclinical hypothyroidism a cardiovascular risk factor?

OBJECTIVES: Subclinical hypothyroidism defined by the presence of elevated TSH levels but normal free T4 level is a common situation. Its consequences on health are yet on debate and the interest of a precocious treatment remains surrounded by controversy. KEY POINTS: The relationship between subclinical hypothyroidism and cardiovascular disease has been evaluated by several cross-sectional and longitudinal studies. Subclinical hypothyroidism has direct but subtle effects on the heart function, on the peripheral vascular resistance, and is associated with a mild elevation of LDL-cholesterol levels; all abnormalities may be partly reversed by a thyroxine supplementation. Data of the literature give insufficient evidence as to whether subclinical hypothyroidism is an independent cardiovascular risk factor. However treatment of subjects with TSH levels up or near to 10 mU/l would probably be beneficial in the prevention of cardiovascular disease. FUTURE PROSPECTS: Based on observational and interventional studies there are some arguments on the benefit of euthyroidism restoration only in patients with TSH levels superior to 10 mU/l.     

Subclinical hypothyroidism: a cardiovascular risk factor?

Although patent hypothyroidism is clearly associated with increased cardiovascular risk, the relationship between infraclinical hypothyroidism and cardiovascular disease remains controversial though probable. This relationship is mediated by the traditional risk factors (lipids, hypertension), by changes in parameters of inflammation and haemostasis, and by a direct effect of thyroid hormones on the vessel wall. The authors review the epidemiological evidence and the mechanisms underlying the association between infraclinical hypothyroidism and cardiovascular risk and the therapeutic implications of this association.     

Postpartum thyroiditis in women with hypothyroidism antedating pregnancy?

In women with hypothyroidism, levothyroxine (LT) requirements after delivery are assumed to return to prepregnancy values. The occasional observation of discordances prompted this study. Forty-one women (31 receiving LT replacement therapy and 10 receiving suppressive therapy for thyroid carcinoma) were followed during the first year after delivery. A control group of 31 nonpregnant women with hypothyroidism (n = 21) or thyroid carcinoma (n = 10) were also followed during a similar period. Twenty-three patients of 41 (56.1%) had discordant requirements at follow-up after delivery vs. 3 of 31 in the control group (9.7%; P < 0.001). The patterns of discordance in the postdelivery group were hyperthyroidism in 12, increase in LT dose in 5, hyper- and hypothyroidism in 5, and recurrence of Graves' disease in 1 women. Those in the control group were increase in LT dose, hyperthyroidism, and hypo- and hyperthyroidism. The rate of patients with discordant prepregnancy-postpartum LT doses was higher in the noncarcinoma subgroup (67.7% vs. 20.0%; P < 0.01), whereas in the control group, both subgroups displayed a similar rate of discordance (9.5% vs. 10%; P = NS). In conclusion, this study documents that women with hypothyroidism antedating pregnancy display changes in LT requirements in the first year after delivery that suggest postpartum thyroiditis.     

Is thyroid-stimulating hormone within the normal reference range a risk factor for atherosclerosis in women?

The relationship between overt hypothyroidism and cardiovascular risk has been well documented and some data also suggest an association between cardiovascular risk and subclinical hypothyroidism. The aim of our study was to investigate, in a large cohort of euthyroid women, the association of thyroid stimulating hormone (TSH) within the normal reference range with cardiovascular risk factors. The study was carried out on 744 women with normal thyroid function (TSH 0.3–4.9 μU/mL). Women with TSH above the median (≥2.1 μU/mL) were more obese, had greater waist girth, were more hypertensive and had higher levels of total cholesterol (TC), serum triglycerides (TG), blood sugar (BG) and lower levels of HDL-cholesterol (HDL-C) than women with TSH below the median. TSH was significantly correlated with body mass index (BMI), waist circumference, BG, TG, TC, HDL-C and hypertension. Multiple backward stepwise regression analysis with age, waist circumference and TSH as independent variables confirmed the strong association of TSH with BG, TG, HDL-C and hypertension. A total of 205 patients (28%) fulfilled the definition criteria of the metabolic syndrome and the prevalence of metabolic syndrome was significantly greater in patients with TSH above than in patients with TSH below the median. Results of logistic analysis, including age and TSH as predictor variables, confirmed the association of TSH with metabolic syndrome.The results of this study suggest that TSH in the upper limits of the reference range (above 2.1 μU/ml) is associated with a less favourable cardiometabolic profile and consequently with a higher risk of developing cardiovascular diseases.     

Is the absence of JAK2V617F mutation a risk factor for bleeding in essential thrombocythemia? An analysis of 106 patients

Background

JAK2^V617F mutation has been recognized as a possible thrombotic risk factor in essential thrombocythaemia (ET). It’s role is probably due to an increased myeloid proliferation and white blood cells (WBC) activation. Only few data are available about the effect of JAK2^V617F on hemorrhagic risk. The aim of our study was to evaluate the influence of the mutational status on hemorrhagic complication.

Methods

We retrospectively analysed laboratory and clinical findings of 106 consecutive patients with ET to evaluate possible relationships between thrombosis, abnormal bleeding, peripheral blood count, overexpression of PRV1 and JAK2^V617F mutational status.

Results

On univariate analysis we found: an association between JAK2^V617F mutation and thrombotic events before or at diagnosis (p<0.003, OR=4.44, 95% CI=1.74–12.4); no statistical correlation between the median value of JAK2^V617F burden and an increased risk of thrombosis (p=0.4, 95% CI= −22.8–10.4); significant relationships between mutated status and higher haematocrit, high WBC count and low platelet count; and a strong correlation between JAK2^V617F and PRV1 overexpression (p<0.0001). Moreover, the presence of the JAK2^V617F mutation and a WBC count greater than 8.4 × 10⁹/L were found to be independent factors related to thrombotic complications in multivariable analysis (p<0.006, OR=3.85, 95% CI=1.3–11.9; and p<0.002, OR=2.8, 95% CI=1.08–7.03, respectively). The prognostic impact of JAK2 mutation status and WBC count on thrombosis was evaluated in the whole cohort. Only new cases occurring in patients without previous thrombotic events were recorded for the analysis. The multivariable analysis showed a statistical correlation between the presence of the mutation and a WBC count greater than 8.12 × 10⁶/L and an increased risk of thrombosis if no cytoreductive treatment was started at diagnosis (JAK2^V617F p=0.02; WBC p=0.02; OR=4.97; 95% CI=1.04–23.8). Finally, wild-type JAK2 was associated with a higher haemorrhagic risk (p=0.02) in univariate analysis but only a platelet count greater than 1,022 × 10⁹/L was associated with an increased risk of bleeding in the multivariable analysis.

Conclusion

Our data confirm the role of both JAK2^V617F as factor associated with an increased risk of thrombosis at the diagnosis and during follow-up in no treated patients. Moreover a WBC count over 8.4×10⁹/L¹ was also strictly associated to an increased risk of thrombosis. Regarding bleedings, our statistical analysis allows to exclude the mutation protective role on haemorrhage.     

Is obesity a new risk factor for gastritis?

Obesity has become a major concern among gastroenterologists due to its large influence on gastrointestinal and hepatic diseases: reflux esophagitis, pancreatitis, gallstone disease, liver fibrosis, and neoplastic tumors of the esophagus, pancreas, and colon. Studies of morbid obese subjects undergoing bariatric surgery have revealed that obesity is related with an increased prevalence of endoscopic and histologic gastritis. A recent study of health check-up subjects demonstrated an association of obesity with endoscopic gastritis and gastric ulcers. We recently investigated the underlying mechanisms of the effects of obesity on endoscopic gastritis in subjects undergoing health check-up examination, and demonstrated that adiponectin, a bioactive molecule released from visceral fat, could be a protective factor of endoscopic gastritis. We would like to propose a new category of gastritis, obesity-related gastritis, which could become dominant in the near future.     

Is thyroid inadequacy during gestation a risk factor for adverse pregnancy and developmental outcomes?

A workshop entitled, "The Impact of Maternal Thyroid Diseases on the Developing Fetus: Implications for Diagnosis, Treatment, and Screening," was held in Atlanta, Georgia, January 12-13, 2004. This paper reports on the individual session that examined thyroid inadequacy during gestation as a risk factor for adverse pregnancy and developmental outcomes. For this session the following papers were presented: "Adverse Pregnancy Outcomes"; "Thyroid Physiology in the Fetus"; "New England Data: Cretinism Revisited-Preventing Fetal Brain Damage when Mothers Have Subclinical Hypothyroidism"; "Dutch Data: Pregnancy, Maternal Thyroid (Dys)function and Outcome of the Offspring"; and "Report on the Wales Controlled Antenatal Thyroid Screening Study (CATS); A Prospective RCT." These presentations were formally discussed by invited respondents well as others in attendance. Salient points from this session about which there was agreement include the following. Maternal hypothyroidism is associated with complications of pregnancy and adverse effects on the fetus. These risks are greater in women with overt hypothyroidism compared to subclinical hypothyroidism, and also appear to be increased in women with euthyroid autoimmune thyroid disease. If maternal hypothyroidism is treated adequately, this appears to reduce the risk for adverse outcomes. The demonstration of a pattern of ontogeny of fetal cerebral cortex deiodinases and thyroid hormone receptors, beginning by 7-8 weeks' gestation, is circumstantial evidence that thyroid hormone plays an important role in fetal neurodevelopment. Significant fetal thyroid hormone production and secretion does not begin until approximately 20 weeks' gestation. If there is a significant role for thyroid hormone in fetal neurodevelopment before 20 weeks' gestation, it likely is of maternal origin. Studies demonstrate low levels of thyroxine in the fetal coelomic fluid and blood prior to 12-14 weeks' gestation. Published data consistently document a relationship between maternal thyroid deficiency during pregnancy and problems with neuropsychological development of the offspring.