High risk of hypopituitarism in patients who recovered from hemorrhagic fever with renal syndrome

CONTEXT: Hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses, is a severe systemic infection, with acute shock, vascular leakage, hypotension, and acute renal failure. Pituitary ischemia/infarction and necrosis are known causes of hypopituitarism, often remaining unrecognized due to subtle clinical manifestations. Cases of hypopituitarism after HFRS were previously only sporadically reported. OBJECTIVE: The aim of this study was to determine, for the first time, the prevalence of hypopituitarism among HFRS survivors. SUBJECTS AND METHODS: In 60 adults (aged 35.8+/-1.3 yr) who recovered from HFRS 3.7 +/- 0.5 yr ago (median 2 yr), assessment of serum T(4), free T(4), TSH, IGF-I, prolactin, cortisol, and testosterone (in males) was followed by insulin tolerance test and/or GHRH+GH-releasing peptide-6 stimulation tests. RESULTS: Severe GH deficiency was confirmed in eight of 60 patients (13.3%): in five with multiple pituitary hormone deficiencies (MPHDs) and isolated in three. Thyroid axis deficiency was confirmed in five of 60 patients (8.3%), all with MPHD. Hypothalamus-pituitary-adrenal axis deficiency was observed in six of 60 (10.0%); in five with MPHD and isolated in one. Gonadal axis deficiency was confirmed in seven of 56 male subjects (12.5%): five with MPHD and isolated in two. Overall six patients (10.0%) had a single pituitary deficit (three GH, two gonadal, and one adrenal), and five (8.3%) had MPHD. The prevalence of patients having any endocrine deficiency was 18% (11 of 60). CONCLUSION: A high prevalence of hypopituitarism after recovery from HFRS is identified, with magnetic resonance imaging revealing atrophic pituitary and empty sella. Awareness is raised to neuroendocrine consequences of HFRS because unrecognized hypopituitarism significantly affects the physical and psychological well-being.     

Growth hormone replacement normalizes impaired fibrinolysis: New insights into endothelial dysfunction in patients with hypopituitarism and growth hormone deficiency

BackgroundCardiovascular morbidity in adult patients with growth hormone deficiency (GHD) and hypopituitarism is increased. Clustering of cardiovascular risk factors leading to endothelial dysfunction and impaired fibrinolysis has also been reported and may account for progression to overt vascular changes in these patients. However, effect of long lasting GH replacement therapy on fibrinolytic capacity in GH deficient patients has not been investigated so far.ObjectiveTo investigate fibrinolysis before and after challenge with venous occlusion in GHD patients with hypopituitarism before and during one year of growth hormone replacement.DesignHospital based, interventional, prospective study.Investigated subjectsTwenty one patient with GHD and fourteen healthy control subjects matched for age, sex and body mass index (BMI).MethodsAnthropometric, metabolic and fibrinolytic parameters were measured at the start and after three, six and twelve months of treatment with human recombinant GH.ResultsAt baseline GHD patients had significantly impaired fibrinolysis compared to healthy persons. During treatment with GH, significant changes were observed in insulin like growth factor 1(IGF-1) [from baseline 6.9(2.4–13.5) to 22.0(9.0–33.0) nmol/l after one month of treatment; p < 0.01] and fibrinolysis. Improvement in fibrinolysis was mostly attributed to improvement of stimulated endothelial tissue plasminogen activator (t-PA) release in response to venous occlusion [from baseline 1.1(0.4–2.6) to 1.9(0.5–8.8) after one year of treatment; p < 0.01].ConclusionGrowth hormone replacement therapy has favorable effects on t-PA release from endothelium and net fibrinolytic capacity in GHD adults, which may contribute to decrease their risk of vascular complications.     

Belgrade virus: a new hantavirus causing severe hemorrhagic fever with renal syndrome in Yugoslavia.

Two biologically and genetically distinct hantaviruses were isolated from blood and urine specimens collected from four Yugoslavian patients with clinically severe hemorrhagic fever with renal syndrome (HFRS). Viral isolates from three patients, designated strains Belgrade 1-3, were distinct from Hantaan, Seoul, Puumala, and Prospect Hill viruses as determined by plaque-reduction neutralization tests and restriction analysis of enzymatically amplified M-segment fragments. The fourth isolate, called Kraljevo, was indistinguishable from Hantaan virus. Strains Belgrade 1 and 2, like the Kraljevo strain, caused a fatal meningoencephalitis in newborn mice inoculated with 100 pfu of virus intracerebrally and intraperitoneally. Strain Belgrade 3 was much less neurovirulent, requiring 30,000 pfu of virus to cause fatal disease in mice. These data indicate that two distinct hantaviruses, one of which constitutes a new serotype, cause clinically severe HFRS in Yugoslavia.     

Assessing pollution in the Danube River near Novi Sad (Serbia) using several biomarkers in sterlet (Acipenser ruthenus L.)

The response of wild fish to pollutants was studied in sterlet (Acipenser ruthenus L.) collected in 2001 and 2002 at two sampling sites in the Danube River near Novi Sad (Serbia): in the vicinity of the oil refinery and at the Danube-Begec, remote from the oil refinery and considered a reference site. The following biomarkers were measured in sterlet collected from these two sites: the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), and glutathione S-transferase and the induction of CYP1A1 in liver and the activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase in serum. The results demonstrated increase in the activity of SOD and GSH-Px in sterlet collected from the Danube-oil refinery (DOR) compared to that from the reference site, while no differences were found in other enzymes. In conclusion, the overall results suggest that an alteration in the activity of SOD and GSH-Px during the observed period reflects the presence of certain prooxidative compounds that can lead to oxidative stress in the liver of sterlet at the DOR site.     

Histopathologic changes in rat kidneys exposed to acute and chronic immobilization stress

Aim of this study was to detect and quantify histological changes in kidneys after exposure to acute and chronic stress. Rats were divided into the groups consisting of 12 animals: control group—freely moving (unstressed); rats subjected to immobilization for 2 h; rats subjected to repeated 2 h immobilization for ten consecutive days; rats subjected to repeated 2 h immobilization for two consecutive days. Eight features of histopathological damage were scored on normal (0) to severe (4) scale. Changes occured in the kidneys during both, acute and chronic stress. The most common type of degeneration is ‘cloudy swelling’ in epithelial cells of proximal and distal tubules and interstitial edema. Chronic stress induces more prominent changes, which inflict more glomeruls than acute stress. Acute and repetitive stress induces mild or moderate histopathologic changes in kidneys. Copyright © 2010 John Wiley & Sons, Ltd.