Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The renin-angiotensin-aldosterone system (RAAS) is characterized by a circadian rhythm (CR) whose acrophase is detectable early in the morning. The prorenin and angiotensin converting enzyme (ACE) show a CR as well. However, while the prorenin is in phase with the RAAS the ACE shows its circadian acrophase in the afternoon suggesting a negative feed-back. The RAAS CR is influenced by many factors. Its mesor is modified by sodium intake. The physical activity and rest affect both the mesor and acrophase. The variations in mesor amplitude and acrophase in aged subjects are conditioned by sex and physical activity. Moreover, the RAAS CR seems to be influenced by the race. In addition, it is abolished by the beta-adrenergic blockade, suggesting the existence of an adrenergic clock. Interestingly, the RAAS CR seems not to be a pacemaker for the blood pressure CR, whose acrophase is early in the afternoon. The RAAS CR is not substantially modified has in essential hypertension. However, the CR of plasma renin activity is disappeared in the low-renin essential hypertension, while the CR of plasma aldosterone is detectable. On the contrary, the aldosterone CR is not detectable in ascitic liver cirrhosis; but, it is restored when the ascites is removed by peritoneal-jugular shunt. No significant variation of the RAAS CR seems to occur in obesity and Cushing's syndrome. The RAAS CR has disappeared in Conn's disease as well as in Bartter's syndrome and Liddle's syndrome. The administration of indomethacine in Bartter's syndrome and of triamterene in Liddle's syndrome is able to restore the RAAS CR. Finally, the RAAS CR is not detectable in the heart or kidney transplanted patients; such a phenomenon could be attributed to cyclosporine and corticosteroids administration and to the denervation of the transplanted organs.
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PMID:[Circadian rhythm of the renin-angiotensin-aldosterone system: a summary of our research studies]. 1555 56

Apparent mineralocorticoid excess (AME) syndrome results from defective 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). This enzyme is co-expressed with the mineralocorticoid receptor (MR) in the kidney and converts cortisol (F) to its inactive metabolite cortisone (E). Its deficiency allows the unmetabolized cortisol to bind to the MR inducing sodium retention, hypokalemia, suppression of PRA and hypertension. Mutations in the gene encoding 11beta-HSD2 account for the inherited form, but a similar clinical picture to AME occurs following the ingestion of bioflavonoids, licorice and carbenoxolone, which are competitive inhibitors of 11beta-HSD2. Reduced 11beta-HSD2 activity may explain the increased sodium retention in preeclampsia, renal disease and liver cirrhosis. Relative deficiency of 11beta-HSD2 activity can occur in Cushing's syndrome due to saturation of the enzyme and explains the mineralocorticoid excess state that characterizes ectopic ACTH syndrome. Reduced placental 11beta-HSD2 expression might explain the link between reduced birth weight and adult hypertension. Polymorphic variability in the HSD11B2 gene in part determines salt sensitivity, a forerunner for adult hypertension onset. AME represents a spectrum of mineralocorticoid hypertension with severity reflecting the underlying genetic defect in the 11beta-HSD2; although AME is a genetic disorder, several exogenous compounds can bring about the symptoms by inhibiting 11beta-HSD2 enzyme. Substrate excess as seen in Cushing's syndrome and ACTH ectopic production can overwhelm the capacity of 11beta-HSD2 to convert F to E, leading up to an acquired form of AME.
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PMID:Apparent mineralocorticoid excess syndrome: an overview. 1576 40

The liver and its pleotropic functions play a fundamental role in regulating metabolism, and is also an inevitable target of multiple metabolic disorders. The numerous and constant relationships and feedback mechanisms between the liver and all endocrine organs is reflected by the fact that an alteration of one oftentimes results in the malfunction of the other. Hypo- and hyperthyroidism are frequently associated with hepatic alterations, and thyroid diseases must be excluded in transaminase elevation of unknown cause. Drugs such as propylthiouracil, used in the treatment of hyperthyroidism, may induce liver damage, and other drugs such as amiodarone, carbamazepine, and several chemotherapeutic agents can lead to both thyroid and liver abnormalities. Liver diseases such as hepatitis, hepatocellular carcinoma, and cirrhosis may cause altered levels of thyroid hormones, and alcoholic liver disease, both due to the noxious substance ethanol as well as to the hepatic damage it causes, may be responsible for altered thyroid function. Both excess and insufficiency of adrenal function may result in altered liver function, and adrenocortical dysfunction may be present in patients with cirrhosis, especially during episodes of decompensation. Again an important player which affects both the endocrine system and the liver, alcohol may be associated with pseudo-Cushing syndrome. Sex hormones, both intrinsic as well as extrinsically administered, have an important impact on liver function. While oestrogens are related to cholestatic liver damage, androgens are the culprit of adenomas and hepatocellular carcinoma, among others. Chronic liver disease, on the other hand, has profound repercussions on sex hormone metabolism, inducing feminization in men and infertility and amenorrhoea in women. Lastly, metabolic syndrome, the pandemia of the present and future centuries, links the spectrum of liver damage ranging from steatosis to cirrhosis, to the array of endocrine alterations that are features of the syndrome, including insulin resistance, central obesity, and hyperlipidaemia. Clinical practice must integrally evaluate the effects of the intricate and tight relationship between the liver and the endocrine system, in order to better address all manifestations, complications, and prevent deterioration of one or the other organ-system.
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PMID:Liver abnormalities and endocrine diseases. 2409 Sep 42

The hallmark manifestations of Cushing's syndrome (CS) are well known, but hypercoagulability is perhaps least recognized. Patients with CS are at increased risk of both spontaneous and postoperative thromboembolism, with the significant majority of events occurring in the lower extremity and pulmonary venous circulations. We present a case of portal vein thrombosis (PVT) occurring in the setting of newly diagnosed CS due to a left adrenal adenoma. Factor VIII activity was approximately 2.5-fold elevated, a known mechanism by which hypercortisolemia predisposes to venous thrombosis. Acute abdominal pain and fever responded well to unfractionated heparin and parenteral antibiotics, and CS was eventually cured by left adrenalectomy. No thromboembolic events have occurred since surgery. PVT is uncommon and usually occurs as a complication of primary or secondary hepatobiliary malignancies and cirrhosis. To the best of our knowledge, this is just the second reported case of PVT due to CS and the first published in the English language literature.
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PMID:Portal Vein Thrombosis in the Setting of Newly Diagnosed Cushing's Syndrome. 2849 82


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