Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multidrug antiretroviral regimens that include human immunodeficiency virus-1 (HIV-1) protease inhibitors are associated with distinct lipodystrophy, hypertriglyceridemia, hyperinsulinemia, and deposition of visceral abdominal adipose tissue. To determine whether these findings are related to abnormalities of adrenal function, we compared the hypothalamic-pituitary-adrenal axes of HIV-positive patients who had evidence of protease inhibitor-associated lipodystrophy (PIAL), control volunteers (CON), and patients with Cushing's syndrome (CS). To elucidate the metabolic consequences of the observed lipodystrophy, we measured basal serum lipids and compared glucose and insulin concentrations during an oral glucose tolerance test. Spontaneous plasma cortisol showed normal diurnal variation in PIAL. Cortisol levels were similar in CON and PIAL, and levels in these groups were less than those in CS at all times of the night or day (P < 0.005). Ovine CRH-stimulated morning plasma cortisol levels were similar in PIAL and CON. ACTH was significantly greater in PIAL than CON (P < 0.05) at 0, 15, and 30 min after CRH stimulation. Urinary free cortisol in PIAL (mean +/- SD, 76 +/- 51 nmol/day) was significant lower than those in CON (165 +/- 64 nmol/day; P < 0.001) and CS (1715 +/- 1203 nmol/day; P < 0.001). However, 17-hydroxycorticosteroid excretion was significantly greater in PIAL (43 +/- 23 micromol/day) than in CON (17 +/- 8 micromol/day; P < 0.001), although lower than that in CS (74 +/- 47 micromol/day; P < 0.01). Scatchard analysis revealed normal glucocorticoid receptor number and affinity in PIAL. Serum triglycerides were significantly greater in PIAL (6.57 +/- 5.63 mmol/L) than in CS (1.78 +/- 0.83 mmol/L; P < 0.001) or CON (1.36 +/- 0.84 mmol/L; P < 0.001). Although triglyceride levels were significantly correlated with body mass index for CON and CS, these were not correlated for PIAL. During an oral glucose tolerance test, similar glucose and insulin values were found in PIAL and CS that were greater (P < 0.05) than CON values at 30, 60, 90, and 120 min. We conclude that the lipodystrophy associated with use of HIV-1 protease inhibitors is a syndrome of increased intraabdominal adiposity with concomitant dyslipidemia and insulin resistance, but without total body weight gain and is distinct from any known form of hypercortisolism. Although urinary cortisol disposition seems to be altered in HIV-infected patients who are being treated with multidrug regimens that include protease inhibitors, the decreased free cortisol and increased 17-hydroxycorticosteroid excretion appear to be unlikely explanations for the observed lipodystrophy. The cause remains to be elucidated.
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PMID:Endocrine and metabolic evaluation of human immunodeficiency virus-infected patients with evidence of protease inhibitor-associated lipodystrophy. 1037 88

Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is diminished and, in severe cases, thyroid-binding protein levels are decreased. In regards to GH, there is an increase in GH secretion with a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see text] changes in cortisol secretion in patients with anorexia nervosa resemble depression. They present with increased urinary free cortisol and serum cortisol levels but without changes in ACTH levels. In contrast to the findings observed in obesity, the ACTH response to CRH is suppressed, suggesting an increased secretion of CRH. The endocrine changes observed in obesity and starvation may complicate the diagnosis of primary endocrine diseases. The increase in cortisol secretion in obesity needs to be distinguished from Cushing's syndrome, the decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished from secondary hypothyroidism, and the increase in cortisol secretion observed in anorexia nervosa requires a differential diagnosis with primary depressive disorder.
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PMID:Effect of obesity and starvation on thyroid hormone, growth hormone, and cortisol secretion. 1205 88

The hormones with a strong influence on the lipid spectrum and the development of atherosclerosis include cortisol, growth hormone and oestrogens. Cortisol accelerates atherosclerosis both through dyslipidemia and through an increase in visceral fat, hypertension, increased insulin resistance and the development of reduced glucose tolerance which may result in diabetes mellitus. Even when a cortisol excess disappears, as is the case of patients cured of Cushing syndrome, arterial walls remain permanently vulnerable to the atherosclerotic process. In conditions involving a lack of growth hormone, dyslipidemia develops and increases the burden on the cardiovascular system if not treated in a timely manner by the substitution of growth hormone. Oestrogens have a double effect: they have an anti-atherogenic effect on artery walls that are not yet damaged by an atherosclerotic process, but where atherosclerosis has already developed they have a prothrombotic effect and destabilise the atheromatous plaques. If oestrogen is to be used as protection against the onset of atherogenesis, it is necessary to start in a period when the atherosclerotic process has not yet begun to damage the woman's arterial walls and it is best to use natural hormones (estradiol) and to prevent endometriosis it should be combined with crystalline progesterone applied locally--inravaginally. Oestrogens should be given in small doses, preferably parenterally. Even this will not prevent genetic oestrogen effects though.
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PMID:[How corticoids, growth hormone and oestrogens influence lipids and atherosclerosis]. 1757 71

Severe arterial hypertension is a hallmark of Cushing syndrome which occurs in 80% of the patients. Additionally, persistent cortisol excess induces obesity, hyperinsulinemia with disturbed glucose tolerance and dyslipidemia which all contribute to the development of hypertension and its deleterious sequelae. Cortisol effects are mediated through diversely distributed intracellular glucocorticoid and mineralocorticoid receptors which are protected by the 11-beta-hydroxysteroiddehydrogenase type 2 in cells of some organs (i.e. kidney) but not in other. A highly complex clinical picture evolves in case of hypercortisolism due to the ubiquitous distribution of steroid receptors with different affinity and binding capacities for glucocorticoids. The present review focuses on the cortisol induced changes in blood pressure regulation which contribute to the development of hypertension.
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PMID:[Glucocorticoids and hypertension]. 1909 17

Depressive and anxiety disorders are associated with an increased risk of cardiovascular disease. Chronic stress induces hypothalamus-pituitary-adrenal (HPA)-axis perturbations, which might subsequently induce atherogenic lipoprotein profiles and adiposity. The aim of the present study was to investigate the relationship between basal saliva cortisol levels and serum lipids and adiposity in psychiatric patients. Eight salivary cortisol samples (awakening; 30, 45, and 60 minutes after awakening; 11:00 AM, 3:00 PM, 7:00 PM, and 11:00 PM) on 2 consecutive days in medication-free outpatients with depressive and/or anxiety disorders (n = 72) and in healthy controls (n = 42) were used to derive 2 measures of HPA-axis function: basal cortisol concentrations (ie, area under the curve [AUC(cortisol)]) and circadian cortisol variability (variability(cortisol)). Index z scores were calculated for dyslipidemia (from serum triglycerides, inverse high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) and adiposity (from body mass index and waist-to-hip ratio). Regression analyses were conducted to determine the contribution of AUC(cortisol) and variability(cortisol) in explaining the variance of, respectively, the lipid and adiposity index. Patients showed a higher mean AUC(cortisol) compared with healthy controls (t = 2.7, P = .01). Both cortisol parameters were independently associated with dyslipidemia in patients after adjustment for age, alcohol use, and smoking habits (beta = .31, P = .02 and beta = -.29, P = .02, respectively), but not in controls. Cortisol measures were not associated with adiposity in either group. We conclude that elevated basal cortisol concentrations and lower circadian cortisol variability were independently associated with a less favorable lipoprotein profile in patients with depressive and/or anxiety disorders. These data lend support to the hypothesis that the relationship between affective disorders and cardiovascular disease is partly mediated by HPA-axis perturbations.
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PMID:Salivary cortisol, serum lipids, and adiposity in patients with depressive and anxiety disorders. 1937 26