Correction to: Transsphenoidal surgery for pituitary adenomas: early results from a single center.

Unfortunately in the original publication, the affiliation of the author Paolo Marzullo was incorrect. The author inadvertently missed out to include his second affiliation.

Transsphenoidal surgery for pituitary adenomas: early results from a single center.

OBJECTIVE: To evaluate early results of transsphenoidal surgery for pituitary adenomas. DESIGN: Retrospective evaluation of 90 consecutive patients undergoing endoscopic pituitary adenoma surgery (2007-2016) at "Maggiore della Carità" Hospital in Novara, Italy. Age at diagnosis, sex, symptoms at presentation, hormonal and radiological data, complications of surgery, and short-term follow-up information were collected. RESULTS: The majority of patients were male (M/F: 1.5/1, mean age at diagnosis 62.1 ± 1.5 years mean ± SEM). Most patients (91.1%) presented with a macroadenoma (27.4 mm ± 1.1 mm mean ± SEM), while 77.8% were non-functioning pituitary adenomas. Clinical presentations related to mass effect were visual impairment (74.0%) and/or hypopituitarism (55.1%). The main surgery complication was insipidus diabetes (12.2%), followed by cerebral hemorrhage (4.4%), cerebrospinal fluid (CSF) leaks (4.4%), syndrome of inappropriate antidiuresis (SIAD) (2.2%), and epistaxis (2.2%); only one patient died because of stroke. Risk of complications was not associated with tumor size (OR = 0.588, 95% CI 0.967-1.081, p = 0.443). Visual function improved in 70.6% of patients, while recovery of normal pituitary function occurred in 48.1%. Early neuroimaging studies demonstrated no residual tumor in 27.6% of patients. Invasion of cavernous sinus (OR = 3.293, 95% CI 0.897-16.738, p = 0.05) and maximum tumor diameter (OR = 6.857, 95% CI 1.039-1.309, p < 0.01) were associated with an unfavorable surgical outcome. CONCLUSIONS: Transsphenoidal endoscopic surgery for pituitary adenomas is safe and is frequently followed by improvement in visual symptoms, whereas recovery of pituitary function is less common. In our patients, complete surgical removal of adenomas is comparable to that of other series, but further investigations will be necessary to clarify the long-term risk of tumor recurrence.

Phenotyping normal kidney function in elderly patients with type 2 diabetes: a cross-sectional multicentre study.

AIMS: Type 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80 years or older who presented with a fully preserved kidney function. METHODS: From an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR > 90 ml/min/1.73 m2 and AER < 30 mg/24 h, or G1A1) with those with mild kidney impairment (eGFR 60-90 ml/min/1.73 m2 and AER < 30 mg/24 h, or G2A1). RESULTS: N = 113,860 had available data for eGFR and AER, 21,648 of whom were aged ≥ 80. G1A1 (n = 278) and G2A1 (n = 6647) patients represented 1.3 and 30.7% of aged T2D patients, respectively, with an average diabetes duration of 16 years. Differences between the G1A1 and G2A1 groups were entered in a multiple logistic regression analysis with and without imputation of missing data. After adjustment and in both imputed and non-imputed datasets, younger age, lower BMI and lower triglycerides were associated with fully preserved versus mildly impaired kidney function. The comparison between G1A1 and G1A2/3 yielded different results. CONCLUSIONS: In a rare population of patients with a fully preserved kidney function despite old age and long-lasting diabetes, lower BMI and triglycerides suggest that protection from lipotoxicity may preserve kidney function over time.

The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison's disease.

PURPOSE: Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated. METHODS: Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy. RESULTS: H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone. CONCLUSIONS: Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.

Retrospective observational analysis of non-irradiated non-functioning pituitary adenomas.

PURPOSE: The management of choice of non-functioning pituitary adenomas (NFPAs) remains debulking surgery when symptomatic. However, patient series systematically reporting the NFPAs outcome that were not treated either surgically, medically or with radiotherapy during long follow-up thereby giving an indication of their natural history are limited. Aim of the present study was to evaluate the natural course of presumed NFPAs, the outcome of confirmed NFPAs during a long follow-up period. METHODS: Between 1993 and 2013, 84 patients with presumed NFPA were studied retrospectively. Patients were enrolled based on the following criteria: imaging suggestive of pituitary adenoma, absence of any biochemical/clinical evidence of hormonal excess, exclusion of prolactinomas and at least one sequential imaging during the follow-up. Repeated assessment of the pituitary function, visual fields and imaging was performed at regular intervals. The follow-up duration was evaluated from the first and last imaging dates. RESULTS: In group F (follow-up without surgery, 33 patients), the macroadenomas showed a 15% probability of tumor growth and reduction. Similar tumor size alterations were observed also for the microadenomas. In group S (surgery, 51 patients), both residual tumors (>1 and <1 cm) following initial surgical resection remain mainly stable until the last imaging. CONCLUSIONS: Based on the given lack of approved medical treatment and the possible risks of surgical intervention in presence of significant comorbidities, our study proposes a conservative approach with a careful follow-up in patients with NFPAs without visual or neurological abnormalities.

Enhanced oxidative stress and platelet activation combined with reduced antioxidant capacity in obese prepubertal and adolescent girls with full or partial metabolic syndrome.

In adults, obesity is a main factor implicated in increased oxidative stress (OS), platelet activation (PA) and impaired antioxidant status (AS), all predisposing factors for cardiovascular disease leading to increased morbidity and mortality. Furthermore, the metabolic syndrome (MetS) is an important cardiovascular risk factor, which progressively develops and may already be present during late childhood or adolescence. However, scarce data exist on oxidative-antioxidant balance and PA in childhood and adolescence in the presence of partial (PMetS) or full MetS. The aim of the study was to evaluate OS, PA, and AS in prepubertal and adolescent obese girls with partial or full MetS. 96 girls with a clinical and metabolic evaluation for obesity and 44 healthy normal-weight sex- and age-matched girls were studied. IDF-adopted criteria were used to define full and partial MetS and the patient population was divided into 4 groups: the first comprised 31 pre-pubertal girls with PMetS (PR-PMetS), the second 37 adolescents with PMetS (AD-PMetS), the third 10 prepubertal girls with full MetS (PR-MetS), and the fourth 18 adolescents with full MetS (AD-MetS). The OS was evaluated by measuring plasma 15-F(2t)-Isoprostane levels (15-F(2t)-IsoP) and protein carbonyls, PA by thromboxane B(2) levels (TXB(2)), and AS by serum vitamin E and plasma total antioxidant capacity (TAC) levels. 15-F(2t)-IsoP, protein carbonyls, and TXB(2) levels were significantly gradually amplified, and vitamin E and TAC reduced, and significantly correlated with obesity from childhood to adolescence and from partial to full MetS. This study demonstrates the loss of the normal homeostatic balance between oxidant-antioxidant state in obese children and adolescents with manifestations of partial and full MetS.

Neuroendocrine effects of citalopram, a selective serotonin re-uptake inhibitor, during lifespan in humans.

OBJECTIVE: Serotonergic system contributes to the regulation of hypothalamus-pituitary-adrenal axis. In humans, serotonergic agonists increase PRL, ACTH, and cortisol, while serotonin (5HT) influence on GH is controversial. Central 5HT activity and neuroendocrine function change during lifespan. DESIGN: To clarify the neuroendocrine response to 5HT across lifespan, we assessed ACTH, cortisol, DHEA, PRL, and GH responses to citalopram (CT) in young adults (YA) (no.=12, 29.2±1.7 yr mean±SEM), middle aged (MA) (no.=12, 54.3±0.9 yr), and elderly (ES) (no.=12, 69.3±0.9 yr) males. All the subjects received placebo (saline iv over 120 min) or CT (20 mg iv over 120 min). Blood samples were taken every 15 min up to 240 min. RESULTS: During placebo, ACTH, cortisol, GH, and PRL were similar in all groups while DHEA showed an age-dependent reduction from middle age (p<0.001). During CT, ACTH, and cortisol were higher than during placebo in YA (p<0.05) and even more in MA (p<0.01 vs placebo, p<0.05 vs YA); in ES, the increase of both ACTH and cortisol (p<0.05 vs placebo) was lower than in MA (p<0.05) and higher than in YA (p<0.05 for cortisol only). No changes were observed for DHEA, GH, and PRL in any group. CONCLUSIONS: Corticotrope response to CT is age-dependent in normal men, being amplified starting from middle age, suggesting precocious changes in the serotonergic neuroendocrine control during lifespan. CT is a useful tool to evaluate the age-dependent serotonergic function in humans.

The response of muscle interstitial F2-isoprostane (8-ISO-PGF2alpha) during dynamic muscle contractions in humans.

8-Iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a characteristic F2-isoprostane which is produced in humans via a free radical-catalysed lipid peroxidation mechanism of arachidonic acid, independent of the cycloxygenase pathway. The measurement of the plasma levels of 8-iso-PGF2alpha was shown to be the most reliable biochemical index of oxidant stress status in the human body. However, there is no reference in literature of local muscle interstitial 8-iso-PGF2alpha production during dynamic muscle contractions. The aim of the present study was to evaluate the response of 8-iso-PGF2alpha during intensive exercise with a cycle ergometer. Two microdialysis probes with CMA-60 microdialysis catheters were inserted into the vastus lateralis muscle of the right leg of six healthy male volunteers. After insertion, these microdialysis probes were attached to a perfusion pump that perfused ringer acetate solution at a rate of 0.3 microl/min. The dialysate fluid samples were collected: (a) during a 30 min rest period and (b) during a 30 min period of dynamic exercise with a cycle ergometer at 150 Watts. Our measurements showed that the levels of 8-iso-PGF2alpha in the interstitial fluid (IF) of the vastus lateralis muscle increase significantly during exercise (from 113.5 +/- 30.2 to 329.9 +/- 69.8 pg/ml, P = 0.05). In conclusion, dynamic muscle exercise produces a local increase of the IF levels of 8-iso-PGF2alpha due to local peroxidation injury of the contractive muscle. The microdialysis method is widely applied, easily repeated and it could contribute in evaluating the local lipid muscle peroxidation during intensive exercise.

The response of muscle interstitial prostaglandin E(2)(PGE(2)), prostacyclin I(2)(PGI(2)) and thromboxane A(2)(TXA(2)) levels during incremental dynamic exercise in humans determined by in vivo microdialysis.

UNLABELLED: The microdialysis in vivo technique allows the isolation, purification and quantitative determination of bioactive molecules with low molecular weight (<20.000 Da) from interstitial fluid (IF) of the muscles. PGE(2)and PGI(2)are vasodilator local hormones, while the TXA(2)is a vasoconstrictor. PGI(2)and TXA(2)are unstable and convert to stable products 6-keto-PGF(1a)and TXB(2), respectively. The purpose of this study was to evaluate the response of PGE(2), PGI(2)and TXA(2)in the IF of human muscle (vastus lateralis) during dynamic exercise with a cycle ergometer. In this study two microdialysis probes were inserted with CMA-60 microdialysis catheters into the vastus lateralis muscle of the right leg of eight healthy volunteers aged 24.1+/-2.1 years, height 177.5+/-1.5 cm and body weight 78.1+/-2.4 kg. After insertion the microdialysis probes perfused at a rate of 3.0 microl/min with Ringer acetate solution. The dialysate fluid was collected a) during the 30' rest period, b) during the 30' exercise period at 100 watts, c) during the 30' exercise period at 150 watts and d) during the 30' rest period after exercise. Our measurements (by the RIA method) showed that the levels of PGE(2)and 6-keto-PGF(1a)in the I.F. of the vastus lateralis muscle increased significantly, while there was a significant decrease in TXB(2)during exercise. The changes in the above biomolecules were increased proportionately with the strain of the subject's muscle. CONCLUSION: Dynamic exercise of the muscles produces a local increase of the vasodilators PGE(2)and PGI(2)while the vasoconstrictor TXA(2)is reduced in the IF of the muscles. This is further evidence that exercise induces propitious biochemical changes. Furthermore, the muscle production of arachidonic acid metabolites during exercise depends on the intensity of the exercise.