To assess the differences between patients with normal glucose tolerance (NGT) and prediabetes/diabetes mellitus (DM) in secondary adrenal insufficiency (SAI). We cross-sectionally evaluated 102, out ...of a total of 140, patients with SAI, who were on hydrocortisone (HC) (n = 50) and cortisone acetate (n = 52) replacement therapy. Clinical, anthropometric, and metabolic parameters were compared in patients with NGT (n = 60) and DM (n = 42). Patients with prediabetes/DM have a more marked family history of DM (p = 0.002), BMI (p < 0.001), higher waist circumference (p < 0.001), total cholesterol (p = 0.012), LDL-cholesterol (p = 0.004), triglycerides (p = 0.031), fasting glucose (p = 0.002), fasting insulin (p = 0.035), glutamate pyruvate transaminase (p = 0.018), HOMA-IR (p = 0.039), area under curves of glucose (p = 0.001) and insulin (p = 0.002), HbA1c (p < 0.001), Visceral adiposity index (VAI) (p = 0.038) and lower ISI-Matsuda (p = 0.008) and oral disposition index (p < 0.001) than patients with NGT. Multivariate analysis showed that family history of DM and VAI are independent predictive factors for DM in patients with SAI. Family history of DM and VAI can be predictors of the development of DM in patients with SAI and need to be investigated during steroid replacement therapy. Interestingly, the type and the dose of replacement steroid do not impact on diabetes mellitus.
There is growing concern regarding the health and safety issues of endocrine-disrupting chemicals (EDCs). Long-term exposure to EDCs has alarming adverse health effects through both hormone-direct ...and hormone-indirect pathways. Non-chemical agents, including physical agents such as artificial light, radiation, temperature, and stress exposure, are currently poorly investigated, even though they can seriously affect the endocrine system, by modulation of hormonal action. Several mechanisms have been suggested to explain the interference of EDCs with hormonal activity. However, difficulty in quantifying the exposure, low standardization of studies, and the presence of confounding factors do not allow the establishment of a causal relationship between endocrine disorders and exposure to specific toxic agents. In this review, we focus on recent findings on the effects of EDCs and hormone system modulators on the endocrine system, including the thyroid, parathyroid glands, adrenal steroidogenesis, beta-cell function, and male and female reproductive function.
Abstract
Steroids affect bone health causing osteoporosis and fractures. The study aims to compare dual-release hydrocortisone (DR-HC) and conventional steroids on bone metabolism in patients with ...primary adrenal insufficiency (PAI). Thirty-five patients with PAI on conventional steroids (group A) and 35 patients switched to DR-HC (group B), consecutively referred at our hospital, were evaluated at baseline and after 18, 36 and 60 months of treatment. After 60 months of follow-up, patients in group A had a significant increase in body mass index (
p
= 0.004) and waist circumference (WC) (
p
= 0.026) and a significant decrease in osteocalcin (
p
= 0.002), bone alkaline phosphatase (
p
= 0.029), lumbar spine bone mass density (BMD) T and Z scores (
p
< 0.001 and
p
= 0.001, respectively) and vertebral fractures rate (
p
= 0.021) than baseline. By contrast, patients in group B had a significant decrease in WC (
p
= 0.047) and increase in bone alkaline phosphatase (
p
= 0.019), lumbar spine BMD T score (
p
= 0.032), femoral neck BMD T and Z scores (
p
= 0.023 and
p
= 0.036, respectively) than baseline. Long-term conventional steroid replacement therapy is associated with a decrease in BMD, notably at lumbar spine, and increase in vertebral fractures rate. By contrast, DR-HC treatment is associated with improvement of BMD.
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.
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.
A very low-calorie ketogenic diet (VLCKD) is characterized by low daily caloric intake (less than 800 kcal/day), low carbohydrate intake (<50 g/day) and normoproteic (1−1.5 g of protein/kg of ideal ...body weight) contents. It induces a significant weight loss and an improvement in lipid parameters, blood pressure, glycaemic indices and insulin sensitivity in patients with obesity and type 2 diabetes mellitus. Cushing’s syndrome (CS) is characterized by an endogenous or exogenous excess of glucocorticoids and shows many comorbidities including cardiovascular disease, obesity, type 2 diabetes mellitus and lipid disorders. The aim of this speculative review is to provide an overview on nutrition in hypercortisolism and analyse the potential use of a VLCKD for the treatment of CS comorbidities, analysing the molecular mechanisms of ketogenesis.
The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing high and rapid morbidity and mortality. Immune system ...response plays a crucial role in controlling and resolving the viral infection. Exogenous or endogenous glucocorticoid excess is characterized by increased susceptibility to infections, due to impairment of the innate and adaptive immune system. In addition, diabetes, hypertension, obesity and thromboembolism are conditions overrepresented in patients with hypercortisolism. Thus patients with chronic glucocorticoid (GC) excess may be at high risk of developing COVID-19 infection with a severe clinical course. Care and control of all comorbidities should be one of the primary goals in patients with hypercortisolism requiring immediate and aggressive treatment. The European Society of Endocrinology (ESE), has recently commissioned an urgent clinical guidance document on management of Cushing’s syndrome in a COVID-19 period. In this review, we aim to discuss and expand some clinical points related to GC excess that may have an impact on COVID-19 infection, in terms of both contagion risk and clinical outcome. This document is addressed to all specialists who approach patients with endogenous or exogenous GC excess and COVID-19 infection.
Adrenal Cushing's syndrome in children Guarnotta, Valentina; Emanuele, Fabrizio; Salzillo, Riccardo ...
Frontiers in endocrinology,
12/2023, Letnik:
14
Journal Article
Recenzirano
Odprti dostop
Adrenal Cushing's syndrome is a rare cause of endogenous hypercortisolism in neonatal and early childhood stages. The most common causes of adrenal CS are hyperfunctioning adrenal tumours, adenoma or ...carcinoma. Rarer causes are primary bilateral macronodular adrenal hyperplasia (PBAMH), primary pigmented adrenocortical disease (PPNAD) and McCune Albright syndrome. The diagnosis represents a challenge for clinicians. In cases of clinical suspicion, confirmatory tests of hypercortisolism should be performed, similarly to those performed in adults. Radiological imaging should be always combined with biochemical confirmatory tests, for the differential diagnosis of adrenal CS causes. Treatment strategies for adrenal CS include surgery and in specific cases medical drugs. An adequate treatment is associated to an improvement of growth, bone health, reproduction and body composition from childhood into and during adult life. After cure, lifelong glucocorticoid replacement therapy and endocrine follow-up are required, notably in patients with Carney's complex disease.
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 < 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.
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