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)

We studied endocrine functions at baseline and after TRH and LHRH stimulation in a group of 7 young male patients with genetic hemochromatosis (HE) without liver damage (i.e. fibrosis and cirrhosis). In five patients endocrine re-evaluations after complete iron depletion was also performed. Mean basal testosterone (T), FSH, LH and PRL were significantly lower than in controls. Serum T increased normally after HCG stimulation. The normal or high increments of LH after LHRH stimulation suggest that secretion capacity of LH was intact and that hypothalamic dysfunction could be responsible for the preclinical gonadal deficiency found in our patients. The response of PRL to TRH indicates that secretion capacity of lactotrophs although present, was decreased and did not improve after phlebotomy therapy. After iron depletion the two patients with the lowest basal T levels showed the highest increments indicating that in the early stages of hypothalamic-pituitary damage gonadal dysfunction is still reversible in HE patients.
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PMID:Preclinical hypogonadism in genetic hemochromatosis in the early stage of the disease: evidence of hypothalamic dysfunction. 140 47

Unlike other pituitary hormones, PRL is under tonic inhibition by the hypothalamus by way of the PRL inhibitory factor, dopamine. GAP and GABA may also be inhibitory. PRL-releasing factors include TRH and VIP and possibly others. Circulating PRL is predominantly monomeric, although some patients with hyperprolactinemia appear to have increased quantities of the less biologically active polymeric forms. PRL is secreted episodically, with an increase in the amplitude of the secretory pulses with sleep. A transitory increase also occurs in response to the protein component of meals. Basal PRL levels increase in response to the hormonal milieu of pregnancy, and suckling postpartum triggers PRL release. Pathologic increases of PRL owing to hypothalamic dysregulation occur with a variety of medications, including the neuroleptics, metoclopramide, antidepressants, methyldopa, reserpine and verapamil, abuse of opiates and cocaine, renal insufficiency, cirrhosis, hypothyroidism, adrenal insufficiency, neurogenic stimulation, and idiopathically. Hyperprolactinemia also may occur from structural lesions of the stalk and hypothalamus, which cause disinhibition with or without maintenance of PRF activity, ectopic neoplasm production, and, most commonly, from prolactinomas. Diagnostic testing consists of routine chemistry and thyroid testing and imaging with MRI or CT. Dopamine agonists are the treatment of choice of prolactinomas of all sizes. Transsphenoidal surgery is an alternative for the patient who does not respond to medical therapy or who wishes definitive tumor removal, realizing that long-term cure is achieved in only 50% to 60% of patients with microadenomas and a much lower number in those with macroadenomas. Radiotherapy is reserved for patients who do respond to either medical or surgical treatment. Patients wishing to become pregnant usually are treated with bromocriptine, although prepregnancy surgical debulking may be advisable for those with large macroadenomas to reduce problems with tumor enlargement.
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PMID:Pathologic hyperprolactinemia. 148 80

Systemic disorders clearly may exert a significant influence on neuroendocrine function. Disorders that cause significant stress to the body, either physical or psychological, may cause a resetting upward of the HPA axis to provide sufficient cortisol to counteract the stress and to help sustain energy substrate levels. GH levels also increase in many of these situations, again promoting sufficient energy substrate levels. In some circumstances the concomitantly low somatomedin activity may be speculated to be adaptative to prevent the insulin-like agonist activity of these substances as well as to prevent energy expenditure in body growth. However, in other situations such as chronic renal failure and cirrhosis, the decreased somatomedin activity may be primary, causing decreased feedback at the hypothalamic-pituitary level and increased GH levels. The stress-induced rise in PRL may also play a minor role in preserving energy substrate since high levels may promote insulin resistance. In most illnesses the 'euthyroid sick syndrome' develops. Whether such patients are 'euthyroid' or mildly hypothyroid is a matter of controversy. The fact that protein losses are increased during fasting when the lowered T3 levels are returned to normal with exogenous T3 supplementation suggests that these patients are indeed hypothyroid and this hypothyroidism serves to conserve energy substrate by decreasing the metabolic rate. The reproductive axis is often impaired with systemic illness. Again, teleologically this may be viewed as an inactivation of non-essential functions in times of stress. It would appear that the changes that occur with systemic illness, in general, are favourable to the organism in that they promote survival. The detailed neurotransmitter and hypophyseotrophic hormone changes resulting in the alteration in pituitary function remain to be elucidated for the most part.
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PMID:Neuroendocrine alterations in systemic disease. 632 68

Prolactin levels are elevated in patients with liver cirrhosis and hepatic encephalopathy. Patients with hepatic encephalopathy also have an abnormal plasma amino acid composition, with a relative excess of aromatic amino acids, and a relative decrease in branched chain amino acid levels. In order to study the effect of the plasma amino acid composition on prolactin release, we measured plasma PRL at 0, 10, 20, 30, 40, 50 and 60 minutes after 400 micrograms TRH, both after infusion of a conventional amino acid mixture and after a branched chain amino acid enriched mixture (BCAA) in 5 patients with cirrhosis of the liver and hepatic encephalopathy. After conventional amino acid infusion, a depressed branched chain/aromatic amino acid ratio was found in all patients, together with an increased PRL response to TRH. After BCAA infusion the branched chain/aromatic amino acid ratio normalized. At the same time the excessive PRL response to TRH stimulation was significantly lower in all patients. This suggests that the elevated PRL levels in hepatic encephalopathy are caused by a disturbance of hypothalamic neurotransmitter systems, due to altered amino acid-neurotransmitter precursor levels.
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PMID:Hyperprolactinemia in hepatic encephalopathy: the effect of infusion of an amino acid mixture with excess branched chain amino acids. 641 78

Urinary excretion of estrogens and plasma concentrations of estrone, estradiol, LH, FSH, PRL, progesterone, testosterone, and sex hormone binding globulin were measured in nine chronic alcoholic women with cirrhosis or alcoholic fatty liver. They were aged 24-40 yr and all had secondary amenorrhea which had lasted for at least 3 months. The response of pituitary gonadotropin secretion to administration of LHRH and estradiol benzoate and of PRL secretion to TRH were also investigated. Urinary excretion of estrogens in the alcoholic women with liver disease was similar to that in normal postmenopausal women and less than half that in normal women of the same age in the midfollicular phase of the menstrual cycle. Plasma estradiol levels in the alcoholic women were lower than in the menstruating women but higher than in the postmenopausal women, whereas their plasma estrone levels were higher than in the menstruating women. Plasma concentrations of progesterone and testosterone in the alcoholic women did not differ from those in the postmenopausal women but were lower than in the menstruating women. In spite of the relative estrogen deficiency plasma LH and FSH levels were not elevated in the alcoholic women. The responses of LH and FSH to LHRH were similar in the patients and in the menstruating women. Intramuscular administration of estradiol benzoate did not increase plasma LH and FSH concentrations in the alcoholic women. Hyperprolactinemia was not found and there were no differences in the PRL responses to TRH between the patients and the control groups. In conclusion, disturbed regulation of gonadotropin secretion is an important factor in the genesis of estrogen deficiency and amenorrhea in alcoholic women with liver disease, although ovarian function may also be directly impaired.
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PMID:Sex hormones in amenorrheic women with alcoholic liver disease. 642 68

Infusion of a mixture of branched-chain 1-amino acids (BCAA; isoleucine, leucine, and valine) in six male patients suffering from hepatic cirrhosis led to an increase in serum GH, while serum PRL was not affected. In the same patients arginine infusion stimulated GH and PRL release. These findings demonstrate that hypothalamo-pituitary responsiveness to amino acid stimulation is preserved in cirrhosis and that administration of these amino acids has some endocrine effect.
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PMID:Changes in pituitary secretion after administration of branched-chain amino acids to patients with hepatic cirrhosis. 666 75

Basal plasma thyroid hormone, testosterone and cortisol levels, TSH and PRL responses to TRH, and LH and FSH responses to LRH were assessed in six young subjects with normal liver function and anatomy before and after portacaval anastomosis. All tests were normal and unchanged by the operations. It is concluded that in patients with normal liver function, portal systemic shunting does not produce alterations in the pituitary-gonadal and pituitary-thyroid axes. The abnormalities of these endocrine functions in patients with cirrhosis are probably related to the severity of hepatocellular dysfunction rather than to the effects of portal systemic shunting.
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PMID:Pituitary and thyroid function before and after portacaval anastomosis in patients with normal livers. 677 96

The relationship between chronic hepatosplenic schistosomiaisis (CHES) and circulating thyroid hormones as well as the TSH response to TRH were investigated in 41 hospitalized CHES patients and compared to those in 11 patients with non-CHES cirrhosis with severe hepatic failure. CHES patients were subdivided into 3 groups depending on the severity of parenchymal dysfunction, based upon a composite clinical and laboratory index. Angiographic and hemodynamic studies of CHES patients revealed altered hepatic arteriograms, suggesting a decreased arterial blood flow associated with an increased venous blood flow from the portal system. A significantly reduced serum concentration of total T4 (but not free T4) was only found in the cirrhotic patients. Compared to CHES groups I and II, CHES group III patients and the non-CHES cirrhotics had significantly lower mean serum T3 levels of 80 +/- 12 and 52 +/- 8 ng/dl, respectively. The serum rT3 concentration was elevated (69 +/- 6.2 ng/dl) only in the cirrhotic patients. Both basal and peak TSH levels after TRH were within the normal range for all 4 groups of patients. The basal (40.7 +/- 8.3 ng/ml) and peak (85.5 +/- 13.7 ng/ml) serum PRL levels T4-binding globulin after TRH administration were only elevated in the cirrhotic group. Although the mean T4-binding globulin values were lower in CHES group III (17.5 +/- 3.2 micrograms/ml) and in the non-CHES cirrhotic group (18.3 +/- 2.1 micrograms/ml) compared to those in groups I (21.8 +/- 2.2 micrograms/ml) and II (20.4 +/- 2.3 micrograms/ml), the differences between groups were not statistically significant. It was concluded that hemodynamic changes without parenchymal failure have little, if any, effect on the hepatic T4 5'-monodeiodination to T3, and that the low T3 and high rT3 state does not modify the pituitary secretion of TSH, presumably by a local (at the thyrotroph level) normal conversion of T4 to T3, even at very low peripheral T3 concentrations.
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PMID:Thyroid function and chronic hepatosplenic schistosomiasis: peripheral conversion of thyroxine to 3,5,3'-triiodothyronine and pituitary-thyroid relationship. 680 3

Chronic liver disease is associated with raised basal and TRH-stimulated PRL and GH levels. In a recent study we found the kidney to be the main site of prolactin elimination in patients with liver disease. In order to determine whether this is specific for PRL or a more general mechanism for polypeptide removal, we studied the elimination of GH, which resembles PRL in molecular weight and primary amino acid sequence, in 5 patients with portal hypertension and hepatic cirrhosis and 5 patients with noncirrhotic portal hypertension. Plasma GH levels were measured before and after TRH in peripheral, hepatic and renal vein samples, taken during diagnostic hepatic vein catheterization. An excessive paradoxical increase of GH after THR stimulation was found in 4 out of 5 cirrhotic patients but in none of the noncirrhotic individuals (p less than 0.025). After TRH the mean hepatic venous levels were significantly lower than the peripheral venous levels in 4 out of 5 noncirrhotic patients but in only 1 of the 5 cirrhotic patients (p less than 0.05). The mean renal vein GH levels were significantly lower than the peripheral levels in 3 out of 5 noncirrhotic patients and in none of the cirrhotic patients. In 2 patients in whom renal and hepatic plasma flow was measured, renal extraction of GH was found to be 0 to 6.4 micrograms, while liver extraction amounted to 22.1 and 34.7 micrograms of GH during the same 60-min period. Despite the similarity in molecular weight and primary amino acid sequence between PRL and GH, GH appears to be mainly taken up by the liver while PRL is mainly eliminated by the kidney in this group of patients with portal hypertension. This suggests that the renal elimination of prolactin is not solely dependent on glomerular filtration. The selective hepatic removal of growth hormone is probably related to a specific action of growth hormone on liver metabolism.
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PMID:Peripheral elimination of growth hormone in chronic liver disease. 680 53

Variations in PRL secretion were observed during chronic hepatic disorders. The aim of our study was to evaluate the behaviour of PRL in patients affected by hepatic cirrhosis. 6 patients (4 males and 2 females) were studied and matched with a group of healthy controls. In all subjects PRL values were evaluated in basal conditions and after TRH stimulation. The results obtained showed higher basal levels of PRL, together with higher and more prolonged TRH responses in patients with hepatopathies than in controls (p < 0.01). These abnormalities in PRL secretion during hepatic cirrhosis could be due to alterations of neurotransmitters at central level.
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PMID:[Blood prolactin patterns in hepatic cirrhosis]. 780 Jan 92


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