Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance.

PURPOSE: Insulin resistance and compensatory hyperinsulinism are the predominant metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism, as well as being compensatory, can also express a condition of reduced insulin clearance. Our aim was to evaluate the differences in insulin action and metabolism between women with PCOS (with normal glucose tolerance) and age- and BMI-matched women with prediabetes (without hyperandrogenism and ovulatory disorders). METHODS: 22 women with PCOS and 21 age/BMI-matched women with prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose infusion rate during clamp (M value); insulin secretion by Insulinogenic index, Oral Disposition Index (DIo) and AUC(2h-insulin) during OGTT; and insulin clearance by the metabolic clearance rate of insulin (MCRI) during clamp. RESULTS: Women with PCOS showed significantly higher levels of AUC(2h-insulin) (p < 0.011), Insulinogenic Index (p < 0.001), DIo (p = 0.002) and significantly lower levels of AUC(2h-glucos)e (p = 0.001). No difference was found between the two groups regarding insulin sensitivity (M value). Lower levels of MCRI were found in women with PCOS [420 (IQR 227-588) vs. 743 (IQR 597-888) ml m(-2) min(-1): p < 0.001]. Furthermore, in the PCOS group, a strong independent inverse correlation was only observed between MCRI and AUC(2h-insulin) (PCOS: ß:-0.878; p < 0.001; Prediabetes: ß:-0.501; p = 0.019). CONCLUSIONS: Our study suggests that in normoglycemic women with PCOS there is peripheral insulin sensitivity similar to that of women with prediabetes. What sets PCOS apart is the hyperinsulinism, today still simplistically defined "compensatory"; actually this is mainly related to decreased insulin clearance whose specific causes and dynamics have yet to be clarified.

Serum visfatin levels in acromegaly: Correlation with disease activity and metabolic alterations.

OBJECTIVE: The studies that have extensively evaluated the relation between adipokines and metabolic parameters in acromegaly treatment are quite discordant. We aimed to evaluate and correlate a set of selected adipokines, known to have a metabolic role, with the disease activity, metabolic status and treatment modalities. DESIGN: Data of 56 consecutive acromegalic patients (31 M and 25 F; aged 54 ± 12 years), admitted to the section of Endocrinology of the University of Palermo during the years 2005-2014, including 16 newly diagnosed untreated (ND), 21 during therapy with somatostatin analogues (SA), 12 with pegvisomant (PE) and 7 after surgical treatment (SU), grouped into uncontrolled (group A: No. 33) and controlled (group B: No. 23) were evaluated. Anthropometric and metabolic parameters, insulin sensitivity indexes, visceral adiposity index (VAI), leptin, soluble leptin receptor, adiponectin, visfatin, resistin, adipsin and non-esterified fatty acids (NEFAs) were assessed. In a subgroup of 21 subjects, the insulin sensitivity index (M value) derived from euglycemic clamp was calculated. RESULTS: Group A showed higher Homa-IR (p < 0.001), VAI (p < 0.001), triglycerides (p < 0.001), visfatin (p < 0.001), and NEFAs (p < 0.001) and lower ISI Matsuda (p < 0.001), M value (p < 0.001), HDL cholesterol (p < 0.001) and leptin (p < 0.001) than group B. ND patients showed higher VAI, triglycerides, Homa-IR, and visfatin and lower ISI Matsuda, M-value, and leptin compared to other groups (all p < 0.050), while no differences were found among SA, PE and SU patients. IGF-1 (p = 0.048), M-value (p = 0.0029) and VAI (p = 0.010) were independently associated with visfatin, while only ISI Matsuda (p = 0.019) was associated with leptin. CONCLUSIONS: In acromegaly visfatin could be considered a useful index of disease activity and metabolic alterations, such as insulin resistance and adipose dysfunction, regardless of the type of treatment.

Revaluation of the clinical and metabolic behavior of children with isolated growth hormone deficiency during GH treatment according to newly proposed note 39 of the Italian Medicines Agency (AIFA).

PURPOSE: This study aimed at evaluating the clinical and metabolic behavior of children with isolated growth hormone (GH)-deficiency (GHD), grouped according to the new AIFA criteria for the appropriateness of use and reimbursement of GH treatment in children. METHODS: The clinical and metabolic data of 310 prepubertal children (220 M, 90 F; mean age 10.8 years) grouped, according to new AIFA note 39, into Group A (No. 181 with a peak of GH <8 µg/l), Group B (No. 103 with a peak of GH ≥8 and <10 µg/l) and Group C (No. 26 with a peak of GH >10 µg/l) were retrospectively analyzed. Group A and B, diagnosed as having GHD, were treated with GH for at least 24 months, while Group C was analyzed only at baseline. RESULTS: At baseline, Group A showed higher waist circumference than B (p = 0.031) and C (p = 0.041), while no difference in metabolic parameters was found between the three groups. After 12 and 24 months of treatment, Group B showed lower height velocity (p < 0.001 and p = 0.049, respectively) than Group A. As regards the metabolic parameters, both after 12 and 24 months of treatment, in Group B we found higher fasting glucose (p < 0.001 and p = 0.020), insulin (p = 0.002 and p = 0.011), Homa-ß (p = 0.020 and p = 0.015) and Homa-IR (both p = 0.001) than Group A, with concomitant lower QUICKI (both p < 0.001) and HDL cholesterol (p = 0.020 and p = 0.011), without difference in other lipid parameters. The HbA1c levels, although always within the normal range, were found higher in Group B than Group A after 12 months (p = 0.015). CONCLUSIONS: According to the new AIFA criteria, the reduction of GH cut-off for GHD diagnosis can be supported by auxological and metabolic data. The real benefits from GH therapy in children with higher stimulated GH levels at diagnosis remains to be better understand.

Visceral adiposity index and DHEAS are useful markers of diabetes risk in women with polycystic ovary syndrome.

OBJECTIVE: On the basis of the known diabetes risk in polycystic ovary syndrome (PCOS), recent guidelines of the Endocrine Society recommend the use of an oral glucose tolerance test (OGTT) to screen for impaired glucose tolerance (IGT) and type 2 diabetes (T2DM) in all women with PCOS. However, given the high prevalence of PCOS, OGTT would have a high cost-benefit ratio. In this study, we identified, through a receiver operating characteristic analysis, simple predictive markers of the composite endpoint (impaired fasting glucose (IFG) or IGT or IFG+IGT or T2DM) in women with PCOS according to the Rotterdam criteria. DESIGN: We conducted a cross-sectional study of 241 women with PCOS in a university hospital setting. METHODS: Clinical, anthropometric, and metabolic (including OGTT) parameters were evaluated. The homeostasis model assessment of insulin resistance (HOMA2-IR), the Matsuda index of insulin sensitivity, and the oral dispositional index and visceral adiposity index (VAI) were determined. RESULTS: Out of 241 women included in this study, 28 (11.6%) had an IFG, 13 (5.4%) had IGT, four (1.7%) had IFG+IGT, and four (1.7%) had T2DM. Among the anthropometric variables examined, the VAI had a significantly higher C-statistic compared with BMI (0.760 (95% CI: 0.70-0.81) vs 0.613 (95% CI: 0.54-0.67); P=0.014) and waist circumference (0.760 (95% CI: 0.70-0.81) vs 0.619 (95% CI: 0.55-0.68); P=0.028). Among all the hormonal and metabolic serum variables examined, DHEAS showed the highest C-statistic (0.720 (95% CI: 0.65-0.77); P<0.001). CONCLUSIONS: In addition to fasting glucose, the VAI and DHEAS may be considered useful tools for prescreening in all women with PCOS without the classical risk factors for diabetes.

Reduction in insulin sensitivity and inadequate ß-cell capacity to counteract the increase in insulin resistance in children with idiopathic growth hormone deficiency during 12 months of growth hormone treatment.

PURPOSE: To evaluate the performance of various indexes of insulin sensitivity and secretion and to identify the most useful indicator of deterioration of glucose metabolism in a cohort of children with growth hormone (GH) deficiency (GHD) during GH treatment. METHODS: In 73 GHD children (55 M, 18 F; mean age 10.5 years) at baseline and after 12 months of treatment, we evaluated a number of surrogate indexes of insulin secretion and sensitivity. In a subgroup of 11 children we also performed an euglycemic hyperinsulinemic clamp. RESULTS: After 12 months, a significant increase in fasting glucose (p < 0.001) and HbA1c levels (p < 0.001) was documented, despite all children remained with a normal glucose tolerance. With regard the insulin secretion, Homa-ß did not show any significant change (p = 0.073), while oral disposition index (DIo) showed a significant decrease (p = 0.031). With regard the insulin sensitivity, Homa-IR significantly increased (p < 0.001) with a concomitant decrease in QUICKI (p < 0.001). ISI Matsuda showed a decrease, although not statistically significant (p = 0.069). In the subgroup of 11 children, the M value derived from clamp showed a significant decrease (p = 0.011) and a significant positive correlation was found between M value and ISI Matsuda both at baseline (ρ 0.950; p = 0.001) and after 12 months (ρ 0.980; p = 0.001) but not with Homa-IR and QUICKI. CONCLUSIONS: 12 months of GH treatment lead to a decrease in insulin sensitivity and impairment in insulin secretion relative to insulin sensitivity even without evident changes in glucose tolerance. DIo has proven to be the most useful indicator of deterioration of glucose metabolism even in cases in which the overt glucose abnormalities have not yet appeared.

Correlation between severity of growth hormone deficiency and thyroid metabolism and effects of long-term growth hormone treatment on thyroid function in children with idiopathic growth hormone deficiency.

BACKGROUND/AIM: The significance of changes in thyroid function in children during growth hormone (GH) treatment remains uncertain. We aimed to evaluate the impact of GH replacement on thyroid status in children with idiopathic GH deficiency (GHD). METHODS: Data of 105 GHD children (82 M, 23 F; aged 11.13 years) during a 36-month follow-up were analyzed. At diagnosis the areas under the curve of GH (AUCGH) were calculated during a GH-releasing hormone + arginine (GHRH-Arg) and insulin tolerance test. RESULTS: A significant ΔfT3 (p < 0.001) was documented at 12 months, without any further change at 24 and 36 months and without fT4 and TSH modifications. Grouping patients according to ΔfT3 at 12 months into those with lower (n = 80, 76%) or greater values than the 75th percentile (n = 25, 24%), the latter showed lower AUCGH and GH peak during a GHRH-Arg (p = 0.018 and 0.014, respectively) and insulin tolerance test (p = 0.023 and 0.020, respectively) at diagnosis. In addition, children with lower GH at diagnosis showed a greater ΔfT3 at 12 months (p = 0.030). CONCLUSIONS: In GHD children, GH treatment is associated with a significant increase in fT3 in the first 12 months, more pronounced in patients with more severe GHD, highlighting the strong correlation between severity of GHD and thyroid metabolism.

No phenotypic differences for polycystic ovary syndrome (PCOS) between women with and without type 1 diabetes mellitus.

CONTEXT: Women with type 1 diabetes mellitus (DM1) have a higher prevalence of polycystic ovary syndrome (PCOS) than the general population. OBJECTIVE: The aim of this study was to clarify, in DM1 women with PCOS (PCOS-DM1), the influence of insulin therapy and glycemic control and evaluate the hormonal and phenotypic differences with age-matched and body mass index (BMI)-matched women with PCOS without diabetes. DESIGN, SETTING, AND PATIENTS: We evaluated 103 DM1 women with and without PCOS treated with intensive insulin therapy; 38 age-matched and BMI-matched women with PCOS without diabetes were compared in a cross-sectional study. OUTCOME MEASUREMENTS: Clinical, anthropometric, and metabolic parameters were evaluated. Hormonal evaluation and ovary ultrasound were performed during the follicular phase of the menstrual cycle. RESULTS: Applying the diagnostic criteria of the Androgen Excess Society, 38 (36.89%) women with DM1 showed PCOS. The 38 PCOS-DM1 women showed no differences in treatment and glycemic control compared with DM1 women without PCOS. The only difference was a higher visceral adiposity index in PCOS-DM1 (1.21±0.70 vs 0.90±0.32; P=.002). PCOS-DM1 showed no phenotypic differences with age-matched and BMI-matched PCOS without diabetes. The hormonal pattern was similar except that higher levels of Δ4androstenedione were found in PCOS-DM1 (12.89±3.49 vs 2.79±1.75 nmol/L; P=.010). CONCLUSIONS: The women with PCOS-DM1 do not exhibit particular phenotypic characteristics compared with nondiabetic women with PCOS. However, this pathological disorder must not be underestimated because it could be an additional cardiovascular risk factor in women with DM1.

Metabolically healthy polycystic ovary syndrome (MH-PCOS) and metabolically unhealthy polycystic ovary syndrome (MU-PCOS): a comparative analysis of four simple methods useful for metabolic assessment.

STUDY QUESTION: Is it possible to distinguish metabolically healthy polycystic ovary syndrome (MH-PCOS) from metabolically unhealthy PCOS (MU-PCOS) by simple diagnostic tools such as body mass index (BMI), waist/hip ratio (WHR), at-risk category suggested by Androgen Excess Society (AES) and visceral adiposity index (VAI)? SUMMARY ANSWER: VAI could be an easy and useful tool in clinical practice and in population studies for assessment of MU-PCOS. WHAT IS KNOWN ALREADY: VAI is a good indicator of insulin sensitivity and cardiometabolic risk in oligo-ovulatory women with PCOS. STUDY DESIGN, SIZE, DURATION: We conducted a cross-sectional study of 232 women with PCOS in a university hospital setting. PARTICIPANTS/MATERIALS, SETTING, METHODS: Anthropometric, hormonal and metabolic parameters were evaluated. An oral glucose tolerance test measured areas under the curve (AUC) for insulin (AUC 2h insulin) and for glucose (AUC 2h glucose). Homeostasis model assessment of insulin resistance (HOMA2-IR), the Matsuda index of insulin sensitivity (ISI), the oral dispositional index (DIo) and VAI were determined. MAIN RESULTS AND THE ROLE OF CHANCE: The prevalence of MU-PCOS according to the different criteria was: BMI, 56.0%; WHR, 18.1%; at-risk criteria of AES, 72.0% and VAI, 34.5%. The likelihood that a woman would exhibit MU-PCOS (except when diagnosed by the WHR criterion) showed a significant positive association with high HOMA2-IR [BMI criterion: (odds ratio (OR): 1.86; 95% confidence interval (CI): 1.43-2.41); risk criteria of AES (OR: 1.86; 95% CI: 1.36-2.56); VAI criterion (OR: 1.45; 95% CI: 1.17-1.80)] and a significant negative association with low ISI Matsuda [BMI criterion: (OR: 0.81; 95% CI: 0.72-0.91); risk criteria of AES (OR: 0.78; 95% CI: 0.69-0.89); VAI criterion (OR: 0.82; 95% CI: 0.71-0.94)]. Only MU-PCOS according to the VAI criterion showed a significant association with low DIo (OR: 0.85; 95% CI: 0.75-0.96); these women also showed a significant association with low luteal progesterone levels (OR: 0.97; 95% CI: 0.95-0.99). LIMITATIONS, REASONS FOR CAUTION: The analysis is limited by the lack of a gold standard definition of metabolic health that would have allowed the execution of a receiver operator characteristic analysis of the four proposed criteria. WIDER IMPLICATIONS OF THE FINDINGS: The results will facilitate the early recognition of cardiometabolic risk in women with PCOS before they develop overt metabolic syndrome.

Body composition assessment for the definition of cardiometabolic risk.

Obesity is associated with a major prevalence of cardiovascular risk factors and high risk of cardiovascular events and contributes to the increase in cardiovascular morbidity and mortality worldwide. Beyond the fat mass per se, the pattern of fat distribution has a profound influence on cardiometabolic risk. The increase in abdominal adipose tissue confers an independent risk, while the amount of gluteofemoral body fat is thought to be protective. Changes in the capacity of different depots to store and release fatty acids and to produce adipocytokines are important determinants of fat distribution and its metabolic consequences. Because of the complexity of the assessment of body fat with imaging techniques, great attention has been paid to other measures of adiposity, such as waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR), which provide information on body fat distribution, although body mass index (BMI) is the established clinical measure to estimate the cardiovascular risk disease associated with excessive body weight. Abdominal obesity is a main predictive factor of the metabolic syndrome, so it is certain that it represents a better marker of cardiovascular risk than BMI. Visceral adiposity index (VAI) has recently proven to be a marker of visceral adipose distribution and function, associated with insulin sensitivity in patients at metabolic risk; however, the evidence needs to be further confirmed. In summary, BMI, WC, WHR, WHtR, and VAI are all useful tools for assessing adiposity/ obesity in clinical practice, and should be evaluated along with other cardiometabolic risk factors to define cardiovascular risk stratification.

The metabolic profile in active acromegaly is gender-specific.

CONTEXT: The sexual dimorphism of the somatotroph axis has been documented, but whether the acromegaly-related metabolic alterations are gender-dependent has never been investigated. OBJECTIVE: The aim of the study was to evaluate the impact of gender on the metabolic parameters in acromegaly. DESIGN: We conducted a retrospective, comparative, multicenter study. PATIENTS: The 307 newly diagnosed acromegalic patients included in the study were grouped by gender: 157 men (aged 48.01 ± 14.28 yr), and 150 women (aged 48.67 ± 14.95 yr; of which 77 were premenopausal and 73 postmenopausal). OUTCOME MEASUREMENTS: We measured each component of the metabolic syndrome (MS), hemoglobin A1c, the areas under the curve (AUCs) of glucose and insulin during 2-h oral glucose tolerance test, basal insulin resistance using the homeostasis model assessment of the insulin resistance index, stimulated insulin sensitivity using the insulin sensitivity index, early insulin-secretion rate using the insulinogenic index, ß-cell function relative to insulin sensitivity using the oral disposition index and the visceral adiposity index (VAI) as the surrogate of visceral fat function. RESULTS: Women showed a higher prevalence of MS (P < 0.001), higher fasting insulin levels (P < 0.001), AUC for insulin (P = 0.002), homeostasis model assessment of the insulin resistance index (P < 0.001), and VAI (P < 0.001) and a lower insulin sensitivity index (P = 0.002) than men, whereas no difference was found in fasting glucose, AUC for glucose, hemoglobin A1c, insulinogenic index, and oral disposition index. In women, fasting glucose and fasting insulin showed a significant trend toward increase (P < 0.001) and decrease (P = 0.004), respectively, from the first to the fourth quartiles of age, whereas VAI showed a trend toward increase in both groups (P < 0.001). A significantly higher prevalence of MS (P < 0.001), increased waist circumference (P < 0.001), low high-density lipoprotein cholesterol (P < 0.001), and overt diabetes mellitus (P < 0.001) was found in postmenopausal women compared with premenopausal women, as well as with men. CONCLUSIONS: The majority of metabolic features in acromegaly are gender-specific. Active acromegaly in women is strongly associated with higher visceral adiposity dysfunction, insulin resistance, and the features of MS. We suggest more accurate metabolic management in acromegalic women, especially in the postmenopausal years.

Visceral adiposity index is associated with insulin sensitivity and adipocytokine levels in newly diagnosed acromegalic patients.

CONTEXT: The visceral adiposity index (VAI) has proved to be a marker of visceral adipose dysfunction, strongly associated with insulin sensitivity in both the general and specific populations of patients at metabolic risk. OBJECTIVE: The objective of the study was to test VAI as a useful tool to assess early metabolic risk in acromegaly. PATIENTS: Twenty-four newly diagnosed acromegalic patients (11 women and 13 men, aged 54.9 ± 13.6 yr) were grouped into those with normal (group A, n = 13, 54.2%) and those with high VAI (group B, n = 11, 45.8%). OUTCOME MEASURES: Glucose, hemoglobin A1c, nadir and area under the curve (AUC) of GH (AUC(GH)) during the oral glucose tolerance test, AUC(Cpeptide) during a mixed-meal tolerance test, M value during euglycemic-hyperinsulinemic clamp, oral dispositional index (DIo), each component of the metabolic syndrome, leptin, adiponectin, TNF-α, and IL-6. RESULTS: The VAI value was positively correlated with the age of patients (ρ = 0.408; P = 0.048), tumor volume (ρ = 0.638; P = 0.001), basal GH (ρ = 0.622; P = 0.001), nadir GH (ρ = 0.534; P = 0.007), AUC(GH) (ρ = 0.603; P = 0.002), IGF-I (ρ = 0.618; P = 0.001), TNF-α (ρ = 0.512; P = 0.010), and AUC(Cpeptide) (ρ = 0.715; p<0.001) and negatively with adiponectin (ρ = -0.766; P < 0.001), M value (ρ = -0.818; P < 0.001), and DIo (ρ = -0.512; P = 0.011). Patients with high VAI showed significantly higher basal GH levels (P = 0.018), AUC(GH) (P = 0.047), IGF-I (P = 0.047), AUC(Cpeptide) (P = 0.018), lower M value (P < 0.001), DIo (P = 0.006), and adiponectin levels (P < 0.001), despite the absence of a significantly higher prevalence in the overt metabolic syndrome and glucose tolerance abnormalities. AUC(GH) proved to be the main independent factor influencing VAI. CONCLUSIONS: In acromegaly, VAI appears to be associated with disease activity, adiponectin levels, and insulin sensitivity and secretion and is influenced independently by GH levels. VAI could therefore be used as an easy and useful new tool in daily clinical practice for the assessment of early metabolic risk associated with active acromegaly.

Visceral adiposity index is associated with significant fibrosis in patients with non-alcoholic fatty liver disease.

BACKGROUND: Metabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD). AIMS: To test a new marker of adipose dysfunction, the visceral adiposity index (VAI), in NAFLD patients to assess whether or not it is associated with host factors, and to investigate a potential correlation with histological findings. METHODS: One hundred and forty-two consecutive NAFLD patients were evaluated by liver biopsy, and clinical and metabolic measurements, including insulin resistance with the homeostasis model assessment (HOMA), and VAI by using waist circumference, body mass index, triglycerides and HDL. Serum levels of TNFα, IL-6, adiponectin and leptin were also assessed. All biopsies were scored for NAFLD activity score (NAS) and its components, and for staging (Kleiner). RESULTS: By multiple linear regression analysis, VAI was independently associated with higher HOMA (P = 0.04), and fibrosis (P = 0.04). In addition, an independent association was found between higher VAI and lower adiponectin levels (P = 0.002). Higher HOMA (OR 1.149, 95% CI 1.003-1.316, P = 0.04), higher VAI (OR 1.446, 95% CI 1.023-2.043, P = 0.03), lobular inflammation (OR 3.777, 95% CI 1.771-8.051, P = 0.001), and ballooning (OR 2.884, 95% CI 1.231-6.757, P = 0.01) were correlated with significant fibrosis (F2-F4) on multiple logistic regression analysis. In particular, the prevalence of significant fibrosis progressively increased from patients with a VAI ≤ 2.1 and HOMA ≤ 3.4 (26%) to those with a VAI > 2.1 and HOMA > 3.4 (83%). CONCLUSIONS: In NAFLD patients, visceral adiposity index is an expression of both qualitative and quantitative adipose tissue dysfunction and, together with insulin resistance, is independently correlated with significant fibrosis.

Cornea in acromegalic patients as a possible target of growth hormone action.

BACKGROUND: GH exerts its effects on many organs and the eye also seems to be a target site, although few authors have investigated the corneal thickness in patients with acromegaly. AIM: To perform a detailed ophthalmological evaluation in acromegalic patients, in relation to disease activity. MATERIAL AND METHODS: Twenty-eight acromegalic patients (11 males, 17 females) and 22 voluntary healthy subjects underwent complete metabolic and ophthalmological evaluation, including retinal thickness (RT), central corneal thickness (CCT), and intraocular pressure values (IOP). RESULTS: Significantly greater CCT values were found in all acromegalic patients in comparison with controls (567 vs 528.5 µm; p<0.001), without concomitant greater corrected IOP. No difference was found for RT. Analyzing these data according to disease activity, uncontrolled patients showed greater CCT values (573.5 vs 559 µm; p=0.002) and corrected IOP (17.4 vs 16 mmHg; p=0.001) than the controlled ones. CCT also correlated with basal and nadir GH after oral glucose load levels, IGF-I levels, and duration of active disease. CONCLUSIONS: Acromegaly is characterized by greater CCT values, supporting the hypothesis that GH excess may have stimulatory effects on the cornea as well as on other target organs. Higher GH levels, disease control status and duration of active disease seem to be the main causes of increased corneal thickness. We suggest a careful and detailed corneal evaluation in acromegalic patients to prevent the potential risk of increased IOP, in addition to the already-known complications.

Effect of multiple cranial burr hole surgery on prevention of recurrent ischemic attacks in children with moyamoya disease.

Moyamoya disease (MMD) is an uncommon cerebrovascular disorder characterized by progressive stenosis of the terminal portion of the internal carotid artery and its main branches. Direct and indirect bypass techniques have been devised with the aim of promoting neoangiogenesis. The current study aimed to investigate the role of multiple cranial burr hole (MCBH) operations in the prevention of cerebral ischemic attacks in children with MMD. Seven children suffering from progressive MMD were submitted to the MCBH and arachnoid opening technique. Ten to 20 burr holes were drilled in the fronto-temporo-parieto-occipital area of each hemisphere in each patient, depending on the site and extent of the disease. All patients were evaluated pre- and postoperatively by means of Barthel index (BI), CT, MR, angio-MR, and angiography. Patients had no recurrence of ischemic attacks postoperatively. Neoangiogenesis was observed in both hemispheres. One patient developed a persistent subdural collection after surgery, thus requiring placement of a subdural-peritoneal shunt. Postoperative BI was statistically significantly improved (P=0.02). This report suggests that MCBH for revascularization in MMD is a simple procedure with a relatively low risk of complications and effective for preventing cerebral ischemic attacks in children. In addition, MCBH may be placed as an adjunct to other treatments for MMD.

Metabolic parameters and adipokine profile during GH replacement therapy in children with GH deficiency.

OBJECTIVE: GH replacement therapy in children with GH deficiency (GHD) mainly promotes linear growth. Not only have very few studies fully analyzed the metabolic consequences of GH therapy, but also the question as to whether GH may affect adipokine secretion has been insufficiently investigated. Our aim was to study the effects of GH replacement therapy on auxological data, lipid and glycemic profiles, insulin homeostasis (HOMA-IR) and serum adipokines in children. METHODS: This was a 1-year prospective study. Thirty-four GHD children (11.6 +/- 2.6 years) and thirty healthy matched controls were enrolled. Children affected by GHD were studied both before beginning continuous GH replacement therapy and again at 12 months. RESULTS: At the beginning of the study, total and LDL cholesterol were higher in GHD children than in controls (P<0.001), whereas HDL cholesterol, triglycerides, insulin, HOMA-IR, leptin, and adiponectin were similar. At 12 months of continuous GH replacement therapy in the GHD group, there was a significant increase in both auxological data and IGF-I (P<0.001); total cholesterol (P<0.001), LDL (P<0.001), triglycerides (P<0.005), and leptin (P<0.001) decreased significantly; HDL (P<0.003), insulin (P<0.001), HOMA-IR (P<0.001) increased while adiponectin was unmodified. Furthermore, IGF-IDelta showed an inverse correlation with leptin Delta (rho = -0.398, P = 0.02). CONCLUSIONS: In GHD children, the evaluation of metabolic parameters proves to be a useful tool for the evaluation of auxological parameters during GH replacement therapy. In our study, GH replacement therapy in GHD children improved final height, restored IGF-I levels, reduced leptin levels, and improved the lipid profile, without producing any unfavorable effects on glucose metabolism.

Endocrine disorders in pediatric - onset Langerhans Cell Histiocytosis.

Langerhans Cell Histiocytosis (LCH) is a rare disorder with a great variety of clinical manifestations. The purpose of this retrospective study was to evaluate the pattern and the long-term course of clinical, laboratorial and radiological findings in pediatric-onset LCH. We reviewed 46 children with histological diagnosis of LCH. Ten children (22%) showed endocrine disorders. Central diabetes insipidus (DI) was observed in all ten patients; GH deficiency was confirmed in four and hypogonadism in two children. There were no adrenal, prolactin or thyroid axis abnormalities. Obesity was observed in three patients. Eight patients showed soft tissue infiltration and five bone involvement. The MRI showed a lack of posterior pituitary bright spot in all DI patients; infundibular infiltration (II) associated or not with sellar or supra-sellar mass was observed in 4 patients. We conclude that the investigation of LCH, a multi-systemic disease, should include central nervous system images. The presence of II and/or DI should raise the diagnosis of LCH. Complete endocrine evaluation, allowing an early hormone therapy, is required to obtain a better quality of life in children with LCH.

Treatment decision in asymptomatic aortic valve stenosis: role of exercise testing.

OBJECTIVE: To determine the prognostic value of exercise testing, valve area, and maximum transaortic pressure gradient in asymptomatic patients with aortic valve stenosis. SETTING: The outpatient service of a tertiary referral centre for cardiology. DESIGN: Prospective clinical study. PATIENTS: 66 consecutive patients with isolated severe aortic stenosis (aortic valve area /= 0.7 cm(2) (p = 0.0021). There was no relation between the end points and transaortic gradient (p = 0.6882). In multivariate analysis, a hazard ratio of 7.43 was calculated for patients with a positive versus a negative exercise stress test. Although asymptomatic in daily life, 6% of the patients (4/66) experienced sudden death; all these had a positive exercise test and an aortic valve area of