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Abstract We investigate the evolution of a gene for paternal care, with pleiotropic effects on male mating fitness and offspring viability, with and without extrapair copulations (EPCs). We develop a population genetic model to examine how pleiotropic effects of a male mating advantage and paternal care are affected by “good genes” and EPCs. Using this approach, we show that the relative effects of each on fitness do not always predict the evolutionary change. We then find the line of combinations of mating success and paternal care that bisects the plane of possible values into regions of positive or negative gene frequency change. This line shifts when either good genes or EPCs are introduced, thereby expanding or contracting the region of positive gene frequency change and significantly affecting the evolution of paternal care. Predictably, a direct viability effect of “good genes” that enhances offspring viability constrains or expands the parameter space over which paternal care can evolve, depending on whether the viability effect is associated with the paternal care allele or not. In either case, the effect of a “good gene” that enhances offspring viability is substantial; when strong enough, it can even facilitate the evolution of poor paternal care, where males harm their young. When nonrandom mating is followed by random EPCs, the genetic regression between sire and offspring is reduced and, consequently, the relative strengths of selection are skewed away from paternal care and toward the male mating advantage. However, when random mating is followed by nonrandom EPCs, a situation called “trading up” by females, we show that selection is skewed in the opposite direction, away from male mating advantage and toward paternal care across the natural range of EPC frequencies.

An 18-year-old primigravida woman underwent emergent percutaneous balloon stent repair of a severe coarctation of the aorta, allowing her to undergo an uneventful remaining pregnancy and the delivery of a healthy baby. Her case also demonstrates the association between maternal coarctation and fetal Shone complex. (Level of Difficulty: Beginner.)

Background: Dual-release hydrocortisone (DR-HC) improves metabolism in patients with adrenal insufficiency. The aims of this study were to compare the cardiovascular and metabolic effects of conventional glucocorticoids (GCs) vs. DR-H C and of high vs. low doses of GCs, after 48 months of observation. Methods: We selected 27 patients on hydrocortisone (mean dose 17.5 ± 4. 2 mg/day) and 20 patients on cortisone acetate (mean dose 37.5 ± 12.1 mg/day) who maintained this treatment (group A) and 53 patients switched to DR-HC (mean dose 22 ± 4.8 mg/day) (group B). At baseline and after 48 months, clinical and metabolic parameters and Framingham Risk Score (FRS) were obtained. Results: After 48 months, patients in group A had a significant increase from baseline in BMI (P < 0.001), waist circumference (P = 0.001), systolic blood pressure (P = 0.001), LDL cholesterol (P = 0.018), HbA1c (P = 0.020) and FRS (P = 0.002). By contrast, patients in group B had a significant decrease in BMI (P = 0.002), waist circumference (P = 0.015), diastolic blood pressure (P = 0.031), total (P = 0.006) and LDL cholesterol (P = 0.005), HbA1c (P < 0.001) and FRS (P = 0.015) compared to baseline. No significant differences between high and low doses of both conventional GCs and DR-HC were observed. Conclusions: DR-HC is associated with an improvement of metabolic parameters and cardiovascular risk compared to conventional GCs, which are associated with a worsening of these parameters, regardless of the dose used.

Objective: To evaluate the impact of gender on the clinical and metabolic parameters in prepubertal growth hormone deficiency (GHD) children at diagnosis and during GH treatment (GHT). Design: The data of 105 prepubertal children (61 males, 44 females, mean age 6.8 ± 0.7 years) affected by idiopathic GHD were retrospectively evaluated. Methods: Body height, BMI, waist circumference (WC), IGF-I, HbA1c, lipid profile, fasting and after-OGTT glucose and insulin levels, insulin sensitivity and secretion indices were evaluated at baseline and after 24 months of GHT. Results: At baseline, no significant difference was found in all clinical, hormonal and metabolic parameters between males and females. After 24 months of GHT, both males and females showed a significant increase in height (both P < 0.001), BMI (both P < 0.001), WC (P < 0.001 and P = 0.004, respectively), IGF-I (both P < 0.001), fasting glucose (P < 0.001 and P = 0.001, respectively), fasting insulin (both P < 0.001) and Homa-IR (both P < 0.001), with a concomitant significant decrease in insulin sensitivity index (ISI) (both P < 0.001) and oral disposition index (DIo) (P = 0.001 and P < 0.001, respectively). At 24 months of GHT, females showed significantly higher BMI (P = 0.027), lower ISI (P < 0.001) and DIo (P < 0.001), in concomitance with a significant greater change from baseline to 24 months of BMI (P = 0.013), WC (P < 0.001), ISI (P = 0.002) and DIo (P = 0.072), although the latter does not reach statistical significance. Conclusions: Twenty-four months of GHT in prepubertal children leads to different metabolic outcomes according to gender, with a greater reduction in insulin sensitivity in females, regardless of auxological and hormonal parameters. Therefore, prepubertal GHD females should probably need a more proper monitoring in clinical practice.

Abstract Background Idiopathic type 1 diabetes mellitus (IDM) is characterized by an onset with insulinopenia and ketoacidosis with negative β-cell autoimmunity markers and lack of association with HLA. The aim of the study is to compare the clinical and metabolic parameters, the macro and microvascular complications, the adipose tissue dysfunction and the insulin secretion and sensitivity indexes in patients with IDM and autoimmune type 1 diabetes mellitus (ADM) at clinical onset. Methods Thirty patients with IDM and 30 with ADM, matched for age and gender, were retrospectively analyzed. BMI, waist circumference, lipids, glycemia, HbA1c, insulin requirement, glutamic oxaloacetic and glutamic pyruvic transaminases (GOT and GPT), glucagon stimulated c-peptide (GSC-pep) test levels, M value during hyperinsulinemic euglycemic clamp and Visceral Adiposity Index (VAI) were obtained from our database. Results Patients with IDM showed a significantly higher BMI (p 0.012), WC (p 0.07), VAI (p 0.004), LDL-cholesterol (p 0.027), GOT (p 0.005), GPT (p 0.001), M value (p 0.006) and GSC-pep peak (p 0.036), with concomitant lower HDL-cholesterol (p

Abstract Background The approach to acromegalic patients with persistent acromegaly after surgery and inadequate response to first-generation somatostatin receptor ligands (SRLs) should be strictly tailored. Current options include new pituitary surgery and/or radiosurgery, or alternative medical treatment with SRLs high dose regimens, pegvisomant (PEG) as monotherapy, or combined therapy with the addition of PEG or cabergoline to SRLs. A new pharmacological approach includes pasireotide, a second-generation SRL approved for patients who do not adequately respond to surgery and/or for whom surgery is not an option. No reports on efficacy and safety of combined therapy with pasireotide and pegvisomant (PEG) in acromegaly are available. Case presentation Here we report the case of a 41-year-old acromegalic man with a mixed GH/PRL pituitary adenoma post-surgical resistant to first-generation SRLs both alone and in combination with cabergoline and PEG who achieved biochemical and tumor control with the combined triple treatment with pasireotide, PEG and cabergoline without adverse events and with a good compliance to treatment. Conclusions Twelve months of therapy with pasireotide, PEG and cabergoline proved to be safe and effective in this particular patient and the clinical improvement of disease resulted in an improved compliance to treatment.

Background: Cardiovascular disease is a frequent complication of type 1 diabetes (T1D). We evaluated the effectiveness of switching from glargine to degludec in reducing the cardiovascular risk factors, the Framingham risk score (FRS) and visceral adiposity index (VAI) in patients with T1D and autoimmune polyglandular syndrome (APS).Methods: We selected 66 T1D outpatients who had been on stable treatment with glargine for at least 5 years. Among them, 30 patients maintained glargine (group A), while 36 were switched to degludec (group B) for 12 months. At baseline and after 12 months of observation, clinical and metabolic parameters, insulin dose, 30-days blood glucose (BG) self monitoring, VAI and FRS were obtained.Results: At baseline, patients in group B had more hypoglycaemic episodes and prevalence of hypertension than those in group A. After 12 months on degludec, patients in group B had a significant decrease in BMI (p = 0.003), waist circumference (p < 0.001), total daily insulin as U/day and U/kg (p = 0.001 for both), basal insulin as U/day and U/kg (p = 0.001 for both), HbA1c (p < 0.001), mean (p = 0.035) and standard deviation of daily BG (p = 0.017), mean pre-meal BG (p = 0.016), number of hypoglycaemic episodes (p = 0.001), VAI (p = 0.012) and FRS (p = 0.019) and a significant increase in HDL-C (p < 0.001), compared to baseline. At 12 months of treatment a significant decrease in BMI (p = 0.017), WC (p = 0.003), SBP (p = 0.001), DBP (p = 0.005), basal insulin as U/day (p = 0.018) and U/kg (p = 0.045), HbA1c (p = 0.040) and FRS (p = 0.010) was observed in group B compared to group A.Conclusions: Our preliminary data suggest that 12 months' treatment with degludec is associated with an improvement of glycaemic control, cardiometabolic and cardiovascular risk, compared to glargine, in patients with T1D and APS.

Acromegaly is a rare disease due to chronic GH excess and to the consequent increase in IGF-1 levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. Indeed, chronic GH excess impairs insulin sensitivity, increases gluconeogenesis, reduces the glucose uptake in adipose tissue and muscle and alters pancreatic β cells function. As a consequence, glucose metabolism alterations are a very frequent complication in acromegaly patients, further contributing to the increased cardiovascular risk and mortality. Treatment modalities of acromegaly differently impact on glucose tolerance. Successful surgical treatment of acromegaly ameliorates glucose metabolism abnormalities. Drugs used to treat acromegaly patients may per se affect glucose homeostasis, therefore influencing patients' management. Indeed pegvisomant has been shown to positively impact on glucose metabolism, while somatostatin analogs, especially pasireotide, can cause hyperglycaemia. On the other hand, robust data on the effect of dopamine agonists on glycaemic profile are still lacking. This review summarizes the available data on diabetes mellitus in acromegaly patients, with a focus on the potential effects of the medical treatment of the disease on glucose homeostasis, providing an overview of the current state of the art.

BackgroundThe growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis has a fundamental impact on glucose metabolism. Therefore, both untreated GH deficiency (GHD) and GH treatment (GHT) may be associated with some metabolic alterations, although the abnormalities of glucose metabolism have been investigated by relatively few studies as main outcomes.AimThe present review summarizes the available data on glucose metabolism in children with GHD, providing an overview of the current state of the art in order to better clarify the real metabolic impact of GHD and GHT.MethodsAmong all the existing studies, we evaluated all original studies that fulfilled our criteria for analysis reporting parameters of glucose metabolism as the primary or secondary objective.ResultsThe reported impact of GHD per se on glucose metabolism is quite homogeneous, with the majority of studies reporting no significant difference in metabolic parameters between GHD children and controls. Conversely, GHT proves to be more frequently associated with a subtle form of insulin resistance, while both fasting glucose and HbA1c levels remain almost always within the normal range.ConclusionThe different methods to study glucose metabolism, the heterogeneity of the populations evaluated, the different doses of GH used together with the variable duration of follow-up may be responsible for discrepancy in the results. Long-term longitudinal studies having glucose homeostasis as their primary outcome are still needed in order better to clarify the real metabolic impact of GHD and GHT in children.

Objective. In acromegaly, both lipotoxicity secondary to GH excess and insulin resistance have a significant impact on the liver. Ultrasonography has shown poor sensitivity in detecting hepatic steatosis and noninvasive methods have been proposed. We evaluated the hepatic steatosis index (HSI), a validated surrogate index of hepatic steatosis, and we correlated it with disease activity and insulin resistance. Design. Thirty-one patients with newly diagnosed acromegaly were studied at diagnosis and after 12 months of treatment with somatostatin receptor ligands. Methods. Glucose and insulin levels, surrogate estimates of insulin sensitivity, and hepatic steatosis through ultrasonography and HSI were evaluated. Results. At diagnosis, ultrasonography documented steatosis in 19 patients (61.2%) while 26 (83.8%) showed high HSI. After 12 months, both GH (p=0.033) and IGF-1 (p

Objective. To evaluate whether two different regimens of weekly injections could lead to similar auxological and metabolic effects in children with growth hormone deficiency (GHD). Design. 32 GHD children (25 males, mean age 10.5 ± 2.2 yr) were randomly assigned to receive daily (group A, 16 patients) or TIW (group B, 16 patients) GHT for 12 months. Methods. Auxological parameters, insulin-like growth factor-I (IGF-I), glucose and insulin during OGTT, glycosylated hemoglobin (HbA1c), lipid profile, the oral disposition index (DIo), the homeostasis model assessment estimate of insulin resistance (Homa-IR), and the insulin sensitivity index (ISI). Results. After 12 months, both groups showed a significant and comparable improvement in height (p

Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis.We considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free androgen index (FAI) was calculated as estimate of biochemical hyperandrogenism.In the entire population, steatosis was observed in 68.8% of patients with PCOS, compared to 33.3 of controls (p

Background Acromegaly is an insidious disorder caused by a pituitary growth hormone (GH)-secreting adenoma resulting in high circulating levels of GH and insulin-like growth factor I (IGF-I). Respiratory disorders are common complications in acromegaly, and can severely impact on quality of life, eventually affecting mortality. Objectives The present study aimed to explore structural and functional lung alterations of acromegalic subjects. Methods We enrolled 10 consecutive patients (M/F: 5/5) affected by acromegaly. In all patients, magnetic resonance imaging (MRI) revealed the presence of pituitary tumor. All patients underwent clinical, lung functional, biological, and radiological assessments. Ten healthy age-matched subjects also served as controls. Results No statistically significant differences in lung function were detected between acromegalic and healthy subjects (p [greater than or equal to] 0.05 for all analyses). However, the diffusing capacity for CO (TLCO) was significantly lower in the acromegalic group than in healthy subjects (TLCO% predicted: 78.1 ± 16 vs. 90 ± 6 %, respectively, p = 0.04; KCO% predicted: 77 ± 16 vs. 93 ± 5 %, p = 0.02, respectively). None of the lung function parameters correlated with duration of the disease, or with inflammatory marker of the airways. In acromegalics, biological (exhaled NO concentrations) and imaging (total lung volume, TLV, and mean lung density, MLD) evaluations were within normal values. The TLV measured by HRCT was 3540 ± 1555 ml in acromegalics, and the MLD was -711 ± 73 HU. None of the lung functional, radiological, and biological findings correlated with GH or IGF-I levels, and no correlation was found with duration of disease. Conclusions In the current study, lung function evaluation allowed to detect early involvement of lung parenchyma, as assessed by TLCO and KCO, even in the absence of parenchymal density alterations of the lung by HRCT. These findings suggest to routinely include the carbon monoxide diffusing capacity in the lung function assessment for an early intervention in acromegaly., Author(s): A. Benfante[sup.1] , A. Ciresi[sup.2] , M. Bellia[sup.3] , F. Cannizzaro[sup.3] , V. Bellia[sup.1] , C. Giordano[sup.2] , N. Scichilone[sup.1] Author Affiliations: (1) Dipartimento Biomedico di Medicina Interna e [...]