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 authors review their experience (1967-present) in the use of cyproterone acetate (CPA) in precocious puberty. CPA was found effective in persistently suppressing pituitary gonadotropic secretion when administered orally at a dose of 50 mg b.i.d. (70-100 mg/d). After the introduction of gonadotropic analogues (GnRHa) for treatment of central precocious puberty, short term use of CPA was found useful to counteract the initial stimulatory effect of the GnRHa as well as an adjunct drug in case of very active adrenarche causing advanced bone age during GnRHa treatment. The final heights of girls treated with CPA and girls treated with D-Trp6-LHRH were found comparable: 157.8+/-5.1 cm vs 159.6+/-6.3 cm, respectively. The main adverse effects were occasional fatigue due to partial adrenal insufficiency with CPA and gynecomastia in a few boys. Liver function tests were normal in all patients with the exception of one boy with severe hypothalamic disease, including precocious puberty, who developed liver cirrhosis 3 years after stopping CPA following 5 years treatment. Other indications for CPA treatment during childhood and adolescence, such as fast puberty, congenital adrenal hyperplasia and acne, are also mentioned.
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PMID:Experience with cyproterone acetate in the treatment of precocious puberty. 1096 25

The liver plays important roles in the clearance and metabolism of sex steroids. Its dysfunction is considered to influence the metabolic pathways of sex steroids, and to result in gynecomastia and other abnormalities of sex steroids. However, the details of its mechanism have not been well-characterized. We therefore examined the enzymes involved in the hepatic clearance and/or metabolism of sex steroids in human liver and its disorders using immunohistochemistry to determine whether there are any abnormalities of expression of these enzymes in human liver disorders. These enzymes are 17beta-hydroxysteroid dehydrogenase (17beta-HSD) type 2, an enzyme that catalyzes the biologically active estrogen, estradiol (E2), to inactive estrogen, estrone (El), and dehydroepiandrosterone sulfotransferase (DHEA-ST), which catalyzes sulfonation of dehydroepiandrosterone (DHEA) to form biologically inactive DHEA-S. A total of 162 cases including normal liver (n=31), chronic hepatitis (n=41), liver cirrhosis (n = 21), hepatocellular carcinoma (n = 47), cholangiocellular carcinoma (n = 22) and fetal liver (n = 4) were examined by immunohistochemistry. Both enzymes were expressed in the hepatocytes around portal area and central vein in normal liver. Immunopositive area for DHEA-ST was significantly larger in chronic hepatitis than in normal liver, but that of 17beta-HSD type 2 in chronic hepatitis was not different from normal liver. There were no significant differences in the immunopositive area for both enzymes between liver cirrhosis and normal liver. In hepatocellular carcinoma, immunoreactivity for both enzymes were categorized into Group A, or low positive group, and Group B, or high positive group. The latter tended to be poorly differentiated carcinoma. In cholangiocellular carcinoma, immunopositive areas of both enzymes were significantly smaller than those of normal liver. These findings indicate that the amount of expression of the enzymes involved in metabolism and/or clearance of sex steroids per hepatocyte did not decrease in liver cirrhosis. Therefore, sex steroids' abnormalities may be due to the decreased quantity of hepatocytes associated with liver cirrhosis. In hepatocellular carcinoma, some poorly differentiated cases were associated with increased expression of 17beta-HSD type 2 but its biological significance needs to be determined by further studies.
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PMID:17Beta-hydroxysteroid dehydrogenase type 2 and dehydroepiandrosterone sulfotransferase in the human liver. 1122 44

We report a population-based case-control study on risk factors for male breast cancer. Data on a broad range of previously suggested risk factors were collected in a set of Scandinavian breast cancer cases and matched controls. Incident cases (n = 282) with histologically verified carcinomas of the breast were identified from notification to the cancer registries of Denmark, Norway and Sweden over a 4-year period 1987-1991 and of these cases, 156 men could be approached and responded. Controls were identified through national central population registers and were matched individually for country, sex and year of birth. Controls with a diagnosis of breast cancer were excluded; 468 of 780 controls responded. Data on risk factors were collected by self-administered questionnaires mailed to the cases between land 2 years after diagnosis and to controls during the same period. The findings were compatible with an increased risk associated with family history of breast cancer (odds ratio (OR) = 3.3, 95% confidence interval (CI) 2.0-5.6), obesity 10 years before diagnosis (OR = 2.1, 95% CI 1.0-4.5) for BMI > 30, diabetes (OR = 2.6, 95% CI 1.3-5.3) and the use of digoxin and methyldopa (OR = 2.0 and 2.1, respectively). The association with family history of breast cancer has been repeated in several studies, while the relation to anthropometric measures has been equivocal. We could not substantiate some associations seen in other studies; namely those with high education, fertility, marital status, testicular injury, liver disease and religion. The detailed questions about gynaecomastia indicated that many cases reported signs of breast cancer as a gynaecomastia. This type of misunderstanding may explain the strong association with gynaecomastia seen in other studies. Several patients died before contact. Thus, risk factors related to a more aggressive male breast cancer or related to high risk of dying (e.g. liver cirrhosis, heavy smoking) may have been missed.
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PMID:Risk factors for male breast cancer--a case-control study from Scandinavia. 1150 5

Gynecomastia develops when there is an increase in the ratio of estrogen to androgens. Whereas mild forms of gynecomastia are frequently encountered in the male population, any breast enlargement that is prominent, painful, progressive or of recent onset always requires a careful evaluation, as it may be an important clue to disease elsewhere. Underlying causes are plenty and include drugs, congenital and acquired disorders of androgen and estrogen production, various tumors, renal failure, cirrhosis of the liver, and thyrotoxicosis. Evaluation includes a careful patient's history, physical examination of sexual characteristics and the breast tissue, and measurements of serum LH, FSH, testosterone, estradiol, hCG-beta, TSH and tests of liver and kidney function.
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PMID:[Disordered hormone regulation in gynecomastia]. 1270 23

The edematous states, specifically those in CHF and cirrhosis of the liver, are associated with excessive aldosterone secretion and represent states of secondary hyperaldosteremia. Aldosterone promotes sodium retention by the renal tubules. Spironolactone, first introduced 50 years ago (1953), blocks the action of aldosterone on renal transport of electrolytes, thus acting as an effective diuretic, and in addition, has potentiating effects on other diuretics, including the thiazides. Spironolactone has undesirable side effects that have limited its clinical use; the most significant are impotence, gynecomastia, and hirsutism. Eplerenone, a recently introduced selective ARA, decreases morbidity and mortality in patients with CHF following MI and has none of the androgenic or estrogenic side effects of spironolactone. Eplerenone is an effective alternative for spironolactone.
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PMID:The resurrection of spironolactone on its golden anniversary. 1504 44

Hepatic fibrolamellar carcinoma (FLC) is an uncommon tumour that differs from hepatocellular carcinoma (HCC) in demographics, condition of the affected liver, tumour markers, and prognosis. FLC characteristically manifests as a large hepatic mass in adolescents or young adults with female predominance (mean age 23 years). Cirrhosis, elevated alpha-fetoprotein levels, and risk factors for HCC such as viral hepatitis are typically absent. FLC is usually associated with serum tumour markers such as vitamin B12 binding protein, and neurotensin. FLC is characterized pathologically by cords of tumour cells surrounded by abundant collagenous fibrous tissue arranged in a parallel or lamellar distribution. FLC usually appears on radiologic images as a lobulated heterogeneous mass with a central scar in an otherwise normal liver. The clinical presentation of patients with FLC is variable. These patients commonly have pain, and palpable right upper quadrant abdominal mass. An uncommon presenting sign is gynaecomastia in men. Use of percutaneous biopsy (FNAB) is beneficial if there is diagnostic uncertainty about the radiologic diagnosis (US, CT MRI). Although FLC is frequently recurrent, patients have a better prognosis than those with HCC, and aggressive surgical liver resection with extended lymphadenectomy or liver transplantation may be indicated. The presence of advanced-stage disease, direct invasion of adjacent organs, lymphadenopathy, or limited metastasis does not preclude attempts at curative resection. In inoperable cases, the patient may benefit from chemotherapy, permitting in up to 50% of these cases a curative resection. The case is reported of a 18-year-old man with bilateral gynecomastia secondary to an unknown hepatic fibrolamellar carcinoma producing oestrogens. Serum alpha-fetoprotein was negative; des-gamma-carboxy prothrombin (DCP) level was elevated. CT scan and MRI showed a solid hepatic tumour (theta 10 cm) without evidence of extrahepatic spreading. By a needle biopsy a fibrolamellar carcinoma was diagnosed. On March 1995 a right hemihepatectomy was performed. The postoperative course was uneventful and the patient recovered. Specimen's histologic examination confirmed the preoperative diagnosis. Intracellular (hepatocytes) oestrogens were found, but oestrogen and androgen receptors were negative. After surgery DCP and oestradiol levels rapidly decreased and gynaecomastia disappeared. A follow-up program was established. On April 2000 a probable recurrence within the caudate lobe was discovered by a liver CT scan without evidence of extrahepatic spreading. Tumour markers, FNAB, and bone scintigraphy were negative. On July 2000 the patient underwent second look laparotomy. Only a coeliac lymphadenopathy was found and a lymphadenectomy performed. Specimen's histologic examination showed a metastatic lymph nodal disease (FLC). The postoperative course was uneventful and the patient recovered. He is currently alive without evidence of recurrence 5 years after the second operation.
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PMID:[Surgical therapy of hepatic fibrolamellar carcinoma]. 1751 32

Male breast cancer accounts for about 1% of all breast cancers and bilateral breast cancer in men is therefore a rare event. Data in literature indicate that approximately 20% of these tumours are due to a probable alteration in the oestrogen metabolism. Hepatocellular carcinoma (HCC) on the other hand, is a much more frequent tumour and in 70-80% of cases is associated with cirrhosis. The proven concomitance of cirrhosis and gynecomastia in HCC or previous intake of oestrogen in breast cancer, would indicate possible involvement of the hormonal metabolism in the appearance of the two neoplastic forms. To our knowledge a case with these two malignant diseases in the same male patient is an exceptional event, rarely reported in literature. The fact that the breast cancer was bilateral in a male patient, the diverse histogenesis of the two breast cancers and the association with HCC in cirrhosis, led us to investigate into any common eziopathogenetic elements.
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PMID:Bilateral breast cancer in a male patient with hepatocellular carcinoma. A case report. 1872 74

The etiology of male breast cancer is largely unknown, reflecting its relative rarity. Although a number of previous studies have suggested relationships with a variety of medical conditions, the results have largely derived from case-control studies and may reflect recall biases. Within the large U.S. Veterans Affairs computerized medical care system database, we had the opportunity to access 26 million hospital discharge records over the period 1969-1996 and to relate various documented medical conditions to the risk of subsequent male breast cancer. This allowed us to calculate relative risks (RR) and 95% confidence intervals (CI) for male breast cancer associated with conditions occurring one or more years after initial hospitalization, adjusted for age, race, calendar year, duration of follow-up, and number of hospital visits. Among 4,501,578 men aged 18-100 years, a total of 642 cases of primary male breast cancer were identified (523 among whites, 119 among blacks). Medical conditions that were significantly related to risk were diabetes (RR 1.30, 95% CI 1.05-1.60), obesity (1.98, 1.55-2.54), orchitis/epididymitis (1.84, 1.10-3.08), Klinefelter syndrome (29.64, 12.26-71.68), and gynecomastia (5.86, 3.74-9.17). Additionally, among black patients, cholelithiasis emerged as a significant risk predictor (3.45, 1.59-7.47). Diseases that have previously been related to male breast cancer risk that were not supported by our study results included thyroid diseases, smoking-related conditions, liver cirrhosis, prostatic hyperplasia, and fractures. After adjustment for obesity, the association with diabetes disappeared, but that with gynecomastia persisted. In multivariate models that simultaneously considered all important medical predictors of risk, significant risks were seen for Klinefelter syndrome (16.83, 6.81-41.62), gynecomastia (5.08, 3.21-8.03), obesity (1.91, 1.50-2.44), and orchitis/epididymitis (1.80, 1.08-3.01). These results support previous speculations that male breast cancer is influenced not only by tissue at risk, but also by hormonal and inflammatory factors.
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PMID:Etiologic factors for male breast cancer in the U.S. Veterans Affairs medical care system database. 1933 May 25

Gynecomastia involves enlargement of the male breast secondary to the proliferation of mammary ductules. It is seen in a number of conditions such as cirrhosis, chronic renal failure, Klinefelter syndrome, and leprosy. Recognition of the cutaneous manifestations of these conditions can help in identifying the correct etiology of the gynecomastia.
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PMID:Cutaneous manifestations of systemic conditions associated with gynecomastia. 2052 39

Gynecomastia is defined as benign proliferation of glandular breast tissue in men. Physiologic gynecomastia is common in newborns, adolescents, and older men. It is self-limited, but can be treated to minimize emotional distress and physical discomfort. Nonphysiologic gynecomastia may be caused by chronic conditions (e.g., cirrhosis, hypogonadism, renal insufficiency); use of medications, supplements, or illicit drugs; and, rarely, tumors. Discontinuing use of contributing medications and treating underlying disease are the mainstay of treatment. Medications, such as estrogen receptor modulators, and surgery have a role in treating gynecomastia in select patients. Treatment should be pursued early and should be directed by the patient.
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PMID:Gynecomastia. 2253 49


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