Vitamin D Deficiency in Cushing's Disease: Before and After Its Supplementation

Background: The primary objective of the study was to assess serum 25-hydroxyvitamin D [25(OH)D] values in patients with Cushing's disease (CD), compared to controls. The secondary objective was to assess the response to a load of 150,000 U of cholecalciferol. Methods: In 50 patients with active CD and 48 controls, we evaluated the anthropometric and biochemical parameters, including insulin sensitivity estimation by the homeostatic model of insulin resistance, Matsuda Index and oral disposition index at baseline and in patients with CD also after 6 weeks of cholecalciferol supplementation. Results: At baseline, patients with CD showed a higher frequency of hypovitaminosis deficiency (p = 0.001) and lower serum 25(OH)D (p < 0.001) than the controls. Six weeks after cholecalciferol treatment, patients with CD had increased serum calcium (p = 0.017), 25(OH)D (p < 0.001), ISI-Matsuda (p = 0.035), oral disposition index (p = 0.045) and decreased serum PTH (p = 0.004) and total cholesterol (p = 0.017) values than at baseline. Multivariate analysis showed that mean urinary free cortisol (mUFC) was independently negatively correlated with serum 25(OH)D in CD. Conclusions: Serum 25(OH)D levels are lower in patients with CD compared to the controls. Vitamin D deficiency is correlated with mUFC and values of mUFC > 240 nmol/24 h are associated with hypovitaminosis D. Cholecalciferol supplementation had a positive impact on insulin sensitivity and lipids

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 12. months 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 12. months 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 12. months 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

Nutritional Intervention in Cushing's Disease: The Ketogenic Diet's Effects on Metabolic Comorbidities and Adrenal Steroids

Background: a very low-calorie ketogenic diet (VLCKD) is associated with improvement of metabolic and cardiovascular disorders. We aimed to evaluate the effects of a VLCKD in patients with Cushing's disease (CD) as adjunctive therapy to treatment for the primary disease. Methods: we evaluated clinical, hormonal and metabolic parameters in 15 patients with CD and 15 controls at baseline after 1 week and 3 weeks of VLCKD and, further, after 2 weeks of a low-carbohydrate ketogenic diet (LCKD). Results: after 5 weeks of diet, a significant decrease in BMI (p = 0.002), waist circumference (WC) (p = 0.024), systolic blood pressure (p = 0.015), diastolic blood pressure (p = 0.005), ACTH (p = 0.026), cortisone (p = 0.025), total cholesterol (p = 0.006), LDL cholesterol (p = 0.017), triglycerides (p = 0.016) and alkaline phosphatase (p = 0.008) and a significant increase in HDL cholesterol (p = 0.017), vitamin D (p = 0.015) and oral disposition index (oDI) (p = 0.004) was observed in the CD patients. A significant decrease in BMI (p = 0.003), WC (p = 0.002), systolic blood pressure (p = 0.025), diastolic (p = 0.007) blood pressure and total cholesterol (p = 0.026) and an increase in HDL cholesterol (p = 0.001) and oDI (p &lt; 0.001) was observed in controls. Conclusions: the current study confirms that a ketogenic diet is effective in improving metabolic disorders in CD and shows that a nutritional approach may be combined with conventional CD therapy in order to improve metabolic and cardiovascular comorbidities

Irisin: A Possible Marker of Adipose Tissue Dysfunction in Obesity

Adipose tissue (AT) secretes pro- and anti-inflammatory cytokines involved in AT homeostasis, including tumor necrosis factor-α (TNFα) and irisin. The functionality of AT is based on a regulated equilibrium between adipogenesis and extracellular matrix (ECM) remodeling. We investigated the contributions of adipose progenitors (ASCs) and adipocytes (AMCs) to TNFα-induced ECM remodeling and a possible implication of irisin in AT impairment in obesity. ASCs and AMCs were exposed to TNFα treatment and nuclear factor–kappa (NF-kB) pathway was investigated: Tissue Inhibitor of Metalloproteinase (TIMP-1), Twist Family Transcription Factor 1 (TWIST-1), and peroxisome proliferator-activated receptor-γ (PPARγ) expression levels were analyzed. The proteolytic activity of matrix metalloproteinases (MMPs) -2 and -9 was analyzed by zymography, and the irisin protein content was measured by ELISA. In inflamed AMCs, a TIMP-1/TWIST-1 imbalance leads to a drop in PPARγ. Adipogenesis and lipid storage ability impairment come with local tissue remodeling due to MMP-9 overactivation. In vitro and ex vivo measurements confirm positive correlations among inflammation, adipose secreting irisin levels, and circulating irisin levels in patients with visceral obesity. Our findings identify the NF-kB downstream effectors as molecular initiators of AT dysfunction and suggest irisin as a possible AT damage and obesity predictive factor

Circulating Irisin Levels as a Marker of Osteosarcopenic-Obesity in Cushing’s Disease

Purpose: To evaluate circulating irisin levels in patients with active and controlled Cushing’s disease (CD). Design: Forty-four patients with CD evaluated during the active phase and after 12 months of biochemical remission and 40 controls were recruited. Methods: Phenotypic, anthropometric, hormonal and metabolic parameters, including insulin sensitivity estimation by homeostatic model of insulin resistance, Matsuda index and oral disposition index and circulating irisin levels were evaluated. Results: Patients with active CD showed lower irisin levels compared to controls (p&lt;0.001) and controlled CD (p&lt;0.001). The independent variables significantly associated with irisin were waist circumference (WC) (p=0.025), body fat percentage (BF%) (p=0.009), PTH (p=0.007) and chair rising test (CRT) (p&lt;0.001) in active CD and WC (p=0.013), BF% (p=0.014), PTH (p=0.038), CRT (p=0.029) and urinary-free cortisol (p&lt;0.001) in controlled CD. Conclusion: Circulating irisin levels tend to be lower in patients with active CD compared to those with controlled CD and controls. They are strongly associated with osteosarcopenia and central obesity in CD and therefore may be a possible marker of diagnosi

Metabolic Profile in a Cohort of Young Sicilian Patients with Klinefelter's Syndrome: The Role of Irisin

Klinefelter's syndrome (KS) is the main cause of hypogonadism and infertility in men and is often related to obesity, metabolic syndrome, and diabetes. The purpose of our real-life observational study was to investigate the metabolic and anthropometric parameters in a population of patients with Klinefelter syndrome compared to a group of healthy age-matched subjects. Methods. In our study, 25 consecutive Caucasian adult outpatients (age range 21-52 years, mean age 32.9 +/- 12.2) with KS in testosterone replacement therapy and 30 healthy men (age range 25-45 years, mean age 32.4 +/- 7.62) were studied. In both groups of subjects, anthropometric indices, lipid profile, glucose metabolic parameters, HbA1c, the homeostasis model assessment estimate of HOMA-insulin resistance (IR), and the insulin sensitivity index (ISI) were evaluated. In addition, we assessed the complete hormonal gonadic status and irisin values in both groups of patients. Results. No significant differences were found in BMI and total blood testosterone levels between KS and control subjects. Patients with KS had significantly higher values of WC (p=0.028), HbA1c (p=0.018), HOMA-IR (p &lt; 0.001), FSH (p &lt; 0.001), LH (p &lt; 0.001), estradiol (p=0.001), and irisin (p=0.029) and significantly lower HDL-cholesterol (p=0.002), AMH (p &lt; 0.001), inhibin B (p &lt; 0.001), and ISI-Matsuda (p &lt; 0.001) compared to healthy controls. Univariate analysis revealed an inverse correlation between irisin and ISI-Matsuda (r = -0.128; p=0.010). These data were then confirmed in multivariate analysis. Conclusions. KS is characterized by early development of metabolic syndrome and in particular by alterations of the glucose metabolism, independently of testosterone levels serum and BMI. Irisin blood levels of Klinefelter's patients are higher than in healthy subjects and positively correlate with the degree of insulin resistance

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

Resistin, visfatin, leptin and omentin are differently related to hormonal and metabolic parameters in growth hormone-deficient children

PURPOSE: The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting. METHODS: This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding protein and retinol-binding protein-4 were evaluated before and after 12 months of treatment. RESULTS: At baseline, no significant difference in metabolic parameters was found between GHD children and controls, except for higher LDL cholesterol (p = 0.004) in the first group. At multivariate analysis, LDL cholesterol was independently associated with resistin (B 0.531; p = 0.002), while IGF-I was the only variable independently associated with visfatin (B 0.688; p < 0.001). After 12 months, a significant increase in fasting insulin (p = 0.008), Homa-IR (p = 0.007) and visfatin (p < 0.001) was found, with a concomitant decrease in LDL cholesterol (p = 0.015), QUICKI (p = 0.001), ISI Matsuda (p = 0.006), leptin (p = 0.015) and omentin (p = 0.003)]. At multivariate analysis, BMI was the only variable independently associated with leptin (B 0.485; p = 0.040). CONCLUSIONS: GH treatment modifies adipokine secretion and the perturbation of some adipokine levels could contribute to the clinical and metabolic changes observed during the follow-up

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