Adrenal insufficiency in acute oral opiate therapy

UNLABELLED: Opiate drugs such as morphine are in extensive use for pain relief and palliation. It is well established that these drugs can cause changes in endocrine function, but such effects are not always sufficiently appreciated in clinical practice, especially in relation to the hypothalamic-pituitary-adrenal (HPA) axis. Herein, we report on an 18-year-old man who was diagnosed with a slipped left femoral epiphysis following a long history of pain in his leg. On examination, he was thought to look relatively young for his age and therefore the orthopaedic surgeons arranged an endocrine assessment, which showed an undetectable concentration of serum cortisol and a suppressed concentration of testosterone; therefore, he was referred urgently with a diagnosis of hypopituitarism. We elicited a history that he had been treated with opiate analgesics for 3 days at the time of his original blood tests. Full endocrine assessment including a short Synacthen test revealed that he now had normal adrenal and pituitary function. We conclude that his morphine therapy had caused profound suppression of his HPA and pituitary-gonadal axes and suggest that clinicians should be aware of these significant changes in patients on even short-term opiate therapy. LEARNING POINTS: Therapy with opiates is the standard therapy for severe acute and chronic pain.Such drugs cause profound changes in endocrine function.Importantly, opiates suppress the HPA axis at a central level.Short-term therapy with morphine could be the cause of biochemical adrenocortical insufficiency.Morphine and related drugs also suppress the pituitary-gonadal axis.After discontinuation of therapy with such drugs, adrenal function improves

Hypovitaminosis D Is Associated with Liver Insulin Resistance in Obese Subjects

Hypovitaminosis D is highly prevalent in obese subjects. Serum 25-hydroxy vitamin D3 [25(OH)D] concentration, the best marker of human vitamin D status, has been reported to be associated with glucose status, insulin resistance (IR) and beta cell function. To specifically investigate the relationship between 25(OH)D and liver IR we performed a comprehensive metabolic assessment (2-h OGTT, hyperinsulinemic euglycemic clamp [HEC], body composition by DXA) in 20 obese non-diabetic subjects (42.9±2.7 yrs; BMI 37.7±0.8 kg/m2) with 25(OH)D insufficiency (<30 ng/mL). Liver IR was estimated using the index by Vangipurapu et al. (-0.091 + [log insulin AUC 0-120 min x 0.400] + [log fat mass% x 0.346] - [log HDL cholesterol x 0.408] + [log BMI x 0.435]). There was a significant inverse correlation between 25(OH)D and the liver IR index (r = -0.514, p = 0.02). This correlation maintained its significance after adjusting for age, gender, total cholesterol, triglycerides and whole body insulin sensitivity (M value assessed by HEC) in multiple linear regression analysis. There was no significant correlation between 25(OH)D and beta cell function estimated by the Disposition Index. Our data suggest that, in obese subjects, low 25(OH)D levels are independently associated with liver insulin resistance, but not with beta cell function. Further studies are needed to clarify the relationship between glucose homeostasis and vitamin D levels

Pregnancy and Prenatal Management of Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive diseases that may cause cortisol insufficiency together with other hormonal alterations. The most common form is 21-hydroxylase deficiency, in which the lack of pituitary negative feedback causes an increase in ACTH and adrenal androgens. Classical forms of CAHs can lead to severe adrenal failure and female virilization. To date, the appropriate management of pregnant CAH patients is still debated regarding appropriate maternal therapy modifications during pregnancy and the risks and benefits of prenatal treatment of the fetus. We conducted a literature search of relevant papers to collect current evidence and experiences on the topic. The most recent and significant articles were selected, and current international guidelines were consulted to update current recommendations and guide clinical practice. Given the lack of randomized clinical trials and other high-quality scientific evidence, the issue is still debated, and great heterogeneity exists in current practice in terms of risk/benefit evaluation and pharmacological choices for pregnancy and prenatal treatment. Glucocorticoid therapy is advised not only in classical CAH patients but also in non-classical, milder forms. The choice of which glucocorticoid to use, and the safety and benefits of dexamethasone therapy aimed at preventing genital virilization are still debated issues. Several advances, however, have been made, especially in terms of fertility and reproduction. This review aims to present the most recent scientific and real-world updates on pregnancy and prenatal management of CAH, with the presentation of various clinical scenarios and specific case-by-case recommendations

Starvation hepatitis and refeeding-induced hepatitis: mechanism, diagnosis, and treatment

: Anorexia nervosa (AN) is one of the most common psychiatric disorders among young adults and is associated with a substantial risk of death from suicide and medical complications. Transaminase elevations are common in patients with AN at the time of hospital admission and have been associated with longer lengths of hospital stay. Multiple types of hepatitis may occur in these patients, including two types that occur only in patients with AN: starvation hepatitis and refeeding-induced hepatitis. Starvation hepatitis is characterized by severe transaminase elevation in patients in the advanced phase of protein-energy deprivation and is associated with complications of severe starvation, such as hypoglycaemia, hypothermia, and hypotension. Refeeding-induced hepatitis is characterized by a milder increase in transaminases that occurs in the early refeeding phase and is associated with hypophosphatemia, hypokalemia, and hypomagnesaemia. Among the most common forms of hepatitis, drug-induced liver injury is particularly relevant in this patient cohort, given the frequent use and abuse of methamphetamines, laxatives, antidepressants, and antipsychotics. In this review, we provided an overview of the different forms of anorexic-associated hepatitis, a diagnostic approach that can help the clinician to correctly frame the problem, and indications on their management and treatment

Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes

We read with interest the article by Kayaniyil et al. that supplied elegant data suggesting that 25- hydroxyvitamin D [25(OH)D] is related to insulin resistance and _-cell function in a large population at high risk for type 2 diabetes and/or metabolic syndrome, thus concluding that 25(OH)D may be an independent risk factor for diabetes. We have, however, some concerns. First, the studied population was mainly composed of obese subjects (the mean BMI was 30.5 kg/m2). Clearly, within a population with such a high BMI, the major variable influencing insulin sensitivity is fat mass. An increased fat mass (within the same BMI) could determine both the reduced insulin sensitivity and 25(OH)D. The two variables therefore correlate, but are not causally related. In our recently published article, we approached this important question by comparing two groups of obese subjects matched by BMI but different in terms of insulin sensitivity: no differences in 25(OH)D concentrations could be found, suggesting that the adipose tissue is its reservoir. Kayaniyil et al. themselves reported a weaker correlation in their obese (BMI 30 kg/m2) subpopulation but, unfortunately, they did not provide data on body composition. Second, although the correlation within the high risk (for diabetes) population is intriguing, a control population is missing. In particular, it is not reported whether the studied population has lower 25(OH)D concentration than an hypothetical control cohort. If this was not the case, the working hypothesis fails. How could normal 25(OH)D determine insulin resistance? Third, if 25(OH)D is involved in the pathogenesis of type 2 diabetes, one would expect that a supplementation of calcitriol or its analogues would ameliorate the glucose metabolism. This was not the case either in insulin-resistant diabetic patients or in healthy subjects (4). As we and others reported, 25(OH)D concentration mainly reflects body fat mass; the reduction of fat mass, rather than vitamin D supplementation, is the main road for the prevention and treatment of insulin resistance and diabetes

Will vitamin D reduce insulin resistance? Still a long way to go

We read with interest the article by Alvarez et al, which aimed to investigate the relations of circulating 25-hydroxyvitamin D [25(OH)D] and parathyroid hormone (PTH) concentrations with direct measurements of insulin sensitivity, after robust measures of body composition and fat distribution were accounted for. We would like to express our opinion and a different interpretation of the data provided by authors, with the hope that other points for discussion are brought up. In a very recent publication, Alvarez et al provided novel findings suggesting that dietary vitamin D is independently associated with insulin sensitivity in African Americans (AAs) but not in European Americans (EAs). Interestingly, the 2 groups were identical for hepatic insulin sensitivity [homeostatic model assessment (HOMA)], whereas Si, a method for measuring insulin sensitivity that encompasses both hepatic and peripheral tissues, was lower in AAs, therefore suggesting a pivotal role for insulin resistance in skeletal muscle [especially in the presence of identical body mass index (BMI)] in correlation with 25(OH)D. In the present article, the authors suggest that 25(OH)D and PTH concentrations are independently associated with whole-body insulin sensitivity and suggest that these variables may influence insulin sensitivity through independent mechanisms. In fact, multiple linear regression analysis indicated that 25(OH)D and PTH concentrations were independently related to Si after adjustment for age, race, and intraabdominal adipose tissue. It is well known, however, that adipose tissue is the natural reservoir for lipo-soluble 25(OH)D. The higher BMI and the higher subcutaneous fat content found in AAs (although the latter difference was not statistically significant) could therefore explain the differences in 25(OH)D concentration, as well as in HOMA index, found by the authors. We examined the effect of 25(OH)D on insulin sensitivity in obese subjects and found a linear correlation between them, which is apparently in agreement with Alvarez et al. Obesity, however, is not invariably associated with insulin resistance, because normal insulin sensitivity can be present in some obese subjects. If 25(OH)D concentration influences insulin sensitivity independently of obesity, it should be found to be low in insulin-resistant obese subjects and high in insulin-sensitive obesity. We divided our obese population into 2 subgroups, according to their insulin sensitivity (low and high). The 2 groups were similar in BMI, age, and sex but did not show any difference in 25(OH)D concentration, thus confirming the hypothesis that 25(OH)D concentrations are not influenced by the degree of insulin resistance but mainly by the adipose tissue\u2019s reservoir, at least in our EA participants. Unfortunately, in the presentstudied population but not in the previous one, AAs had higher BMI (and HOMA) and the actual role of these variables in determining hypovitaminosis D was not ruled out. In conclusion, we are certain that 25(OH)D concentration mainly reflects body fatmass, either subcutaneous or visceral; the reduction of fat mass, rather than vitamin D supplementation, is the best route for the prevention and treatment of insulin resistance and diabetes

Myoinositol combined with alpha-lipoic acid may improve the clinical and endocrine features of polycystic ovary syndrome through an insulin-independent action

The aim of our study was to investigate the effects of a combined treatment with alpha-lipoic acid (ALA) and myoinositol (MYO) on clinical, endocrine and metabolic features of women affected by polycystic ovary syndrome (PCOS). In this pilot cohort study, forty women with PCOS were enrolled and clinical, hormonal and metabolic parameters were evaluated before and after a six-months combined treatment with ALA and MYO daily. Studied patients experienced a significant increase in the number of cycles in six months (p < 0.01). The free androgen index (FAI), the mean androstenedione and DHEAS levels significantly decreased after treatment (p < 0.05). Mean SHBG levels significantly raised (p < 0.01). A significant improvement in mean Ferriman\u2013Gallwey (F\u2013G) score (p < 0.01) and a significant reduction of BMI (p < 0.01) were also observed. A significant reduction of AMH levels, ovarian volume and total antral follicular count were observed in our studied women (p< 0.05). No significant changes occurred in gluco-insulinaemic and lipid parameters after treatment. The combined treatment of ALA and MYO is able to restore the menstrual pattern and to improve the hormonal milieu of PCOS women, even in the absence of apparent changes in insulin metabolism

Low levels of 25(OH)D and insulin-resistance: 2 unrelated features or a cause-effect in PCOS?

BACKGROUND & AIMS: Recent investigations have identified low vitamin D status as a hypothetical mechanism of insulin-resistance in Polycystic Ovary Syndrome (PCOS). Instead, some authors supported the hypothesis that low vitamin D levels and insulin-resistance are 2 unrelated features of body size in PCOS. Hence, we aimed to explore the association of 25-hydroxyvitamin D (25(OH)D) with anthropometric, metabolic and hormonal features in PCOS. METHODS: We assessed the association of low 25(OH)D levels with endocrine parameters, insulin-sensitivity evaluated by hyperinsulinemic euglycemic clamp (HEC) and body composition measured by DEXA in 38 women affected by PCOS. RESULTS: Low 25(OH)D (25(OH)D\ua0<\ua050\ua0nmo/L) was detected in 37% of the entire cohort of patients. Body Mass Index (BMI), in particular total fat mass (p\ua0<\ua00.001), resulted to be the most predictor factor of 25(OH)D levels whereas Sex Hormone Binding Globulin (SHBG), Free Androgen Index (FAI), glucose uptake and fat free mass were not. CONCLUSIONS: Our data demonstrated that in PCOS low 25(OH)D levels are significantly determined by the degree of adiposity

25-Hydroxyvitamin D concentration correlates with insulin-sensitivity and BMI in obesity

The prevalence of hypovitaminosis D is high among obese subjects. Further, low 25-hydroxyvitamin D (25(OH)D) concentration has been postulated to be a risk factor for type 2 diabetes, although its relation with insulin-sensitivity is not well investigated. Thus, we aimed to investigate the relationship between 25(OH)D concentration and insulin-sensitivity, using the glucose clamp technique. In total, 39 subjects with no known history of diabetes mellitus were recruited. The association of 25(OH)D concentration with insulin-sensitivity was evaluated by hyperinsulinemic euglycemic clamp. Subjects with low 25(OH)D (<50\ua0nmol/l) had higher BMI (P = 0.048), parathyroid hormone (PTH) (P = 0.040), total cholesterol (P = 0.012), low-density lipoprotein (LDL) cholesterol (P = 0.044), triglycerides (P = 0.048), and lower insulin-sensitivity as evaluated by clamp study (P = 0.047). There was significant correlation between 25(OH)D and BMI (r = -0.58; P = 0.01), PTH (r = -0.44; P < 0.01), insulin-sensitivity (r = 0.43; P < 0.01), total (r = -0.34; P = 0.030) and LDL (r = -0.40; P = 0.023) (but not high-density lipoprotein (HDL)) cholesterol, and triglycerides (r = 0.45; P = 0.01). Multivariate analysis using 25(OH)D concentration, BMI, insulin-sensitivity, HDL cholesterol, LDL cholesterol, total cholesterol, and triglycerides, as the cofactors was performed. BMI was found to be the most powerful predictor of 25(OH)D concentration (r = -0.52; P < 0.01), whereas insulin-sensitivity was not significant. Our study suggested that there is no cause-effect relationship between vitamin D and insulin-sensitivity. In obesity, both low 25(OH)D concentration and insulin-resistance appear to be dependent on the increased body size