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 To evaluate 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 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 3 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-β (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, was found higher in group B than group A after 12 months (p=0.015). Conclusions Accordingly with 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 better understand

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 (AUCGH) during the oral glucose tolerance test, AUCCpeptide 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), AUCGH (ρ = 0.603; P = 0.002), IGF-I (ρ = 0.618; P = 0.001), TNF-α (ρ = 0.512; P = 0.010), and AUCCpeptide (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), AUCGH (P = 0.047), IGF-I (P = 0.047), AUCCpeptide (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. AUCGH 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 acromegal

Prevalence and clinical features of polycystic ovarian syndrome in adolescents with previous childhood growth hormone deficiency.

BACKGROUND: Growth hormone (GH) plays a role in the regulation of ovarian function but there are limited data in women with GH deficiency (GHD). Our aim was to evaluate the features of polycystic ovarian syndrome (PCOS) in women with previous GHD. METHODS: Data of 22 adolescents previously GH-treated (group A) were compared with those of 22 women with classical PCOS (group B) and 20 controls (group C). RESULTS: Group A showed higher testosterone (p=0.048) and prevalence of menstrual irregularities (p<0.001) than group C. Compared to the group B, group A showed lower diastolic blood pressure (p=0.004), degree of hirsutism (p=0.005), testosterone (p=0.003) and prevalence of polycsytic ovaries (POC) morphology (p=0.024), with higher HDL-cholesterol (p=0.035) and 17-β-estradiol (p=0.009). CONCLUSIONS: Adolescents with previous GHD show a higher prevalence of PCOS than controls, but with milder metabolic and hormonal features than adolescents with classical PCOS. A careful long-term follow-up is advisable in these patients

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, OGTTwould have ahigh 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 IFGCIGT 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 IFGCIGT, 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); PZ0.014) and waist circumference (0.760 (95% CI: 0.70-0.81) vs 0.619 (95% CI: 0.55-0.68); PZ0.028). 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

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 0·50 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

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 un-healthy PCOS (MU-PCOS) by simple diagnostic tools such as body mass index (BMI), waist/hip ratio (WHR), at-risk category suggestedby 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 withPCOS.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. Anoral glucose tolerance test measured areas under the curve (AUC) for insulin (AUC2h insulin) and for glucose (AUC2h glucose). Homeostasismodel assessment of insulin resistance (HOMA2-IR), the Matsuda index of insulin sensitivity (ISI), the oral dispositional index (DIo) and VAIwere 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 diagnosedby the WHR criterion) showed a significant positive association with high HOMA2-IR [BMI criterion: (odds ratio (OR): 1.86; 95% confidenceinterval (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 significantnegative 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 thatwould 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 withPCOS before they develop overt metabolic syndrome