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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin is secreted by the white adipose tissue and modulates energy homeostasis. Nutritional, neural, neuroendocrine, paracrine, and autocrine factors, including the sympathetic nervous system and the adrenal medulla, have been implicated in the regulation of leptin secretion. Classic congenital adrenal hyperplasia (CAH) is characterized by a defect in cortisol and aldosterone secretion, impaired development and function of the adrenal medulla, and adrenal hyperandrogenism. To examine leptin secretion in patients with classic CAH in relation to their adrenomedullary function and insulin and androgen secretion, we studied 18 children with classic CAH (12 boys and 6 girls; age range 2-12 yr) and 28 normal children (16 boys and 12 girls; age range 5-12 yr) matched for body mass index (BMI). Serum leptin concentrations were significantly higher in patients with CAH than in control subjects (8.1 +/- 2.0 vs. 2.5 +/- 0.6 ng/ml, P = 0.01), and this difference persisted when leptin values were corrected for BMI. When compared with their normal counterparts, children with CAH had significantly lower plasma epinephrine (7.1 +/- 1.3 vs. 50.0 +/- 4.2, P < 0.001) and free metanephrine concentrations (18.4 +/- 2.4 vs. 46.5 +/- 4.0, P < 0.001) and higher fasting serum insulin (10.6 +/- 1.4 vs. 3.2 +/- 0.2 microU/ml, P < 0.001) and testosterone (23.7 +/- 5.3 vs. 4.6 +/- 0.5 ng/dl, P = 0.003) concentrations. Insulin resistance determined by the homeostasis model assessment method was significantly greater in children with classic CAH than in normal children (2.2 +/- 0.3 vs. 0.7 +/- 0.04, P < 0.001). Leptin concentrations were significantly and negatively correlated with epinephrine (r = -0.50, P = 0.001) and free metanephrine (r = -0.48, P = 0.002) concentrations. Stepwise multiple linear regression analysis indicated that serum leptin concentrations were best predicted by BMI in both patients and controls. Gender predicted serum leptin concentrations in controls but not in patients with classic CAH. No association was found between the dose of hydrocortisone and serum leptin (r = -0.17, P = 0.5) or insulin (r = 0.24, P = 0.3) concentrations in children with CAH. Our findings indicate that children with classic CAH have elevated fasting serum leptin and insulin concentrations, and insulin resistance. These most likely reflect differences in long-term adrenomedullary hypofunction and glucocorticoid therapy. Elevated leptin and insulin concentrations in patients with CAH may further enhance adrenal and ovarian androgen production, decrease the therapeutic efficacy of glucocorticoids, and contribute to later development of polycystic ovary syndrome and/or the metabolic syndrome and their complications.
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PMID:Children with classic congenital adrenal hyperplasia have elevated serum leptin concentrations and insulin resistance: potential clinical implications. 1199 50

Patients with congenital adrenal hyperplasia attributable to 21-hydroxylase deficiency are treated with glucocorticoids. Glucocorticoid administration, even in substitution doses, may cause decreased bone mineral density (BMD) and obesity. The purpose of this study was to determine BMD, lean mass, and fat mass in young adult male (M, n = 15) and female (F, n = 15) patients with 21-hydroxylase deficiency, who had been treated with currently recommended low doses of glucocorticoids. Measurements were performed with dual-x-ray absorptiometry. In addition, calcaneal ultrasound measurements were performed (broadband ultrasound attenuation and speed of sound). Results were compared with those in age- and sex-matched controls; to adjust for height, lean and fat mass were divided by (height)(2). M and F patients [M, 21.7 +/- 2.4; F, 20.6 +/- 2.9 yr old (mean +/- SD)] were shorter than the controls (M, P < 0.001; F, P < 0.003) and their body mass indices were higher [M patients (25.0 +/- 3.6) vs. controls (22.3 +/- 1.9 kg/m(2)) (P < 0.02); F patients (25.5 +/- 4.5) vs. controls (21.9 +/- 2.3 kg/m(2)) (P < 0.02)]. BMD values (lumbar spine L1-L4, femoral neck, and total body) were not different from controls. Calcaneal ultrasound measurements showed that M patients had higher speed of sound values [M patients (1564 +/- 38) vs. controls (1529 +/- 29 m/sec) (P < 0.01)]. Lean mass in M and F patients was not different from controls when adjusted for height. Fat mass was higher in M and F patients when adjusted for height [M patients 5.6 +/- 2.9 vs. controls 2.7 median (1.7-7.0 min-max) kg/m(2) (P < 0.04); F patients 8.7 +/- 2.8 vs. controls 5.8 (4.3-10.7) kg/m(2) (P < 0.02)]. Relative fat mass (fat mass as a percentage of the total body mass) was higher in patients, compared with controls [M patients 22.0 +/- 9.1 vs. controls 12.8 (8.5-27.0)% (P < 0.04); F patients 34.1 +/- 5.0 vs. controls 29.0 +/- 5.1% (P < 0.02)]; this resulted from increased fat mass, not from decreased lean mass. Fat distribution over the body was not different in patients and controls. No significant correlations were found between cumulative glucocorticoid doses in the last 0.5, 2, or 5 yr or mean salivary morning levels of 17-hydroxyprogesterone and androstenedione in the last 5 yr on one hand and bone parameters, lean mass, or fat mass on the other hand. We conclude that, at prevailing low-dose glucocorticoid regimens, young adult patients with 21-hydroxylase deficiency have normal BMD. Their lean mass is in accordance with height, but fat mass is increased, with a normal distribution over the body. This results in a higher fat percentage of the total body and a higher body mass index than in healthy peers. Because overweight and increased fat mass are associated with the metabolic syndrome and increased cardiovascular risk, weight management should have appropriate attention in the follow-up of congenital adrenal hyperplasia patients, to prevent overweight-associated morbidity.
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PMID:Normal bone mineral density and lean body mass, but increased fat mass, in young adult patients with congenital adrenal hyperplasia. 1262 82

PCOS is a metabolic syndrome that exists throughout the world with much clinical heterogeneity. PCOS is now appreciated as encompassing two interrelated metabolic phenomena--insulin resistance and hyperandrogenism. Patients present with oligo-amenorrhea and clinical hyperandrogenism, and the diagnosis is based on clinical grounds with few laboratory tests necessary. Because patients are at higher than normal risk for diabetes, glucose intolerance, and hyperlipidemia, and perhaps at higher risk for coronary heart disease, newly diagnosed patients with PCOS should be evaluated for glucose intolerance and hyperlipidemia. The cornerstone of therapy today includes weight management, and further therapeutic intervention is focused on reproductive and cardiovascular health and treatment of insulin resistance. Clinical case continued The 17-year-old mentioned in the beginning of this article probably does have PCOS. She fits the clinical criteria: oligo-ovulation and hyper-androgenism (the acne and hirsutism). In addition, she is obese, which is also associated with PCOS. Her TSH and prolactin were normal, and as her presentation was not suggestive of an adrenal tumor or congenital adrenal hyperplasia (she had mild hirsutism, and those diagnoses are associated with more severe hyperandrogenism), no further laboratory evaluation was deemed necessary. Once the diagnosis was made, she was screened for lipid abnormalities and for glucose intolerance. Her LDL was 150, HDL 35; oral glucose tolerance test (OGTT) was normal. A pregnancy test was negative, and she was started on OCPs. Devoting herself to exercise and dietary change, she lost 10 pounds in her first 3 months after diagnosis. Her hirsutism and acne have improved with the OCPs and weight loss, and her menses are regular. She has elected to defer oral insulin sensitizers until her weight loss has stabilized. Findings PCOS is common in reproductive-aged women. Diagnosis is clinical and is supported by lab findings; there is significant clinical heterogeneity. Insulin resistance is likely central to the pathophysiology along with androgen excess. Health implications include infertility, diabetes, endometrial cancer, hyperlipidemia, and possibly coronary heart disease. Treatment is evolving and includes weight loss, OCPs, and insulin sensitizers.
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PMID:Polycystic ovary syndrome: a review for primary providers. 1502 92

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders resulting from deficiency of one of the five enzymes required for synthesis of cortisol in the adrenal cortex. The most common form of the disease is classic 21-hydroxylase deficiency, which is characterized by decreased synthesis of glucocorticoids and often mineralocorticoids, adrenal hyperandrogenism and impaired development and function of the adrenal medulla. The clinical management of classic 21-hydroxylase deficiency is often suboptimal, and patients are at risk of developing in tandem iatrogenic hypercortisolism and/or hyperandogenism. Limitations of current medical therapy include the inability to control hyperandrogenism without employing supraphysiologic doses of glucocorticoid, hyperresponsiveness of the hypertrophied adrenal glands to adrenocorticotropic hormone (ACTH) and difficulty in suppressing ACTH secretion from the anterior pituitary. Puberty imposes increased difficulty in attaining adrenocortical suppression despite optimal substitution therapy and adherence to medical treatment. Alterations in the endocrine milieu at puberty may influence cortisol pharmacokinetics and, consequently, the handling of hydrocortisone used as replacement therapy. Recent studies have demonstrated a significant increase in cortisol clearance at puberty and a shorter half-life of free cortisol in pubertal females compared with males. Furthermore, children with classic CAH have elevated fasting serum insulin concentrations and insulin resistance. The latter may further enhance adrenal and/or ovarian androgen secretion, decrease the therapeutic efficacy of glucocorticoids and contribute to later development of the metabolic syndrome and its complications.
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PMID:Classic congenital adrenal hyperplasia and puberty. 1555 90

Congenital adrenal hyperplasia (CAH) due to deficiency of 21-hydroxylase is a disorder of the adrenal cortex characterised by cortisol deficiency, with or without aldosterone deficiency, and androgen excess. Patients with the most severe form also have abnormalities of the adrenal medulla and epinephrine deficiency. The severe classic form occurs in one in 15,000 births worldwide, and the mild non-classic form is a common cause of hyperandrogenism. Neonatal screening for CAH and gene-specific prenatal diagnosis are now possible. Standard hormone replacement fails to achieve normal growth and development for many children with CAH, and adults can experience iatrogenic Cushing's syndrome, hyperandrogenism, infertility, or the development of the metabolic syndrome. This Seminar reviews the epidemiology, genetics, pathophysiology, diagnosis, and management of CAH, and provides an overview of clinical challenges and future therapies.
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PMID:Congenital adrenal hyperplasia. 1596 50

Classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a common autosomal recessive disorder characterized by impaired adrenocortical and adrenomedullary function, and adrenal hyperandrogenism. Compared to normal subjects, patients with classic CAH have increased incidence of obesity and visceral adiposity, hyperinsulinism and insulin resistance, hyperleptinemia, hypertension, and hyperandrogenism. It is likely that the impaired adrenomedullary function and intermittent treatment-related hypercortisolism may account for the above abnormalities, and may predispose these subjects to the development of metabolic syndrome-related endothelial dysfunction and atherosclerotic cardiovascular disease in adulthood. Nonpharmacologic and pharmacologic interventions targeting obesity and/or insulin resistance may offer an improved outcome in terms of cardiovascular morbidity.
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PMID:Metabolic syndrome manifestations in classic congenital adrenal hyperplasia: do they predispose to atherosclerotic cardiovascular disease and secondary polycystic ovary syndrome? 1714 32

Prenatal treatment of congenital adrenal hyperplasia (CAH) with dexamethasone to minimize the genital virilization of external genitalia of affected girls has been in use since the mid-1980s. The positive effect of reducing virilization is now established. However, experimental data from animal studies and observations on adverse medical events in human newborns have raised concerns about the long-term safety of the treatment. Most animal studies on prenatal treatment with synthetic glucocorticoids have been designed to mimic treatment for lung maturation in preterm infants. The primary focus has been on a possible impact on fetal programming and the development of the metabolic syndrome with insulin resistance, type 2 diabetes, and high blood pressure. Altered reactivity to stress as a function of differences in reactivity of the HPA axis and glucocorticoid receptor function have been assayed. Effects on cognition, especially memory, have been observed. In children at risk for CAH and treated prenatally with dexamethasone, no overall effects on full-scale IQ have been observed, but a negative effect on verbal working memory has been reported. Contradictory effects on social behavior with respect to shyness and inhibition have been discussed. There is an urgent need for in-depth studies of long-term outcome in prenatal treatment of CAH regarding both maternal side effects and possible negative metabolic as well as cognitive and behavioral effects in the growing fetus and the child in her development into adulthood.
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PMID:Long-term outcome of prenatal treatment of congenital adrenal hyperplasia. 1849 35

We investigated for evidence of early metabolic syndrome irrespective of body mass index (BMI) in subjects with premature pubarche (PP). Ten children with PP were compared with controls matched for age, sex, ethnicity, and BMI. Congenital adrenal hyperplasia and other known causes of PP were excluded by standard methods. Anthropometry, blood pressure (BP), dual-energy x-ray absorptiometry body scan, fasting blood lipid profile, and cytokines were obtained. The children were divided into 2 groups: (1) the total group of children with PP, and their age-, sex-, ethnicity-, and BMI-matched controls and (2) those with PP and normal BMI (<19 kg/m(2)) and their matched controls selected from the original groups. The PP subjects with normal BMI (S(1)) showed significantly higher systolic BP (P = .028), diastolic BP (P = .028), and mean arterial pressure (P = .018) compared with matched controls (C(1)). Nevertheless, for both groups, all the above parameters were statistically not significant when corrected for height. Fat distribution in PP subjects indicated significantly higher android (P = .047) and android-gynoid ratio (P = .013). Normal-BMI PP children had significantly higher android-gynoid ratio fat distribution compared with their matched controls (P = .037). Trunk fat percentage (p: 0.04) and trunk fat (grams) (P = .007) were significantly elevated in PP children compared with matched controls. Again, for both groups, all the above parameters were not statistically significant when corrected for height. The PP subjects had significantly higher tumor necrosis factor (TNF)-alpha (P = .038) and interleukin-8 (picograms per milliliter) (P = .05) compared with matched controls. Normal-BMI PP children also had higher TNF-alpha (P = .028) compared with matched controls. When corrected for height, TNF-alpha was higher in the total (P = .037) and normal-BMI (P = .043) PP children. Premature pubarche can be linked to markers of the metabolic syndrome in lean children.
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PMID:Evidence of metabolic syndrome in lean children with premature pubarche at diagnosis. 1850 54

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a group of autosomal disorders of the adrenal cortex characterised by cortisol deficiency, with or without aldosterone deficiency, and androgen excess. Congenital adrenal hyperplasia shows a range of severity. The severe classic form occurs in one in 15000 births worldwide, and the mild non classic form is a common cause of hyperandrogenism. Neonatal screening for congenital adrenal hyperplasia and gene specific prenatal diagnosis is now possible. Standard hormone replacement fails to achieve normal growth and development for many children with congenital adrenal hyperplasia, and adults could experience hyperandrogenism, infertility, and metabolic syndrome.
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PMID:[Congenital adrenal hyperplasia]. 1867 65

Polycystic ovary syndrome (PCOS) is the most common endocrine cause of hirsutism, acne, and pattern alopecia. It is a heterogeneous syndrome of hyperandrogenic anovulation that is typically due to intrinsic ovarian dysfunction, which is often aggravated by insulin-resistant hyperinsulinemia with its risks of diabetes mellitus and metabolic syndrome and their complications. Because there are many pitfalls to androgen assays, evaluation for hyperandrogenemia is suggested in women with moderate or severe hirsutism or hirsutism equivalents, menstrual irregularity, acanthosis nigricans, or intractable obesity. An endocrinologic work-up is necessary to rule out other hyperandrogenic disorders that require specific therapy (e.g., virilizing tumors, nonclassic congenital adrenal hyperplasia, hyperprolactinemia, and Cushing's syndrome). Ultrasonography helps in the differential diagnosis and may demonstrate the polycystic ovaries that have recently been vetted as an alternative to oligo-anovulation as a diagnostic criterion. Management of PCOS is determined by symptomatology. For those women not desiring pregnancy, the most common therapies are oral contraceptive pills, antiandrogens (contraindicated in the absence of adequate contraception), and insulin-lowering treatments (which have little effect on hirsutism).
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PMID:What every physician should know about polycystic ovary syndrome. 1884 13


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