Metabolic alterations in patients who develop traumatic brain injury (TBI)-induced hypopituitarism.

OBJECTIVE: Hypopituitarism is associated with metabolic alterations but in TBI-induced hypopituitarism data are scanty. The aim of our study was to evaluate the prevalence of naïve hypertension, dyslipidemia, and altered glucose metabolism in TBI-induced hypopituitarism patients. DESIGN: Cross-sectional retrospective study in a tertiary care endocrinology center. 54 adult patients encountering a moderate or severe TBI were evaluated in the chronic phase (at least 12 months after injury) after-trauma. Presence of hypopituitarism, BMI, hypertension, fasting blood glucose and insulin levels, oral glucose tolerance test (if available) and a lipid profile were evaluated. RESULTS: The 27.8% of patients showed various degrees of hypopituitarism. In particular, 9.3% had total, 7.4% multiple and 11.1% isolated hypopituitarism. GHD was present in 22.2% of patients. BMI was similar between the two groups. Hypopituitaric patients presented a higher prevalence of dyslipidemia (p<0.01) and altered glucose metabolism (p<0.005) with respect to non hypopituitaric patients. In particular, triglycerides (p<0.05) and HOMA-IR (p<0.02) were higher in hypopituitaric TBI patients. CONCLUSIONS: We showed that long-lasting TBI patients who develop hypopituitarism frequently present metabolic alterations, in particular altered glucose levels, insulin resistance and hypertriglyceridemia. In view of the risk of premature cardiovascular death in hypopituitaric patients, major attention has to been paid in those who encountered a TBI, because they suffer from the same comorbidities and may present other deterioration factors due to complex pharmacological treatments and restriction in participation in life activities and healthy lifestyle.

Measurement of height velocity is an useful marker for monitoring pituitary function in patients who had traumatic brain injury.

To assess the incidence of abnormal neuroendocrine function post-traumatic brain injuriy (TBI) in a large group of paediatric patients and its correlations with clinical parameters (Glasgow coma scale-GCS, Glasgow outcome scale-GOS, TC marshall scale, height velocity). We evaluated 70 patients [58 M, 12 F; age at the time of TBI (mean ± SEM) 8.12 ± 4.23 years] previously hospitalized for TBI at the "Regina Margherita" Hospital, in Turin and "Maggiore della Carità Hospital" in Novara, Italy, between 1998 and 2008. All patients included underwent: auxological, clinical, hormonal and biochemical assessments at recall (after at least 1 year from TBI to T0); auxological visit after 6 months (T6) and hormonal assessments at 12 months (T12) in patients with height velocity (HV) below the 25th centile. At T0, 4 cases of hypothalamus-pituitary dysfunction had been diagnosed; At T6 20/70 patients had an HV <25th centile, but no one had HV < the 3rd centile limit. At T12, among the 20 patients with HV <25th centile, in 13 patients the HV was below the 25th centile and GHRH + Arginine test has been performed. Four subjects demonstrated an impaired GH peak and were classified as GH deficiency (GHD). Of these 4 subjects, 3 subjects showed isolated GHD, while one patient showed multiple hypopituitarism presenting also secondary hypocortisolism and hypothyroidism. The GCS at admission and GOS do not correlate with the onset of hypopituitarism. A simple measurement of the height velocity at least 1 year after the TBI, is enough to recognize patients with a pituitary impairment related to GH deficiency. We suggest to follow-up paediatric population who had TBI with auxological evaluations every 6 months, limiting hormonal evaluation in patients with a reduction of height velocity below the 25th centile limit.

[Neurofibromatosis type 1 and hypertension in pediatrics: case report]. / neurofibromatosi 1 ed ipertensione arteriosa in eta pediatrica: caso clinico.

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by cafe-au-lait spots, axillary and inguinal freckling, cutaneous neurofibromas with a variable clinical expression, iris Lisch nodules, and multiple tumors, in particular optic nerve and other central nervous system gliomas. About 6% of patients develop hypertension due to renovascular diseases, mid-aortic syndrome, or pheochromocytoma. We present a case of a 8 year old girl with primary diagnosis of NF1suffering of skin and encefalic neurofibromas, inguinal freckling, café-au-lait spots, optic nerve glioma, headache, facial flushing. The 24-h ambulatory blood pressure revealed hypertension without paroximal attacks. Urinary metanephrines, serum aldosteron, renin and kalemia were constantly normal. Magnetic resonance imaging (MRI) and angioMRI excluded stenoses of the renal arteries or adrenal masses. Standard 2D echocardiography was normal. The antihypertensive medication controlled pressure values. We concluded for hypertension due to a low-grade vasculopathy. The periodic monitoring of blood pressure in NF1 patients, accompanied by appropriate diagnostic modalities and physical examination, is essential to precociously diagnose hypertension and avoid life-threatening organ damages and increased mortality.

Etiopathogenetic advances and management of holoprosencephaly: from bench to bedside.

Holoprosencephaly (HPE) is a complex brain malformation caused by impaired or incomplete midline division of the prosencephalon. It's characterized by cerebral and facial anomalies of different levels of severity. Both genetic and environmental factors are known to cause HPE, but they cover only few cases. Genetic causes are responsible for about 20% of cases: they are chromosomal abnormalities and gene mutations: up to date, nine genes (SHH, ZIC2, SIX3, TGIF, PATCHED1, TDGF1/CRIPTO, FAST1, GLI2 and DHCR) are definitely associated with HPE, but many others candidate gene are under investigation. The diagnosis of HPE is usually prenatal and is based on systematic ultrasound scan (US) and magnetic resonance imaging (MRI). Children with HPE have many medical problems in agreement with the severity of the brain malformation: craniofacial abnormalities, neurological signs, endocrine disorders, oromotor and dysautonomic dysfunction, thus requiring a multidisciplinary team for symptomatic treatment of manifestations, prevention of complications and parental support. Genetic counselling is an important step, often made difficult by extreme phenotypic variability, genetic heterogeneity, and a high risk of recurrence in apparently sporadic cases. In conclusion it can be concluded that we are far from a complete explanation of the etiopathogenesis. Future researches on genomic rearrangements all over the genome with techniques like the CGH array should lead to the identification of other causal genes and could improve diagnosis and prognosis. A skill multidisciplinary approach is mandatory to offer the better clinical assistance to patients and their parents.

Update on epidemiology, etiology, and diagnosis of adult growth hormone deficiency.

The most updated guidelines for the diagnosis of adult GH deficiency (GHD) come from the GH Research Society Consensus Workshop held in Sydney, Australia, in 2007. Regarding who to test for GHD, advice should be extended from primitive hypothalamic- pituitary diseases and cranial irradiation to include brain injuries (Traumatic Brain Injury in particular). Regarding how to test for GHD, the insulin tolerance test (ITT) remains a provocative test of reference; among classical provocative test, glucagon test has also been validated. Above all, GHRH + arginine and GHRH + GH-secretagogues are now considered, at least, as reliable as ITT for the diagnosis of adult GHD. Interestingly, it is now accepted that very low IGF-I represents definite evidence of severe GHD in congenital forms of GHD and also in patients with acquired multiple hypopituitarism. These patients would skip provocative test; however, as normal IGFI levels do not rule out severe GHD, patients suspected for hypopituitarism showing normal IGF-I levels must undergo a provocative test of GH secretion. Retesting the GH status in the transition age is of major relevance in order to decide about continuing or not recombinant human GH replacement in adult life.

A prospective evaluation of the effect of atazanavir on the QTc interval and QTc dispersion in HIV-positive patients.

BACKGROUND: Atazanavir (ATV), an HIV protease inhibitor (PI) that may be preferred for the treatment of HIV-infected patients with cardiovascular comorbidities because of its favourable effects on plasma lipids, has been associated with cardiac rhythm disturbances. OBJECTIVE: To quantify the effect of ATV on corrected QT (QTc) and QTc dispersion (QTd), markers of the potential for cardiac dysrhythmia, in patients switching from other PIs to ATV. METHODS: In this prospective, single-centre, open-label study, 12-lead electrocardiograms were performed for subjects at baseline, 2 h after the first dose of ATV, and 1 month after initiation of ATV. RESULTS: Twenty-one patients (19 received ritonavir-boosted ATV) completed the study. There was a trend towards an increase in the QTc at 2 h after the first dose [mean+/-standard deviation 3.19+/-8.0 ms; 95% confidence interval (CI) -0.47 to 6.85 ms; P=0.084]. There was no difference between QTc values at baseline and at 1 month (-1.5+/-8.75 ms; 95% CI -5.50 to 2.46; P=0.43). There was a nonsignificant decrease in the QTd between baseline and 2 h (-5.1+/-15.19 ms; 95% CI -13.22 to 2.96; P=0.197) and between baseline and 1 month (-0.61+/-15.04 ms; 95% CI -8.1 to 6.87; P=0.865). A significant increase in the PR interval (7.4+/-10.7 ms; 95% CI 2.5 to 12.25 ms; P=0.005) was observed at 1 month. CONCLUSIONS: The use of ATV did not result in increases in the QTc interval or QTd. However, PR interval monitoring may be warranted in patients with underlying heart block or those treated with atrioventricular nodal blocking agents.

Comparative mapping reveals partial conservation of synteny at the apomixis locus in Paspalum spp.

In plants, gametophytic apomixis is a form of asexual reproduction that leads to the formation of seed-derived offspring that are genetically identical to the mother plant. A common set of RFLP markers, including five rice anchor markers previously shown to be linked to apomixis in Paspalum simplex, were used to detect linkage with apomixis in P. notatum and P. malacophyllum. A comparative map of the region around the apomixis locus was constructed for the three Paspalum species, and compared to the rice map. The locus that controls apomixis in P. simplex was almost completely conserved in the closely related species P. malacophyllum, whereas it was only partially represented in the distantly related species P. notatum. Although strong synteny of markers was noted between this locus and a portion of rice chromosome 12 in both P. simplex and P. malacophyllum, the same locus in P. notatum was localized to a hybrid chromosome which carries markers that map to rice chromosomes 2 and 12. All three Paspalum species showed recombination suppression at the apomixis locus; in the case of P. notatum, this might be due to a heterozygosity for a translocation that most probably negatively interferes with chromosomal pairing near the locus. A common set of markers that show linkage with apomixis in all three Paspalum species define a portion of the apomixis-controlling locus that is likely to contain genes critical for apomictic reproduction.

Plant regeneration from callus of apomictic and sexual lines of Paspalum simplex and RFLP analysis of regenerated plants.

Culture conditions have been established for the induction of callus from different explants of Paspalum simplex. Fast-growing calli were obtained from hypocotyls and roots excised from 5-day-old seedlings on culture medium containing 2,4-dichlorophenoxyacetic acid and kinetin. Rapid plant regeneration from both apomictic and sexual lines was achieved when the medium was supplemented with alpha-naphthaleneacetic acid and benzylaminopurine. Restriction fragment length polymorphism analysis of the apomixis-controlling region of the regenerated plants showed an absence of restriction site variation for the loci analysed, whereas various degrees of variation were detected for the DNA methylation sites of the same loci.

Apomixis and sexuality in Paspalum simplex: characterization of the mode of reproduction in segregating progenies by different methods.

Segregating progenies of crosses between sexual and apomictic genotypes of Paspalum simplex were analysed for the formation of meiotic versus aposporous embryo sacs, zygotic versus parthenogenetic embryos, and autonomous versus pseudogamous endosperms by using cytoembryological and flow cytometric analyses. Reduced and unreduced 8-nucleated embryo sacs were the final product of female gametophyte development in sexual and aposporous genotypes, respectively. An incomplete penetrance of parthenogenesis was detected in aposporous genotypes. The relative DNA content of endosperm nuclei revealed the normal 2:1 maternal to paternal ratio in sexuals and a 4:1 ratio in apomicts, indicating insensitivity of the apomictic genotypes to endosperm imprinting. Apospory, parthenogenesis and pseudogamy are located on a relatively large linkage group and are inherited together with previously developed molecular markers as a single genetic unit in segregating progenies.