Polymorphisms in von Willebrand factor gene promoter influence the glucocorticoid-induced increase in von Willebrand factor: the lesson learned from Cushing syndrome

Cushing syndrome (CS) features high-glucocorticoid secretion and an associated hypercoagulable state often involving an increase in von Willebrand factor (VWF). To identify any influence of VWF promoter on glucocorticoid haemostatic effects, four polymorphic positions (-3267, -2708, -2659 and -2525) segregating as haplotypes 1 (GCAG) or 2 (CTGA) were analysed in 50 CS patients with high VWF (group I) and normal VWF (group II) levels, divided by ABO group. Genotype distribution differed significantly between the two groups: in group I, 25·8% had genotype 1/1, 22·6% had 2/2 and 38·7% had 1/2; in group II, 0% had genotype 1/1, 57·9% had 2/2 and 31·6% had 1/2 ( P  = 0·03). Patients' genotypes also differed from those of controls ( P  = 0·003 for group I, P  = 0·03 for group II). Haplotype 1 was prevalent in group I, haplotype 2 in group II ( P  = 0·002), both with frequencies differing from controls ( P  < 0·001 and P  = 0·009). By odds ratio analysis, genotype 1/1 carried a 12 times greater risk of high-VWF levels than genotype 2/2, and haplotype 1 carried a five times greater risk than haplotype 2. Our findings suggest that VWF promoter haplotypes influence the corticosteroid-mediated increase in VWF.     

The prevalence of secondary neoplasms in acromegalic patients: possible preventive and/or protective role of metformin

International Journal of Clinical Oncology - Acromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both...     

Multimodal use of computed tomography in early acute stroke, part 2

Computed tomography (CT) scan remains the most widely technique in the cerebrovascular emergency, as it is largely available, minimally invasive, fast, cheap and reliable. Noncontrast enhanced CT (NeCT) imaging can show early signs of infarction in ischemic stroke; however, it could not show if the ischemic tissue is irreversibly damaged. CT perfusion (CTP) imaging has been shown to predict stroke location and size and can provide information about ischemic cerebral parenchyma not definitively compromised. CT angiography (CTA) could highlight stenosis or occlusion both in intracranial and extracranial vessels. By combining NeCT, CTP, and CTA the entire cerebrovascular axis can be imaged during acute stroke. Currently, the term "multimodal CT" indicates the combined use of these three techniques in order to obtain a complete picture of the extension of ischemic damage in acute stroke patients.     

A meta-iodobenzylguanidine scintigraphic scoring system increases accuracy in the diagnostic management of pheochromocytoma

As observed by other authors, normal adrenal medullary tissue frequently gives an apparently positive meta-iodobenzylguanidine (MIBG) scan in cases studied using 123I-MIBG and less frequently 131I-MIBG. The aim of this study was to assess the usefulness of a scoring system, based on different uptakes of the radiopharmaceutical, to improve the accuracy of 123I-MIBG scintigraphy in patients with either adrenal or extra-adrenal pheochromocytomas. Charts from 67 consecutive patients (29 males and 38 females, median age 48 years, range 14-80 years) with suspected pheochromocytoma (either sporadic or familial: multiple endocrine neoplasia (MEN) 2a, MEN2b, Von Hippel-Lindau, neurofibromatosis type 1) who underwent 123I-MIBG scintigraphy (scans acquired 4-24 h after injection) from 1991 to 2004, were independently reviewed by two experienced nuclear medicine physicians using liver uptake as a reference (scores: 1, uptake absent or less than the liver; 2, equal to the liver; 3, moderately more intense than the liver; 4, markedly more intense than the liver). Interfering medications were discontinued for the appropriate time before MIBG injection. Histological data were obtained for all patients who underwent adrenalectomy. Scintigraphies were classified as positive using the following criteria: extra-adrenal focal uptake, adrenal enlargement together with non-homogeneous uptake and adrenal uptake more intense than the liver (score 3-4). After surgical resection, as confirmed by histological findings and long-term follow-up (range 1-14 years, average 9.25 years), 43 patients were considered true positives using the proposed scoring system, 20 were true negatives, four were false negatives and none was false positive. In conclusion, the proposed scoring system demonstrated high specificity (100%), sensitivity (91.5%) and accuracy (94%) in the management of pheochromocytoma. Positive predictive value and negative predictive value were 100% and 83.3% respectively. Normal adrenal tissue uptake was correctly discriminated from pheochromocytomas in 18 out of 20 patients, with adrenal uptake equal to the liver (grade 2), using the proposed cut-off level.     

HLA and hormonal studies in 5 patients with late-onset 21-hydroxylase deficiency syndrome (21OHDS)

Late-onset 21-hydroxylase deficiency (21OHD) presents biochemical evidence of 21OHD and virilization in peri-or postpubertal age; it has been demonstrated that late-onset 21OHD is linked to HLA system. We present the HLA typing, the baseline and the ACTH-stimulated hormonal levels in 5 patients with late-onset 21OHD and in their family members. We identified 3 HLA identical male sibs within their respective families, 2 sibs sharing one haplotype with the affected member and 2 homozygous normal sibs. We observed elevated baseline (greater than 4 ng/ml) and ACTH-stimulated 17-hydroxyprogesterone levels, increased baseline Androstenedione levels, slightly elevated or normal DHEA-S and Testosterone values and subnormal response of Cortisol levels to ACTH in patients and in the HLA-identical sibs, reduced SHBG levels in patients but not in their identical sibs. The heterozygous family members presented hyperresponsiveness of 17-hydroxyprogesterone but not of androgens after ACTH. We confirm that late-onset of 21OHD is an autosomal recessive disease linked to HLA-B; there is in fact biochemical evidence of mild 21OHD in patients and in their HLA identical sibs and 17-hydroxyprogesterone levels in the range of heterozygotes for classical 21OHD in parents and sibs predicted by HLA to be carriers. Thus HLA typing and hormonal data, particularly 17-hydroxyprogesterone, are useful, also in this form of congenital hyperplasia, in detecting heterozygotes.     

Risk of Low Energy Availability in National and International Level Paralympic Athletes: An Exploratory Investigation

(1) Background: The purpose of this study was to examine the symptoms of low energy availability (LEA) and risk of relative energy deficiency in sport (RED-S) symptoms in para-athletes using a multi-parameter approach. (2) Methods: National level para-athletes (n = 9 males, n = 9 females) completed 7-day food and activity logs to quantify energy availability (EA), the LEA in Females Questionnaire (LEAF-Q), dual energy X-ray absorptiometry (DXA) scans to assess bone mineral density (BMD), and hormonal blood spot testing. (3) Results: Based on EA calculations, no athlete was at risk for LEA (females < 30 kcal·kg⁻¹ FFM·day⁻¹; and males < 25 kcal·kg⁻¹ FFM·day⁻¹; thresholds for able-bodied (AB) subjects). Overall, 78% of females were “at risk” for LEA using the LEAF-Q, and 67% reported birth control use, with three of these participants reporting menstrual dysfunction. BMD was clinically low in the hip (<−2 z-score) for 56% of female and 25% of male athletes (4) Conclusions: Based on calculated EA, the risk for RED-S appears to be low, but hormonal outcomes suggest that RED-S risk is high in this para-athlete population. This considerable discrepancy in various EA and RED-S assessment tools suggests the need for further investigation to determine the true prevalence of RED-S in para-athlete populations.