Multiple Endocrine Neoplasia Type I

Opinion statement Multiple endocrine neoplasia type I is a rare autosomal dominant disorder with many endocrine and nonendocrine manifestations. Hyperparathyroidism, islet cell tumors, and pituitary tumors are diagnosed most commonly in these patients. There is controversy regarding treatment of the different manifestations and screening modalities of this disorder because no large series has determined the best therapeutic approach. Our institution advocates early screening with biochemical and radiographic testing in patients with a definite predilection for this disorder. Patients with hyperparathyroidism should undergo early surgical intervention of at least three and a half glands combined with bilateral upper thymectomy through a cervical incision. Although the recurrence rate is high, disease-free survival can be for as long as 30 years. Pituitary tumors are predominantly prolactinomas and growth hormone-releasing tumors. Prolactinomas usually require pharmacologic therapy, whereas growth hormone-releasing tumors are treated surgically. Enteropancreatic tumors should be treated surgically or medically, depending on the hormone secreted. Insulinomas respond well to distal pancreatectomy, with enucleation of the tumor from the head and uncinate process of the pancreas. However, there is controversy regarding the surgical treatment of gastrinomas. Carcinoid tumors should be treated with early surgical intervention. Adrenal lesions are thought to occur in association with pancreatic lesions and commonly have an indolent course. Adrenocortical cancers are uncommon in patients with multiple endocrine neoplasia type I. Skin lesions can be excised when cosmetically unappealing.     

High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients

Background and Aim: We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T₃₀) the low‐dose 1‐µg short synacthen test (LD‐SST); and (ii) the prognostic value of SFC and STC. Methods: Consecutive, hemodynamically stable, cirrhotic patients (34 Child–Pugh class A, 29B, and 32C) underwent the LD‐SST. Patients were followed for at least 12 months to assess non‐transplant‐related mortality. Results: Child–Pugh class C patients had significantly higher basal levels of SFC than Child–Pugh class A or B patients. Prevalence of suspected adrenal dysfunction ranged between 7.4% (T₀ STC < 138 nmol/L) and 49.4% (change in STC < 250 nmol/L) according to the threshold used. In receiver–operator curve analysis, the area‐under‐the‐curve values were 0.67 for T₃₀ SFC (0.51–0.79), 0.81 for Child–Pugh score (0.70–0.88), and 0.79 for albumin level (0.63–0.88). During the follow‐up period, 16 patients with high T₃₀ SFC (≥ 78.9 nmol/L) (26.2%) and one patient with low T₃₀ SFC (< 78.9 nmol/L) (3.4%) died (P = 0.027 for high vs low T₃₀ SFC, log–rank test). Albeit not statistically significant, the risk of death for patients with T₃₀ SFC ≥ 78.9 nmol/L was fivefold higher than for patients with lower levels after adjusting for cirrhosis severity and level of albumin. Conclusions: One‐year, non‐transplant‐related mortality is high among patients with T₃₀ levels of SFC ≥ 78.9 nmol/L (26.2%). These findings might result from latent inflammatory stress in hemodynamically stable cirrhotic patients, detected by adrenal testing.     

Impaired Culprit Vessel Flow in Acute Coronary Syndromes Ineligible for Thrombolysis

The majority of patients with acute myocardial infarction and other acute coronary syndromes (ACS) are considered ineligible for thrombolysis and do not routinely receive reperfusion therapy. We hypothesized that predictors and outcomes of angiographically impaired culprit vessel flow can be identified and compared. This trial evaluated the outcomes following triage angiography in acute coronary syndromes ineligible for thrombolytic therapy. Eligible patients (n=201) with<24 hours of symptoms were randomized to early triage angiography and subsequent therapies based on the angiogram versus conventional medical therapy. This analysis was performed in 165 patients, from experimental and control arms, in whom angiography was performed on the index hospitalization with the outcome of interest being target vessel flow (Thrombolysis In Myocardial Infarction [TIMI] grades 0 to 2) on initial angiography. Patients with and without impaired culprit lesion flow were similar with respect to age, gender, diabetes, and prior coronary disease. A family history of premature coronary disease was more common in those with impaired flow, 50.0 versus 28.5% (p=0.02). Abnormal culprit vessel flow was found in 19.2% of patients who underwent angiography within 6 hours of symptom onset; however, after 24 hours this rate was reduced to 11.7%. Impaired culprit lesion flow can be expected in approximately 20% of patients presenting with ACS who are ineligible for reperfusion therapy by conventional guidelines and therefore represents an opportunity for early intervention within 6 hours of the onset of symptoms in these patients.     

Chromosomal aberrations by comparative genomic hybridization in thyroid tumors in patients with familial nonmedullary thyroid cancer.

PURPOSE: Nonmedullary thyroid cancer is the most common form of thyroid cancer and its familial form (FNMTC) is increasingly recognized as a distinct clinical entity. However, the genetic background of FNMTC is still poorly understood and the causative gene(s) have not yet been identified. METHODS: Because comparative genomic hybridization allows for screening of the entire tumor genome simultaneously for chromosomal gains and/or losses without prior knowledge of potential aberrations, we used this technique in thyroid normal and neoplastic samples from FNMTC patients (1) to analyze whether chromosomal aberrations would correlate with inheritance pattern, and/or clinicopathologic features and (2) to compare comparative genomic hybridization (CGH) findings in familial tumors with those already known in sporadic differentiated thyroid cancers. RESULTS: No common germline or somatic chromosomal aberrations were observed in patients with FNMTC because the frequencies and most locations of chromosomal aberrations in familial tumors were also common in sporadic tumors. However, some somatic aberrations were only found in familial tumors (gains in 2q, 3q, 18p, and 19p). Common aberrations in familial tumors corresponded to several locations of candidate genes already reported for sporadic thyroid tumorigenesis. CONCLUSIONS: Our findings suggest that chromosomal aberrations in thyroid tumors in patients with FNMTC are not related to inheritance pattern but rather to tumorigenesis.     

Association of Longitudinal Glycemia with Diffusion Weighted Imaging Lesions in Spontaneous Intracerebral Hemorrhage

ObjectivesHigher glycemia on admission has been associated with diffusion weighted imaging (DWI) lesions in patients with spontaneous intracerebral hemorrhage (sICH). However, the influence of longitudinal glycemia after admission and during a patient's hospitalization on DWI lesions in sICH has not been studied. Our aim was to compare longitudinal glycemia in sICH patients with and without DWI lesions.Material and MethodsGlycemia measurements were abstracted on participants enrolled in a prospective observational study examining predictors for DWI lesions in sICH. Univariate analysis was used to compare mean longitudinal glycemia in sICH patients with and without DWI lesions. Logistical regression was used to determine whether mean longitudinal glycemia was predictive of DWI lesions.ResultsDWI lesions were found in 60 of the 121 (49.6%) participants. Mean time-to-MRI was 99.6 h (SD ± 89). During this time interval, 2,101 glucose measurements were analyzed with a median number of 7 (IQR 12, 1-261) measurements per patient. Mean longitudinal glycemia was higher in the DWI positive group compared to the DWI negative group until time-to-MRI (132 mg/dL vs 122 mg/dL, p = 0.03). Mean longitudinal glycemia was found to be predictive of DWI lesions (OR 1.02, 95% CI 1.005 to 1.035, p = 0.011).ConclusionsMean longitudinal glycemia was higher in sICH patients with DWI lesions compared to those without DWI lesions. Future research into the association between higher glycemia and DWI lesions in sICH may provide insight into a pathophysiologic mechanism.     

Chimeric Derivatives of Hepatitis B Virus Core Particles Carrying Major Epitopes of the Rubella Virus E1 Glycoprotein

Three variants of the major rubella virus (RV) E1 protein virus-neutralizing epitope from position 214 to 285 were exposed on the hepatitis B virus (HBV) C-terminally truncated core (HBcΔ) in a virus-like particle (VLP) vector and were produced in Escherichia coli. All three chimeras demonstrated VLPs in bacterial cell lysates, but only HBcΔ-E1(245-285) demonstrated the correct VLP structure after purification. The other chimeras, HBcΔ-E1(214-285) and HBcΔ-E1(214-240), appeared after purification as non-VLP aggregates of 100 to 900 nm in diameter according to dynamic light scattering data. All three variants possessed the intrinsic antigenic activity of RV E1, since they were recognized by natural human anti-RV E1 antibodies and induced an anti-RV E1 response in mice. HBcΔ-E1(214-240) and HBcΔ-E1(245-285) can be regarded as prototypes for a putative RV vaccine because they were able to induce antibodies recognizing natural RV E1 protein in RV diagnostic kits.     

Body image satisfaction and depression in midlife women: the Study of Women’s Health Across the Nation (SWAN)

With aging, women’s bodies undergo changes that can affect body image perception, yet little is known about body image in midlife. The purpose of this study was to examine associations between body image and depressive symptoms in Caucasian and African–American midlife women from the Study of Women’s Health Across the Nation (SWAN) Chicago site. Body image was measured using the Stunkard Adult Female Figure Rating Scale, and a clinically significant level of depressive symptoms was defined as Center for Epidemiologic Studies Depression Scale (CES-D) score of ≥16 (N?=?405; N?=?63 (15.6 %) with clinically significant levels of depressive symptoms). Differences between perceived actual, perceived ideal, and actual body size and responses to questions concerning weight satisfaction and attractiveness were examined using logistic regression for associations with a CES-D score of ≥16. Women with body image dissatisfaction (odds ratio (OR)?=?1.91; p?=?0.04) or who perceived themselves as “unattractive” (OR?=?7.74; p?<?0.01) had higher odds of CES-D of ≥16. We found no significant difference by race. Our results were not confounded by BMI. These results suggest that midlife women with poor body image may be more likely to have clinically significant levels of depressive symptoms. Larger prospective studies are needed to better understand this association.     

Does Bethesda Category Predict Aggressive Features in Malignant Thyroid Nodules?

Background

It has been speculated that the Bethesda Classification System for thyroid fine-needle aspirate (FNA) may be used to predict aggressive features among histologically proven malignancies. We sought to evaluate whether malignancies that were characterized as Bethesda category V or VI have more aggressive features than malignancies that were category III or IV.

Methods

A prospectively maintained database was reviewed to identify thyroid malignancies treated at a single center from 2004 to 2009. Only cancers that could be definitively matched to a preoperative FNA were included. Associations between Bethesda category, patient demographics, histopathologic findings, and outcomes were examined.

Results

A total of 360 cancers were analyzed: 73 (20 %) were Bethesda category III or IV and 287 (80 %) were category V or VI. The majority of Bethesda III and IV cancers were follicular variants of papillary thyroid carcinoma (fvPTC), whereas the majority of Bethesda V and VI cancers were classic PTC (52 and 67 %, respectively, p < 0.01). Extrathyroidal extension (30 vs. 16 %, p = 0.02), lymph node metastases (50 vs. 31 %, p = 0.05), and multifocality (51 vs. 37 %, p = 0.03) were more common among Bethesda V and VI nodules. However, when Bethesda III or IV classic PTC and fvPTC were compared to Bethesda V or VI cancers of the same histologic subtype, there were no differences in any features. Recurrence and overall survival were the same in all groups.

Conclusions

Bethesda category may help to predict the most likely histologic subtype of thyroid cancer, but it does not have any prognostic significance once the histologic diagnosis is known.