Gestational diastolic hypertension with gene mutation-related pheochromocytoma positive at 18F-DOPA PET/CT: Diagnostic and therapeutic implications / Hipertensión diastólica gestacional con feocromocitoma relacionado a mutación genética y PET/TC con 18F-DOPA positiva: implicaciones diagnósticas y terapéuticas

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Arterial hypertension and thyroid disorders: what is important to know in clinical practice?

This review describes the pathogenic mechanisms of blood pressure (BP) regulation and long-term control in thyroid disorders. Variations from the euthyroid status affect virtually all physiological systems but the effects on the cardiovascular system are particularly pronounced. Thyroid disorders induce several hemodynamic changes leading to elevated BP as a consequence of their interaction with endothelial function, vascular reactivity, renal hemodynamic and renin-angiotensin system. However, in thyroid disorders, the regulation of BP and the development and maintenance of variable forms of arterial hypertension (HT) are different. Hyperthyroidism results in an increased endothelium-dependent responsiveness secondary to the shear stress induced by the hyperdynamic circulation, and contributes to reduce vascular resistance. Conversely, hypothyroidism is accompanied by a marked decrease in sensitivity to sympathetic agonists with an increase of peripheral vascular resistance and arterial stiffness. Furthermore in animal models, hypothyroidism reduces the endothelium-dependent and nitric oxide-dependent vasodilatation. HT due to thyroid disorders is usually reversible with achievement of euthyroidism, but in some cases pharmacological treatment for BP control is required. In hyperthyroidism, ß-blockers are the first-choice treatment to control BP but when they are contraindicated or not tolerated, ACE-inhibitors or calcium-channel blockers (CCB) are recommended. Hypothyroidism is a typical low rennin HT form showing a better antihypertensive response to CCB and diuretics; indeed in hypothyroidism a low-sodium diet seems further to improve BP control. Randomized clinical trials to compare the efficacy on BP control of the antihypertensive treatment in thyroid disorders are needed.

Endocrine arterial hypertension: therapeutic approach in clinical practice.

This review describes the therapeutic approach of endocrine arterial hypertension in clinical practice. In mineralocorticoid-related hypertension, adrenalectomy is the treatment of choice for aldosterone-producing adenomas and monolateral primary aldosteronism, whereas pharmacologic blood pressure (BP) control is indicated for the other forms of primary aldosteronism such as bilateral adrenal hyperplasia. Spironolactone is the drug of choice, but intolerable side effects limit its use; amiloride or eplerenone are a valid alternative. If BP remains uncontrolled, angiotensin converting enzyme inhibitors (ACE-I), angiotensin II receptor antagonists (AII-RA) and calcium channel blockers (CCB) may be added. Hypertension accompanying Cushing's syndrome can be approached with surgery, but antihypertensive treatment both pre- and postoperative is required as well. Eplerenone, AII-RA and ACE-I are indicated, while peroxisome proliferator activated receptor upsilon agonists may help for the insulin resistance syndrome. Drugs that suppress steroidogenesis should be used with care because of their serious side effects. Subjects with catecholamine-dependent hypertension due to a neuroendocrine neoplasm need to undergo preoperative alpha-adrenergic blockade with phenoxybenzamine or doxazozine. When adequate alpha-adrenergic blockade is achieved, beta-adrenergic blockade with low dose propranolol may be added. If target BP is not achieved, CCB and/or metyrosine are indicated. Laparoscopic adrenalectomy is the procedure of choice for solitary intra-adrenal neoplasms <8 cm. Acute hypertensive crises that may occur before or during surgery should be treated intravenously with sodium nitroprusside, phentolamine, nicardipine or labetalol. For malignant neoplasms, chemo- and radiopharmaceutical therapy may be considered.

Endocrine arterial hypertension: diagnostic approach in clinical practice.

Endocrine arterial hypertension (EAH) a condition in which hormone excess results in clinically significant hypertension is a rare cause of hypertension. However in the last years its prevalence has increased, mostly due to the improvement of diagnostic work-up. In clinical practice, hypertensive subjects with suspicion of EAH currently undergo hormonal screening of the renin-aldosterone and catecholamines and glucocorticoids excess. This paper reviews current understanding for earlier recognition of the main forms of EAH and discusses screening laboratory methods and localization techniques that have enhanced the clinician's ability to make the diagnosis of EAH. Primary aldosteronism (PA) has recently been recognised as the most frequent cause of EAH. The aldosterone to renin ratio (ARR) is a highly recommended screening test for PA. When ARR is increased, confirmatory tests as saline infusion or fludrocortisone suppression are required. Differential diagnosis of PA requires adrenal gland imaging by computed tomography (CT) or magnetic resonance imaging (MRI), biochemical testing of the aldosterone response to posture, and selective adrenal venous sampling to differentiate unilateral aldosterone-producing adenoma from bilateral hyperplasia. Hypertension is frequently found in endogenous Cushing's Syndrome (CS). Twenty-four-hour urinary free cortisol measurement is the gold standard for the diagnosis of CS, but it must be confirmed by the overnight dexamethasone suppression test. CT and MRI are the primary imaging studies to perform, while scintigraphy is a useful confirmatory method. The most specific and sensitive diagnostic test for catecholamine-producing neoplasms is determination of urinary metanephrine levels; the neoplasms can be located by CT, MRI and metaiodo-benzylguanidine scintigraphy.

[Lipid peroxidation and LDL modifications in nondiabetic patients with ischemic heart disease: the role of insulin action]. / Perossidazione lipidica e modificazioni delle LDL in pazienti non diabetici con cardiopatia ischemica: il ruolo dell'azione insulinica.

BACKGROUND: Nondiabetic patients with advanced coronary artery disease (CAD) were assessed for lipid peroxidation, LDL modifications and insulin action. Twenty-four patients and 10 normal controls were studied. METHODS: Insulin tolerance test (Kitt), glucose, insulin lipoproteins, electronegatively charged, modified, low density lipoproteins (LDL-) and the thiobarbituric acid reactivity (TBARS), as an index of lipid peroxidation, were determined. RESULTS: No difference was observed in insulin action (determined by insulin tolerance test) between patients with CAD (3.31 +/- 0.28%/min; range 0.73-6.13) and normal controls (3.59 +/- 0.42; range 1.76-6.06). The percentage of modified, electronegative LDL (LDL -) was higher in patients with CAD (0.5 +/- 0.48%; range 1.3-9.2) than that of controls (2.80 +/- 0.33; range 1.00-4.00; p = 0.013). TBARS were significantly (P = 0.043) higher in CAD patients (3.49 +/- 0.17 nmol/ml; range 2.4-5.5) than normal controls (1.47 +/- 0.12; range 1.07-2.10). A significantly negative correlation was observed between Kitt and TBARS (r= - 0.48; p = 0.016), and a significant (r = 0.46; p = 0.022) positive correlation was observed between plasma glucose and TBARS. On the contrary no correlation has been observed between LDL- and TBARS. CONCLUSIONS: We conclude that in patients with advanced coronary artery disease: A) there are increased circulating levels of modified low density lipoprotein; B) there is evidence of increased lipid peroxidation. This latter process is significantly influenced by the degree of insulin action.

Chronic hepatitis in childhood: the spectrum of the disease.

During a multicentre study of chronic hepatitis in childhood diagnosed by biopsy, the spectrum of the disease has been evaluated in 196 consecutive patients, including 157 from Northern Italy and 39 from Southern Italy. Only 31% of patients in the former group and 27% in the latter were symptomatic when first seen: the majority of cases being seen after familial screenings for hepatitis B virus (HBV) markers or during intercurrent infections, thus suggesting that the frequency of chronic hepatitis in childhood might be largely underestimated in our area. In Southern and Northern Italy 83% of symptomatic and 95% of asymptomatic patients were hepatitis B surface antigen (HBsAg) positive in serum; only 15 (8.3%) of these children were born to mothers known to be HBsAg positive at delivery, but a high circulation of HBV was found in their families: in fact more than 65% of household contacts in Northern Italy and more than 90% in Southern Italy had serological evidence of past or ongoing HBV infection. These data indicate that, although familial screenings for HBV could have enhanced the percentage of HBsAg positive asymptomatic cases, chronic hepatitis in Italian children is mainly caused by HBV infection acquired in the familial setting through horizontal transmission. Such findings also emphasise the importance of mass vaccination of infants as the most effective means to prevent chronic type B hepatitis in childhood in our area. Among HBsAg positive children 55% had histological features of chronic active hepatitis and 85% were hepatitis Be antigen (HBeAg) positive in serum. Anti-HBe positive hepatitis was significantly more frequent in Southern than in Northern Italy in parallel with the significantly higher prevalence (17%) of hepatitis delta virus infection in that area. Of the 16 HBsAg negative cases included in the study three had autoimmune hepatitis, three Wilson's disease, one alpha1 antitrypsin deficiency, and nine had cryptogenic hepatitis, often associated to mild liver lesions resembling those seen in our adult patients with chronic non-A, non-B hepatitis unrelated to percutaneous exposure.

Acute non-A, non-B hepatitis in childhood.

A prospective study of acute symptomatic viral hepatitis in childhood was started at the Department of Infectious Diseases of Padua (Italy) in 1978. During an 8-year period, 93 consecutive patients (aged 3 months to 12 years) fulfilled the diagnostic criteria, including five (5.5%) cases classified as non-A, non-B hepatitis. This figure is lower than that generally reported in adult patients, probably because of a lower exposure of children to blood and contaminated materials. Two of the five children with non-A, non-B hepatitis had received blood transfusions, while three had no history of parenteral exposure. Although the outcome of the illness was favorable in all five patients, a variety of clinical features could be observed: two children had a mild, short-lasting disease, anicteric in one case, while three had a polyphasic pattern of transaminases with delayed biochemical resolution, including one patient with deep jaundice and severe early phase features. These findings suggest that in children, as well as in adults, non-A, non-B hepatitis is probably a heterogeneous entity induced by different agents with different modes of transmission.

IgM antibody to hepatitis B core antigen in children with chronic type B hepatitis.

IgM antibody to hepatitis B core antigen (anti-HBc IgM) was investigated by an antibody-capture radioimmunoassay (serum dilution 1:4000) in serum samples from 31 untreated children with chronic hepatitis B who were followed prospectively for 1-7 years. At the start, all patients were positive for hepatitis B e antigen (HBeAg), and anti-HBc IgM was detected in 23 cases, including 15 out of 16 with chronic active hepatitis and 7 out of 14 with chronic persistent hepatitis. A significant positive correlation was found between anti-HBc IgM levels and severity of liver damage (P less than 0.05), while an inverse relationship was found between anti-HBc IgM levels and distribution of hepatitis B core (HBcAg) antigen in the liver as detected by immunofluorescence. In fact 75% of anti-HBc IgM positive patients showed a focal HBcAg pattern (less than 40% positive nuclei), whereas 87% of antibody negative cases exhibited a diffuse HBcAg expression (more than 60% stained nuclei). During follow-up, seroconversion from HBeAg to anti-HBe with subsequent remission of liver disease occurred in 82% of patients presenting with detectable levels of anti-HBc, including three out of seven cases with chronic persistent hepatitis, but in none of the cases that were initially negative (P less than 0.01). These results indicate that during the natural course of chronic hepatitis B in children, anti-HBc IgM levels in serum reflect the degree of host immune response to infected hepatocytes. The close correlation between anti-HBc IgM seropositivity and seroconversion from HBeAg to anti-HBe suggests that anti HBc IgM may have a prognostic value during the follow-up of children with chronic HBeAg positive hepatitis B.

Prognosis of chronic hepatitis B transmitted from HBsAg positive mothers.

Nine children born to HBsAg positive mothers, who became chronic HBsAg carriers with associated liver disease, were followed for five to 10 years. Five children with active hepatitis or active cirrhosis at presentation achieved complete remission within six years, while three HBeAg positive patients with minimal histological lesions remained unchanged.

Epidemiology of hepatitis A in northern Italy: a seven-year survey.

During a seven-year survey of acute symptomatic viral hepatitis in Padua (Northern Italy), the epidemiological features of hepatitis A were evaluated in 207 consecutive patients (120 males, mean age 22.7 +/- 11.4 years). The annual attack rate of the disease decreased significantly (p less than 0.05) between 1978 and 1979 (0.11/1000 inhabitants) and 1981 and 1984 (0.04-0.03/1000 inhabitants), mainly due to its declining prevalence in the pediatric age. In parallel with the shifting of hepatitis A towards adulthood, single sources of infection, mainly associated with adult life-style such as foreign travel and raw shellfish ingestion, have become more and more prominent. The spread of drug abuse has not influenced the epidemiology of hepatitis A in our area.

Chronic evolution of acute hepatitis type B: prevalence and predictive markers.

During a prospective study of acute symptomatic viral hepatitis, started in 1978, 664 consecutive adult patients, including 223 drug abusers, fulfilled the diagnostic criteria (anti-HBc IgM positivity) for acute type B hepatitis. In order to evaluate the outcome of the disease, 443 patients were followed for up to 12 months after the onset. 2.4% of the infections became chronic; the rate did not significantly differ between drug addicts and non-drug abusers, suggesting that chronic hepatitis is a rare complication of acute symptomatic hepatitis type B. Ongoing liver damage after clearance of HBsAg from serum was observed in drug abusers only (14% of the cases). Clinical, biochemical and virological features of the acute phase in patients with ongoing infection were compared with those of uncomplicated cases. Anicteric hepatitis and lower transaminase values were significantly (p less than 0.05) associated to a chronic evolution of the disease, as well as a higher prevalence of HBV-DNA, DNA polymerase and HBcAg positivity in serum. Testing HBV-DNA and DNA polymerase early in the course of the infection appeared to be of high predictive value for the subsequent outcome of the illness.

Liver cirrhosis associated with chronic hepatitis B virus infection in childhood.

We evaluated the prevalence and the clinical features of liver cirrhosis associated with chronic hepatitis B virus (HBV) infection in a prospective study of 292 consecutive children who were chronic HBsAg carriers with increased aminotransferase activity. Liver histologic changes at presentation were consistent with cirrhosis in 10 (3.4%) patients (100% boys, mean age 4.0 +/- 3.3 years). In none of the remaining children, including 166 with histologic evidence of chronic active hepatitis, did the condition progress to cirrhosis during an observation period of 1 to 10 years. This lack of progression suggests that cirrhosis is an early complication of chronic HBV disease in some patients. A higher prevalence of delta infection and increased incidence of blood transfusions were observed in patients with cirrhosis, supporting the hypothesis that superinfection with delta or non-A, non-B agents may play a synergistic role. Eight of 10 patients had histologic features of disease activity at presentation, although only two had symptoms. During follow-up, persistence of disease activity was observed only in the three delta antigen-positive patients. None of the patients with inactive cirrhosis have developed signs of liver failure or portal hypertension.

Hepatitis B virus replication in acute glomerulonephritis with chronic active hepatitis.

A 3 year old boy who had chronic active hepatitis type B with features of ongoing liver damage and active virus replication, developed acute membranous glomerulonephritis two years after the clinical onset of liver disease, when both hepatitis B e antigen and antibody were detectable in serum. After withdrawal of short term steroid treatment and resolution of hepatitis B virus replication, both glomerulonephritis and chronic hepatitis went into remission. Some months later hepatitis B surface antigen was no longer found in serum.

Prognostic value of hepatitis B core antigen (HBcAg) expression in the liver of children with chronic hepatitis type B.

During a prospective follow-up study of 65 children with chronic hepatitis B, the HBcAg expression pattern in the liver was investigated, by immunofluorescence, in relation to biochemical and histological features and to the evolution of the disease. HBcAg was detected in 50 (77%) cases, with a diffuse pattern of distribution (more than 60% positive nuclei) in 20 cases, and with a focal pattern (less than 40% positive nuclei) in 30 cases. The diffuse pattern significantly prevailed in younger children, while the focal pattern was more frequent in children beyond 10 years of age. Transaminase levels were higher and histological features of activity were more frequent in patients with the focal pattern than in those with a diffuse pattern. Twenty-five hepatitis B e antigen (HBeAg) positive children, all initially HBcAg positive, were followed prospectively for 24 months. Seroconversion to anti-HBe, with subsequent normalization of transaminases, occurred in 72% of cases with a focal pattern, but only in 21% of those with a diffuse HBcAg pattern. In four patients transition from the diffuse to the focal pattern was observed during follow-up. These results suggest that, in children with chronic hepatitis B, the diffuse HBcAg pattern in the liver might reflect an earlier phase of infection. In HBeAg positive cases the focal HBcAg pattern may represent a prognostic marker of short-term favourable evolution of the disease.