Lacrimal gland herniation in Graves ophthalmopathy: a simple and useful MRI biomarker of disease activity.

BACKGROUND: Lacrimal gland (LG) involvement in patients with Graves ophthalmopathy (GO) has been considered as a potential cause of the associated GO symptoms and different studies demonstrated the LG involvement in patients with GO than healthy controls. The aim of this study was to evaluate LG involvement, through measurement of its herniation, using a magnetic resonance imaging (MRI) index, in patients with different GO activities. METHODS: Thirty-two consecutive Caucasian patients affected by GO were enrolled and grouped in group A (16 with inactive GO, CAS < 3) and B (16 with active GO, CAS ≥ 3) according to their GO activity. All patients underwent clinical-endocrinological assessment, a complete ocular evaluation, and orbital MRI examination. RESULTS: No difference was found between the hormonal parameters, thyroid ultrasound-derived parameters, and thyroid-stimulating hormone (TSH) receptor (TSH-R) antibodies (TRAb) levels in group B and those in group A. The LG herniation (LGH) measurement evaluated by MRI was significantly higher in group B for both right (10.1 (7.3-17) vs. 7 (0-3.4) mm; p = 0.004) and left (8.5 (6.6-13) vs. 5.8 (0-12) mm; p = 0.026) eye than group A. A positive correlation was found between TRAb and LGH herniation (Rho 0.462, p = 0.009). CONCLUSIONS: Measurement of LGH seems to be a good marker of the disease and GO activity. KEY POINTS: • Lacrimal gland herniation is a simple index related to disease activity • Lacrimal gland herniation is correlated to TRAb levels • Lacrimal gland evaluation could be useful to differentiate active from inactive Graves ophthalmopathy in an early stage of disease.

Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual-release hydrocortisone treatment: a 36-month retrospective analysis.

OBJECTIVE: Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement of anthropometric and metabolic parameters. The aim of the study was to evaluate the effects of DR-HC on insulin secretion and sensitivity and cardiometabolic risk, indirectly expressed by the visceral adiposity index (VAI). DESIGN AND PATIENTS: Retrospective analysis of 49 patients, 13 with primary and 36 with secondary adrenal insufficiency (AI), respectively, on conventional glucocorticoid treatment at baseline and switched to DR-HC for 36 months. Overall, 24 patients had AI-pre-diabetes (impaired fasting glucose, impaired glucose tolerance and the combination), and 25 had AI-normal glucose tolerance (NGT). MEASUREMENTS: Clinical and metabolic parameters, including VAI, insulin secretion and sensitivity indexes (fasting insulinaemia, AUC2 h insulinaemia , oral disposition index [Dio] and ISI-Matsuda), were evaluated. RESULTS: In patients with AI-NGT and AI-prediabetes, a significant decrease in BMI (P = .017 and P < .001), waist circumference (P = .008 and P < .001), HbA1c (P = .034 and P = .001) and a significant increase in HDL-C (P = .036 and P = .043) was, respectively, observed. In addition, in prediabetic patients, only we found a significant decrease in insulinaemia (P = .014), AUC2 h insulinaemia (P = .038) and VAI (P = .001), in concomitance with a significant increase in DIo (P = .041) and ISI-Matsuda (P = .038). CONCLUSIONS: Long-term DR-HC therapy is associated with an improvement in insulin secretion and sensitivity in patients with prediabetes. However, all patients appear to benefit from the treatment in terms of improvement of metabolic and anthropometric parameters. Larger studies are required to confirm our preliminary data.

Higher doses of cabergoline further improve metabolic parameters in patients with prolactinoma regardless of the degree of reduction in prolactin levels.

OBJECTIVE: Currently available studies that fully analyse the metabolic parameters in patients with prolactinoma are scarce and discordant. The aim of this study was to evaluate the metabolic effects of cabergoline (CAB) treatment in patients with newly diagnosed prolactinoma in relation to disease control and CAB dosage. DESIGN: This is a retrospective clinical-based therapy analysis. PATIENTS: Forty-three patients with prolactinoma (eight men, 35 women), aged 33·65 ± 11·23 years, were evaluated metabolically at baseline and after 12 months of CAB treatment. MEASUREMENTS: Body mass index (BMI), systolic and diastolic blood pressure, waist circumference (WC), lipid profile, haemoglobinA1c (HbA1c), glucose and insulin levels (and their areas under the curve, AUC) after an oral glucose tolerance test, homoeostasis model assessment of insulin resistance (Homa-IR) index, insulin sensitivity index (ISI) Matsuda, oral disposition index (DIo) and visceral adiposity index (VAI) were measured at baseline and after 12 months of treatment. RESULTS: Twelve months of CAB reduced WC (P < 0·001), total (P = 0·001) and low-density lipoprotein \terol (P < 0·001), triglycerides (P = 0·024), fasting insulin (P < 0·001), AUCINSULIN (P < 0·001), HbA1c (P = 0·022), Homa-IR (P < 0·001) and VAI (P < 0·001), with a concomitant increase in high-density lipoprotein cholesterol (P < 0·001) and in ISI Matsuda (P < 0·001), regardless of the degree of reduction in prolactin levels. The patients receiving higher doses (>0·50 mg/week) of CAB showed lower BMI (P = 0·009), fasting insulin (P = 0·001), Homa-IR (P < 0·001) and VAI (P = 0·018) and higher ISI Matsuda (P = 0·002) and DIo (P = 0·011), compared with those on lower doses. CONCLUSIONS: A significant metabolic improvement was observed in patients with prolactinoma after 12 months of CAB treatment, especially when higher doses were used, highlighting the importance of considering the metabolic profile in these patients and the role of active treatment with high CAB doses.

Clinical and metabolic effects of first-line treatment with somatostatin analogues or surgery in acromegaly: a retrospective and comparative study.

To evaluate the metabolic effects of first-line somatostatin analogues or surgery in acromegaly. Retrospective, comparative, 12-month follow-up. Two hundred and thirty one patients (123 men, age 47.32 ± 14.63 years) with active acromegaly, first line treatments were somatostatin analogues in 151 (65.4%) and surgery in 80 (34.6%). Metabolic syndrome (MS) parameters, glucose, insulin and GH during oral glucose tolerance test, stimulated insulin sensitivity by insulin sensitivity index (ISI Matsuda), early and total insulin-secretion rate by insulinogenic index and AUC(INS), visceral adiposity function, expressed by visceral adipose index (VAI). Somatostatin analogues treatment improved all MS parameters and significantly reduced fasting glucose (P < 0.001), HbA1c (P = 0.014) and the prevalence of DM (P = 0.003) when disease control was achieved. Both somatostatin analogues and surgery improved ISI Matsuda (P < 0.001) and reduced AUC(INS) (P < 0.001) and VAI (P < 0.001 and P = 0.003, respectively). Only in controlled somatostatin analogues-treated patients a significant reduction in insulinogenic index (P = 0.010) was observed. ISI Matsuda showed a significant independent correlation with IGF-1 levels (ß = -0.258; P = 0.001) and VAI score (ß = -0.430; P < 0.001). VAI was independently correlated with IGF-1 (ß = 0.183; P = 0.004). Both somatostatin analogues and surgery can safely be used as first-line therapy in acromegaly, without any untoward effects on glucose tolerance. The control of acromegaly is the main determinant of beneficial effects on general features of insulin sensitivity. VAI could represent an additional link between disease control and insulin sensitivity.

Circulating Irisin Levels in Children With GH Deficiency Before and After 1 Year of GH Treatment.

Purpose: To evaluate circulating irisin levels in children with GH deficiency (GHD) and any relation with clinical and metabolic parameters. Patients: Fifty-four prepubertal children (mean age, 7.4 ± 0.8 years) with idiopathic GHD treated with GH for at least 12 months and 31 healthy short children as control subjects. Methods: Body height, body mass index (BMI), waist circumference (WC), IGF-I, HbA1c, lipid profile, fasting and after-oral glucose tolerance test glucose and insulin, insulin sensitivity indices, and irisin levels were evaluated at baseline and after 12 months of GH replacement (GHR). Results: At baseline, children with GHD, in addition to having lower growth velocity (P < 0.001), GH peak after stimulation tests (both P < 0.001), and IGF-I (P < 0.001), showed significantly lower irisin (P < 0.001) and higher BMI (P < 0.001) and WC (P = 0.001), without any difference in metabolic parameters, than control subjects. After GHR, children with GHD showed a significant increase in height (P < 0.001), growth velocity (P < 0.001), IGF-I (P < 0.001), fasting glucose (P = 0.002) and insulin (P < 0.001), homeostasis model assessment estimate of insulin resistance (P < 0.001), and irisin (P = 0.005), with a concomitant decrease in BMI (P = 0.001) and WC (P = 0.003). In multivariate analysis, the independent variables significantly associated with irisin were BMI (P = 0.002) and GH peak (P = 0.037) at baseline and BMI (P = 0.005), WC (P = 0.018), and IGF-I (P < 0.001) during GHR. Conclusions: We report that GHR leads to an increase in irisin levels, strongly related to a decrease in BMI and WC, and to an increase in IGF-I; these changes are among the main goals of GHR. These data confirm the favorable effects of GHR in children.

Glucose Metabolism in Children With Growth Hormone Deficiency.

BACKGROUND: The 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. AIM: The 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. METHODS: Among 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. RESULTS: The 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. CONCLUSION: The 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.

Comparison between euglycemic hyperinsulinemic clamp and surrogate indices of insulin sensitivity in children with growth hormone deficiency.

OBJECTIVE: Data about the impact of growth hormone treatment (GHT) on insulin sensitivity in children are quite controversial, due to the different surrogate indices that have been used. DESIGN: We evaluated insulin sensitivity through the euglycemic hyperinsulinemic clamp, considered the gold standard technique, in 23 children affected by growth hormone deficiency (GHD) at baseline and after 12months of GHT and in 12 controls with short stature at baseline, and we compared the clamp-derived index (M-value) with the most commonly used surrogate index of insulin sensitivity, as ISI Matsuda, and with circulating plasma markers of insulin sensitivity, as adiponectin and resistin levels. RESULTS: At baseline, no significant difference in all metabolic parameters between GHD children and control subjects was found. After 12months of GHT, GHD children showed a significant increase in fasting insulin (p<0.001) and resistin (p=0.028) and a decrease in ISI Matsuda (p<0.001) and M-value (p<0.001), without significant change in fasting glucose, HbA1c and adiponectin. In GHD children, M-value showed a significant but weak correlation with ISI Matsuda (rho 0.418, p=0.047) at baseline, while no correlation with other parameters was found. After 12months of GHT, M-value did not show any significant correlation with any other metabolic parameter analyzed. CONCLUSIONS: This study highlights the limit of the evaluation of insulin sensitivity performed through surrogate indices or circulating markers, which may lead to controversial data and do not correlate with the gold standard technique to evaluate insulin sensitivity.

Hepatic Steatosis Index in Acromegaly: Correlation with Insulin Resistance Regardless of the Disease Control.

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 < 0.001) significantly decreased and, overall, 58% of patients were classified as controlled. Ultrasonography documented steatosis in all the same initial 19 patients, while only 14 patients (45.1%) showed high HSI (p < 0.001). A significant reduction in HOMA-IR (p = 0.002) and HSI (p < 0.001) and increased ISI Matsuda (p < 0.001), was documented. The change of HSI from baseline to 12 months was found to be directly correlated with the change of ISI (Rho -0.611; p = 0.004) while no correlation was found with the change of GH or IGF-1 levels and other parameters. CONCLUSIONS: In acromegaly, HSI is mainly related with insulin resistance and the reduction of GH and IGF-1 levels, and above all the improvement in insulin sensitivity leads to an improvement of this surrogate index of hepatic steatosis.

Liraglutide Improves Cardiovascular Risk as an Add-on to Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real-life 48-Month Retrospective Study.

INTRODUCTION: Although liraglutide is widely recognized to have glycemic and extra-glycemic effects, few studies have compared these effects in relation to hypoglycemic treatment starting from the diagnosis of diabetes. We evaluated the effectiveness of liraglutide in reducing the Framingham risk score (FRS) and visceral adiposity index (VAI) in relation to first-line hypoglycemic treatment from diagnosis of type 2 diabetes, continued without any changes. METHODS: We selected 105 diabetic outpatients who were treated with liraglutide for at least 48 months as an add-on therapy to metformin alone (group A, n = 52) or insulin secretagogues (group B, n = 53) from diagnosis time. RESULTS: Although both groups showed a reduction in BMI, waist circumference, blood pressure, HbA1c and triglycerides, only group A showed a significant reduction in FRS (p < 0.001) and VAI (p = 0.012) after 48 months. No significant intergroup difference was found for any parameters at either baseline or 48 months, with the exception of FRS at 48 months, lower in group A (p = 0.002), regardless of duration of disease, improvement in glycemic control and VAI. CONCLUSION: Our data show that during a 48-month follow-up liraglutide was more efficacious in reducing cardiovascular risk than when it was used as add-on therapy to the first-line therapy from diagnosis with metformin and not with insulin secretagogues.

The metabolic outcomes of growth hormone treatment in children are gender specific.

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.

Higher cardiometabolic risk in idiopathic versus autoimmune type 1 diabetes: a retrospective analysis.

BACKGROUND: Idiopathic type 1 diabetes mellitus (IDM) is characterized by an onset with insulinopenia and ketoacidosis with negative ß-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 < 0.001), than patients with ADM. In addition, patients with IDM showed a more marked familial history for diabetes (p 0.005) and a higher percentage of hepatic steatosis (p 0.001), visceral obesity (p 0.032) and hypercholesterolemia (p 0.007) compared to patients with ADM. CONCLUSIONS: Patients with IDM show many metabolic complications at onset, such as visceral obesity, hepatic steatosis and hypercholesterolemia and a higher cardiometabolic risk, than patients with ADM, similarly to patients with type 2 diabetes at onset.

Author Correction: Liraglutide Improves Cardiovascular Risk as an Add-on to Metformin and Not to Insulin Secretagogues in Type 2 Diabetic Patients: A Real-life 48-Month Retrospective Study.

Author Correction to: Diabetes Ther (2018) 9:363-371.

Diabetes Secondary to Acromegaly: Physiopathology, Clinical Features and Effects of Treatment.

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 ß 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.

Improved Cardiovascular and Cardiometabolic Risk in Patients With Type 1 Diabetes and Autoimmune Polyglandular Syndrome Switched From Glargine to Degludec Due to Hypoglycaemic Variability.

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.

Growth hormone and hematopoiesis: A retrospective analysis on a large cohort of children with growth hormone deficiency.

OBJECTIVE: Few large-scale studies regarding the impact of GH deficiency (GHD) on hematopoiesis in children have been reported. Our aim was to investigate hematopoiesis indices in a large cohort of GHD children at diagnosis and during GH treatment (GHT) and any correlation with hormonal parameters. DESIGN: Clinical and biochemical data of children with idiopathic GHD at diagnosis and annually up to 36 months of GHT were retrospectively evaluated. Overall, 255 children reached 12 months, 140 children 24 months and 86 children 36 months of follow-up during GHT. RESULTS: At baseline, 18.4% of GHD children and 10.1% of controls showed normocytic anemia. GHD children showed lower hemoglobin (Hb) (p = 0.007), red blood cells (RBC) (p < 0.001) and hematocrit (Ht) (p = 0.001) than controls. During GHT, the percentage of anemic patients decreased from 18.4 to 5.4-3.5 and 4.6% after 12 (p = 0.001), 24 (p < 0.001) and 36 months (p < 0.001) of GHT, respectively. In both anemic and non-anemic patients, a significant increase in Hb (p < 0.001, <0.001 and 0.002), RBC (all p < 0.001) and Ht (all p < 0.001) was found after 12, 24 and 36 months of GHT. The Hb levels were significantly correlated with the GH peak after stimulation test (p < 0.001) at baseline and with IGF-I levels at 36 months of GHT (p = 0.002). CONCLUSIONS: A significant improvement in erythropoiesis indices occurs during GHT, regardless of any previous presence of anemia.

Effects of pasireotide treatment on coagulative profile: a prospective study in patients with Cushing's disease.

INTRODUCTION: Cushing's disease (CD) is characterized by procoagulative profile. Treatment with cortisol-reducing medications might normalize the coagulation impairment potentially eliminating the risk of thromboembolic complications. AIM: The aim of this prospective study is to evaluate the effectiveness of 6-12 months of treatment with pasireotide (Signifor®, Novartis) 600 µg twice daily on coagulative factors in 21 patients (16 females, mean age 46 ± 12.2 years) with CD. Biochemical, hormonal (urinary free cortisol, UFC; late night salivary cortisol, LNSC; ACTH) and coagulative parameters as Protrombin time (PT), aPTT, factors VIII, IX and XI, antithrombin III, protein C, protein S, fibrinogen, were evaluated at baseline and during therapy. RESULTS: UFC showed a significant reduction from baseline (3.2 ± 1.8 vs. 1.0 ± 0.8, p < 0.0001) with normalization in 13/21 (61.9%) and in 7/16 (43.8%) at 6 and 12 months, respectively. On the same way LNSC returned to normal in 5/11 at 6 months, showing a trend to reduction (8.6 ± 5 vs. 4.1 ± 2.9), even though without statistical significance (p = 0.07). Throughout the treatment period there was an increase in serum glycaemia (5.5 ± 2.3 vs. 6.8 ± 2.3 mmol/L, p = 0.09), with a concomitant significant increase in HbA1c after 6 months (40.7 ± 8.4 vs. 50.7 ± 12.3 mmol/mol, p = 0.006). Regarding coagulative parameters, no differences were found neither in clotting nor in anticoagulant factors during therapy. No patients developed thrombotic complication during treatment. CONCLUSIONS: Pasireotide resulted an effective treatment in controlling hypercortisolism in more than half of CD patients with partial restoration also of circadian cortisol secretion. No significant improvements were observed on clotting factors; this fact might depend on persistence of typical alteration of CD, such as obesity and hypertension, and reflects also on the worsening in glucide metabolism induced by the drug. Clinical implications of persistent procoagulative impairment while on medical therapy should be considered.

Direct and indirect effects of Growth Hormone Deficiency (GHD) on lung function in children: A mediation analysis.

BACKGROUND: Studies on pulmonary function tests (PFTs) in Growth Hormone Deficiency (GHD) children are lacking. The aims of this study were: (i) to investigate PFTs in GHD pre-pubertal children with respect to Controls, before starting Growth Hormone Therapy (GHT) (T0); (ii) to evaluate changes of PFTs in GHD vs Controls, after 1-year GHT (T1). For both aims the mediation analysis (MA) was applied to evaluate the extent to which the relationship between GHD and PFTs could be ascribed to a height-mediated (indirect) or a GH direct effect. METHODS: 47 pre-pubertal GHD children (aged 5-14 years) underwent PFTs at T0 and T1. At T0, 47 healthy children matched for age and sex were enrolled as Controls. A MA was performed to assess the relationship between GHD and PFTs and height. Statistical analyses were performed using the statistical software R (https://cran.r-project.org/mirrors.html). A p-value <0.05 was considered significant. MEASUREMENTS AND MAIN RESULTS: At T0, PFTs indices were significantly lower in GHD than in Controls. From T0 to T1 a significant improvement was found in PFTs. The percentages of the mediated effect on FVC, FEV1, FEF25-75% and TLC were <50% at T0, suggesting that the direct effect was prevalent. At T1, the percentages of the mediated effect for spirometry indices were ≥50%, indicating that the indirect (height-mediated) effect was the most relevant. CONCLUSIONS: The study shows that pre-pubertal children with GHD have an impairment of lung function not exclusively attributable to the indirect (height-mediated) effect, but also to the direct GH action which is mitigated after 1-year of GHT.

The visceral adiposity index is associated with insulin sensitivity and IGF-I levels in adults with growth hormone deficiency.

The visceral adiposity index, based on anthropometric and metabolic parameters, has been shown to be related to adipose tissue function and insulin sensitivity. We aimed to evaluate the performance of the visceral adiposity index in adult patients with growth hormone deficiency. We enrolled 52 patients(mean age 51 ± 13 years) with newly diagnosed growth hormone deficiency and 50 matched healthy subjects as controls at baseline. At baseline and after 12 and 24 months of treatment we evaluated anthropometric measures, lipid profile, glucose and insulin during an oral glucose tolerance test, hemoglobin A1c, homeostasis model assessment estimate of insulin resistance, quantitative insulin sensitivity check index, insulin sensitivity index Matsuda, insulin-like growth factor-I and visceral adiposity index. At baseline growth hormone deficiency patients showed higher waist circumference (p < 0.001), low-density lipoprotein cholesterol (p < 0.001) and visceral adiposity index (p = 0.003) with lower insulin sensitivity index (p = 0.007) and high-density lipoprotein cholesterol (p = 0.001) than controls. During growth hormone treatment we observed a significant increase in insulin-like growth factor-I (p < 0.001), high-density lipoprotein (p < 0.001) with a trend toward increase in insulin sensitivity index (p = 0.055) and a significant decrease in total cholesterol (p < 0.001) and visceral adiposity index (p < 0.001), while no significant changes were observed in other clinical and metabolic parameters. The visceral adiposity index was the only parameter that significantly correlated with growth hormone peak at diagnosis (p < 0.001) and with insulin-like growth factor-I and insulin sensitivity index both at diagnosis (p = 0.009 and p < 0.001) and after 12 (p = 0.026 and p = 0.001) and 24 months (p < 0.001 and p = 0.001) of treatment. The visceral adiposity index, which has shown to be associated with both insulin-like growth factor-I and insulin sensitivity, proved to be the most reliable index of metabolic perturbation, among the most common indexes of adiposity assessment and a marker of benefit during treatment in adult growth hormone deficiency patients.

The Daily Consumption of Cola Can Determine Hypocalcemia: A Case Report of Postsurgical Hypoparathyroidism-Related Hypocalcemia Refractory to Supplemental Therapy with High Doses of Oral Calcium.

The consumption of soft drinks is a crucial factor in determining persistent hypocalcemia. The aim of the study is to evaluate the biochemical mechanisms inducing hypocalcemia in a female patient with usual high consumption of cola drink and persistent hypocalcemia, who failed to respond to high doses of calcium and calcitriol supplementation. At baseline and after pentagastrin injection, gastric secretion (Gs) and duodenal secretion (Ds) samples were collected and calcium and total phosphorus (Ptot) concentrations were evaluated. At the same time, blood calcium, Ptot, sodium, potassium, chloride, magnesium concentrations, and vitamin D were sampled. After intake of cola (1 L) over 180 min, Gs and Ds and blood were collected and characterized in order to analyze the amount of calcium and Ptot or sodium, potassium, magnesium, and chloride ions, respectively. A strong pH decrease was observed after cola intake with an increase in phosphorus concentration. Consequently, a decrease in calcium concentration in Gs and Ds was observed. A decrease in calcium concentration was also observed in blood. In conclusion, we confirm that in patients with postsurgical hypoparathyroidism, the intake of large amounts of cola containing high amounts of phosphoric acid reduces calcium absorption efficiency despite the high doses of calcium therapy.

More Favorable Metabolic Impact of Three-Times-Weekly versus Daily Growth Hormone Treatment in Naïve GH-Deficient Children.

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 < 0.001) and IGF-I (p < 0.001). As regards the metabolic parameters, in both groups, we found a significant increase in fasting insulin (p < 0.001 and p = 0.026) and Homa-IR (p < 0.001 and p = 0.019). A significant increase in fasting glucose (p = 0.001) and a decrease in ISI (p < 0.001) and DIo (p = 0.002) were only found in group A. CONCLUSIONS: The TIW regimen is effective and comparable with the daily regimen in improving auxological parameters and has a more favorable metabolic impact in GHD children. This trial is registered with ClinicalTrials.gov NCT03033121.