[Show abstract][Hide abstract] ABSTRACT: Candida bloodstream infections (BSI) represent an important problem in Intensive Care Units (ICUs). The epidemiology of candidemia is changing with an increase in the proportion of Candida (C.) non-albicans.
An Italian 2-year observational survey on ICU was conducted to evaluate the species distribution and possible differences between BSI caused by C. albicans and C. non-albicans. For comparative purposes, we performed a European literature-based review to evaluate distribution and frequency of Candida spp. causing ICU candidemia, during the period 2000-2013.
This laboratory-based survey involved 15 microbiology centers (GISIA-3 study). All candidemia episodes in adult patients were considered. Data were prospectively collected from 2007 to 2008. PubMed was searched for peer-reviewed articles.
In total, 462 candidemia episodes were collected. C. albicans accounted for 49.4% of the isolates, followed by C. parapsilosis (26.2%) and C. glabrata (10.4%). Mortality was higher in patients with C. non-albicans than C. albicans (47.3% vs. 32.4 %, p > 0.05). Among risk factors, parenteral nutrition was more common (p = 0.02) in non-albicans candidemia, while surgery was more frequent (p = 0.02) in C. albicans candidemia. Twenty-four relevant articles were identified. C. albicans was the predominant species in almost all studies (range 37.9% -76.3%). C. glabrata was commonly isolated in the German-speaking countries, France, UK and North Europe; C. parapsilosis in Turkey, Greece and Spain.
Although C. non-albicans BSI is increasing, our study shows that C. albicans is still the predominant species in ICU candidemia. There are differences in the epidemiology of Candida BSI among European countries, with a prevalence of C. glabrata and C. parapsilosis in Northern and Southern countries, respectively.
European review for medical and pharmacological sciences 03/2014; 18(5):661-74. · 1.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pregnancy is becoming a relatively common event in patients with pituitary tumors (PT), due to the increasing availability of medical treatments, which control pituitary diseases associated with the development of PT. However, the presence of PT and its treatment may be a disturbing factor for pregnancy, and pregnancy significantly influences the course and the management of PT. This review summarizes the knowledge about the management of PT during pregnancy and the occurrence of pregnancy in patients with pre-existent PT, focusing on secreting PT characterized by hormonal excess and on clinically non-functioning PT often associated to hormone deficiency, which configure the hypopituitaric syndrome.
Journal of endocrinological investigation 02/2014; 37(2):99-112. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We compared the risk factors, the diagnostic tools and the outcome of filamentous fungal infections (FFIs) in hematological patients (HAEs) and non-hematological patients (non-HAEs).
Prospective surveillance (2009-2011) of proven and probable FFIs was implemented in 23 Italian hospitals.
Out of 232 FFIs, 113 occurred in HAEs and 119 in non-HAEs. The most frequent infection was invasive aspergillosis (76.1 % for HAEs, 56.3 % for non-HAEs), and the localization was principally pulmonary (83.2 % for HAEs, 74.8 % for non-HAEs). Neutropenia was a risk factor for 89.4 % HAEs; the main underlying condition was corticosteroid treatment (52.9 %) for non-HAEs. The distribution of proven and probable FFIs was different in the two groups: proven FFIs occurred more frequently in non-HAEs, whereas probable FFIs were correlated with the HAEs. The sensitivity of the galactomannan assay was higher for HAEs than for non-HAEs (95.3 vs. 48.1 %). The overall mortality rate was 44.2 % among the HAEs and 35.3 % among the non-HAEs. The etiology influenced the patient outcomes: mucormycosis was associated with a high mortality rate (57.1 % for HAEs, 77.8 % for non-HAEs).
The epidemiological and clinical data for FFIs were not identical in the HAEs and non-HAEs. The differences should be considered to improve the management of FFIs according to the patients' setting.
[Show abstract][Hide abstract] ABSTRACT: Objective
Acromegalic patients have increased mortality. The objective of the study was to compare the effect of different therapies for acromegaly on mortality.Design&Methods
Mortality of 438 consecutive acromegalic patients was compared to that of the general population by standardized mortality ratio(SMR);the effect of different therapies on survival was evaluated by Cox regression analysis.ResultsTwenty patients(4·5%) died between 1999 and 2009.Age and sex-adjusted SMR was 0·70(95% C.I., 0·43-1·08).Cox regression analysis revealed that, in the whole population, both general risks factors(age and the physical status), and specific factors for acromegaly(macroadenoma, hypopituitarism and uncontrolled disease) were associate with death. The most compromised patients at diagnosis had higher mortality(p=0·001), which occurred also in patients with controlled acromegaly.Death occurred in 2·4%(adenomectomy), 2·6%(adenomectomy followed by somatostatin analogues, SSA) and 11·4%(SSA as primary therapy) patients.The risk of death was higher in patients receiving SSA as primary therapy(Hazard Ratio, HR 5·518, 95% C.I., 1·058-28·767, p=0·043) than in all patients submitted to adenomectomy; however, a higher risk of death occurred only in diabetic patients treated with SSA alone(HR, 21·936, 95% CI, 1·557-309·04, p=0·022).Radiotherapy was associated with increased mortality, which occurred in patients with the more locally advanced disease.Conclusions
Therapies of acromegaly and comorbidities have lowered mortality to the level of the general population;SSA alone or following pituitary adenomectomy was comparable to curative neurosurgery on survival in non-diabetic patients; on the contrary, SSA as primary therapy, may be less effective than adenomectomy in reducing mortality in diabetic patients.
European Journal of Endocrinology 07/2013; · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The clinical conditions associated with GH excess and GH deficiency are known to be associated with an increased risk for cardiovascular morbidity and mortality, suggesting that either an excess or a deficiency in GH and/or IGF-I is deleterious for cardiovascular system. In patients with acromegaly chronic GH and IGF-I excess commonly causes a specific cardiomyopathy characterized by a concentric cardiac hypertrophy associated with diastolic dysfunction, and, in later stages, with systolic dysfunction ending in heart failure if GH/IGF-I excess is not controlled. Abnormalities of cardiac rhythm and anomalies of cardiac valves can also occur. Moreover, the increased prevalence of cardiovascular risk factors, such as hypertension, diabetes mellitus and insulin resistance, as well as dyslipidemia, confer an increased risk for vascular atherosclerosis. Successful control of the disease is accompanied by a decrease of the cardiac mass and improvement of cardiac function and an improvement in cardiovascular risk factors. In patients with hypopituitarism, GH deficiency has been considered the underlying factor of the increased mortality when appropriate standard replacement of the pituitary hormones deficiencies is given. Either childhoodonset or adulthood-onset GH deficiency are characterized by a cluster of abnormalities associated with an increased cardiovascular risk, including altered body composition, unfavourable lipid profile, insulin resistance, endothelial dysfunction and vascular atherosclerosis, a decrease in cardiac mass together with an impairment of systolic function mainly after exercise. Treatment with recombinant GH in patients with GH deficiency is followed by an improvement of the cardiovascular risk factors and an increase in cardiac mass together with an improvement in cardiac performance. In conclusion, acromegaly and GHD are associated with an increased risk for cardiovascular morbidity and mortality, but the control of GH/IGF-I secretion reverses cardiovascular abnormalities and restores the normal life expectancy.
Journal of endocrinological investigation 11/2012; · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:Percutaneous radiofrequency thermal ablation (RTA) was reported as an effective tool for the management of thyroid nodules (TNs). The aim of this study was to investigate the effects of RTA and to establish whether they were treatment-related by comparison with a matched, untreated control group.Patients and Methods:The study population included 40 patients with compressive TNs: 22 had nontoxic TNs, and 18 had toxic TNs and were treated with methimazole. In all patients, a fine-needle aspiration cytology was performed to exclude a thyroid malignancy.Study Design:Twenty patients were treated with RTA (group A), and 20 others did not receive any treatment (group B). At baseline, age, gender, and TN features did not differ significantly between groups. All patients were clinically, biochemically, and morphologically evaluated at baseline and after 1, 3, 6, and 12 months.Results:TN volume significantly decreased in group A (1.8 ± 0.3 ml at 12 months vs. 13.3 ± 1.8 ml at baseline; P < 0.0001) and remained stable in group B [11.7 ± 1.5 ml at 12 months vs. 11.2 ± 1.5 ml at baseline; P = not significant (NS)]. At 3-, 6-, and 12-month evaluations, TN volume was significantly lower in group A than in group B (P < 0.005). At the end of the follow-up, pressure symptoms were improved in all patients in group A but persisted unchanged in group B. In group A, hyperthyroidism completely recovered in 40% and improved in 40% of patients with toxic TNs, whereas it persisted in all patients with toxic TNs in group B. RTA was safe and well tolerated in all patients.Conclusions:RTA induced a marked TN volume shrinkage resulting in parallel improvement of pressure symptoms. In most patients with toxic TNs, hyperthyroidism significantly improved as well. RTA may represent a valid therapeutic approach in patients with TNs not receiving conventional treatments.
The Journal of clinical endocrinology and metabolism 09/2012; · 6.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To describe demographic and hormonal characteristics, comorbidities (diabetes mellitus and hypertension), therapeutic procedures and their effectiveness, as well as predictors of morbidity and mortality in a nationwide survey of Italian acromegalic patients.
Retrospective multicenter epidemiological study endorsed by the Italian Society of Endocrinology and performed in 24 tertiary referral Italian centers. The mean follow-up time was 120 months.
A total of 1512 patients, 41% male, mean age: 45±13 years, mean GH: 31±37 μg/l, IGF1: 744±318 ng/ml, were included. Diabetes mellitus was reported in 16% of cases and hypertension in 33%. Older age and higher IGF1 levels at diagnosis were significant predictors of diabetes and hypertension. At the last follow-up, 65% of patients had a controlled disease, of whom 55% were off medical therapy. Observed deaths were 61, with a standardized mortality ratio of 1.13 95% (confidence interval (CI): 0.87-1.46). Mortality was significantly higher in the patients with persistently active disease (1.93; 95% CI: 1.34-2.70). Main causes of death were vascular diseases and malignancies with similar prevalence. A multivariate analysis showed that older age, higher GH at the last follow-up, higher IGF1 levels at diagnosis, malignancy, and radiotherapy were independent predictors of mortality.
Pretreatment IGF1 levels are important predictors of morbidity and mortality in acromegaly. The full hormonal control of the disease, nowadays reached in the majority of patients with modern management, reduces greatly the disease-related mortality.
European Journal of Endocrinology 05/2012; 167(2):189-98. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Context: Usefulness of circulating Chromogranin A (CgA) for the diagnosis of neuroendocrine tumors (NEN) is controversial. The aim of the present study was to assess the actual role of this marker as diagnostic tool. Methods: Serum blood samples were obtained from 42 subjects affected with NEN, 120 subjects affected with non-endocrine neoplasias (non-NEN) and 100 non-neoplastic subjects affected with benign nodular goitre (NNG). Determination of CgA was performed by means of immunoradiometric assay. Results: The CgA levels among NEN-patients were not significantly different from NNG and non-NEN subjects. The Receiver operating characteristic (ROC) curves analysis failed to identify a feasible cut-off value for the differential diagnosis between NEN and the other conditions. Conclusion: Serum CgA is not helpful for the first-line diagnosis of NEN.
[Show abstract][Hide abstract] ABSTRACT: Abstract: In recent years, a significant increase in the incidence of male infertility has been observed
and described in the international literature, raising questions about its causes. Several authors have
suggested that exposure to environmental pollution may contribute to a perceived decline in semen
quality worldwide. Although several studies have been conducted about the effects on male fertility
caused by exposure to heavy metals in the workplace, research on the effects caused by continued
exposure to low doses of heavy metals pollution in urban areas is still scarce.
The aim of this study is to identify the relationships between high concentrations of heavy metals and
male infertility in the metropolitan area of Naples. We considered only those elements (Al, As, Cd, Cr,
Cu, Hg, Mn, Mo, Pb, Sb, Tl, Zn) that previous studies have indicated as possible candidates to have some
influence on human semen quality.
We measured semen quality among 600 subjects selected from a sample of 1237 men regularly
examined at the andrology laboratory of the University of Naples "Federico II" for problems related to
male fertility. Using statistical methods the semen data (semen volume, sperm concentration, sperm
total count, sperm motility, pH) were compared with the geochemical distribution of heavy metals in
soils of the Napoli metropolitan area.
Results show a strong correlation between anomalous Pb and Sb concentrations and fertility disorder.
A weaker correlation was also observed with Hg and Zn while the anomalous concentration values of
the other elements (Al, As, Cd, Cr, Cu, Mn, Mo and Tl) appears to have no correlation with male
Journal of Geochemical Exploration 01/2012; 112:218-225. · 1.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We have previously demonstrated that HMGA1B and HMGA2 overexpression in mice induces the development of GH and prolactin (PRL) pituitary adenomas mainly by increasing E2F1 transcriptional activity. Interestingly, these adenomas showed very high expression levels of PIT1, a transcriptional factor that regulates the gene expression of Gh, Prl, Ghrhr and Pit1 itself, playing a key role in pituitary gland development and physiology. Therefore, the aim of our study was to identify the role of Pit1 overexpression in pituitary tumour development induced by HMGA1B and HMGA2. First, we demonstrated that HMGA1B and HMGA2 directly interact with both PIT1 and its gene promoter in vivo, and that these proteins positively regulate Pit1 promoter activity, also co-operating with PIT1 itself. Subsequently, we showed, by colony-forming assays on two different pituitary adenoma cell lines, GH3 and αT3, that Pit1 overexpression increases pituitary cell proliferation. Finally, the expression analysis of HMGA1, HMGA2 and PIT1 in human pituitary adenomas of different histological types revealed a direct correlation between PIT1 and HMGA expression levels. Taken together, our data indicate a role of Pit1 upregulation by HMGA proteins in pituitary tumours.
Endocrine Related Cancer 12/2011; 19(2):123-35. · 5.26 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neuroendocrine tumors (NETs) can be sporadic or they can arise in complex hereditary syndromes. Patients with hereditary NETs can be identified before the development of tumors by performing genetic screenings. The aim of the study was to evaluate the clinical and prognostic impact of a preclinical genetic screening in subjects with hereditary NET syndromes. 46 subjects referred for hereditary NET syndrome [22 MEN1, 12 MEN2, 12 Familial Paragangliomatosis (FPGL)] were enrolled and divided in 2 groups (group A, 20 subjects with clinical appearance of NET before the genetic diagnosis; group B, 26 subjects with genetic diagnosis of hereditary NET syndromes before the clinical appearance of NETs). The main outcome measures were severity of disease, prognosis, and survival. The rate of surgery for MEN1-, MEN2-, FPGL4-related tumors was 90% in group A and 35% in group B (p<0.01). Both symptoms related to tumors and symptoms related to therapies were significantly less frequent in group B than in group A (p<0.05). Tumor stage was locally advanced or metastatic in 50% of group A and in no one of group B (p<0.01). The mortality rate was 25% in group A and 0% in group B (p<0.05). An early genetic screening for hereditary NET syndromes results in an improvement in clinical presentation and morbidity. A potential impact of the genetic screening on the mortality rate of these subjects is suggested and needs to be investigated in further and more appropriate studies.
Hormone and Metabolic Research 10/2011; 43(11):794-800. · 2.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aging is associated with decay in the somatotroph axis, that has been considered to cause many of the catabolic sequelae of normal aging. The physiological changes that the human body undergoes during aging are similar to those observed in GH deficiency (GHD). Changes of aging are represented by increased fat mass, increased cardiovascular risk, reduced muscle mass, reduced exercise tolerance, decreased strength and impaired quality of life. Some authors conjecture that the elderly could be GH deficient and would benefit from GH treatment. However, the endocrine pattern of aging is distinct from the decrease of GH/IGF-I levels associated with hypopituitarism, although there is not sufficient evidence for a clear therapeutic role of GH treatment during somatopause. So, further studies are needed to evaluate the real benefit of somatotropic treatment in aging. This review is focused on the effects of the somatopause and summarize the potentials for a therapeutic role of the recombinant human GH (rhGH) or of GH secretagogues in aging.
[Show abstract][Hide abstract] ABSTRACT: The most frequent cause of death in acromegaly is cardiomyopathy.
To evaluate determinants of acromegalic cardiomyopathy.
Observational, open, controlled, retrospective study.
Two hundred and five patients with newly diagnosed active acromegaly (108 women and 97 men; median age 44 years) and 410 non-acromegalic subjects sex- and age-matched with the patients.
Left ventricular (LV) mass index (LVMi), transmitral inflow early-to-atrial (E/A) peak velocity ratio, and LV ejection fraction (LVEF) were measured by Doppler echocardiography to determine the prevalence of LV hypertrophy (LVH), diastolic and systolic dysfunction. The role of age, estimated disease duration, body mass index, GH and IGF1 levels, systolic and diastolic blood pressure, lipid profile and glucose tolerance in determining different features of the acromegalic cardiomyopathy was investigated.
Compared with controls, the patients had lower E/A, LVEF, high-density lipoprotein (HDL)-cholesterol levels and higher LVMi, total- and low-density lipoprotein (LDL)-cholesterol, triglycerides, glucose and insulin levels, homeostatic model assessment of insulin resistance (HOMA-R) and HOMA-β. The relative risk to develop mild (odds ratio (OR)=1.67 (1.05-2.66); P=0.027) or severe hypertension (OR=1.58 (1.04-2.32); P=0.027), arrhythmias (OR=4.93 (1.74-15.9); P=0.001), impaired fasting glucose/impaired glucose tolerance (OR=2.65 (1.70-4.13); P<0.0001), diabetes (OR=2.14 (1.34-3.40); P=0.0009), LVH (OR=11.9 (7.4-19.5); P<0.0001), diastolic (OR=3.32 (2.09-5.31); P<0.0001) and systolic dysfunction (OR=14.2 (6.95-32.2); P<0.0001), was higher in acromegaly. The most important predictor of LVH (t=2.4, P=0.02) and systolic dysfunction (t=-2.77, P=0.006) was disease duration and that of diastolic dysfunction was patient's age (t=-3.3, P=0.001). Patients with an estimated disease duration of >10 years had a relative risk to present cardiac complications three times higher than patients with estimated disease duration ≤5 years.
The prevalence of different features of cardiomyopathy is 3.3-14.2 times higher in the acromegalic than in the non-acromegalic population. The major determinant of cardiomyopathy is disease duration.
European Journal of Endocrinology 08/2011; 165(5):713-21. · 3.14 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Fat mass (FM) in overweight/obese subjects has a primary role in determining low-grade chronic inflammation and, in turn, insulin resistance (IR) and ectopic lipid storage within the liver. Obesity, aging, and FM influence the growth hormone/insulin-like growth factor (IGF)-I axis, and chronic inflammation might reduce IGF-I signaling. Altered IGF-I axis is frequently observed in patients with Hepatic steatosis (HS). We tested the hypothesis that FM, or spleen volume and C-reactive protein (CRP)--all indexes of chronic inflammation--could affect the IGF-I axis status in overweight/obese, independently of HS.
The study population included 48 overweight/obese women (age 41 ± 13 years; BMI: 35.8 ± 5.8 kg/m2; range: 25.3-53.7), who underwent assessment of fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA), cholesterol and triglycerides, HDL-cholesterol, transaminases, high-sensitive CRP, uric acid, IGF-I, IGF binding protein (BP)-1, IGFBP-3, and IGF-I/IGFBP-3 ratio. Standard deviation score of IGF-I according to age (zSDS) were also calculated. FM was determined by bioelectrical impedance analysis. HS severity grading (score 0-4 according liver hyperechogenicity) and spleen longitudinal diameter (SLD) were evaluated by ultrasound.
Metabolic syndrome (MS) and HS were present in 33% and 85% of subjects, respectively. MS prevalence was 43% in subjects with increased SLD. IGF-I values, but not IGF-I zSDS, and IGF-I/IGFBP-3 ratio were significantly lower, while FM%, FPI, HOMA, ALT, CRP, were significantly higher in patients with severe HS than in those with mild HS. IGF-I zSDS (r = -0.42, r = -0.54, respectively; p < 0.05), and IGFBP-1 (r = -0.38, r = -0.42, respectively; p < 0.05) correlated negatively with HS severity and FM%. IGF-I/IGFBP-3 ratio correlated negatively with CRP, HS severity, and SLD (r = -0.30, r = -0.33, r = -0.43, respectively; p < 0.05). At multivariate analysis the best determinants of IGF-I were FM% (β = -0.49; p = 0.001) and IGFBP-1 (β = -0.32; p = 0.05), while SLD was in the IGF-I/IGFBP-3 ratio (β = -0.43; p = 0.004).
The present study suggests that lower IGF-I status in our study population is associated with higher FM, SLD, CRP and more severe HS.
Journal of Translational Medicine 08/2011; 9:136. · 3.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In patients with well-differentiated (WD) neuroendocrine tumors (NET), long-acting octreotide (LAR), conventionally administered at a dose of 30 mg every 28 days, has well-documented anti-secretive but limited antiproliferative effects.
The objective of this study was to evaluate a different schedule of LAR treatment consistent with a shorter interval between administrations (21 days) in WDNET patients with progressive disease at standard-dose interval.
Twenty-eight patients followed for diagnosis and therapy of WDNET who had tumor progression during therapy with LAR 30 mg every 28 days were enrolled. Clinical, biological, and objective tumor response was evaluated after LAR 30 mg every 21 days. Time to progression was also evaluated after LAR 30 mg every 21 days and compared to LAR 30 mg every 28 days.
The treatment with LAR 30 mg every 21 days resulted in complete and partial control of clinical symptoms in 40% and 60% of cases, respectively. Circulating neuroendocrine markers were significantly decreased in 30% of cases. A stabilization of disease was obtained in 93% and objective response in 7%. The median time to progression was significantly longer by using the shortened interval of LAR administration as compared to the standard one (30 vs 9 months, p<0.0001). The treatment was safe and well tolerated.
The shortened schedule of LAR administration was able to re-institute control of clinical symptoms, to decrease level of circulating neuroendocrine markers and to increase time to progression in patients previously escaping from a standard schedule treatment.
Journal of endocrinological investigation 07/2011; 35(3):326-31. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity and insulin resistance predispose individuals to the development of both metabolic syndrome and non-toxic nodular thyroid diseases.
The aim of this observational, cross-sectional study is to evaluate the relationship between metabolic syndrome and multinodular nontoxic goiter in an inpatient population from a geographic area with moderate iodine deficiency.
We examined 1422 Caucasian euthyroid inpatients. Thyroid volume was determined by ultrasound of the neck. A fine-needle aspiration biopsy was performed to evaluate single thyroid nodules and dominant nodules ≥15 mm in euthyroid multinodular goiter. The diagnosis of metabolic syndrome was made according to the criteria of the American Heart Association/ National Heart, Lung, and Blood Institute.
Of the sample, 277 patients had clinical evidence of multinodular nontoxic goiter, 461 met the criteria for the diagnosis of metabolic syndrome, and 132 were found to have both conditions. After adjusting for age, gender, body mass index, nicotinism, parity, alcohol intake, thyroid function, and metabolic syndrome- related pharmacological treatment, metabolic syndrome was found to be an independent risk factor for the occurrence of multinodular non-toxic goiter. The relationship between metabolic syndrome and multi nodular non-toxic goiter was apparent in both men and women.
In this study of euthyroid inpatients, we demonstrate that metabolic syndrome is an independent risk factor for the occurrence of multinodular non-toxic goiter in a geographic area with moderate iodine deficiency. We propose that patients meeting the criteria for metabolic syndrome should be screened for the presence of multinodular non-toxic goiter.
Journal of endocrinological investigation 07/2011; 35(4):407-12. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this review is to focus on the roles of PTH in bone remodeling. PTH plays a central role in regulating calcium-phosphate metabolism and its production increases in response to low serum calcium levels. A continue hypersecretion of PTH, as occurs in primary hyperparathyroidism, leads to bone resorption. On the other hand, there is clear evidence of the anabolic properties of PTH.When administered at a low dose and intermittently, this hormone seems to be able to exert positive effects on bone volume and microarchitecture. The effects of PTH are mediated by PTH/PTH-related protein receptor, a G protein that can activate the cAMP-dependent protein kinase (PK)A and calcium-dependent PKC; the activation of PKA account for most of the PTH anabolic action. The anabolic actions of PTH involve direct effects on osteoblasts and indirect effects mediated by activation of skeletal growth factors (IGF-I) and inhibition of growth factor antagonists, such as sclerostin. PTH enhances the number and the activation of osteoblast through 4 pathways: increasing osteoblast proliferation and differentiation, decreasing osteoblast apoptosis and reducing the negative effects of peroxisome proliferator activator (PPAR)γ receptor on osteoblast differentiation. Moreover PTH enhances the Wnt-β catenin pathway, that is central to osteogenesis and bone formation, inhibiting sclerostin. Finally, PTH induces the synthesis of IGF-I and, due to its prodifferentiating and pro-survival effects on osteoblasts, this could be a key mediator of PTH effect on osteoblasts. In conclusion, the intermittent administration of PTH has a pleiotropic anabolic effect on bone; further studies about mechanisms of action of PTH could be a starting point to new osteoporosis treatments.
[Show abstract][Hide abstract] ABSTRACT: AM: Patients with Fabry disease (FD), a genetic disorder caused by lysosomal a-galactosidase-A enzyme deficiency and characterized by a systemic accumulation of globotriaosylceramides, present high prevalence of subclinical hypothyroidism. The pathogenic mechanism is thought not to be related to anti-thyroid autoimmunity and may be dependent by intra-thyroid lipid accumulation. In this study, it was investigated whether thyroid function recovers in FD after long-term enzyme replacement therapy (ERT).
Study population included 14 FD patients (7 females, 7 males, aged 21-62 years) and 14 sex- and age-matched normal subjects. Thyroid function was evaluated in each patient at baseline and after the beginning of ERT with rh-a-galactosidase-A (1 mg/kg/BW every 2 weeks) for three years.
TSH levels were higher in FD patients than in controls (P<0.05). In FD patients, TSH levels were higher before than after ERT (1.9±0.2 vs 1.2±0.2 mU/L, P<0.01) while fT3 and fT4 levels were normal at baseline and unchanged after ERT. At baseline, TSH levels were >3 mU/L in three patients and normalize after ERT. Anti-Tg and/or anti-TPO titres were positive in 14% of patients and 21% of controls. After ERT, the rate of autoimmunity was unchanged. At the thyroid ultrasonography, a slight hypoechoic pattern was found in 71% of patients at baseline and decreased to 43% after ERT.
Primary hypothyroidism in FD patients is reverted after long-term ERT. A screening of thyroid function and periodical re-evaluation during ERT is mandatory in all FD patients.
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: Aggressive tumors of the pituitary gland are classically defined as pituitary tumors with a massive invasion of the surrounding anatomical structures and rapid growth. They are notoriously difficult to manage and are associated with poor prognosis because the therapeutic options are limited and the tumors are generally unresponsive to therapy. AREAS COVERED: This review focuses on treatment options for aggressive pituitary tumors, including surgery, radiotherapy and medical treatment, as well as focusing on the promising therapeutic options for aggressive pituitary tumors, evaluating the literature of the last 15 years. With the exception of prolactinomas, surgery is the first-line option, but most aggressive pituitary tumors often require repeated surgery. Pharmacotherapies are useful when surgery is unlikely to improve symptoms, or as an adjunct therapy to surgery. In prolactinomas, dopamine agonists are the first-line treatment and normalize prolactin levels in most patients, even those with macroprolactinomas. Somatostatin analogs are effective agents for primary therapy, pre-operatively or post-operatively to control tumor re-expansion of pituitary adenomas. However, dopamine agonists and somatostatin analogs are not as effective as they are for the treatment of non-aggressive adenomas. When surgery and pharmacotherapy fail, radiotherapy is a useful third-line strategy. Conventional chemotherapy is poorly effective but recent case reports with the temozolomide, an alkylating agent, have provided better results in the short term. EXPERT OPINION: Aggressive pituitary tumors are associated with poor prognosis as therapeutic options are limited. Moreover, they tend to recur quickly after initial treatment, are generally unresponsive to therapy, and are difficult to manage. To improve the overall response rate, the early application of current therapeutic approaches with the incorporation of new therapeutic developments is mandatory.
Expert Opinion on Pharmacotherapy 03/2011; 12(10):1561-70. · 2.86 Impact Factor